ALTERNATIVE

SOURCES OF HUMAN

PLURIPOTENT STEM

CELLS

ALTERNATIVE SOURCES 

OF 

HUMAN PLURIPOTENT 

STEM CELLS 

A White Paper of 

The President’s Council on Bioethics

Washington, D.C. 

May 2005 

www.bioethics.gov 

v

Contents 

LETTER OF TRANSMITTAL TO THE PRESIDENT ix 

MEMBERS OF THE PRESIDENT’S COUNCIL ON BIOETHICS xi 

COUNCIL STAFF AND CONSULTANTS xv 

PREFACE xvii 

Introduction 1

I. Pluripotent Stem Cells Derived from Organismically 

Dead Embryos (Landry-Zucker Proposal) 8 

 A. Is It Ethically Sound? 11 

1. Can we be certain that the IVF embryos used in 

 this proposal are really dead? 11 

 2. Will not this proposal put embryos at additional 

 risk? 14 

 3. Changing practices and incentives for IVF 

 practitioners. 15 

 4. Issues for informed consent. 16 

 5. For ethical purposes, is there a sufficiently strong 

 analogy between harvesting cells from dead 

 embryos and harvesting organs or removing 

 tissues from dead persons? 17 

 B. Is It Scientifically Sound? 18 

1. Can one find objective markers for organismic 

 death? 18 

 2. Can one in fact get usable pluripotent stem cells 

 from dead embryos? 19 
vi ALTERNATIVE SOURCES

OF HUMAN PLURIPOTENT STEM CELLS

 3. Will the stem cells derived from dead embryos 

 be normal and healthy? 20 

 C. Is It “Realistic”? 21 

1. Scientific acceptance. 21 

2. Eligibility for federal funding. 22

II. Pluripotent Stem Cells via Blastomere Extraction from 

Living Embryos 24 

 A. Is It Ethically Sound? 25 

1. Harm to the embryo? 25 

2. Are the removed blastomeres not themselves 

 the equivalent of embryos or capable of 

 developing into them? 29 

3. May one perform non-harmful blastomere 

 extraction on embryos that are NOT going 

 to become children? 30 

4. Can the research necessary to test this 

 proposal be conducted in an ethically 

 acceptable manner? 30 

 5. Changing the practices of assisted 

 reproduction. 31

 B. Is It Scientifically Sound? 32 

 C. Is It “Realistic”? 34 

 1. Scientific acceptance. 34 

 2. Eligibility for federal funding. 35 
CONTENTS vii 

III. Pluripotent Stem Cells Derived from Biological 

Artifacts 36 

 A. Is It Ethically Sound? 38 

1. Would not this “artifact” really be a very 

 defective embryo? 38 

2. The ethics of egg procurement. 40 

3. Ethical concerns about ANT itself. 41 

4. Concerns about ANT on “slippery slope” 

 grounds. 42 

 B. Is It Scientifically Sound? 45 

 C. Is It “Realistic”? 47 

1. Scientific acceptance. 47 

2. Eligibility for federal funding. 48 

 D. Pluripotent Stem Cells via “Parthenogenesis.” 48 

IV. Pluripotent Stem Cells via Somatic Cell 

Dedifferentiation 50 

 A. Is It Ethically Sound? 51 

 B. Is It Scientifically Sound? 51 

 C. Is It “Realistic”? 54 

1. Scientific acceptance. 54

2. Eligibility for federal funding. 54 
viii ALTERNATIVE SOURCES

OF HUMAN PLURIPOTENT STEM CELLS

Conclusion 55 

Endnotes and References 62 

Appendix: Personal Statements 75 

MICHAEL S. GAZZANIGA 76 

ROBERT P. GEORGE 79 

(JOINED BY MARY ANN GLENDON, 

 AND ALFONSO GÓMEZ-LOBO) 

WILLIAM HURLBUT 82 

JANET D. ROWLEY 89 

MICHAEL J. SANDEL 91 

GLOSSARY OF TERMS 93
ix 

LETTER OF TRANSMITTAL TO

THE PRESIDENT OF THE UNITED STATES

The President’s Council on Bioethics 

1801 Pennsylvania Avenue, N.W., Suite 700 

Washington, D.C. 20006 

May 10, 2005 

The President 

The White House 

Washington, D.C. 

Dear Mr. President: 

I am pleased to present to you Alternative Sources of Human 

Pluripotent Stem Cells, a White Paper of the President's Council 

on Bioethics. 

Since the publication of our report, Monitoring Stem Cell 

Research, in January of 2004, the Council has continued to ponder 

and discuss the ethical challenges posed by human embryonic 

stem cell research and the demands of scientists to develop new 

human embryonic stem cell lines. While they may well in the 

future prove to be of considerable scientific and therapeutic 

value, new human embryonic stem cell lines cannot at present be 

obtained without destroying human embryos. As a consequence, 

the worthy goals of increasing scientific knowledge and 

developing therapies for grave human illnesses come into 

conflict with the strongly held belief of many Americans that 

human life, from its earliest stages, deserves our protection and 

respect. 

Seeking to advance biomedical science while upholding 

ethical norms, the Council has taken a keen interest in recent 

suggestions that science itself might provide a way around this 
x ALTERNATIVE SOURCES

OF HUMAN PLURIPOTENT STEM CELLS

ethical dilemma. Accordingly, we have been looking into ways 

of obtaining pluripotent, genetically stable, and long-lived 

human stem cells (the functional equivalent of human 

embryonic stem cells) that do not involve creating, destroying, or 

harming human embryos. We have found that there are, broadly 

speaking, four such possible approaches: stem cells might be 

obtainable from dead embryos; from living embryos, by nondestructive biopsy; from bioengineered embryo-like artifacts; and 

from reprogrammed adult somatic cells. In this White Paper, we 

introduce each of these four approaches and offer a preliminary 

analysis of their strengths and weaknesses, ethical, scientific, and 

practical. 

While different members of the Council assess the merits of 

the four proposals differently, the Council shares the view that 

the group of proposals here discussed—and others like them 

that they may stimulate—deserve the nation’s careful and 

serious consideration. We offer this White Paper both to enrich 

and inform public discussion of the ethical dimensions of stem 

cell research and especially to encourage scientists to explore 

these and other possible ways to press forward with pluripotent 

stem cell research in ways that all Americans can wholeheartedly support. 

Mr. President, allow me to join my Council colleagues and 

our fine staff in thanking you for this opportunity to offer you 

and the American people our assistance in the critical efforts to 

promote a biomedical science that will simultaneously serve 

human needs and preserve human dignity. 

 Sincerely, 

 

 Leon R. Kass, M.D. 

Chairman
xi

MEMBERS OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

LEON R. KASS, M.D., PH.D., Chairman. 

Addie Clark Harding Professor, The College and the 

Committee on Social Thought, University of Chicago. Hertog 

Fellow, American Enterprise Institute. 

BENJAMIN S. CARSON, SR., M.D.

Professor and Director of Pediatric Neurosurgery, Johns 

Hopkins Medical Institutions. 

REBECCA S. DRESSER, J.D., M.S. 

Daniel Noyes Kirby Professor of Law and Professor of Ethics in 

Medicine, Washington University, St. Louis. 

DANIEL W. FOSTER, M.D. 

Professor of Internal Medicine, John Denis McGarry, Ph.D. 

Distinguished Chair in Diabetes and Metabolic Research, 

University of Texas Southwestern Medical School. 

FRANCIS FUKUYAMA, PH.D. 

Bernard L. Schwartz Professor of International Political 

Economy, Paul H. Nitze School of Advanced International 

Studies, Johns Hopkins University. 

MICHAEL S. GAZZANIGA, PH.D. 

David T. McLaughlin Distinguished University Professor, 

Professor of Psychological and Brain Sciences, Director of the 

Center for Cognitive Neuroscience, Dartmouth College. 
xii ALTERNATIVE SOURCES

OF HUMAN PLURIPOTENT STEM CELLS

ROBERT P. GEORGE, J.D., D.PHIL. 

McCormick Professor of Jurisprudence, Director of the James 

Madison Program in American Ideals and Institutions, 

Princeton University. 

MARY ANN GLENDON, J.D., M. COMP. L. 

Learned Hand Professor of Law, Harvard University. 

ALFONSO GÓMEZ-LOBO, DR. PHIL. 

Ryan Family Professor of Metaphysics and Moral Philosophy, 

Georgetown University. 

WILLIAM B. HURLBUT, M.D. 

Consulting Professor in Human Biology, Stanford University. 

CHARLES KRAUTHAMMER, M.D. 

Syndicated Columnist. 

PETER A. LAWLER, PH.D.

Chairman of the Department of Government and International 

Studies, Dana Professor of Government, Berry College. 

PAUL MCHUGH, M.D. 

University Distinguished Service Professor of Psychiatry, Johns 

Hopkins School of Medicine. Professor, Department of Mental 

Health, Bloomberg School of Public Health, Johns Hopkins 

University. 

GILBERT C. MEILAENDER, PH.D. 

Phyllis & Richard Duesenberg Chair in Christian Ethics, 

Valparaiso University. 

JANET D. ROWLEY, M.D. 

Blum-Riese Distinguished Service Professor of Medicine, 

Molecular Genetics and Cell Biology, and Human Genetics, 

Pritzker School of Medicine, University of Chicago. 
MEMBERS OF THE COUNCIL xiii 

MICHAEL J. SANDEL, D.PHIL. 

Anne T. and Robert M. Bass Professor of Government, 

Harvard University.

DIANA J. SCHAUB, PH.D. 

Chairman of the Department of Political Science, Loyola 

College, Maryland. 

JAMES Q. WILSON, PH.D. 

James A. Collins Professor of Management and Public Policy 

Emeritus, University of California, Los Angeles. Reagan 

Professor of Public Policy, Pepperdine University. 

xv 

COUNCIL STAFF AND CONSULTANTS

Richard Roblin, Ph.D. 

Acting Executive Director 

Yuval Levin Laura Harmon, Esq.

former Senior Aide 

Acting Executive Director to the Chairman 

Tonia Busse Emily Jones

Staff Assistant Executive Administrator 

Bonnie Cameron Adam Schulman, Ph.D.

Staff Assistant Senior Research Consultant 

Eric Cohen O. Carter Snead, Esq.

Senior Research Consultant General Counsel 

Judith E. Crawford Audrea R. Vann

Administrative Director Information Technology 

 Specialist 

Diane M. Gianelli Bethany Warner

Director of Communications Receptionist/Staff Assistant 

Ginger Gruters Lee L. Zwanziger, Ph.D.

Staff Assistant Senior Research Analyst 

xvii 

Preface 

Alternative Sources of Human Pluripotent Stem Cells is a White 

Paper of the President’s Council on Bioethics, which was created 

by President George W. Bush on November 28, 2001, by means 

of Executive Order 13237. 

The Council’s purpose is to advise the President on 

bioethical issues related to advances in biomedical science and 

technology. In connection with its advisory role, the mission of 

the Council includes the following functions: 

• To undertake fundamental inquiry into the human and 

moral significance of developments in biomedical and 

behavioral science and technology. 

• To explore specific ethical and policy questions related to 

these developments. 

• To provide a forum for a national discussion of bioethical 

issues. 

• To facilitate a greater understanding of bioethical issues. 

The President left the Council free to establish its own priorities 

among the many issues encompassed within its charter and to 

determine its own modes of proceeding. 

Stem cell research has been of interest to, and associated in 

the public mind with, this Council since its creation. Taking up 

the charge given to us by President Bush in his August 9, 2001, 
ALTERNATIVE SOURCES

OF HUMAN PLURIPOTENT STEM CELLS

xviii 

speech on stem cell research, the Council has from its beginnings 

been monitoring developments in this fast-paced and exciting 

field of research. In January 2004, the Council published a report, 

Monitoring Stem Cell Research, which provided an overview of the 

law, ethics, and science of stem cell research. That report was 

intended to serve as a source of clear, intelligible, and useful 

information for both policymakers and the general public 

regarding the current state of this important research and of the 

debates that surround it. 

Much of the ethical controversy over stem cells derives from 

the fact that, until now, the only way to obtain human 

pluripotent stem cell lines has been to derive them from living 

human embryos by a process that necessarily destroys the 

embryos. If a way could be found to derive such stem cell lines 

without creating and destroying human embryos, a good deal of 

that ethical controversy would subside. 

The present White Paper may be regarded as a new 

contribution to the stem cell discussions. It reports on some 

recent developments that deserve public notice because of their 

potential for finding a morally uncontroversial means of 

obtaining pluripotent human stem cells. Over the past six 

months, the Council has been looking into specific scientific 

proposals for obtaining pluripotent, genetically stable, and longlived human stem cells by methods that would not involve 

destroying or endangering human embryos. In December 2004, 

the Council heard presentations of two such proposals, one by 

Drs. Donald Landry and Howard Zucker of the Columbia 

University College of Physicians and Surgeons, and the other by 

Dr. William Hurlbut of Stanford University (and a member of 

this Council). In March 2005, the Council discussed a staff 

working paper in which these two proposals, as well as two 

others, were explained and analyzed. 
PREFACE xix 

That staff working paper, extensively revised and improved 

in light of Council discussions and member comments, is what 

the Council is now issuing as a White Paper, Alternative Sources 

of Human Pluripotent Stem Cells. In its present form, the White 

Paper has also benefited from expert review by three prominent 

scientists (Andrew Fire of the Stanford University School of 

Medicine, Markus Grompe of the Oregon Health & Science 

University, and Janet Rossant of the Samuel Lunenfeld Research 

Institute in Toronto, Ontario), as well as consultation with 

scientists at the National Institutes of Health. 

The White Paper introduces the four proposals and begins an 

analysis of their strengths and weaknesses, ethical, scientific, and 

practical. Because the scientific and practical merits of these 

proposals are in large part empirical matters, not settled in 

advance by mere speculation, we give special weight to the 

ethical analysis. We also explore, in a preliminary way, whether 

these alternative avenues of deriving and using pluripotent stem 

cells are likely to be embraced by scientists or to become eligible 

for federal funding. 

It remains to be seen whether any of these proposals will 

succeed scientifically, and more discussion is surely required on 

some of the ethical issues we have identified. Nevertheless, 

having conducted this “preliminary hearing,” we believe that 

several of these possibilities have sufficient merit to commend 

them now to wider public attention and further scientific 

investigation. People of all moral and political persuasions 

should be pleased to learn that scientists and others are 

creatively seeking morally unproblematic and uncontroversial 

ways to advance this promising area of scientific research. 

In creating this Council, President Bush expressed his desire 

to see us 
ALTERNATIVE SOURCES

OF HUMAN PLURIPOTENT STEM CELLS

xx 

consider all of the medical and ethical ramifications of 

biomedical innovation. . . . This council will keep us 

apprised of new developments and give our nation a 

forum to continue to discuss and evaluate these 

important issues. As we go forward, I hope we will 

always be guided by both intellect and heart, by both our 

capabilities and our conscience. 

It has been our goal in the present White Paper, as in all of our 

work, to live up to these high hopes and noble aspirations. 

 LEON R. KASS, M.D. 

 Chairman 
Alternative Sources 

of 

Human Pluripotent 

Stem Cells 

1 

Introduction 

 Human embryonic stem cells hold great interest 

because of their pluripotency—their capacity to give rise to 

the various specialized cells of the body—and because of 

their longevity—their ability to be propagated for many 

generations in laboratory culture without losing their 

pluripotency. Until now, these cells have been obtainable 

only from living human embryos [at the 100-to-200-cell 

(blastocyst) stage of development] by a process that 

necessarily destroys the embryos and that therefore makes 

this research ethically controversial. Over the past several 

years, the ethical controversy has been the subject of 

federal (and state) legislation and public policy and of 

ongoing public debate.*

 

 

*

 Since 1995, Congress has annually enacted legislation (the Dickey 

Amendment) that prohibits the use of federal funds for research in 

which human embryos are destroyed or harmed. In 2001, President 

George W. Bush instituted the current policy, which permits federal 

funding for research on those embryonic stem cell lines already in 

existence, but not for derivation or use of any new lines (the creation of 

which would require new embryo destruction). Vigorous debates 

continue about the ethics of embryonic stem cell research, as well as 

about the federal funding policy. For a synoptic view of these ethical 

and political discussions, including a history of the relevant public 

policy decisions, see Monitoring Stem Cell Research: A Report of the 

President’s Council on Bioethics (2004), especially chapters two and three. 

For the text of the Dickey Amendment, see endnote 10. 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

2

 The President’s Council on Bioethics is committed to 

the goals of advancing biomedical science and upholding 

ethical norms. Notwithstanding our sometimes sharp 

individual ethical differences, we have recognized that all 

parties to the debates about embryo research have 

something vital to defend, and not only for themselves but 

for all of us.1 As members of a national public bioethics 

body, we are also mindful of the need to understand and 

respect the strongly held ethical views of our fellow 

citizens, even when we do not share them. For these 

reasons, we must be receptive to any creative scientific or 

technical suggestions that might enable scientists to 

proceed with their research in ways that would not raise 

ethical questions or violate the ethical principles of many 

Americans. 

 Accordingly, in an effort to find ethically 

uncontroversial ways to advance human embryonic stem 

cell research, the Council has recently been looking into 

specific proposals for obtaining pluripotent, genetically 

stable, and long-lived human stem cells by methods that 

would meet the moral standard of not destroying or 

endangering human embryos in the process. This White 

Paper introduces these proposals and begins an analysis of 

their strengths and weaknesses, ethical, scientific, and 

practical. Because the scientific and practical merits of these 

proposals are in large part empirical matters, not settled in 

advance by mere speculation, we give special weight to the 

ethical analysis. We also explore, in a preliminary way, 

whether these alternative avenues of deriving and using 

pluripotent stem cells are likely to be embraced by 

scientists or to become eligible for federal funding. 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

3

 Conceptually, four broad approaches present 

themselves. The stem cells could be derived: (1) by 

extracting cells from embryos already dead; or (2) by nonharmful biopsy of living embryos; or (3) by extracting cells 

from artificially created non-embryonic but embryo-like 

cellular systems (engineered to lack the essential elements 

of embryogenesis but still capable of some cell division and 

growth); or (4) by dedifferentiation of somatic cells back to 

pluripotency. In each of these four cases, the scientific 

standard by which success should be measured is only the 

desired functional capacity of the cells derived—stable 

pluripotency—and not their origin (embryos, adults, or 

artificial embryo-like clusters of cells). Should stem cells 

obtainable by one or another of these methods turn out to 

have exactly the same properties and capacities as 

embryonic stem cells (ESCs), their value for scientific 

research should be no different from that of standard ESCs. 

 Recently, more or less detailed examples of each of 

these four approaches have been proposed or discussed. 

 According to the first proposal, pluripotent human stem 

cells are to be derived from early IVF embryos (roughly 4-8 

cells) that have spontaneously died (as evidenced by the 

irreversible cessation of cell division) but some of whose 

blastomeres*

 appear normal and healthy. Crucial to this 

 

*

 A “blastomere” (literally, a part of a “blast” or embryo) is a cell 

contained within an early embryo (up to two days after conception), 

which comprises a small number of such blastomeres. Thus a 4-celled 

embryo contains four blastomeres, and an 8-celled embryo contains 

eight blastomeres. Beyond the 8-cell stage, on the third day after 

conception, the early embryo turns into a compact sphere known as a 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

4

approach is (a) enunciating a concept of organismic death 

of an early embryo and (b) devising criteria that permit a 

determination that embryonic death has occurred. In 

addition, to satisfy the moral standard, only those oncefrozen embryos that are thawed and that die spontaneously 

during efforts to produce a child will be eligible for postmortem cell extraction. This proposal was presented at the 

Council’s December 3, 2004, meeting by Drs. Donald 

Landry and Howard Zucker of the Columbia University 

College of Physicians and Surgeons. 

 According to the second proposal, pluripotent stem cells 

are to be derived from blastomeres obtained by biopsy of 

an early human embryo. Crucial to this approach is finding 

a stage of early embryonic development at which (a) the 

removal of one or a few cells by biopsy can be carried out 

without harming the embryo, while (b) the cell or cells 

removed from the embryo are usable as a source of 

pluripotent stem cells. 

 The third approach comprises a variety of proposals for 

engineering “biological artifacts” possessing some of the 

developmental capacities of natural embryogenesis (but 

lacking the organismal character of human embryos) and 

containing cells from which pluripotent stem cell lines can 

 

morula; and on the fifth day after conception, the morula becomes a 

blastocyst (100-200 cells), a hollow ball of cells surrounding an inner 

cell mass. The cells of an embryo at the morula or blastocyst stage, 

being more differentiated than those of a 4-8-cell embryo, will not be 

referred to here as blastomeres, although some authors use the term to 

describe any cells of an embryo before it cavitates to become a 

blastocyst. 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

5

be derived. Crucial to this approach is demonstrating both 

(a) that the developing entity is truly not a human embryo 

and (b) that the cells derived from it are in fact normal 

human pluripotent cells. In addition, one must show that 

creating such biological artifacts does not itself introduce 

other ethical problems. One such proposal (“Altered 

Nuclear Transfer”) was presented at the Council’s 

December 3, 2004, meeting by Council Member Dr. William 

Hurlbut. 

 The fourth proposal involves reprogramming human 

somatic cells, perhaps with the aid of special cytoplasmic 

factors obtained from oocytes (or from pluripotent 

embryonic stem cells), so as to “dedifferentiate” them back 

into pluripotent stem cells. Crucial to this approach is 

discovering a way to reverse cell differentiation all the way 

to pluripotency, but not (as in cloning) even further back to 

totipotency.*

 This White Paper describes each of these proposals and 

examines them with a view to the following three 

questions: 

 Ethical Question: Is it ethically sound? That is, would the 

proposed method overcome the ethical objections that have 

been raised against current methods of deriving embryonic 

 

*

 A totipotent cell (for example, the fertilized egg or zygote) is one that 

can give rise to the entire organism, including the extra-embryonic 

membranes; a pluripotent cell (for example, an embryonic stem cell) is 

one that can give rise to many if not all the different cell types of the 

human body, but not to the whole organism as a living integrated 

entity. 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

6

stem cells that entail the destruction of human embryos? 

And does the proposed method raise new ethical 

difficulties of its own that make it problematic, worrisome, 

or even unacceptable?*

 Feasibility Question: Is it scientifically sound? That is, 

might it reliably produce stable, pluripotent stem cell lines 

of sufficient quality for biomedical research and, in due 

course, for clinical trials in human beings? 

 Practical Question: From the perspective of both public policy 

and research practice, is this proposal “realistic”? That is, are 

there good reasons for believing that, if it is found to be 

scientifically feasible, it might be adoptable—by scientists 

as useful, by policy makers as legally eligible for federal 

 

*

 The discussions in this paper take for granted the existing practices of 

assisted reproduction, including in vitro fertilization, the storage of 

frozen embryos for later reproductive use, and preimplantation genetic 

screening and diagnosis (PGD) of in vitro embryos prior to their 

transfer to initiate a pregnancy. These practices raise ethical issues of 

their own, and some people (including some Council members) object 

to them altogether. Although we recognize that there are many, and 

often deep, questions connected with the growing control over all 

aspects of human procreation, we will (for the most part) not be 

analyzing or arguing those questions here. We recommend, however, 

that they not be lost sight of, especially as the political acceptability of 

some of the proposals reviewed here will be influenced by where 

people stand on those larger questions. And clearly, some people will 

evaluate the proposals here under review not solely in themselves, but 

also by assessing their relationship to and potential effect on the way 

assisted reproduction is practiced, and by judging whether the 

proposed uses of dead embryos, blastomere biopsy, egg harvesting, 

and altered nuclear transfer create incentives for engaging in practices 

they deem misguided, unethical, or unwise. 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

7

support, and by the people and their elected officials as 

morally worthy of federal support? (In considering these 

questions, as we will in each case below, we are not to be 

understood either (a) to be making predictions about what 

scientists will in fact believe or (b) to be offering 

recommendations for what policy makers should in fact do. 

The first must await the arrival of relevant options; the 

second must depend on an assessment of the ethical claims 

and on prudential judgments to be made in specific 

circumstances that we cannot predict. Still, practical people 

will want to know whether any of this could become useful 

scientific practice or wise public policy, and we are obliged 

to discuss some aspects of these questions.)*

 

*

 Even if one or more or of these alternative sources of pluripotent stem 

cells were to meet all these requirements (ethical soundness, scientific 

feasibility, eligibility for federal funding, and broad acceptability to 

scientists), there would still remain the question of whether the cost of 

pursuing such alternatives—the necessary investment of scientific 

energy and resources, and the possible diversion of such energy and 

resources from other promising avenues of research—would outweigh 

the benefits. This White Paper does not pretend to answer that serious 

question, for it cannot be answered a priori, in advance of knowing 

empirically those costs and benefits. Moreover, how any person 

answers that question will depend on how strongly he or she cares 

about the additional “benefits” and “costs” of requiring scientific 

research to respect certain moral boundaries and strongly held moral 

qualms, in this case about protecting the moral worth of embryonic 

human life. 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

8

I. Pluripotent Stem Cells Derived from Organismically 

Dead Embryos (Landry-Zucker Proposal2) 

 This proposal begins by making a close analogy with 

the use of human cadavers for biomedical research or as 

sources of organs. Today, we find morally and socially 

acceptable the removal (with consent) of vital organs from 

no-longer-living developed human beings once they have 

been declared dead.3 Therefore, Landry and Zucker 

suggest, we should also find morally and socially 

acceptable the removal (with consent) of materials for stem 

cell derivation from no-longer-living undeveloped human 

beings (human embryos) once they have been declared 

dead. Applying the traditional concept of death—the 

irreversible loss of the integrated functioning of an 

organism as a whole—to the earliest stages of human life, 

Landry and Zucker propose a concept of organismic death for 

the early-stage human embryo: the irreversible loss of the 

capacity for “continued and integrated cellular division, 

growth and differentiation.”*

 As the criterion for determining 

organismic death of an embryo produced by in vitro 

fertilization (IVF), they propose the “irreversible cessation 

of cell division in the embryo observed in vitro.” 

 After fertilization in vitro, a high percentage of human 

embryos that reach the 4- or 8-cell stage undergo 

 

*

 From reference 2: “We propose that the [minimal] defining capacity of 

a 4- or 8-cell human embryo is continued and integrated cellular 

division, growth and differentiation. We further propose that an 

embryo that has irreversibly lost this capacity, even as its individual 

cells are alive, is properly considered organismically dead.” 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

9

spontaneous “cleavage arrest”—that is, their cells simply 

stop dividing. The vast majority of these arrested embryos 

do not resume cell division, never form blastocysts, and are 

incapable of successfully implanting in the uterus. In most 

cases, spontaneous cleavage arrest is associated with 

chromosomal abnormalities in the cells of the developing 

embryos. Yet some of the arrested embryos turn out to be 

“mosaic”—that is, some of their cells exhibit chromosomal 

abnormalities, while others appear to be (chromosomally, 

at least) normal blastomeres. It is these normal-appearing 

blastomeres in cleavage-arrested, mosaic embryos that may 

turn out to be a source of embryonic stem cells. Landry and 

Zucker propose that those embryos that have undergone 

irreversible cleavage arrest should be declared 

organismically dead and hence suitable (with proper 

consent) for harvesting of blastomeres for stem cell 

derivation.*

 

To identify when organismic death occurs in IVF 

embryos, Landry and Zucker propose a two-part research 

strategy. First, they propose a “natural history” study to 

determine just when a non-flourishing embryo in vitro 

ceases cell division irreversibly: 

Previously frozen early embryos that have failed to 

divide within 24 hours of thawing and are [therefore] 

 

*

 The cells of an organismically dead embryo have stopped dividing 

altogether; their cleavage arrest is considered irreversible in the sense 

that the cells show no tendency to resume dividing while remaining part 

of the dead embryo. Of course, the goal of the Landry-Zucker proposal is 

to retrieve from these dead embryos some cells that can be induced to 

resume dividing under conditions conducive to stem cell derivation. 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

10

no longer wanted [because they are no longer fit] for 

their original reproductive purpose are observed 

every few hours for several additional 24-hour 

periods.*

 After observing several hundred embryos, 

the time beyond which no arrested embryo resumes 

division can be determined. One can reasonably 

conclude that embryos that have not divided by this 

period will not divide at any later time, i.e., they are 

organismically dead. 

Second, they propose an experimental study to attempt 

to identify physical or biochemical cellular markers that 

correlate with the arrest of cell division and in whose 

presence any arrested embryo could be declared dead: 

[IVF] Embryos declared [organismically] dead could 

then be characterized for secreted or cell surface 

markers or spectroscopic signatures that correlate 

with the arrest of cell division. These markers and 

signatures could then be tested for their predictive 

value. In this manner the criteria for determining the 

death of a human embryo could be refined. 

 

*

 It might be asked why Landry and Zucker confine their attention to 

embryos that have been frozen and then thawed, as opposed to “fresh” 

never-frozen embryos. The answer is that, in current IVF practice, 

healthy-looking embryos that have reached the 4- or 8-cell stage but are 

not selected for transfer to the uterus are generally frozen for possible 

future transfer attempts. To delay freezing such embryos while looking 

for signs of cleavage arrest would, arguably, subject the embryos to 

additional risk, contrary to the intention of the proposal. In contrast, 

the embryos of interest to Landry and Zucker—frozen embryos that are 

thawed out but never resume cell division—are not, in current IVF 

practice, either transferred to the uterus or frozen a second time. 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

11

According to Landry and Zucker, determining criteria 

of organismic death through the natural history study 

would be sufficient to commence efforts to derive human 

embryonic stem cells from dead embryos; the subsequent 

experimental study could facilitate this effort by rendering 

the determination of embryonic death more certain and 

reliable. 

A. Is It Ethically Sound? 

The Landry-Zucker proposal is based on an attractively 

simple ethical idea: it should be permissible to harvest cells 

from embryos that have died (provided of course that their 

deaths have not been caused or hastened for such 

purposes). Yet the final ethical assessment of this proposal 

will depend very much on exactly how it is implemented, 

within the practices and protocols of IVF. Several other 

pertinent questions have been raised as well. 

1. Can we be certain that the IVF embryos used in this proposal 

are really dead? 

This challenge unites two separate concerns, one about 

knowing whether the criteria for death have been met in 

any particular case, the other about the criteria themselves. 

Landry and Zucker propose to harvest cells from 4- or 

8-cell thawed human embryos that have irreversibly ceased 

to divide. Since the harvested cells are to serve as a source 

of stem cells, it is not feasible to wait for the death and 

dissolution of each and every cell before declaring the 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

12

embryo dead and eligible for use in research. To be useful 

for the project, the arrested embryos must contain at least 

some viable cells that retain normal developmental 

potential. Some of these cells, for example, might resume 

dividing if extracted and placed in the proper milieu. How, 

then, can we be sure that such an embryo is really dead? 

More generally, can we confidently declare that an embryo 

is dead just because all of its cells have stopped dividing? 

What exactly do we mean by the “organismic death” of an 

embryo? 

It must be acknowledged that the concept of organismic 

death—the death of an organism as a whole—has not been 

commonly applied to an embryo, that is, to any largely 

undifferentiated organism so close to the beginning of its 

life. Moreover, even granting the applicability of the 

concept, identifying the criteria for determining organismic 

death for an embryo is, at least for now, more difficult than 

it is for an adult, owing to the absence of any integrating 

vital organs. Unlike a person at the end of life, an embryo 

has no identifiable controlling organ—no brain to be 

considered “brain dead,” no heart that has ceased to beat 

and circulate the blood. For now, our judgment that an 

embryo has lost “integrated function as an organism” must 

be based simply on the observed absence of coordinated 

cell division. It is partly for that reason that Landry and 

Zucker hope that studies might reveal biochemical markers 

that would put the phenomenological finding of irreversible

cleavage arrest on a sounder, “more objective” footing. 

Yet despite these uncertainties, as Landry and Zucker 

suggest, the life of an embryo (as of any organism) is more 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

13

than just the sum of the lives of its constituent cells; and the 

death of an embryonic organism-as-a-whole is not the same 

thing as the death of its constituent cells. For the embryo to 

develop as an integrated organism, there must be an 

integrated set of internal signals directing the 

differentiation, development, and growth of the 

multicellular organism as a whole. The breakdown or 

absence of that set of signals amounts to the death of the 

developing embryo, manifested most clearly in the 

irreversible cessation of coordinated, organized cell 

division. Just as a person can be declared dead even while 

some of his organs and cells continue for a time to function 

and grow, so an embryo can undergo organismic death 

even while some of its individual cells may remain alive as 

cells, capable of further division if isolated and placed in a 

suitable environment. 

Landry and Zucker point to studies showing that a 

substantial proportion of IVF embryos, after thawing, never 

exhibit any further cell division, even though some of their 

blastomeres appear otherwise normal. It is these embryos, 

they suggest, that can be unambiguously declared 

“organismically dead,” and whose normal-looking 

blastomeres may be suitable candidates for embryonic stem 

cell derivation.*

 

*

 Yet here, too, a caution must be observed. As discussed elsewhere in 

this paper (see section 2 on p. 29, as well as endnote 18), we do not 

know precisely when, in embryonic development, human blastomeres 

cease to be totipotent, that is, individually capable of growing into a 

complete human being. To avoid the possibility that the cells extracted 

from a dead embryo might be totipotent, it would perhaps be advisable 

to carry out the Landry-Zucker proposal using somewhat older 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

14

2. Will not this proposal put embryos at additional risk? 

The Landry-Zucker proposal involves scrutinizing 

thawed IVF embryos for signs of death and extracting cells 

from organismically dead embryos. A reasonable concern 

is that this procedure should not expose any living human 

embryos to risks they would not ordinarily encounter in 

the practice of assisted reproduction. Sharing this concern, 

Landry and Zucker place special strictures on which 

embryos are to be used, both in natural history studies to 

determine the criteria of death and in subsequent stem cell 

derivations. The only embryos that would be considered 

for use would be those (1) that were originally created with 

reproductive intent, (2) that were thought healthy enough 

to be kept alive in cryostorage for possible second or third 

child-producing attempts, and (3) that, after thawing, 

turned out, alas, to be dead. The natural history research 

proposed by Landry and Zucker would simply continue to 

watch those embryos that were not making any 

developmental progress, in order to determine more 

precisely exactly when they were irreversibly incapable of 

further development. No living embryo would be subject 

to manipulative intervention or to any procedure that 

increased its exposure to harm. No new or extra embryos 

would be created for such research, and no embryo would 

be deliberately killed or otherwise exposed to harm. This 

“death watch” study proposed by Landry and Zucker 

seeks only to discover which embryos are already dead, not 

to induce weak or doomed embryos to die. 

 

cleavage-arrested embryos (containing 8 cells or more) rather than 

embryos as early as the 4-cell stage. 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

15

3. Changing practices and incentives for IVF practitioners. 

The proposed experiments to determine the natural 

history of organismic death in IVF embryos should be done 

in a way that does not compromise the safety of, or make 

more physically or psychologically onerous, current IVF 

clinical procedures. They also should not change incentives 

and practices regarding embryo production. Some people 

worry that approving the use of dead embryos for stem cell 

derivation will lead to the creation of even more embryos 

than are now produced in excess of reproductive need, 

precisely so that some could be allowed to die for the sake 

of getting stem cells from them. Yet it is important to note 

that, under the Landry-Zucker proposal, embryos that 

divide normally upon thawing, but are allowed to die by a 

human decision (not to transfer them into a woman’s 

uterus), would not be eligible for donation. Precisely in 

order to avoid participation or complicity in the death of 

any embryos, their proposal restricts use to only those 

embryos that fail altogether to divide upon thawing and 

that have thus died “on their own.” For now, no change of 

practice or incentives would be likely or necessary, since 

many embryos are thawed for a second reproductive trial 

and, of these, a sizeable fraction (in some cases, close to one 

half) fail to develop.4 Still, going forward it will be 

important to provide oversight and assurance that the 

desire for material useful for the natural history study or 

for stem cell derivation does not increase either the number 

of frozen embryos that are thawed in an attempt to 

produce a second pregnancy or the number created for 

reproductive purposes in the first place. It would be an 

ethically dubious innovation if the implementation of the 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

16

Landry-Zucker proposal were to change the incentives or 

the practices of IVF embryo creation or storage in these 

ways.*

4. Issues for informed consent. 

Additional discussions with the embryo-producing, 

child-seeking patients that explain (and seek consent for) 

the proposed experiment and use will be required. And a 

fitting informed-consent form will have to be developed 

and approved. While this is well within the scope of 

present practice, it will necessarily involve discussion of 

the likely death of some embryos created by the IVF 

procedure. Many clinicians shy away from using the word 

“death” to describe what happens to the embryos that do 

not develop in vitro, fearful that such a designation would 

imply that those embryos were in fact alive and that they 

might therefore be held at fault for their resulting deaths. 

Nevertheless, only a frank discussion of these facts could 

produce meaningful consent from the patients. Discussion 

and suitably documented agreements will also be needed 

to address additional questions, including who owns the 

commercial rights to any human pluripotent stem cell line 

created by this research. 

 

*

 To turn this morally scrupulous proposal into morally scrupulous 

practice would seem to require protocols and enforceable regulations 

that would provide very strict monitoring and oversight. The political 

acceptability of the Landry-Zucker proposal might hinge on having a 

regulatory system in place so that there would be some way to track 

IVF embryos (as the Canadians do), thus ensuring that abuses do not 

creep in. 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

17

5. For ethical purposes, is there a sufficiently strong analogy 

between harvesting cells from dead embryos and harvesting 

organs or removing tissues from dead persons? 

Landry and Zucker base the ethical justification of their 

proposal on the analogy with end-of-life organ donation. 

Yet the analogy is not altogether exact: unlike the physician 

caring for a dying patient, the IVF clinician does not in 

general treat the death of an embryo as a grave matter. 

Certain standard IVF procedures, including superovulation 

and cryopreservation of excess embryos, knowingly 

increase the likelihood that many individual embryos will 

die or be discarded;5 but this is not generally considered a 

reason to forgo production and freezing of “extra” 

embryos. Some observers, troubled by these aspects of the 

clinical context in which this proposal would be carried out 

and disinclined to benefit by complicity in these practices, 

do not find the analogy with organ donation sufficiently 

compelling to justify the extraction of cells from dead IVF 

embryos, especially when the intended use of the extracted 

cells is scientific research rather than the immediate use of 

organs to save dying patients. 

Nonetheless, an exact analogy with organ donation is 

not required to show that what Landry and Zucker are 

proposing is what they claim it to be: a morally preferable

alternative to the intentional destruction of embryos. Death 

comes spontaneously to many embryos, both in vivo and in 

vitro, and it is difficult to see how dissecting spontaneously 

dead embryos can be said to harm them. And if the 

principle “Once dead, then usable”—of course, with 

informed consent and showing respect for the corpse—
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

18

works ethically for removing transplantable organs or 

research materials from dead adult human beings, it 

should work equally well for dead human embryos 

(provided, again, that the embryos are indeed dead and 

that their prospective users have not deliberately killed 

them or neglected them so that they would die). In the end, 

whether this proposal proves to be morally acceptable and 

practically wise remains to be seen. 

B. Is It Scientifically Sound?

The Landry-Zucker proposal has yet to be tested, 

though it is technically possible to begin testing it 

immediately, not only in animals but also in humans. Three 

basic questions need to be answered: Can objective markers 

of organismic death be found? Can pluripotent stem cells 

be derived from dead embryos? If so, will they be 

chromosomally (and otherwise) normal? 

1. Can one find objective markers for organismic death? 

It seems likely that the natural history study will 

identify “duration without cleavage” as one objective 

marker of embryonic organismic death, but the exact 

criterion has yet to be established.*

 Whether additional 

biochemical markers can be identified is not yet known, 

but, according to Landry and Zucker, their discovery is not 

 

*

 “Failure to cleave 24 hours after thawing” may not prove to be a 

sufficient criterion for organismic death, since, in the study by Laverge, 

et al. [see endnote 4], roughly 10% of embryos meeting that criterion 

showed some sign of further cleavage by 48 hours after thawing. 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

19

essential for the immediate implementation of the 

proposal. Ultimately, the issue of markers is largely an 

empirical question: one will not know the answer until the 

effort to find them is made. 

2. Can one in fact get usable pluripotent stem cells from dead 

embryos? 

Once embryos in vitro have been determined to be 

organismically dead, a basic scientific question, still 

unanswered, is whether pluripotent stem cells can then be 

derived, starting from any remaining blastomeres. There is 

reason to believe that some cells in arrested embryos may 

retain their developmental potential, which can be 

reactivated by transferring them to the appropriate milieu; 

but the evidence is very preliminary.6 In addition, recent 

work by Dr. Nicolai Strelchenko and colleagues (working 

at Chicago’s Reproductive Genetics Institute headed by Dr. 

Yury Verlinsky) has described the production of human 

pluripotent stem cells derived by culturing blastomeres 

removed from morula-stage (8-24-cell) human embryos.*7

The next step would be to show that stem cells can be 

derived from single blastomeres extracted from 8-cell 

embryos.† It would then have to be shown that similar 

 

*

 Note that most embryologists reserve the term “morula” for embryos 

of more than 8 cells. See footnote starting on page three above. 

† Deriving stem cells from isolated single blastomeres may prove 

significantly more challenging than deriving them from disaggregated 

blastocysts or morulae; in human ESC derivations achieved so far, 

groups of cells have been cultured together, and it is not known 

whether the presence of other cells is necessary for the derivation of 

embryonic stem cells from a single blastomere. 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

20

results can be obtained using blastomeres extracted from 

organismically dead IVF embryos. 

3. Will the stem cells derived from dead embryos be normal and 

healthy? 

Questions have been raised regarding whether 

pluripotent stem cell lines isolated from organismically 

dead IVF embryos would be abnormal, and in particular, 

aneuploid (that is, having more or fewer than the normal 

number of chromosomes).8 The answer cannot be given in 

advance, but there are reliable methods for determining it 

in every case. Each isolated pluripotent cell line would be 

grown in vitro, so that a detailed study could subsequently 

be done on the chromosome complement of each cell line. 

Such testing would identify those pluripotent stem cell 

lines with a normal chromosome complement; repeated 

karyotype testing throughout the period of laboratory 

culture and storage could confirm that the chromosome 

complement remains normal. Moreover, while pluripotent 

stem cell lines with a normal chromosome complement 

would have the broadest potential therapeutic 

applicability, pluripotent stem cell lines with specific 

abnormal chromosome complements (for example, three 

copies of chromosome 21, as is observed in people with 

Down syndrome) could be useful in basic studies of how 

(in this example) the presence of the extra chromosome 

affects differentiation processes that subsequently lead to a 

human genetic disease. 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

21

C. Is It “Realistic”?

Two kinds of practical questions have been raised: First, 

will scientists want to work with these cells? And, second, 

will the research be supportable by federal funding, under 

the legislative and administrative restrictions now in place? 

1. Scientific acceptance. 

Scientists understandably want to work only with the 

best materials. Why, it is asked, would they settle for cells 

derived from dead embryos, especially since embryos that 

die early are generally abnormal, either chromosomally or 

in other ways?*

 And why should they bother trying to 

develop these cells lines, when they can use existing ESC 

lines or derive new ones at will from living IVF (“spare” or 

newly created) embryos? One answer is that they would 

welcome such cell lines if research using them were eligible 

for federal funding. But a better answer, and on the main 

question, is this: there is simply no way to know in advance 

whether cells derivable from dead embryos are in fact in 

any way inferior to cells derivable from still living 

blastocysts. One must do the experiment and see. 

 

* Council Member Janet Rowley has suggested that it would be strange, 

while allowing large numbers of unwanted but otherwise normal and 

viable IVF embryos to die, to ask scientists to make strenuous efforts to 

rescue cells, potentially normal but potentially abnormal, only from 

those thawed embryos that have spontaneously stopped dividing.
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

22

2. Eligibility for federal funding. 

The Landry-Zucker proposal aims to provide a basis for 

future attempted isolations of pluripotent human stem cells 

by a procedure in which no embryos are killed for the 

purposes of research. Only embryos that are found to have 

died in the context of standard IVF clinical procedures 

would be used in attempts to produce the stem cells. Such 

experiments would ordinarily be considered human tissue 

research and require local IRB approval. After that, most 

states would permit the research.9 It is somewhat more 

difficult to determine whether experiments to evaluate and 

implement the Landry-Zucker proposal would be eligible 

for federal funding under current law and policy. Two 

federal policies are particularly relevant: the Dickey 

Amendment10 and President Bush’s embryonic stem cell 

policy statement of August 9, 2001.11 The purpose of the 

Dickey Amendment is to deny federal funds for any 

experiment in which living human embryos are killed or 

harmed, while the intent of the President’s policy is to 

promote embryonic stem cell research without sanctioning 

or encouraging future destruction of human embryos*

; both 

policies will have to be re-examined in the context of 

organismically dead IVF embryos. Assuming LandryZucker criteria for embryonic death are established and 

 

*

 The President’s August 9, 2001, policy (see endnote 11), which offers 

federal funding for research on embryonic stem cell lines only if those 

lines were derived before the date of the policy, is intended “to allow 

us to explore the promise and potential of stem cell research without 

crossing a fundamental moral line, by providing taxpayer funding that 

would sanction or encourage further destruction of human embryos 

that have at least the potential for life.” 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

23

clinically met, it would appear that federal funding for the 

further manipulation of such dead embryos would not 

violate either the letter or the spirit of the Dickey 

Amendment.*

 It is less clear whether the same could be said 

of the natural history studies to determine the precise 

criteria for embryonic organismic death, especially because 

federal funding has never been available for IVF research 

or practice or any treatment whatsoever of ex vivo 

embryos.† Nevertheless, a strong argument can be made 

that the mere observation of embryos that had 

spontaneously ceased to divide hardly constitutes doing 

them harm or causing their death. Whether the President’s 

policy and budget for federal funding of stem cell research 

would—or should—be expanded to support either 

research to derive stem cells from dead embryos or 

research on stem cell lines already derived from dead 

embryos with private support is a question whose answer 

will depend not only on the issue of legal eligibility but 

also on the assessment of other ethical, scientific, and 

prudential considerations of the sort we have just 

discussed. 

 

*

 The use of federal funds for the derivation of stem cells from doomed 

but still-living embryos (the so-called “spare” embryos, unwanted for 

transfer in efforts to produce a child) violates the letter of the Dickey 

Amendment; the use of federal funds for research on embryonic stem 

cells derived by someone else’s prior destruction of a living embryo 

violates the spirit of the Dickey Amendment. Deriving stem cells only 

from already dead embryos seems not to commit either of these 

violations. 

† The Dickey Amendment has been enacted with the support of many 

members of Congress who are unwilling to “take for granted” the 

practices mentioned in the footnote on page six, including freezing of 

embryos or even IVF itself. 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

24

II. Pluripotent Stem Cells via Blastomere Extraction from 

Living Embryos 

Pluripotent stem cell lines could, in theory, be derived 

starting from small numbers of cells (“blastomeres”) 

removed from living human embryos. Is there a stage of 

early human embryonic development at which cells, 

capable of developing in vitro into pluripotent stem cells, 

can be extracted without harming the embryo’s prospects 

for developing into a live-born child?*

Blastomere extraction from living IVF embryos is 

currently performed to conduct what is called 

“preimplantation genetic diagnosis” (PGD). PGD is a 

procedure increasingly being used in conjunction with 

assisted reproductive technologies to test IVF embryos for 

genetic and chromosomal abnormalities prior to uterine 

transfer for beginning a pregnancy. PGD generally involves 

removal of a blastomere or two from living 6-8-cell 

embryos, and subsequent genetic tests on the removed 

blastomeres. Following the genetic screening, the desired 

embryos, from which one or two blastomeres have been 

removed, are then transferred to women to initiate 

pregnancy. Although estimates vary widely, one recent 

report suggested that more than 1,000 babies had been born 

 

*

 At present, embryonic stem cells are typically derived by extracting 

cells from the inner cell mass of the embryo at the blastocyst (roughly 

100-cell) stage; this entails the destruction of the trophectoderm (that is, 

the outer ring of cells in the spherical blastocyst structure, the 

precursor of the fetal contribution to the placenta) and the death of the 

embryo. 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

25

worldwide following PGD.12 Thus, apparently normal 

children have been born following removal of one or two 

blastomeres from the 6-8-cell embryo. However, long-term 

studies to determine whether this procedure produces 

subtle or later-developing injury in children born following 

PGD have been recommended13 and are sorely needed.

As indicated above, Dr. Nicolai Strelchenko and his 

colleagues have shown that embryonic stem cells can be 

derived from human embryos containing 8-24 cells (see 

reference 7). In their method, all the cells of the embryo are 

disaggregated and cultured on feeder cells (and the embryo 

is killed in the process). It may be some time before stem 

cell lines can be reliably derived from single cells extracted 

from early embryos, and in ways that do no harm to the 

embryo thus biopsied. But the initial success of the 

Verlinsky group’s efforts at least raises the future 

possibility that pluripotent stem cells could be derived 

from single blastomeres removed from early human 

embryos without apparently harming them. * 

A. Is It Ethically Sound? 

1. Harm to the embryo? 

With the Landry-Zucker proposal, the major ethical 

issue concerned the question of whether the embryos 

would in fact be truly dead. Here, the major ethical issue 

 

*

 A similar idea was proposed by Representative Roscoe Bartlett of 

Maryland as far back as 2001. 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

26

concerns the question of possible harm (and perhaps also 

benefit) to the still-living embryo whose cells are removed. 

Removal of blastomeres from developing IVF embryos in 

vitro is currently done primarily in the context of avoiding 

pregnancies at risk for genetic disease. Toward that end, 

the PGD techniques are used to test a group of embryos 

with a view to identifying those embryos that can be 

transferred to the woman without carrying known markers 

for genetic disease. (The embryos that do carry the 

abnormal genes are discarded.) Strictly speaking, embryo 

biopsy as currently practiced in PGD cannot be said to be 

undertaken for any future child’s benefit, since the 

procedure does not directly help those embryos that are 

ultimately implanted. Also, the genetically healthy 

embryos that are transferred to initiate a pregnancy will 

have been subjected to the as-yet-unknown risks of the 

blastomere biopsy procedure. For many individuals and 

couples, the known short-term and potential long-term 

risks of the PGD technique are thought to be more than 

balanced by the desire of the couple to have their own 

biological child free from a specific genetic disease. Others 

believe this practice is unethical, since it involves 

discriminating against genetically disabled embryos and 

ultimately discarding them. There also remains substantial 

debate about the ethical propriety of using PGD in two 

specific cases: (1) to identify embryos that would give rise 

to children who could serve as compatible bone marrow 

donors for sick siblings,14 and (2) to determine the sex of 

the embryos in order to be sure that only embryos of the 

desired gender were transferred.15
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

27

How would the ethical analysis change if living embryo 

blastomere extraction were to be performed not for PGD 

but for stem-cell derivation? Assuming that single 

blastomeres extracted from early embryos could in fact be 

used to derive pluripotent human stem cells, would this 

procedure pass ethical scrutiny? Since the removal of a cell 

or two from the embryo is not (usually) fatal, the 

individual embryo that is biopsied is not killed. However, 

since the blastomere extraction is not being performed for 

the good of the embryo, it might be hard to justify the 

procedure ethically. As Dr. Gerald Schatten told the 

Council in December 2002, “Embryo biopsy is a 

complicated technique, and it’s a very expensive technique, 

and it’s not clear that it is completely innocuous. So you 

would not go into embryo biopsy unless there were 

compelling reasons for actually going through all of the 

costs and expense and heroics of ART [assisted 

reproductive technologies].”16 And even when prospective 

parents do elect to use ART, subjecting otherwise healthy 

embryos to biopsy procedures in order to derive stem cells 

seems ethically troubling. Indeed, even if the biopsied 

embryo and the resulting child were not physically 

harmed, a strong line of moral argument might still lead 

one to object on the grounds that the embryo is being 

treated merely as a means to another’s ends. For there are 

more ways to do injustice to another human being than by 

actions that do discernable or manifest harm. Using human 

beings for purposes of no benefit to them and without their 

knowing consent is one such injustice, even if doing so 

results in no evident or eventual harm to body or psyche. 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

28

Such worries or objections might be moderated should 

the blastomere removal be undertaken, at least in part, for 

the possible benefit of the future child. As noted earlier, in 

embryo biopsy for PGD, sometimes two blastomeres are 

removed. This raises the futuristic possibility that one cell 

could be used for genetic diagnosis, while the other cell is 

used to derive a line of stem cells genetically autologous to 

the embryo and the child it becomes. Looking still farther 

ahead, patients using IVF without concern for genetic 

disease (and hence not interested in ordinary PGD) might 

nonetheless consider blastomere removal solely for the 

purpose of deriving immunologically compatible stem cells 

for their future child. Some might consider such a practice 

ethically justified on the grounds that the child born after 

uterine transfer of the embryo might later derive medical 

benefit from the existence of a genetically matched line of 

pluripotent stem cells, stored in case he needs it for future 

disease therapy. Others, however, doubt the wisdom of 

exposing the prospective child (while an embryo) to a 

hazardous procedure merely for the sake of some 

hypothetical future benefit, or of encouraging parents to 

practice embryo biopsy simply or mainly as a source of 

“personalized” stem cells should their future child 

someday have need of them.17 Besides, genetically matched 

stem cells can be more effectively derived using the 

newborn’s umbilical cord blood (a well-established 

procedure), though it is unclear whether the stem cells 

isolatable from cord blood will have all the same capacities 

as embryonic stem cells. 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

29

2. Are the removed blastomeres not themselves the equivalent of 

embryos or capable of developing into them? 

Another possible source of ethical concern has to do 

with the totipotency of early-stage human blastomeres in 

vivo.18 After the first cleavage of the fertilized human egg 

in vivo, both resulting blastomeres are capable of forming a 

complete embryo that grows into a child.*

 It is not certain at 

what point in embryonic development in vitro (as in IVF) 

such totipotency of the blastomeres disappears; it may be 

that, by the 8-cell stage, sufficient differentiation has taken 

place that individual human blastomeres are no longer 

individually totipotent without aggregating them or 

combining them with other early embryos. Clearly, 

however, if the blastomere removed for biopsy has the 

potential to develop into an embryo and a child on its own, 

some would find destruction of that blastomere ethically 

objectionable. And, in any case, little would have been 

gained ethically if the goal of the entire enterprise was a 

non-controversial procedure for deriving stem cells that 

did so while avoiding destruction of living embryos. 

 

*

 Identical twinning can apparently take place during at least two 

stages of the in vivo development process: Spontaneous separation of 

the blastomeres at the two-cell stage leads to the formation of twins 

with two separate placentas (about 1/3 of cases); while embryo splitting 

at the blastocyst stage leads to the formation of identical twins that 

share the same placenta (about 2/3 of cases). 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

30

3. May one perform non-harmful blastomere extraction on 

embryos that are NOT going to become children? 

If embryo biopsy proves to be a usable source of 

pluripotent stem cells, some might argue that it would be 

ethically permissible to carry out such a procedure—not 

fatal and perhaps not harmful at all—not only on embryos 

that were soon to be transferred to a woman, but also on 

IVF “spare” embryos that are not ultimately selected for 

uterine transfer. Indeed, because of the still unknown risk 

of harm from blastomere removal to the child subsequently 

emerging from a biopsied embryo, some have suggested 

that the biopsy procedure can be ethically done only on an 

embryo that is definitely not going to become a child. 

Others, however, consider any proposed utilitarian 

treatment of such embryos to be morally unacceptable, 

since it necessarily classifies “spare” (and still living) 

embryos as ethically available for research uses. 

4. Can the research necessary to test this proposal be conducted 

in an ethically acceptable manner? 

Learning how to implement this proposal—even for the 

variation that would only seek stem cells that might 

eventually benefit the child whose embryonic beginning 

was biopsied to obtain them—has its own ethical 

difficulties. Techniques would have to be developed for 

deriving pluripotent stem cells, not only from whole earlystage human embryos, but also from individual 

blastomeres extracted from an embryo. It may prove 

difficult to develop and refine those techniques without 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

31

exposing many human embryos to death and injury.* If 

embryo biopsy is to be embraced as a morally 

uncontroversial way to derive stem cells, the research 

needed to test the proposal and perfect the technique 

would have to avoid killing or harming human embryos. It 

is far from clear that the necessary research can be 

accomplished with this restriction in place. Even if a 

perfected technique could someday derive stem cells from 

single blastomeres harmlessly obtained, the failure to 

satisfy this testing-stage ethical requirement could render 

this option ethically little better than the currently 

controversial methods for deriving embryonic stem cells. 

5. Changing the practices of assisted reproduction. 

There is ethically more at stake in this proposal than the 

fate of individual biopsied embryos. There are also large 

issues raised by the direct intrusion of research objectives 

into the practice of reproductive medicine, while it is being 

practiced (that is, in the moments when decisions about 

embryo transfer are still being made). The Landry-Zucker 

proposal would make available for stem cell derivation 

only those embryos that had already died. In contrast, this 

embryo-biopsy proposal would manipulate still-living 

embryos immediately destined for reproductive transfer. 

From the perspective of the would-be parents, is it really 

better for them (and for their child-to-be) if those 

performing PGD are concerned not only with good 

diagnosis but also with procuring useful cells for a research 

 

*

 Indeed, in the initial studies showing the potential usefulness of 

morula-stage human embryos as a source of stem cells, many human 

embryos were obviously destroyed. 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

32

colleague? Decisions about how many and which embryos 

to transfer are often made in stressful circumstances, where 

timing is critical and the doctor’s attention is limited. 

Bringing scientists (or considerations of research) into this 

process, for reasons having nothing to do with the wellbeing of parents and their children-to-be, would seem to be 

a dubious intrusion. It would also make assisted 

reproduction seem even more like manufacture, a process 

with many side uses and side benefits, rather than simply a 

way to help people have children. To say the least, much 

careful planning and oversight would be needed to prevent 

the research interest from adversely affecting the way 

reproductive medicine is practiced and the meaning it has 

for the larger society. 

B. Is It Scientifically Sound?

The recent work of Strelchenko and colleagues with 

disaggregated 8-24-cell embryos suggests that whole 

human embryos as early as the 8-cell stage are potentially 

usable as a source of pluripotent stem cells. This work 

would have to be reproduced and refined before we could 

be certain that embryos at such an early stage are indeed a 

dependable source of stem cells. It would then have to be 

shown that stem cells can also be derived from isolated 

blastomeres extracted from an 8-cell embryo.*

 It seems far 

 

*

 Studies with mouse embryos have shown that isolated 8-cell 

blastomeres will develop into vesicles of trophectoderm, containing 

little or no inner cell mass, making derivation of ESC lines difficult. 

And there is no reason to believe that things will be different in 

humans. However, there has been one published report claiming 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

33

from certain that enough cells can be extracted from the 

embryo to derive stem cells while also avoiding injury to 

the embryo. 

On the question of whether biopsy can be safely 

performed on early stage embryos, there is mixed evidence 

from animal studies. Krzyminska and colleagues, working 

with mouse embryos, found that “biopsy had the least 

impact when performed at the 8-cell stage.” When 

performed on 8-cell embryos, they found that biopsy did 

not significantly impair development in vitro or the rate of 

implantation after transfer; but compared to intact 

embryos, fewer biopsied embryos (52% versus 71%) 

resulted in viable fetuses.19 Because human PGD is such a 

novel, still small, and as-yet-unstudied practice, we do not 

have good data for the implantation rate for biopsied—as 

compared with non-biopsied—human embryos. 

In any event, since apparently healthy children have 

been born after embryo biopsy at the 8-cell stage,*

 it would 

 

derivation of mouse ESC lines from isolated 8-cell blastomeres: One cell 

line was obtained from 52 dissociated 8-cell stage embryos. (See 

Delhaise, F., et al., “Establishment of an embryonic stem cell line from 

8-cell stage mouse embryos,” European Journal of Morphology 34, 237-243 

[1996].) The Council is grateful to Dr. Janet Rossant for these 

observations. 

*

 Granting that apparently healthy children have been born following 

IVF and PGD, does removal of one or two blastomeres from the early 

human embryo have no effect on the child who is later born? We cannot 

be certain. There is some evidence (at least in mice) for asymmetrical 

division and distinct cell fates at the early cleavage stages. (See 

Piotrowska-Nitsche, K., et al., “Four-cell stage mouse blastomeres have 

different developmental properties,” Development 132, 479-490 [2005].) 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

34

appear to be possible to safely remove one or two 

blastomeres from an 8-cell embryo in order to try to 

generate a line of pluripotent human stem cells. Only 

further research and effort can settle the matter. 

C. Is It “Realistic”? 

Let us assume that a stage of human embryonic 

development can be identified at which cells can be 

removed without injuring the still-living embryo, that a 

non-injurious procedure for removing the cells is perfected, 

and that the cells can then be used to derive pluripotent 

stem cells. Will scientists want to work with these cells? 

And will the stem cell research be supportable by federal 

funding, that is, both eligible under the legislative 

restrictions and embraceable by administrative policies 

now in place? 

1. Scientific acceptance. 

Whether this approach is likely to be adopted by 

scientists in the future as a way to produce pluripotent 

human stem cell lines depends on several unknowns, 

central among them the efficiency of the process (for 

example, how many good stem cell lines are obtainable 

from how many biopsied embryos, and at what cost of 

effort and expense). A further crucial consideration will be 

 

It is possible that the loss of one or two blastomeres is entirely rectified, 

but even if development proceeds in a healthy manner, it may be that 

the child born is somehow a different child than the one that would 

have resulted from an undisturbed embryo. 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

35

the properties of the pluripotent stem cells that are 

produced by blastomere disaggregation of early embryos. 

If the resulting pluripotent stem cells turned out to be as 

good as or better than the current human embryonic stem 

cell lines (derived from the inner cell mass of blastocysts, a 

later stage of embryonic development), prospects for using 

this approach would improve. If, however, the proposal 

were deemed ineligible for federal funding, the prospects 

for this approach would not look very good, given that 

there are several other well-established methods for 

producing human embryonic stem cells. 

2. Eligibility for federal funding. 

An argument could be advanced that this approach 

complies with the Dickey Amendment, as long as the 

embryos biopsied are truly not harmed. But there is today 

insufficient evidence to determine whether biopsied 

embryos are, by virtue of the procedure or the removal of 

cells, in fact at risk of harm. Thus, although any derived 

pluripotent cell lines might be eligible for funding, doing 

the prior research to derive them might not be. A second 

obstacle facing such prior research would be the 

longstanding Congressional opposition to all federal 

funding of any activities involving in vitro fertilization. 

Whether the President’s policy and budget for federal 

funding of stem cell research would—or should—be 

expanded to support research on stem cell lines derived 

(with private support) from biopsied embryos is a question 

whose answer will depend not only on the issue of legal 

eligibility but also on the assessment of other ethical, 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

36

scientific, and prudential considerations of the sort we have 

just discussed. 

III. Pluripotent Stem Cells Derived from 

Biological Artifacts*

Under this heading are various proposals to construct a 

biological artifact, lacking the moral status of a human 

embryo, from which pluripotent stem cells could then be 

derived. For example, Council Member William Hurlbut 

has advocated what he calls “altered nuclear transfer” 

(ANT), a procedure that, if successful, would offer a way to 

produce pluripotent stem cells within “a limited cellular 

 

*

 Here, as in so many other ethically charged situations, terminology 

matters enormously. One must take special pains not to prejudice 

consideration of the ethical issues by choice of terms that, intentionally 

or unintentionally, incline readers and hearers one way rather than 

another. This case is no exception. Precisely because the purpose here is 

to create an entity that is not in fact a human embryo, but that is 

nevertheless enough like a human embryo that it too contains cells that 

can be cultured to give rise to pluripotent stem cells, the artificially 

produced entity must be at once “non-embryonic” yet “embryo-like.” 

But if the product is referred to as an “embryo-like” or (by analogy to 

“android”) “embryoid” body, people may be encouraged to 

overemphasize its resemblance to an embryo and to slight the claim 

that this product is decidedly not a human embryo. On the other hand, 

if the product is referred to as a “non-embryonic” body or structure, 

people may be encouraged to think that its desired non-embryonic 

character has in fact been achieved. Since a major ethical issue turns on 

whether or not the biological artifact is truly not a living human 

embryo, all prejudgment by terminological fiat should be, where 

possible, avoided. We therefore usually call it (merely) a “biological 

artifact,” denoting its origin but leaving its essential status open. 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

37

system that is biologically and morally akin to a complex 

tissue culture.”20 This proposal, as yet untested 

experimentally (even in animals), is conceptually based on 

modifying the procedure of somatic cell nuclear transfer 

(SCNT), now used to produce cloned embryos. In standard 

SCNT, a somatic cell nucleus is introduced into an oocyte 

(egg cell) whose own nucleus has been removed. The 

product is a cloned embryo (virtually identical, at least 

genetically, to the organism from which the donor nucleus 

was taken), the functional equivalent of a fertilized egg that 

is capable (at least in some cases) of developing into all 

later stages of the organism. ANT, the modified procedure 

proposed by Hurlbut, involves altering the somatic cell 

nucleus before its transfer to the oocyte, and in such a way 

that the resulting biological entity, while being a source of 

pluripotent stem cells, would lack the essential attributes and 

capacities of a human embryo. For example, the altered 

nucleus might be engineered to lack a gene or genes that 

are crucial for the cell-to-cell signaling and integrated 

organization essential for (normal) embryogenesis.21 It 

would therefore lack organized development from the very 

earliest stages of cell differentiation. Such an entity would 

be a “biological artifact,” not an organism. Removal of cells 

from, or even disaggregation of, this artifact would not be 

killing or harming, for there is no living being here to be 

killed or harmed. After extraction from this artifact, the 

cells could have the missing gene or genes reinserted, with 

a view to deriving “normal” pluripotent stem cells from 

them. 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

38

A. Is It Ethically Sound? 

 In offering his proposal for ANT, Hurlbut emphasizes 

that no embryo would ever be created or destroyed; since 

the genetic alteration is carried out in the somatic cell 

nucleus before transfer, the biological artifact is “brought 

into existence with a genetic structure insufficient to 

generate a human embryo.” Hurlbut compares the product 

of ANT to certain ovarian teratomas and hydatidiform 

moles, genetically or epigenetically abnormal natural 

products of failed fertilization that are not living beings but 

“chaotic, disorganized, and nonfunctional masses.” If, as 

Hurlbut suggests, the biological artifact is ethically 

equivalent to a tissue culture, teratoma, or mole, there 

would seem to be nothing ethically problematic about 

harvesting stem cells from it. Nonetheless, a number of 

ethical questions and concerns have been raised about this 

proposal. 

1. Would not this “artifact” really be a very defective embryo? 

Some people have wondered about the accuracy of the 

claim that no embryo creation or destruction is entailed by 

the proposal. They understand that the proposed biological 

artifact has, from the beginning, a built-in genetic defect 

that prevents it from developing normally. Yet they worry 

that this is not the production of a non-human entity but 

the deliberate creation of a doomed or disabled human 

embryo, or, in other words, that Hurlbut’s proposal 

amounts to creating and using “bad or sick embryos,” 

rather than “non-embryonic entities.” Hurlbut’s claim that 

his method would not yield a defective embryo rests on the 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

39

fact that a genetic alteration sufficient to prevent 

embryogenesis is introduced into the nucleus before it is 

transferred to the oocyte, and that the alteration would be 

so fundamental that it would preclude the integrated 

organization that characterizes a human embryonic 

organism. If no embryo is created, then none is violated, 

mutilated or destroyed (which would be the case if the 

alteration were introduced after normal fertilization). 

Nonetheless, some critics wonder how the product of 

that nuclear transfer is in fact essentially different from—

and less an embryo than—a fertilized egg into which the 

same disabling genetic alteration is introduced only after

normal fertilization. A person’s perception of the truth in 

this matter may depend on how easy it is to turn the 

genetic defect on or off. The easier it is to activate and 

deactivate the genetic defect, the more this proposal looks

like interfering with the normal development of an embryo 

rather than manufacture of an artificial non-organismic 

structure. Unless it can be shown that the artifact is not

truly an embryo—that is, that it lacks (by design) the 

possibility of becoming not only a live-born human but an 

organized, differentiating early human embryo and fetus—

there will likely be ethical debate on whether it is 

permissible to continue “abusing” the embryo-like entity 

by suppressing the genes it needs for development. 

Furthermore, even if the artifact were conclusively shown to 

lack genes indispensable for becoming an organized,

differentiating human embryo, some critics might continue 

to insist that it was destined to become a defective, severely 

deformed human embryo, the defect and deformity having 

been deliberately inflicted on it by the scientist. 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

40

Experimental work in animals, however, might help 

resolve these questions and allay these concerns. If, for 

example, the biological artifact begins to grow in ways that 

resemble unorganized cells in a tissue culture, critics may 

gain confidence in the non-embryonic character of the 

product. 

2. The ethics of egg procurement. 

Like ordinary cloning-for-biomedical-research (SCNT), 

this altered nuclear transfer proposal requires a (probably 

large) supply of human oocytes, which would have to be 

donated, purchased, or produced for research purposes. 

Some will find this troubling, and on multiple grounds. 

Obtaining human oocytes currently requires hormonal 

stimulation and superovulation in the women who would 

be donating or selling their eggs, practices that carry 

significant medical risks to the women, risks not easily 

justified when they themselves or their prospective 

children are not the beneficiaries of the oocyte retrieval (as 

are women undergoing these procedures in hopes of 

having children). In addition to the medical risks, there are 

also ethical concerns about the practice of commercializing 

human reproductive tissue and about any buying and 

selling of eggs: the exploiting of poor women, the 

coarsening of society’s sensibilities, the developing of 

markets in (reproductive) human tissues. More deeply, one 

critic suggests, we must consider the implications and the 

consequences of coming to regard human eggs and sperm 

as fungible raw materials, to be used in ways that have 

nothing to do with their procreative biological and human 

meaning. There is a risk that, in seeking to avoid the 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

41

problem of embryo destruction, we would thus be 

furthering a dehumanized and utilitarian view of human 

beginnings as bad as the one that this alternative proposal 

was trying to combat.22

There is, at least in theory, the possibility that human 

oocytes can be obtained not from women egg donors by 

superovulation but from ovaries surgically removed from 

patients or harvested from cadavers. The ooocyte 

precursors extracted from these ovaries could then be 

matured in vitro. Alternatively, the ovaries could be 

transplanted into animal hosts and eggs produced by 

hormonal stimulation of the animals.23 Research in this area 

is at a very preliminary stage. And the objections just noted 

to non-reproductive uses of human reproductive tissue 

could also be raised to obtaining eggs in these non-invasive 

ways, should they ever become possible. 

3. Ethical concerns about ANT itself.

To some observers, the procedures involved in ANT are 

inherently objectionable. Certain commentators, for 

example, find the very idea of tampering to put something 

destructive into the human genome, even for a good cause, 

morally and aesthetically offensive. Some find it 

aesthetically repulsive and ethically suspect to be creating

such neither-living-nor-nonliving, near-human artifacts, a 

practice they regard as ethically no improvement over

destroying early embryos. Other critics of the ANT proposal 

argue that, while it is ethically acceptable to modify the 

human genome for treatment (with consent) of individuals 

with known genetic disorders, it is quite another thing to 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

42

do so for other than therapeutic purposes or to do so in 

eggs or sperm before there is an existing needy individual. 

Some think this is a major ethical boundary that ought not 

to be crossed lightly.24 Others are troubled by the attitude 

of mastery or hubris implied in a project that aims at 

engineering a human biological artifact. 

In response to these objections, Hurlbut replies that the 

ANT technique would be used only for serious scientific 

research within the frame of therapeutic purposes 

beneficial to a large population whose medical needs are of 

grave concern. Further, he points out that we accept many 

medical and research practices that are aesthetically ugly 

and morally worrisome, from cutting into a living body or 

brain, to giving people a dose of disease for vaccination, to 

growing great sheets of skin from cells harvested from 

foreskins. We do these things—and many others like 

them—in the service of the higher goal of healing, the very 

goal to which the ANT proposal is dedicated.25

4. Concerns about ANT on “slippery slope” grounds. 

Several worries have been expressed not about the 

proposal itself but about what it might lead to, or about 

what it might be seen as justifying in the future. For some, 

the proposal appears to open the door to a troubling new 

field of biomedical engineering. True, its initial relatively 

modest goal is only to produce a biological artifact capable 

of yielding pluripotent human stem cells while not itself 

being a complete human organism with developmental 

potential. And if, in the process, definite criteria could be 

established for distinguishing between the not-human and 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

43

the human, this proposal might have the salutary effect of 

erecting boundaries that would open avenues for scientific 

advance without threatening human dignity, boundaries 

that do not now govern the practices of human embryo 

research in the private sector. But, extrapolating into the 

future from an ANT precedent, pursuing this proposal 

could—whether intentionally or not—help to launch a new 

field of bioengineering, devoted to manufacturing 

intermediate biological forms that are sufficiently human to 

yield useful biomedical materials, but not so human that it 

would be unethical to destroy or exploit them. Hurlbut’s 

arguments could be adapted to justify the deliberate 

production of teratomas, hydatidiform moles, inter-species 

hybrids, and other ill-formed, non-viable, but potentially 

useful biological artifacts. Once we start down the road of 

deliberately engineering artificial entities with some human 

properties, it is not obvious how bright ethical boundaries 

between the acceptable and the unacceptable can be drawn. 

A second “slippery slope” concern has to do with the 

flexibility of the developmental stage at which disordered 

growth is set to begin. Hurlbut’s proposal involves 

building in a genetic alteration that causes development to 

go irretrievably awry from the very start of embryonic 

development. But suppose a useful genetic modification 

were achieved that entailed chaotic and disorganized 

development only at a later stage of embryonic (or even 

fetal) development. Could not the ethical reasoning in 

defense of ANT be used to argue that such furtherdeveloped but still inherently defective entities are “fetuslike but not actual fetuses,” and hence ethically suitable for 

exploitation and destruction? (The same question is 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

44

relevant for ongoing destructive embryo research using 

normal IVF embryos, whose exploitation and destruction 

are justified because of the human benefits they might 

eventually bring.) It would certainly be troubling if the 

ethical case for ANT could be used to justify the creation 

and destruction of fetus-like entities. Hurlbut’s proposal, 

seeking a source of pluripotent human stem cells, confines 

its attention to the early stages of embryonic development. 

But someone looking for a source of tissues or even 

primordial organs might be tempted to apply his reasoning 

to later and later stages of development, not excluding the 

deliberate production of anencephalic fetuses or even 

newborns, useful as a source of organs and tissues. 

Hurlbut’s criterion for being a truly human organism—

“organization of the species-typical kind”—would appear 

to be inherently malleable and open to interpretation (and 

even mischief). 

Arguments that worry about future extensions of 

present techniques, or future applications to dubious ends, 

or future uses of current ethical justifications to validate 

later unsavory practices, while worth considering, tend to 

assume that people are either unable or unwilling to draw 

the necessary distinctions and erect the necessary ethical 

boundaries between current acceptable practices and future 

unacceptable ones—an assumption that is readily subject to 

dispute. But since the truth of this assumption cannot be 

known in advance, and can only be demonstrated case by 

case and then only by going forward and running the 

predicted risks, there is at least some reason to wonder 

whether any newly devised technological solution to the 

ethical problem of embryo destruction will not, in the end, 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

45

be creating or contributing to ethical problems worse than 

the one it set out to cure. 

B. Is It Scientifically Sound? 

Although the proposal for ANT has yet to be tested, 

several scientists have indicated that they believe that it can 

easily be made to work, and a few are apparently ready to 

try it out in non-human animals. It would be crucial to 

show that the disorganizing genetic or epigenetic alteration 

introduced into the somatic cell nucleus before transfer 

could be fully controlled, with predictable results, and fully 

reversed without residual abnormalities in the derived cells 

extracted from the embryo-like artifact. For unless the 

genetic engineering were fully reversible, the resulting 

stem cells would likely carry genetic or other alterations 

that might compromise the value of the stem cells. 

Moreover, there may be a tension in this proposal between 

ethical considerations, which require that insurmountable 

developmental barriers be genetically built into the 

embryo-like entity from the start, and technical feasibility, 

which would favor simpler barriers to development that 

are easily and completely reversible. Presumably, the more 

hard-wired the introduced defect is, the more difficult it 

will be to reverse. However, it is quite possible that, with a 

sufficiently determined research program, even the more 

technically daunting versions of the proposal could be 

achieved. 

It is important to note that both some of the strengths 

and some of the weaknesses of the ANT proposal come 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

46

from the fact that it is basically a form of SCNT or cloning. 

On the positive side, if successful, ANT could provide stem 

cells with a much greater diversity of genotypes than is 

possible under current methods of stem cell derivation (or 

under the other two proposals we have considered so far*

), 

allowing a far wider range of medical possibilities such as 

disease modeling or drug testing. Likewise, ANT would 

allow the generation of pluripotent stem cell lines with preengineered alterations (such as enhanced immune response 

or correction of a genetic defect) that might make them of 

more scientific interest or therapeutic value. 

On the negative side, however, attempts to clone 

mammals have so far resulted in high rates of death, 

deformity, and disability in the animals that come to birth 

following SCNT. In 2002, research in the laboratory of 

Rudolph Jaenisch at MIT showed that, in cloned mice, 

about 4% of genes function abnormally, owing mainly not 

to mutations but to departures from normal activation or 

expression of certain genes.26 It is not yet known whether 

similar genetic or epigenetic abnormalities will also be 

found in any stem cell lines that might be derived by ANT. 

Such problems are much less likely to be encountered in 

stem cell lines derived from IVF embryos. 

 

*

 This advantage would, however, be shared by the next proposal, 

somatic cell dedifferentiation. 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

47

C. Is It “Realistic”? 

1. Scientific acceptance. 

Compared to deriving human embryonic stem cells 

from normal blastocysts, procedures such as ANT are quite 

complex and would yield cells that would then have to be 

restored to genetic normality before stem cell lines could be 

derived. Many scientists, we suspect, would be reluctant to 

attempt such challenging feats with no rational purpose 

other than to satisfy the ethical objections of others, and 

one prominent scientist in the stem cell and cloning field 

has recently made such a complaint publicly 

(notwithstanding the fact that the company for which he 

works has filed a patent application for precisely such a 

procedure).27 Other scientists have reacted to news of the 

ANT proposal by describing it as exceedingly complex and 

technically challenging, not even testable without timeconsuming experiments involving substantial investment 

of precious resources.28 Even if federal funding for research 

on ANT-derived stem cell lines were approved, stem cell 

scientists might prefer to seek private funding of 

unrestricted stem cell research rather than follow 

procedures that seem to them burdensome and 

scientifically useless. Also, as Hurlbut himself 

acknowledges, proof of principle and safety-and-efficacy 

experiments need first to be done in animals, and it might 

be many months or even years before this process could be 

perfected using human tissues. Many stem-cell scientists, 

eager to press forward, are unlikely to wait for these new 

lines, especially if they are not themselves bothered by the 

embryo destruction that necessarily results when stem cell 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

48

preparations are derived, as they are now, from unused 

IVF embryos. On the other hand, there may be some 

scientists, either opposed themselves to destroying 

embryos or hoping to find a way around the current 

federal funding restrictions, who would be willing and 

even eager to test Hurlbut’s proposal in animals, and 

several have apparently volunteered their collaborative 

services for such animal trials. 

2. Eligibility for federal funding. 

 If the biological artifacts created and destroyed under 

this proposal were persuasively shown not to be human 

embryos, the proposal would presumably be deemed 

consistent with the Dickey Amendment and therefore 

eligible for federal funding. Whether the President’s policy 

and budget for federal funding of stem cell research 

would—or should—be expanded to support research on 

ANT or other biological artifacts (even in animals) is a 

question whose answer will depend not only on the issue 

of legal eligibility but also on the assessment of other 

ethical, scientific, and prudential considerations of the sort 

we have just discussed. 

D. Pluripotent Stem Cells via “Parthenogenesis.” 

 Besides Hurlbut’s ANT proposal, other methods of 

constructing embryo-like artificial structures are under 

investigation, including a technique recently demonstrated 

by Karl Swann and colleagues at the University of Wales 

College of Medicine, in which a human oocyte is 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

49

biochemically “tricked into thinking it has been 

fertilized.”29 The treated eggs divide to the blastocyst stage 

(50-100 cells), at which point stem cells can presumably be 

derived.30 Although it undergoes several cycles of cell 

division, the “parthenogenetic” (that is, unfertilized but 

still developing) blastocyst-like entity is assumed by most 

commentators to lack entirely the potential for 

development as a human being, and is therefore, arguably, 

not really an embryo.*

 If this is correct, then this technique 

might provide another means for deriving pluripotent stem 

cells without creating or destroying embryos. Yet the only 

experiment that could prove whether this plausible 

assumption is in fact correct—transferring a 

parthenogenetic embryo to a woman to try to bring it to 

birth—cannot be ethically attempted. In the absence of such 

proof, the biological and moral status of the 

parthenogenetic blastocysts is likely to remain in doubt and 

controversial. Still, those who are convinced that 

parthenogenetic embryos have no chance of development 

beyond the blastocyst stage are likely to have few ethical 

objections to the production and use of such entities.31 It 

remains to be seen whether viable and genetically stable 

pluripotent stem cells can be derived from these 

parthenogenetic blastocysts and whether imprinting and 

other issues related to their parthenogenetic origin might 

limit their utility in research or potential clinical trials. 

Under the present terms of the Dickey Amendment, this 

proposal would be unlikely to be eligible for federal 

 

*

 However, live-birth parthenogenesis takes place naturally in certain 

amphibians and has been induced artificially even in mice. See Kono, 

T., et al., “Birth of parthenogenetic mice that can develop to adulthood” 

(Letters to Nature), Nature 428, 860-864 (2004). 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

50

funding, since the amendment specifically prohibits the use 

of federal funds for research that may cause harm to an 

embryo produced by, among other means, 

parthenogenesis. 

IV. Pluripotent Stem Cells via Somatic Cell 

Dedifferentiation 

 A quite different route to the production of pluripotent 

stem cells would be to reprogram differentiated somatic 

cells so as to restore to them the pluripotency typical of 

embryonic stem cells. The obstacles here are not ethical, but 

technical. Because it involves neither the creation nor the 

destruction of human embryos, the common ethical 

objection to human embryonic stem cell research would 

not apply. But it would take new scientific advances and 

new technological innovation before such 

“dedifferentiation” of somatic cells back into pluripotent 

stem cells could be achieved. Several suggestions have, 

however, been offered for how such dedifferentiation 

might be achieved, and the value of success cannot be 

overstated. For if it were possible to undo the 

differentiation of somatic cells, running development in 

reverse back to the state of pluripotency, it would in 

principle be possible for autologous pluripotent stem cells 

to be obtained from the body of any human being. Such 

individualized stem cells would then be available as a 

potential source of personalized, immuno-compatible 

regenerative therapies. 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

51

A. Is It Ethically Sound?

There would seem to be nothing to object to ethically if 

procedures were developed to turn somatic cells into 

pluripotent stem cells, non-embryonic functional 

equivalents of embryonic stem cells. Of course, if the 

dedifferentiation were pursued beyond (mere) 

pluripotency to the point of yielding a totipotent cell—in 

effect, a cloned human zygote—the moral status of such a 

cell would become a serious issue, as would the 

permissibility of using it either for reproductive or for 

research purposes. For a totipotent cell is, arguably, an 

organism at the unicellular stage, and a strong case could 

be made that the product is not a pluripotent stem cell but 

an embryo. 

B. Is It Scientifically Sound? 

 Research into dedifferentiation of somatic cells is at a 

preliminary stage, and it is much too early to know 

whether this will succeed. It may prove possible to culture 

specific populations of somatic cells—cells that may be 

especially susceptible to dedifferentiation—under 

conditions that might get them to reverse their 

differentiating epigenetic changes, thereby leading them to 

become more multipotent or even completely pluripotent; 

there is also some hope of identifying and isolating the 

chemical factors present in oocytes and other cells (such as 

ESCs) that are responsible for maintaining or restoring cells 

to pluripotency, and of using these chemicals to 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

52

dedifferentiate ordinary somatic cells (without the further 

need for oocytes or embryos). 

In nature, limited dedifferentiation is involved in the 

regeneration of missing limbs in amphibians, though the 

precise mechanism is not yet known.32 Studies have shown 

that some adult human somatic cell types (blood, liver, 

muscle) can be chemically dedifferentiated back into their 

corresponding multipotent progenitor cells (that is, adult 

stem cells).33 Several research laboratories have reported 

the direct isolation of cells from bone marrow of children 

or adults that, when cultured in vivo, have or acquire the 

capacity to differentiate into many mature cell types, 

including cells originating from all three embryonic germ 

layers.34 These cultured human multipotent cells also show 

the presence of certain biochemical properties ordinarily 

found only in human embryonic stem cells. It is interesting 

to speculate that it may be the same bone marrow stem 

cells, cultured in vitro under different conditions, that 

revert in some cases to (rather modestly multipotent) 

mesenchymal stem cells, in some other cases (further back) 

to the clearly multipotent adult progenitor cells, and in still 

other cases (yet to be achieved) to the ur-primordial stem 

cell, the fully pluripotent stem cell, functionally equivalent 

to an embryonic stem cell (though not of embryonic origin). 

If such “graded dedifferentiations” are indeed the cause of 

the variations seen among the cultivated stem cells now 

known to arise from bone-marrow stem cells, further 

research—using also stem cells obtained from umbilical 

cord blood—might very well turn out to yield the big 

payoff: fully pluripotent stem cells, obtainable at will and 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

53

altogether without any involvement of embryos—and well 

suited for autologous transplantation. 

Another possible approach to somatic cell 

dedifferentiation relies on knowledge that might be gained 

through cloning-for-biomedical-research. In SCNT or 

cloning, a somatic cell nucleus is reprogrammed back to 

totipotency by transfer into an enucleated oocyte. 

Presumably, cytoplasmic factors that are present in the 

oocyte (and that may also be present in cultured embryonic 

stem cells*

) are responsible for the dedifferentiation that 

takes place. If and when these cytoplasmic factors can be 

identified and isolated, it may be possible to use them—

instead of SCNT into oocytes—to coax some ordinary 

somatic cells to dedifferentiate back to the pluripotent 

stage.35 Once again, should the process of dedifferentiation 

go too far, back to totipotency, the end result will not be a 

stem cell but the functional equivalent of a zygote, and one 

would be back in the ethical soup from which this proposal 

was intended to provide an escape. Great care would 

therefore have to be exercised to ensure that 

dedifferentiation, if and when it occurs, goes only so far 

and no further. Given the complexity of the process, and 

how little we now know about the factors that regulate 

differentiation and its opposite, it is not likely that this 

(second) approach will yield results in the near future. 

 

*

 The Council is grateful to Dr. Markus Grompe for this observation. 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

54

C. Is It “Realistic”? 

1. Scientific acceptance. 

Certainly, dedifferentiation of somatic cells back to their 

corresponding progenitor cells will likely be welcomed as a 

powerful new way to produce large quantities of 

multipotent adult stem cells. If dedifferentiation is 

perfected to the point of yielding cells as pluripotent as 

embryonic stem cells, there is no reason to doubt that this 

procedure would be widely embraced and the cells 

obtained widely used. An additional—clinical—potential 

benefit of such cells would be that specialized cells derived 

from them (for example, heart muscle cells, nerve cells) 

could be reintroduced therapeutically into the patient from 

whom they were derived without risk of immunological 

rejection. 

2. Eligibility for federal funding. 

Because this research does not involve human embryos 

at any stage, it would not offend either the letter or the 

spirit of the Dickey Amendment. Aside from the concern 

that dedifferentiation might proceed too far (resulting in 

the functional equivalent of a zygote), there would appear 

to be no obstacle to, or reason to oppose, federal funding of 

research on dedifferentiation of somatic cells. 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

55

Conclusion 

The United States has been engaged in a vigorous 

ethical debate about embryonic stem cell research, 

prompted by tensions between the desire for biomedical 

progress and respect for nascent human life. The scientific 

and medical promise of stem cells has generated enormous 

excitement among researchers and patient groups. The 

ethical issues raised by embryo research have roused 

considerable public attention and concern. Many people 

share the hope that stem cell research will eventually save 

lives and yield the promised remedies for numerous 

chronic illnesses. Many people (including many who are 

eager for regenerative medicine to succeed) share the 

concern that embryonic stem cell research depends on 

destroying human embryos and cheapens human life by 

creating and using it for experimentation. 

Some people hope that stem cells derived from nonembryonic sources (known as adult stem cells) will turn 

out to be as good as stem cells derived from embryos, but it 

is too early to tell which sort of stem cells will be most 

useful for the treatment of which diseases. Some believe 

that current federal law and policy governing the funding 

of embryonic stem cell research are too restrictive, and that 

the existing embryonic stem cell lines will not prove 

adequate for the work ahead. Others believe that medical 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

56

progress must not be purchased by destroying human life, 

even at its earliest stages, and that creation of human 

embryos specifically for use in research should be 

outlawed. 

Mindful of the moral weight of the arguments on the 

various sides of this controversy, and charged with finding 

ways for science to proceed while respecting moral norms, 

the Council has taken seriously a number of recent 

proposals and suggestions for techniques to derive new 

pluripotent stem cell lines in ways that might be ethically 

uncontroversial. 

This White Paper has summarized several current 

proposals for obtaining pluripotent human stem cells that 

do not require destroying human embryos. In each case, we 

have examined whether the proposal is ethically sound, 

scientifically feasible, and practically “realistic.” The inquiry 

we have undertaken constitutes no more than a preliminary 

hearing, designed mainly to see whether there are any 

insuperable ethical, scientific, or practical objections to 

further consideration of these proposals. Because all of 

these proposals are relatively new, the ethical issues they 

raise need more discussion, and much research would be 

needed before it became clear which of them, if any, would 

succeed. Likewise, further legal interpretation and sober 

political deliberation would be required to determine 

which of the proposals are, under current law, eligible for 

federal funding and which are both ethically and 

scientifically deserving of such official national support. We 

hope that our analyses of the ethical, scientific, and 

practical aspects of these proposals will contribute to a 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

57

more informed and comprehensive scrutiny of their 

respective merits. 

The analyses of this White Paper, while preliminary, do 

lead to the following provisional assessments. The last 

proposal, dedifferentiating somatic cells back to 

pluripotency, seems ethically the most unobjectionable, but 

for now scientifically and technically uncertain; recent 

derivations (from adults) of relatively undifferentiated 

multipotent stem cell lines*

 may be an encouraging, albeit 

preliminary, step toward this goal. The first proposal, 

seeking to derive stem cells from organismically dead 

embryos, has yet to be tested, even in animals. But the 

natural history studies proposed could be undertaken 

forthwith and in an ethical manner, not only in animals but 

also in humans, and we might learn soon whether reliable 

objective criteria for determining death of IVF embryos can 

be developed. The second proposal, seeking to develop 

stem cells from blastomeres extractable from living 

embryos, is also now technically feasible, though large 

ethical difficulties remain, concerning especially the 

propriety of imposing risks of embryo biopsy and 

blastomere removal on the born child the embryo might 

become, solely for research of no benefit to him or her. The 

third proposal, seeking to derive stem cells from 

genetically engineered artificial entities, is technically the 

most demanding and ethically the most complex and 

puzzling. Even its proponents agree that it would need to 

be carefully tested in animals before any thought of human 

trials could be countenanced. 

 

*

 See endnote 34. 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

58

Among these several proposals, the Council has no 

unanimous recommendation to make. Different Council 

members are drawn more to one or less to another of the 

four proposals. Each of us weighs the ethical issues 

differently. And we have differing views on which 

approach is likely to succeed technically or to be useful 

practically. A few of us may suspect that the quest for 

alternative sources of stem cells is misguided, and that we 

should continue using the embryos we have (or can 

produce directly) in order to get any new stem cell lines we 

need. 

Yet on the limited ethical threshold question—“Does this 

proposal appear to meet a minimum ethical standard to 

justify further serious consideration and scientific 

exploration?”—the Council offers the following provisional 

conclusions.36 

The first proposal, deriving cells from organismically dead 

embryos. Although it raises some serious ethical questions, 

we find this proposal to be ethically acceptable for basic 

investigation in humans, provided that stringent guidelines 

like those proposed by Drs. Landry and Zucker are strictly 

observed. The results of such investigations would help to 

determine whether the method would in fact prove 

ethically acceptable in the long run. 

The second proposal, blastomere extraction from living 

embryos. We find this proposal to be ethically unacceptable 

in humans, owing to the reasons given in the ethical 

analysis: we should not impose risks on living embryos 

destined to become children for the sake of getting stem 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

59

cells for research. This approach could, of course, be 

attempted in animals, but we do not yet see how results 

from animal experimentation could alter this assessment of 

ethical propriety in humans. We do not expect this method 

to become ethically acceptable for human trials in the 

future. 

The third proposal, cells derived from specially engineered 

biological artifacts. Because this proposal raises many serious 

ethical concerns, we do not believe that it is at this time

ethically acceptable for trials with human material. 

Although a few of us are not eager to endorse even animal 

and other laboratory work investigating potential human 

applications, most of us believe the proposal offers enough 

promise to justify animal experimentation, both to offer 

proof of feasibility and utility and to get evidence bearing 

on some of the ethical issues. We find no insuperable 

ethical objections to pursuing this proposal in animal 

models, which is, we note again, all that the proponents 

now seek to do. The possibility of any future endorsement 

of trying this approach in humans will depend upon a 

more thorough ethical analysis made possible in part by 

animal experiments. 

The fourth proposal, cells obtained by somatic cell 

dedifferentiation. We find this proposal to be ethically 

unproblematic and acceptable for use in humans, if and 

when it becomes scientifically practical, provided the line 

between pluripotency and totipotency can be maintained, 

as discussed in the ethical analysis. 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

60

Despite any differences among us about the merits of 

each proposal, the Council shares the view that the group 

of proposals here discussed—and others like them that 

they might stimulate—deserve the nation’s careful and 

serious consideration. Because the Council is 

wholeheartedly committed both to the advancement of 

science for the betterment of humankind and to the defense 

of human freedom, dignity, and the value of human life, 

we are pleased to endorse these proposals as worthy of further 

public discussion, and we are pleased to encourage their 

scientific exploration in accordance with the preliminary ethical 

judgments just offered. A good part of our uncertainty today 

about the merits of these proposals rests on the paucity of 

available scientific evidence and of demonstrated technical 

prowess. Both enthusiasts and skeptics regarding these 

proposals should agree at least on this: that further 

empirical studies will be needed before the true potential of 

these proposals can be properly assessed. 

We conclude by stressing that while these four 

proposals are the ones that seem most worthy of analysis 

and discussion at this time, it is altogether possible, indeed 

likely, that other avenues to human pluripotent stem cells 

not requiring the destruction of human embryos may be 

proposed or discovered in the future. By limiting ourselves 

to these current proposals, we do not intend to exclude any 

additional ones. On the contrary, we publish this White 

Paper to encourage scientists to creatively devise other and 

better proposals and to highlight the appeal of the larger 

purpose: to find ways to advance pluripotent stem cell 

research that all our fellow citizens can wholeheartedly 

support. That end is, in the view of the Council, a desirable 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

61

goal for our society and one that justifies making the extra 

effort to seek out, assess, and attempt new, ethically 

uncontroversial methods of stem cell derivation. 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

62

Endnotes and References 

1 President’s Council on Bioethics, Human Cloning and Human Dignity: 

An Ethical Inquiry, July 2002, pp. xxx and 121. For discussion of these 

competing goods, see Chapter Six, “Ethics of Cloning-for-BiomedicalResearch.” See also Chapter Three (“Recent Developments in the 

Ethical and Policy Debates”) of Monitoring Stem Cell Research: A Report 

of the President’s Council on Bioethics, January 2004. 

2 Landry, D. W. and H. A. Zucker, “Embryonic death and the creation 

of human embryonic stem cells,” The Journal of Clinical Investigation 114, 

1184-1186 (2004). The transcript of the presentation and discussion of 

this proposal at the December 3, 2004 Council meeting is available 

online at www.bioethics.gov (see session 6). This proposal was 

anticipated in Grinnell, F., “Defining embryo death would permit 

important research,” The Chronicle of Higher Education 49(36), B13 (May 

16, 2003), and Grinnell, F., “Human embryo research: from moral 

uncertainty to death,” American Journal of Bioethics 4, 12-13 (2004). 

3 Although there is a broad consensus on the ethics of posthumous 

organ donation, there are some who have raised questions about the 

adequacy of the criterion (typically, “brain death”) by which death 

(“irreversible loss of integrated functioning of the person”) is 

established. See President’s Commission for the Study of Ethical Problems in 

Medicine and Biomedical and Behavioral Research. Defining Death: A Report 

on the Medical, Legal, and Ethical Issues in the Determination of Death

(Washington: The Commission, 1981); Veatch, R. M., “The Conscience 

Clause,” in The Definition of Death: Contemporary Controversies, ed. S. J. 

Youngner, et al. (Baltimore, Md.: Johns Hopkins University Press, 

1999), 137-160; Shewmon, D. A., “Brainstem death, brain death and 

death: a critical re-evaluation of the purported evidence,” Issues in Law 

and Medicine 14, 125-145 (1998); and Shewmon, D. A., “Chronic brain 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

63

death: meta-analysis and conceptual consequences,” Neurology 51, 

1538-1545 (1998). 

4 Landry and Zucker (op. cit.) refer to a study by Laverge, et al., in 

which, “out of 166 frozen embryos thawed for further growth, 78 

embryos remained arrested at 24 hours after thawing, and 71 showed 

no sign of further cleavage at 48 hours.” See Laverge, H., et al., 

“Fluorescent in-situ hybridization on human embryos showing 

cleavage arrest after freezing and thawing,” Human Reproduction 13, 

425-429 (1998). 

5 D. H. Edgar and coworkers estimate that “the implantation potential 

of a population of embryos was reduced by ~30% by being subjected to 

cryopreservation.” See Edgar, D. H., et al., “A quantitative analysis of 

the impact of cryopreservation on the implantation potential of human 

early cleavage stage embryos,” Human Reproduction 15, 175-179 (2000). 

 See also the following studies cited by Laverge, et al. (in the paper 

mentioned in endnote 4): Camus, M., et al., “Human embryo viability 

after freezing with dimethylsulfoxide as a cryoprotectant,” Fertility and 

Sterility 51, 460–465 (1989); Levran, D., et al., “Pregnancy potential of 

human oocytes—the effect of cryopreservation,” New England Journal of 

Medicine 323, 1153–1156 (1990); Van Steirteghem, A., et al., 

“Cryopreservation of human embryos,” Bailliere’s Clinical Obstetrics and 

Gynaecology 6, 313–325 (1992); and Van der Elst, J., et al., “Prospective 

randomized study on the cryopreservation of human embryos with 

dimethylsulfoxide or 1,2-propanediol protocols,” Fertility and Sterility

63, 92–100 (1995).

6 Recently, animal studies have shown that some individual 

blastomeres, removed from embryos that have ceased developing, can 

survive, grow, and function normally if they are transplanted into a 

still-living embryo that is itself developing normally. For example, in 

their presentation to the Council, Landry and Zucker pointed out work 

by Byrne and coworkers that showed that cells from abnormal partial 

blastulae of cloned amphibian embryos could be “rescued” by grafting 

them to normal host embryos where they contributed to several tissues.

See Byrne, J. A., Simonsson, S., Gurdon, J. B., “From intestine to muscle: 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

64

nuclear reprogramming through defective cloned embryos,”

Proceedings of the National Academy of Sciences USA 99(9), 6059-6063 

(April 30, 2002).

7 Strelchenko, N., et al., “Morula-derived human embryonic stem cells,” 

Reproductive BioMedicine Online 9(6), 623-629 (2004). See also U.S. Patent 

Application 20040229350, “Morula derived embryonic stem cells,” filed 

November 18, 2004. 

8 The question was raised by Council Member Dr. Paul McHugh, at the 

December 2004 Council meeting. For discussion of this point, see the 

transcript of the December 3, 2004 meeting (session 6), available online 

at www.bioethics.gov. 

9 Studies reporting the derivation of human embryonic stem cell lines 

starting from excess blastocysts from IVF procedures and supported by 

private funding include: (1) Mitalipova, M., et al., “Human embryonic 

stem cell lines derived from discarded embryos,” Stem Cells 21, 521-526 

(2003), and (2) Cowan, C. A., et al., “Derivation of embryonic stem cell 

lines from human blastocysts,” New England Journal of Medicine 350, 

1353-1356 (2004).

10 The Dickey Amendment, named for its author, former Representative 

Jay Dickey of Arkansas, has been attached to the Health and Human 

Services authorization bill each year since 1995. The provision reads as 

follows: 

SEC. 510. 

(a) None of the funds made available in this Act may be used for— 

 (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 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

65

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 

U.S.C. 289g(b)). 

(b) For purposes of this section, the term ‘human embryo or embryos’ 

includes 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. 

The section of the Code of Federal Regulations (CFR) to which the 

Dickey Amendment refers reads as follows: 

45 CFR §46.208 Activities directed toward fetuses in utero as 

subjects. 

(a) No fetus in utero may be involved as a subject in any activity

 covered by this subpart unless: 

 

 (2) the risk to the fetus imposed by the research is minimal and 

 the purpose of the activity is the development of important

 biomedical knowledge which cannot be obtained by other means.

The section of the Public Health Service Act to which the Dickey 

Amendment refers reads as follows: 

§289g. Fetal research 

(b) Risk standard for fetuses intended to be aborted and fetuses

 intended to be carried to term to be same 

In administering the regulations for the protection of human research

 subjects which— 

 (1) apply to research conducted or supported by the Secretary;

 (2) involve living human fetuses in utero; and 

(3) are published in section 46.208 of part 46 of title 45 of the 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

66

 Code of Federal Regulations or any successor to such regulations—

the Secretary shall require that the risk standard (published in section 

46.102(g) of such part 46 or any successor to such regulations) be the 

same for fetuses which are intended to be aborted and fetuses which are 

intended to be carried to term. 

The minimal risk standard governing research on fetuses is defined in 

the CFR as follows: 

45 CFR §46.102 

(i) Minimal risk means that the probability and magnitude of harm or 

discomfort anticipated in the research are not greater in and of 

themselves than those ordinarily encountered in daily life or during the 

performance of routine physical or psychological examinations or tests. 

11 See “Remarks by President George W. Bush on Stem Cell Research,” 

as made available by the White House Press Office, August 9, 2001. 

12 Genetics and Public Policy Center, “Preimplantation Genetic Diagnosis: 

A Discussion of Challenges, Concerns and Preliminary Policy Options 

Related to the Genetic Testing of Human Embryos,” Washington, D.C. 

(2004). 

13 PGD can only be performed on embryos created through IVF. There 

are already questions about whether specific forms of IVF (in the 

absence of PGD) lead to an increased incidence of some rare genetic 

diseases. (See for example, Gosden, R., et al., “Rare congenital 

disorders, imprinted genes, and assisted reproductive technology,” 

Lancet 361, 1975-1977 [2003].) In its 2004 report, Reproduction and 

Responsibility, the Council issued a recommendation to “undertake a 

federally funded longitudinal study of the impact of ARTs (Assisted 

Reproduction Technologies) on the health and development of children 

born with their aid.” 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

67

14 See, among other articles, Adams, K. E., “Ethical considerations of 

applications of preimplantation genetic diagnosis in the United States,” 

Biomedicine and Law 22, 489-504 (2003); Rechitsky, S., et al., 

“Preimplantation genetic diagnosis with HLA matching,” Reproductive 

BioMedicine Online 9, 210-221 (2004); Sheldon, S. and S. Wilkinson, 

“Should selecting savior siblings be banned?” Journal of Medical Ethics

30, 533-537 (2004). 

15 American Society for Reproductive Medicine, Ethics Committee 

Report, “Sex selection and preimplantation genetic diagnosis,” Fertility 

and Sterility 72, 595-598 (1999); The Ethics Committee of the American 

Society of Reproductive Medicine, “Sex selection and preimplantation 

genetic diagnosis,” Fertility and Sterility 82 (Suppl. 1), S245-248 (2004).

16 See, transcript of the December 13, 2002 Council meeting (session 6), 

available online at www.bioethics.gov. 

17 Cohen, E., personal communication to the Council, commenting on 

this proposal. 

18 Can single blastomeres extracted from a 4- or 8-cell embryo ever give 

rise to a whole organism? For human blastomeres, the answer is not 

known, and there are substantial ethical objections to performing the 

experiments that could assess this question. In mice, apparently normal 

and fertile animals have been produced from single blastomeres 

isolated from a 4-cell embryo (and from two blastomeres isolated from 

an 8-cell embryo); but the blastomeres had to be cultured in the 

presence of cells from “carrier embryos.” See Tarkowski, A. K., 

Ozdzenski, W., Czolowska, R., “Mouse singletons and twins developed 

from isolated diploid blastomeres supported with tetraploid 

blastomeres,” International Journal of Developmental Biology 45(3), 591-

596 (2001). In experiments with non-human primates (rhesus 

monkeys), Chan, et al., [see “Clonal propagation of primate offspring 

by embryo splitting,” Science 287, 317-319 (2000)] have reported that 

two blastomeres isolated from an 8-cell embryo gave rise to a live-born 

monkey they called Tetra. See also Schramm, R. D. and A. M. Paprocki, 

“Strategies for the production of genetically identical monkeys by 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

68

embryo splitting,” Reproductive Biology and Endocrinology, 2, 38 (2004). 

19 Krzyminska, U. B., Lutjen, J., O’Neill, C., “Assessment of the viability 

and pregnancy potential of mouse embryos biopsied at different 

preimplantation stages of development,” Human Reproduction 5(2), 203-

208 (1990).

20 Quotations from Hurlbut are from his paper presented to the Council 

on December 3, 2004, “Altered Nuclear Transfer as a morally 

acceptable means for the procurement of human embryonic stem cells,” 

available online in the December 2004 Council meeting background 

materials at www.bioethics.gov. For Council discussion of his paper, 

see transcript of the December 3, 2004 meeting (session 6), also 

available online at www.bioethics.gov. 

21 Chawengsaksophak, K., et al., “Cdx2 is essential for axial elongation 

in mouse development,” Proceedings of the National Academy of Sciences 

USA 101(20), 7641-7645 (May 18, 2004). 

22 Cohen, E., op. cit. 

23 See, Gook, D. A., et al., “Oocyte maturation, follicle rupture and 

luteinization in human cryopreserved ovarian tissue following 

xenografting,” Human Reproduction 18(9) 1772-1781 (2003). 

24 See, for example, the public comment made to the Council by Jaydee 

Hanson, representing the International Center for Technology 

Assessment, at the December 2004 meeting (session 7), the transcript of 

which is available online at www.bioethics.gov. 

25 For discussion of these issues, see transcript of the Council’s March 4, 

2005, meeting (session 5), available online at www.bioethics.gov. 

26 Humpherys, D., et al., “Gene expression in cloned mice derived from 

embryonic stem cell and cumulus cell nuclei,” Proceedings of the 

National Academy of Sciences USA 99(20), 12889-12894 (October 1, 2002).
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

69

27 Robert Lanza, “The troubling prospect of genetic manipulation” 

(Letter), Washington Post, p. A20, December 13, 2004. Curiously, in 

September 2002, Advanced Cell Technology, the company for which 

Dr. Lanza works, filed a patent for producing genetically altered 

artificial embryo-like entities, partly for the same purpose. The 

company’s patent application summarizes the main idea: “Methods for 

making human ES cells and human differentiated cells and tissues for 

transplantation are described, whereby the cells and tissues are created 

following somatic cell nuclear transfer. The nuclear transfer donor is 

genetically modified prior to nuclear transfer such that cells of at least 

one developmental lineage are de-differentiated, that is, unable to 

develop, thereby resolving the ethical dilemmas involved in 

reprogramming somatic cells back to the embryonic stage.” (United 

States Patent Application 20020132346.) 

28 See, Melton, D. A., Daley, G. Q., Jennings, C. G., “Altered nuclear 

transfer in stem-cell research—a flawed proposal,” New England Journal 

of Medicine 351, 2791 (2004).

29 Rogers, N. T., et al., “Phospholipase C{zeta} causes Ca2+ oscillations 

and parthenogenetic activation of human oocytes,” Reproduction 128(6), 

697-702 (2004). See also Lin, H., et al., “Multilineage potential of 

homozygous stem cells derived from metaphase II oocytes,” Stem Cells

21, 152-161 (2003). 

30 While it has not yet been demonstrated using humans oocytes, José 

Cibelli and coworkers have recently succeeded in obtaining a line of 

pluripotent stem cells from parthenogenetically activated eggs of the 

long-tailed macaque (a nonhuman primate). See Cibelli, J. B., et al., 

“Parthenogenetic stem cells in nonhuman primates,” Science 295, 819 

(2002). 

31 See, Kiessling, A. A., “Eggs Alone—Human parthenotes: an ethical 

source of stem cells for therapies?” Nature 434, 145 (2005). 

32 Brockes, J. P., “Amphibian limb regeneration: rebuilding a complex 

structure,” Science 276, 81-87 (1997). 
ALTERNATIVE SOURCES 

OF HUMAN PLURIPOTENT STEM CELLS

70

33 See, for example, Chen, S., et al., “Dedifferentiation of lineagecommitted cells by a small molecule,” Journal of the American Chemical 

Society 126(2), 410-411 (2004); Odelberg, S. J., et al., “Dedifferentiation of 

mammalian myotubes induced by msx1,” Cell 103(7), 1099-1109 (2000); 

and McGann, C. J., Odelberg, S. J., Keating, M. T., “Mammalian 

myotube dedifferentiation induced by newt regeneration extract,” 

Proceedings of the National Academy of Sciences USA 98(24), 13699-13704 

(November 20, 2001). 

34 The best known research is by Catherine Verfaillie and coworkers at 

the Stem Cell Institute at the University of Minnesota Medical School. 

See, for a recent update, Dr. Verfaillie’s review essay on “Multipotent 

Adult Progenitor Cells” (MAPCs), published as Appendix J in 

Monitoring Stem Cell Research: A Report of the President’s Council on 

Bioethics, January 2004 (also available online at www.bioethics.gov). A 

more recent publication, by scientists at the University of Miami in 

collaboration with French scientists, reports the cultivation of 

pluripotent human cells from bone marrow (of human adults and 

children), after a unique expansion and selection procedure under 

conditions that were designed to mimic the in vivo environment of the 

early human embryo. According to the report, these cells can be grown 

for extended periods of time in culture, express genes similar to those 

expressed by embryonic stem cells in culture, and can be stimulated to 

differentiate into various adult tissue types, including neuronal and 

pancreatic islet tissue. See D’Ippolito, G., et al., “Marrow-isolated adult 

multilineage inducible (MIAMI) cells, a unique population of postnatal 

young and old human cells with extensive expansion and 

differentiation potential,” Journal of Cell Science 117, 2971-2981 (2004). 

The relation between the MIAMI cells and Dr. Verfaillie’s MAPCs is 

unclear, although it is possible that the MIAMI cells may be somewhat 

less differentiated than the MAPCs. The research from both 

laboratories needs to be reproduced by other scientists before its true 

promise can be assessed. See also Yoon, Y-S., et al., “Clonally expanded 

novel multipotent stem cells from human bone marrow regenerate 

myocardium after myocardial infarction,” The Journal of Clinical 

Investigation 115, 326-338 (2005), and Kogler, G., et al., “A new human 
A WHITE PAPER OF

THE PRESIDENT’S COUNCIL ON BIOETHICS

71

somatic stem cell from placental cord blood with intrinsic pluripotent 

differentiation potential,” Journal of Experimental Medicine 200, 123-135 

(2004). 

35 See, in particular, Byrne, J. A., et al., “Nuclei of adult mammalian 

somatic cells are directly reprogrammed to oct-4 stem cell gene 

expression by amphibian oocytes,” Current Biology 13, 1206-1213 (2003), 

and Gurdon, J. B., Byrne, J. A., Simonsson, S., “Nuclear reprogramming 

and stem cell creation,” Proceedings of the National Academy of Sciences 

USA 100 (Suppl. 1), 11819-11822 (September 30, 2003). 

36 For the Council’s discussion that gave rise to these provisional 

conclusions, see transcript of the Council’s March 4, 2005, meeting 

(session 5), available online at www.bioethics.gov. 

APPENDIX 

75 

Personal Statements

 The preceding text constitutes the official body of this White Paper; 

it stands as the work of the entire Council. In the interest of 

contributing further to public discussion of the issues, and of enabling 

individual members of the Council to speak in their own voice on one 

or another aspect of this White Paper, we offer in this Appendix 

personal statements from those members who have elected to submit 

them: 

 Statement of Michael S. Gazzaniga, Ph.D. 76 

 Statement of Robert P. George, D.Phil., J.D., 79 

 (joined by Mary Ann Glendon, J.D., M. Comp. L., 

 and Alfonso Gómez-Lobo, Dr. phil.) 

 Statement of William B. Hurlbut, M.D. 82 

 Statement of Janet D. Rowley, M.D., D.Sc. 89 

 Statement of Michael J. Sandel, D.Phil. 91 
ALTERNATIVE SOURCES

OF HUMAN PLURIPOTENT STEM CELLS

76

Personal Statement of Dr. Gazzaniga 

I do not support publishing this report with the implied 

endorsement that special efforts be made in the scientific areas 

described. While some of the suggestions could be explored in a 

scientific setting, most are high-risk options that only have an outside 

chance of success and raise their own complex set of ethical questions. 

Of primary concern: this effort is a diversion from the simple task at 

hand which is to move forward with the established laboratory 

techniques, that are already grounded on a clear ethical basis, for 

studying embryonic stem cell research and biomedical cloning. 

The simple proposals that are now widely accepted by the majority 

of ethicists and scientists alike are as follows: 

Allow the use of spare IVF embryos to develop more human stem 

cell lines. These are entities that do not possess a single neuron and are 

ready to go and can create tens of thousands of cell lines. Put another 

way, a piece of DNA is not a human being. A human being is an entity 

with a functioning brain consisting of billions of neurons with trillions 

of synapses that develops over time and with crucial interactions with 

the environment. 

Allow biomedical cloning (SCNT) to go forward. This laboratory 

procedure has been tested and it works. SCNT can only be carried out 

in a laboratory and the 14-day-old entity that results from the 

procedure also has not a single neuron. After the specific stem cells are 

harvested by 14 days, the remaining tissue is disposed of. 

From a purely scientific point of view I offer the following remarks 

on the alternative suggestions made by the Council, based on 

consultation with stem cell experts: 

Proposal 1, the Landry-Zucker proposal, is absolutely dependent on 

defining a battery of “death markers.” The criteria they offer lack the 

specificity and selectivity required. To what degree, for example is 

“embryo-dead” analogous to “brain dead?” What are the long-term 
APPENDIX: PERSONAL STATEMENTS 77

consequences (through adulthood) of using blastomeres from “dead” 

morulae? These are answerable, but formidable problems. Blastomere 

removal must be validated in vitro and in vivo, with respect to mitosis, 

survival, differentiation, etc., none of which are inaccessible. No 

assumption whatsoever can be made that these are “normal cells.” At 

the same time, these questions are scientifically accessible. 

Proposal 2, relies on biopsy, and this represents a new field, which 

must be explored experimentally. For example, and most obviously, 

what is the relationship of cellular to organ removal and 

transplantation? Are the biological rules homologous? We need the 

data. 

Proposal 3, Bill Hurlbut’s proposal, is also scientifically tractable, 

though fraught with ethical conundrums. Defective nuclear transfer 

could certainly be accomplished in theory, though issues of viability, 

etc., would be paramount. And replacing genes at the “wrong” time 

could be devastating either acutely or chronically. Although a myriad 

of additional potential problems could be cited, they are again 

empirical, not theoretical. Why delay what we know works with this 

sideshow? As pointed out in the paper, one of the leading stem cell 

research scientists in the world, Dr. Doug Melton at Harvard, has 

written an article in the New England Journal of Medicine dismissing this 

idea both scientifically and practically. 

Proposal 4, dedifferentiation, is similarly approachable scientifically, 

though it is a high-risk strategy. Questions, however, raised with this 

idea can be answered with a huge and costly scientific program in 

place. 

At the same time and from an ethical perspective, I must add that I 

find this proposal strained at best. Winding the clock back on a 

developed somatic cell and to stop it at a critical point is supposed to 

be void of ethical issues while letting a cell grow forward to just before 

the same point as with SCNT is not ethical? 

This is the potentiality argument in reverse. In one version the film 

of life is running forward and in the other it is running in reverse. In 

both scenarios humans are making decisions about life and its origins. 
ALTERNATIVE SOURCES

OF HUMAN PLURIPOTENT STEM CELLS

78

It reveals how the so-called ethical concerns are being laid over 

molecular events moving either forward or backward in time. 

In summary, these proposals, in spite of being experimentally 

approachable, are, ultimately, high-risk gambles. Each presents 

formidable, but not impossible, technical problems. The scientific 

challenges must not be confounded with the complex moral issues. 

Most troubling, this effort dilutes the essential question: Is the United 

States of America going to allow embryonic stem cell research and 

biomedical cloning to go forward using the now widely accepted 

techniques used by the private sector, by the State of California, and by 

dozens of other countries, or is it going to remain hostage to the 

arbitrary views of those with certain beliefs about the nature of life and 

its origins? 

MICHAEL S. GAZZANIGA 
APPENDIX: PERSONAL STATEMENTS 79

Personal Statement of Professor George 

(joined by Professor Glendon and Dr. Gómez-Lobo)

I support the Council’s efforts to identify means of obtaining 

human pluripotent stem cells for biomedical research that do not 

involve killing or harming human embryos and do not invite the 

exploitation of women to obtain ova. If such means can be identified, 

research involving embryonic or embryonic-type stem cells could go 

forward, and be funded by the federal government, without ethical 

qualms and controversy. Assuming that supporters of embryonic stem 

cell research and its public funding are sincere in saying that they have 

no intention or desire to derive tissue or organs from post-implantation 

human embryos or from human fetuses, this would bring to a close—

honorably and without rancor—a divisive chapter in our recent 

history. Frankly, I do not see how any person of goodwill could be 

opposed to such a resolution of the matter. 

I commend everyone who has stepped forward to propose possible 

methods of obtaining human pluripotent stem cells while fully 

respecting human life at every stage of development. I thank our 

Council’s staff and consultants who have helped to provide in this 

White Paper a thorough, if necessarily in some ways still preliminary, 

analysis of each of the four proposals we sketch and analyze. Although 

I do not hold out hope of obtaining pluripotent stem cells harmlessly 

via blastomere extraction from living human embryos (proposal II), I 

believe that each of the other three proposals merits further exploration 

(including, where indicated, experimental research involving nonhuman animal cells) and analysis. 

The best long-term solution is likely to be somatic cell 

dedifferentiation (proposal IV). But while scientists work towards the 

goal of dedifferentiating somatic cells back to their corresponding 

progenitor cells, it may be possible ethically to employ one or both of 

the other two methods, namely deriving cells from embryos that have 

died (proposal I) or from nonembryonic entities produced by altered 

nuclear transfer (proposal III). I say, with emphasis, may be because 

serious moral and practical concerns have been raised about both 
ALTERNATIVE SOURCES

OF HUMAN PLURIPOTENT STEM CELLS

80

proposals. Research and further analysis will be required to determine 

whether the proposed methods are technologically possible and 

ethically sound. That research and analysis should, in my opinion, go 

forward. 

Of the four possible methods explored in our White Paper, the one 

that has attracted the most intense interest outside the Council is 

altered nuclear transfer. There are two major concerns: (1) the question 

whether the entity produced would be truly non-embryonic, and not a 

disabled embryo or an embryo genetically programmed for a 

premature death; and (2) the question whether ova could be supplied 

without subjecting women to the painful and possibly dangerous 

process of superovulation. Neither of these questions is, strictly 

speaking, ethical, though both have what I consider to be decisive 

ethical implications. Like Dr. Hurlbut, who has taken the lead in 

formulating this proposal, I will not support altered nuclear transfer as 

a method of obtaining human pluripotent stem cells unless it can be 

shown that (1) the procedure truly and reliably produces 

nonembryonic entities, rather than damaged embryos, and (2) it is 

possible to carry out altered nuclear transfer on the scale required 

without subjecting women to harmful and exploitative practices. 

I recognize that some people have objections to altered nuclear 

transfer even if these conditions are met. Dr. Krauthammer, for 

example, objects even if the sources of stem cells created can be shown 

truly to be nonembryonic. Because Dr. Krauthammer also objects (as I 

do) to the creation for destruction of true embryos (by cloning or any 

other method), I take his concerns very seriously and welcome his 

criticisms of my own more permissive view. I would not finally 

endorse altered nuclear transfer using human cells prior to engaging 

the argument with him more fully and considering with the utmost 

care the considerations he adduces against it. 

It is more difficult to credit the ethical objections to altered nuclear 

transfer of those who support the creation of true embryos to be 

destroyed in biomedical research. How can it be right deliberately to 

create and destroy true human embryos—beings that no one can deny 

are human individuals in the embryonic stage of development—yet 

somehow wrong to produce disorganized growths that are the moral 

equivalent of gamete tumors rather than embryos? 
APPENDIX: PERSONAL STATEMENTS 81

One final point: the effort in which I am happy to join to find 

morally legitimate means of obtaining embryonic or embryonic-type 

stem cells should not be interpreted as indicating any acceptance of the 

hyping of the therapeutic promise of embryonic stem cell research that 

has marred the debate over the past four years. This promotion of 

exaggerated expectations dishonors science and shames those 

responsible for it by cruelly elevating the hopes of suffering people and 

members of their families. It should be condemned. 

ROBERT P. GEORGE 

(JOINED BY MARY ANN GLENDON 

AND ALFONSO GÓMEZ-LOBO) 
ALTERNATIVE SOURCES

OF HUMAN PLURIPOTENT STEM CELLS

82

Personal Statement of Dr. Hurlbut 

Since I find myself in the unusual position of being both a member 

of the Council and, at the same time, the principal advocate of one of 

the four proposals here under consideration, I am mindful that a 

delicate balancing of roles is required in the way I frame the following 

remarks. I shall take care that my comments not cross the line 

separating impartial analysis of the four proposals from partisan 

advocacy of one of them. 

While I believe that, by and large, the White Paper, like a good 

preliminary hearing at law, does an admirable job of presenting the 

four proposals and beginning their ethical, scientific, and practical 

analysis, it seems to me deficient in two main respects. First, I think 

there is much more to be said about the importance, for the future, of 

finding a scientific and ethical solution to the problem of deriving 

human stem cell lines. Second, I think that some of the ethical concerns 

raised about the ANT proposal could have been answered more 

effectively. In the brief remarks that follow, I will try to supply these 

two deficiencies. 

1. General comments about the importance of the project 

In our report Human Cloning and Human Dignity: An Ethical Inquiry

(July 2002), I joined colleagues who called for a moratorium on cloningfor-biomedical-research. I believed that our nation needed time to 

consider more thoroughly the moral status of ex vivo human embryos 

and to seek scientific methods for procuring embryonic stem cells that 

could sustain social consensus for a unified federal policy. This White 

Paper both deepens the dialogue and encourages progress toward 

these goals, but it does not make it sufficiently clear why it is urgent 

that we succeed. 

The past three years have been characterized by controversy about 

the scientific prospects for embryonic (versus adult) stem cells and a 

widening political divide over the ethics of ESC research. Advances 
APPENDIX: PERSONAL STATEMENTS 83

have been made in the study of ES cells, yet predictions of imminent 

cures have been moderated by a recognition of the technical difficulties 

in emulating in vitro the intercellular signals and microenvironments 

that promote cell differentiation within natural embryogenesis. 

Nonetheless, scientists generally believe that ESC research is both 

essential to the broader study of both natural development and 

pathogenesis and promising for medical interventions against a range 

of serious diseases. They also believe that, without NIH support for 

newly created ES cell lines, progress in this important realm of research 

will be severely constrained. 

Yet even as these scientific prospects have become clearer, 

advances in our understanding of developmental biology have 

strengthened the case of those with ethical objections to embryo 

destruction. New scientific evidence supports the idea that there is an 

integrated unity and unbroken continuity of development from 

fertilization onward—and undercuts claims that the early embryo is an 

“inchoate clump of cells,” available for instrumental use with little or 

no moral concern. 

These findings have solidified the convictions of many people that 

any instrumental use of human embryos must be acknowledged as a 

choice for destruction of human life (albeit at a very early stage of 

development), justified not by scientific evidence or moral reason but 

by a purely utilitarian calculus based on the promise of cures and even 

commercial considerations. This approach, grounded not on principle 

but on a balance of benefits, would seem vulnerable to being easily 

persuaded toward additional exceptions and extensions as further 

promising projects become evident.

Beyond their destruction for the procurement of ES cells, some fear 

the industrial scale production of living human embryos for a wide 

range of research in natural development, toxicology, and drug testing. 

These concerns have already been aggravated by proposals to use ES 

cells in the creation of human-animal chimeras, including projects 

involving their gestation to various stages of development in the 

wombs of animals. Furthermore, some see ominous implication in the 

evidence that later stage human embryos (beyond 14 days) can provide 
ALTERNATIVE SOURCES

OF HUMAN PLURIPOTENT STEM CELLS

84

the critical conditioning environment for the transformation of adult 

stem cells into useful cell types, tissues, and possibly organs.*

Our current conflict over the moral status of the human embryo 

reflects deep differences in our basic convictions and is unlikely to be 

resolved through deliberation or debate. Likewise, a purely political 

solution will leave our country bitterly divided, eroding the social 

support and sense of noble purpose that is essential for the public 

funding of biomedical science. Furthermore, the emerging patchwork 

of state policies threatens to create a situation in which many patients 

will enter the hospital with qualms about the moral foundations on 

which their treatments have been developed. The traditional sanctuary 

of compassionate care at the most vulnerable and sensitive moments of 

human life is becoming an arena of controversy and conflict. 

As we enter the era of developmental biology, we will face many 

more moral dilemmas; the current conflict over ES cells is just the first 

of a series of difficult controversies over the experimental use of 

emerging life that will require us to define with clarity and precision 

exactly which boundaries we seek to defend.† Chimeras, parthenotes, 

and projects involving the reaggregation of ES cell products will 

continue to challenge our definitions of human life. How we act now in 

the stem cell dilemma will set a precedent for all future efforts to exploit 

nascent human life for scientific ends. There is thus much more at stake 

than the proposals herein discussed. 

The proposals presented in this White Paper open a realm of 

intellectual inquiry and creative scientific investigation in the search for 

 

* See Yokoo, T., et al., “Human mesenchymal stem cells in rodent wholeembryo culture are reprogrammed to contribute to kidney tissue,” Proceedings 

of the National Academy of Sciences USA 102(9), 3296-3300 (March 1, 2005).

† These studies will not be limited to ES cells and the first few days of 

embryogenesis, since there are compelling scientific and medical reasons to 

seek an understanding of the entire trajectory of human biology from 

fertilization to natural death. Beyond the obvious benefit of understanding the 

fundamental biological factors behind the estimated 200,000 birth defects per 

year, it is becoming increasingly evident that pathologies that manifest 

themselves in adult life (such as hypertension, diabetes, etc.) are influenced by, 

or have their origins in, early development. 
APPENDIX: PERSONAL STATEMENTS 85

a solution to our current impasse over the procurement of embryonic 

stem cells. Such a solution must be grounded in deep ethical reflection 

and in careful preliminary studies with animal cells. The 

incommensurate good of human life, and the corresponding danger of 

its instrumental use (thereby violating the principle we are trying to 

protect), mean that the highest levels of caution must prevail as we 

proceed forward with this project. We must initiate the cooperative 

dialogue that is essential to frame the moral principles that can at once 

defend human dignity and promote the fullest prospects for scientific 

progress and its medical applications. 

2. Answers to ethical concerns raised about ANT 

Throughout this report we draw a distinction between pluripotency, 

the capacity to give rise to many if not all the different cell types of the 

human body, and totipotency, the capacity to give rise to the whole 

organism as an integrated living being. Employing these concepts in 

the search for a technological solution to our ethical impasse, we must 

consider any entity that has the intrinsic potential to develop as a 

human organism (totipotency) as bearing the inviolability of a human 

life.*

 This status applies regardless of its means of production or 

present location. 

Proposals 1 (Landry-Zucker) and 3 (Altered Nuclear Transfer) may 

hold the best near-term promise for practical application, yet they also 

raise the most difficult conceptual considerations. Landry-Zucker 

would extract ES cells from embryos that are no longer totipotent, and 

Altered Nuclear Transfer (ANT) would create and extract ES cells from 

“biological artifacts” that never rise to the level of totipotency. Both 

proposals shift the ethical debate from the question of when a normal 

embryo is a human being with moral worth, to the more fundamental 

question of what component parts and organized structure constitute 

the minimal criteria for considering an entity a living human organism. 

Each of these proposals draws on the idea that a living organism is 

a self-subsisting being, a coordinated and coherent whole with the 

 

*

 A practical measure of this intrinsic potential would be the ability to develop 

when provided the support and nurture of a natural gestational environment 

or its technological equivalent. 
ALTERNATIVE SOURCES

OF HUMAN PLURIPOTENT STEM CELLS

86

capacity for self-directed development, maintenance, and repair. The 

very word organism implies organization, an overarching principle of 

unity, a cooperative interaction of interdependent parts subordinated 

to the good of the whole. For an embryonic organism, this implies an 

inherent potency, a drive in the direction of the mature form. By its 

very nature, an embryo is a developing being, its wholeness defined by 

both its manifest expression and its latent potential; it is the phase of 

human life in which the organismal whole produces its organic parts. 

For Landry-Zucker, the conceptual and moral challenge is to define 

the meaning of “embryo death,” the cessation of integrated form and 

the totipotent capability that characterizes a living human embryo. A 

secondary, scientific challenge is to identify a physical marker of this 

state. For Altered Nuclear Transfer, the conceptual and moral challenge 

is the more difficult task of defining the boundary between mere 

cellular growth lacking integrated form and a living organism. The 

scientific challenge of ANT is to find the right genetic or epigenetic 

alteration to ensure that pluripotent cells can be produced while not 

creating an embryonic human being. It is here that the White Paper, in 

my view, does not make sufficiently clear how the proposal in fact 

meets that challenge.

That an ANT product might during its earliest stages visually 

resemble an embryo does not make it an embryo, for an entity’s 

fundamental nature must ultimately be based on its internal 

biochemical structure and organization. Likewise, cell division and 

growth are not sufficient evidence that the entity is a human embryo. 

Even an egg without a nucleus, when artificially activated, has the 

developmental power to divide to the eight-cell stage, yet clearly is not 

an embryo, or even an organism. Moreover, the possibility that the 

alteration could be reversed does not affect the fact that the targeted 

alteration has preempted the ANT entity from having the nature (the 

ontological status) of an embryo. 

The product of ANT would, by intention, lack the active potential 

and inviolable moral nature of a living human being. Without this 

moral standing, there is no obligation of repair because there is no 

living being to be repaired. Nonetheless, even such a limited biological 

entity should be accorded a certain cautionary respect as with all 

human tissues, though not the full protection of human life. 
APPENDIX: PERSONAL STATEMENTS 87

Some fear that the precedent of intentional genetic intervention 

(essential to ANT), and its justifying argument based on the intrinsic 

insufficiency of the entity produced, could become the basis for further 

projects in the bioengineering of ever more human-like “intermediate 

biological forms.” This is a serious consideration, but one that would 

be better addressed to those who maintain an “intermediate moral 

status” (worthy of dignity but not inviolability) for the human embryo 

and already accept the destruction of fully normal human beings at an 

early stage of their development. 

The very foundation of the moral argument for ANT should work 

to mitigate the concerns about the “slippery slope” potential for ES cell 

research. Since ANT seeks to defend human dignity from conception, it 

is less likely to lead to such indiscriminate and instrumental use of 

human life than the practices it seeks to preempt. By establishing a 

principled concern for the protection of human life from fertilization to 

natural death, ANT sets a firm foundation for the later distinctions 

necessary for further moral discrimination. Other proposals for the 

procurement of ES cells (SCNT and “leftover” IVF embryos) give little 

or no guidance to override the persuasive power of further promise 

from extending exceptions to moral principles. By establishing the 

primacy of ethical principle as the foundation of all scientific progress, 

ANT could help set the foundation and frame for the additional ethical 

dilemmas that will inevitably arise with advances in developmental 

biology. The difficult definitions and distinctions established in the 

moral deliberations associated with the ANT proposal could help chart 

the course and protect the path of future projects in this emerging 

arena of biology. If slippery slope arguments express prudential 

concerns, it seems reasonable to weigh ANT against the much more 

slippery scenario that will likely follow in its absence. 

Finally, there is the less easily argued but wider wisdom of our 

intuitive aesthetic response, and the concern that somehow we may 

violate or distort the principles of natural order that sustain the 

coherence and sense of significance of human life. I consider this the 

most compelling objection to both ANT and the whole of the modern 

project of biological intervention in the natural world. Clearly, no 

project that enters into such proximity with the most central and sacred 

realms of human life should be undertaken without a sense of 
ALTERNATIVE SOURCES

OF HUMAN PLURIPOTENT STEM CELLS

88

cautionary concern and serious purpose. Employing these powers of 

our most basic biology demands a sensitive awareness of the radiance 

of respect that must attend any technological use of body parts or 

processes apart from their proper place in the larger purposes of life. 

Nonetheless, where great good is possible, human tissues and organs 

have been used in the service of healing, and in this coming era of 

control over the primary forces of developmental biology, we will learn 

to use partial trajectories of organic growth even apart from their 

context within the living whole of the human body. The moral 

concerns and sensitivities that animate the proposal for ANT can, in 

fact, enable us to do so without losing our humanity.

WILLIAM B. HURLBUT 
APPENDIX: PERSONAL STATEMENTS 89

Personal Statement of Dr. Rowley 

Proposal 1 

Landry and Zucker propose to thaw out embryos to follow the 

natural history of “dead” embryos. Because they do not know in 

advance which embryos will not divide and which will, some portion 

of embryos (about half) will continue to divide and will be healthy 

embryos. What happens to these healthy embryos? The proposal says 

healthy embryos in excess of those to be implanted will be allowed to 

die while scientists struggle to recoup a few living cells from the dead 

embryos! This seems to me to be the height of folly. As noted on page 

21 in a footnote, I raised this concern during the public discussion. 

Proposal II 

I think this is risky research, although I recognize it is currently 

done as part of prenatal genetic diagnosis. In the latter case, it is done 

to prevent implantation of an embryo with a serious disease present in 

the parents; in the former, in the present proposal, it is done to 

circumvent a problem that causes ethical concerns to some people. 

There are at least two critical questions: can you get a cell line from one 

cell or two, and does it harm the embryo that will subsequently be 

implanted? Just because experiments in mice seem to indicate that it is 

feasible in mice (but with increased inter-uterine mortality), does not 

mean it will work for human embryos. In support of this proposal, it is 

absurd to say that this cell line, if it grows, will be a source of cells for 

the child later in life. A much more effective procedure would be to 

harvest stem cells from the cord blood and preserve them. 

Proposal III 

This proposal is scientifically unsound, and for individuals 

concerned about manipulating human oocytes for experiments, it 

should be ethically unacceptable! It has proven very inefficient to 

remove the nucleus from a human oocyte and to replace it with a 
ALTERNATIVE SOURCES

OF HUMAN PLURIPOTENT STEM CELLS

90

normal, unmanipulated nucleus from a donor. In the proposed 

experiments, the donated nucleus will be made defective by some 

uncertain genetic strategy. The defective nucleus will be inserted into 

the enucleated oocytes, the oocytes will be stimulated to grow, and 

then the genetic defect will be corrected so that the cells are “normal.” 

In my view, this research asks women to donate oocytes for research 

that is highly unlikely to result in cell lines that would be useful for 

treating sick patients, which is the purpose of trying to perfect the 

development of human embryonic stem cell lines. 

Proposal IV 

This proposal does not involve embryos, but rather differentiated 

cells. The purpose aims to dedifferentiate these cells. At least some of 

the purported successes with this strategy have had flaws when 

examined carefully. This proposal should be submitted to the National 

Institutes of Health and if it passes peer review with a sufficiently high 

score to be funded, then the research will go forward. 

My concerns with many of these proposals is that they will use 

financial resources that would be better devoted to proposals that are 

likely to be more productive. I find the notion that it is ethically sound 

to let healthy embryos die rather than use them to try to develop cell 

lines that could benefit sick and dying patients totally baffling. We talk 

about protecting human dignity. We should strive to help patients with 

serious illnesses that could potentially be treated with embryonic stem 

cells to live as fulfilling and dignified lives as is humanly possible. The 

research proposed in this White Paper largely fails to achieve this good, 

and thus I cannot support proposals I, II and III. 

JANET D. ROWLEY 
APPENDIX: PERSONAL STATEMENTS 91

Personal Statement of Professor Sandel 

I share the goal of seeking ethically uncontroversial ways of 

pursuing embryonic stem cell research. In my view, the first proposal 

(deriving cells from dead embryos) and the fourth (somatic cell 

dedifferentiation) are ethically acceptable and worthy of further 

exploration. I find the third proposal (deriving cells from specially 

engineered biological artifacts) to be morally objectionable. 

As one who supports embryonic stem cell research, I do not regard 

the early embryo as inviolable. But neither do I regard it as disposable, 

open to any use we may desire or devise. For this reason, embryo 

research carries a special moral burden; it is justified only for the sake 

of saving human lives or curing devastating diseases. The proposal to 

genetically engineer a nonviable, embryo-like being would remove the 

moral burden by creating something that, lacking the capacity to 

develop into a human person, would be wholly disposable, 

presumably for any purpose, weighty or trivial. The very project of 

creating such a being is morally troubling, for reasons that are wellstated in the ethical analysis (pp. 38-45 above). I therefore do not 

believe that this proposal should be encouraged or endorsed. 

MICHAEL J. SANDEL 

93 

Glossary*

Adult stem cell: An undifferentiated cell found in a differentiated 

tissue that can renew itself and (with certain limitations) differentiate to 

yield all the specialized cell types of the tissue from which it originated. 

(NIH) 

Altered Nuclear Transfer (ANT): A proposed method, using a 

modified form of somatic cell nuclear transfer (SCNT), of producing a 

biological artifact from which human pluripotent stem cells could be 

derived. 

Anencephalic fetus: A fetus with a congenital defect related to 

development of the brain, with absence of the bones of the cranial vault 

and absent or rudimentary cerebral and cerebellar hemispheres, 

brainstem, and basal ganglia. (SMD)

Aneuploid: Having an abnormal number of chromosomes. (SMD) 

Autologous: Derived or transferred from the same individual’s body. 

 

Biological artifact: As employed here, this phrase denotes an 

artificially created non-embryonic but embryo-like cellular system, 

engineered to lack the essential elements of embryogenesis but still 

capable of some cell division and growth. 

 

*

 Definitions marked “(CR)” are from the Council’s report on human cloning 

(Human Cloning and Human Dignity: An Ethical Inquiry, Washington, D.C.: 

Government Printing Office, 2002). Definitions marked “(NIH)” are from the 

National Institutes of Health online stem cell glossary at 

http://stemcells.nih.gov (accessed April 1, 2005). Definitions marked “(NRC)” 

are from the National Research Council report, Stem Cell Research and the Future 

of Regenerative Medicine (Washington, D.C.: National Research Council, 2001). 

Definitions marked “(SMD)” are from Stedman’s Medical Dictionary. 
ALTERNATIVE SOURCES

OF HUMAN PLURIPOTENT STEM CELLS

94

Biopsy: Process of removing tissue from patients for diagnostic 

examination. (SMD) 

Blastocyst: In mammals, an early stage of embryonic development at 

which the embryo (roughly 100-200 cells) is a hollow sphere made up 

of an outer layer of cells (the trophectoderm), a fluid-filled cavity (the 

blastocoel), and a cluster of cells on the interior (the inner cell mass). 

Blastomere: A cell contained within an early embryo (up to two days 

after conception, at which point the embryo comprises about 8 

blastomeres). 

Blastomere biopsy: Removal of one or two blastomeres from the 

embryo in vitro at about the 8-cell stage, usually in order to perform 

preimplantation genetic diagnosis and screening. 

Blastula: An early stage of embryonic development (roughly 100-200 

cells) at which the cells of the morula are rearranged to form a hollow 

sphere; at this stage of embryonic development in humans and other 

mammals, the embryo is generally called a blastocyst. 

Bone marrow: The soft, fatty, vascular tissue that fills most bone 

cavities and is the source of red blood cells and many white blood cells. 

Chimera: In experimental embryology, the individual produced by 

grafting an embryonic part of one animal on to the embryo of another, 

either of the same or of another species. (SMD) 

Chromosomes: Structures inside the nucleus of a cell, made up of long 

pieces of DNA coated with specialized cell proteins, which are 

duplicated at each mitotic cell division. Chromosomes thus transmit 

the genes of the organism from one generation to the next. (CR) 

Cleavage arrest: Spontaneous cessation of cell division in an early 

embryo. 

Cloned embryo: An embryo arising from the somatic cell nuclear 

transfer process as contrasted with an embryo arising from the union of 

an egg and sperm. (CR)
GLOSSARY 95

Cloning:

Cloning-to-produce-children—Production of a cloned human embryo, 

formed for the (proximate) purpose of initiating a pregnancy, with the 

(ultimate) goal of producing a child who will be genetically virtually 

identical to a currently existing or previously existing individual. 

Cloning-for-biomedical-research—Production of a cloned human embryo, 

formed for the (proximate) purpose of using it in research or for 

extracting its stem cells, with the (ultimate) goals of gaining scientific 

knowledge of normal and abnormal development and of developing 

cures for human diseases. 

Human cloning—The asexual reproduction of a new human organism 

that is, at all stages of development, genetically virtually identical to a 

currently existing, or previously existing, human being. (CR)

Cord blood: Blood in the umbilical cord and placenta. 

Cryopreservation and Cryostorage: Freezing of IVF embryos for later 

use. 

Cytoplasmic: Of or pertaining to the substance of a cell, exclusive of 

the nucleus. (SMD) 

Dedifferentiation: A procedure whereby differentiated, somatic cells 

are restored to a more undifferentiated, multipotent condition. 

Diploid: Refers to the full complement of chromosomes in a somatic 

cell, distinct for each species (forty-six in human beings). (CR)

Embryo: (a) In humans, the developing organism from the time of 

fertilization until the end of the eighth week of gestation, when it 

becomes known as a fetus. (NIH) (b) The developing organism from 

the time of fertilization until significant differentiation has occurred, 

when the organism becomes known as a fetus. An organism in the 

early stages of development. (CR) 

Embryogenesis: That phase of prenatal development involved in 

establishment of the characteristic configuration of the body of the 
ALTERNATIVE SOURCES

OF HUMAN PLURIPOTENT STEM CELLS

96

embryo; in humans, embryogenesis is usually regarded as extending 

from the end of the second week to the end of the eighth week, after 

which the product of conception is usually spoken of as a fetus. (Based 

on SMD) 

Embryonic germ layers: The three initial tissue layers arising in the 

embryo—endoderm, mesoderm, and ectoderm—from which all other 

somatic tissue-types develop. (NRC) 

Embryonic stem cells (ESCs): Primitive (undifferentiated) cells, 

derived from the inner cell mass of the embryo, that have the potential 

to become a wide variety of specialized cell types. (Based on NIH) 

Enucleated oocyte: An egg cell from which the nucleus has been 

surgically removed. 

Ex vivo: Outside the body, frequently the equivalent of “in vitro”; the 

opposite of “in vivo.” 

Fertilization: The process whereby male and female gametes unite. 

(NIH) 

Fetus: A developing human from usually two months after conception 

to birth. (NIH) 

Gamete: A reproductive cell (egg or sperm). (CR) 

Gene: A functional unit of heredity that is a segment of DNA located in 

a specific site on a chromosome. A gene directs the formation of an 

enzyme or other protein. (NIH) 

Genome: The total gene complement of a set of chromosomes. (SMD) 

Genotype: The genetic constitution of an organism or a group of 

organisms. (SMD) 

Hydatidiform mole: An abnormality during pregnancy; a tissue mass 

or growth that forms within the uterus as the result of a genetic error 

during the fertilization process. 
GLOSSARY 97

Implantation: The attachment of the blastocyst to the lining of the 

uterus, and its subsequent embedding there. (Based on SMD) 

In vitro fertilization (IVF): The union of an egg and sperm, where the 

event takes place outside the body and in an artificial environment (the 

literal meaning of “in vitro” is “in glass”; for example, in a test tube). 

(CR) 

Inner cell mass: The cluster of cells inside the blastocyst. These cells 

give rise to the embryonic disk of the later embryo and, ultimately, the 

fetus. (NIH) 

IVF embryo: An embryo produced by in vitro fertilization. 

Karyotype: The chromosome characteristics (number, shape, etc.) of an 

individual cell or cell line, usually presented as a systematized array in 

pairs. (SMD) 

Lineage: The descendants of a common ancestor. 

Mesenchymal stem cells: Cells from the immature embryonic 

connective tissue. A number of cell types come from mesenchymal 

stem cells, including chondrocytes, which produce cartilage. (NIH) 

Morphology: Configuration or structure, shape. 

Morula: An early stage of embryonic development (roughly 16-64 cells) 

at which the embryo is a solid spherical mass of cells, resulting from 

the early cleavage divisions of the zygote; so called because of its 

resemblance to a “little mulberry” (in Latin, morula). 

Mosaic: Possessing two or more genetically different cell types; an 

early embryo is said to be mosaic when some of its cells exhibit 

chromosomal abnormalities while others appear chromosomally 

normal. 

Multipotent adult progenitor cells (MAPCs): Cells isolated from bone 

marrow that can be differentiated into cells with characteristics of 

cartilage, fat, and bone. 
ALTERNATIVE SOURCES

OF HUMAN PLURIPOTENT STEM CELLS

98

Multipotent cell: A cell that can produce two or more different types of 

differentiated cells; adult stem cells are multipotent. 

Oocyte: Unfertilized egg cell. 

Organismic death (of an embryo)—concept and criterion: As 

proposed by Landry and Zucker, the concept of organismic death for an 

early-stage human embryo is defined by irreversible loss of “the 

capacity for continued and integrated cellular division, growth, and 

differentiation”; their proposed criterion for determining organismic 

death is “irreversible cessation of cell division in the embryo observed 

in vitro.” 

Parthenogenesis: A form of reproduction in which an unfertilized egg 

develops into a new individual (SMD); the process of inducing an 

unfertilized egg to initiate cell division. 

Parthenote: The primary product of parthenogenesis; more precisely, 

an unfertilized egg that has been activated to initiate cell division. 

Placenta: The oval or discoid spongy structure in the uterus from 

which the fetus derives it nourishment and oxygen. (NRC) 

Pluripotent cell: A cell that can produce all the cell types of the 

developing body; embryonic stem cells, as well as the inner cell mass 

cells of the blastocyst, are pluripotent. 

Pluripotent stem cell: Any stem cell that has the same functional 

capacity—that is, stable pluripotency—as an embryonic stem cell, 

though not necessarily the same origin.

Preimplantation genetic diagnosis (PGD): A method of testing IVF 

embryos for chromosomal or genetic disorders before they are 

transferred to the uterus; typically one or two blastomeres are removed 

for genetic testing at about the 8-cell stage of embryonic development. 

Somatic cell: Any cell of an organism other than the gametes. (Based 

on SMD) 
GLOSSARY 99

Somatic cell nuclear transfer (SCNT): A method of cloning: transfer of 

the nucleus from a donor somatic cell into an enucleated oocyte to 

produce a cloned embryo. 

Stem cells: Stem cells are undifferentiated multipotent precursor cells 

that are capable both of perpetuating themselves as stem cells and of 

undergoing differentiation into one or more specialized types of cells. 

(CR) 

Stem cell line: Stem cells which have been cultured under in vitro 

conditions that allow proliferation without differentiation for months 

to years. (NIH) 

Superovulation: Drug-induced stimulation of a woman’s ovaries to 

produce many mature oocytes in a single menstrual cycle. 

Teratoma: A tumor consisting of different types of tissue, as of skin, 

hair, and muscle, caused by the development of independent germ 

cells. (SMD) 

Totipotent cell: A cell that can give rise to the entire organism, 

including the extra-embryonic membranes; the fertilized egg or zygote 

is totipotent. 

Trophectoderm: In early embryos at the blastocyst stage, the outer 

layer of cells that will give rise to the placenta. 

Uterine transfer: Transfer of an IVF embryo to a woman’s uterus with 

a view to implantation and gestation. 

Xenotransplantation: A transplant of tissue from an animal of one 

species to an animal of another species. 

Zygote: The diploid cell that results from the fertilization of an egg cell 

by a sperm cell. (CR)