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NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences (NAS), the National Academy of Engineering (NAE), and the Institute of Medicine (IOM). It is a result of work done by the Panel on Scientific and Medical Aspects of Human Cloning, a joint panel of the Committee on Science, Engineering, and Public Policy (COSEPUP) and the Board on Life Sciences (BLS). The members of the panel responsible for the report were chosen for their special competences and with regard for appropriate balance.
COSEPUP is a joint committee of NAS, NAE, and IOM. It includes members of the councils of all three bodies. For more information on COSEPUP, see www.nationalacademies.org/cosepup.
The Board on Life Sciences (BLS) is a unit under the Division on Earth and Life Studies of the National Research Council. For more information on BLS, see www.nationalacademies.org/bls.
Library of Congress Cataloging-in-Publication Data
Scientific and medical aspects of human reproductive cloning / Committee on Science, Engineering, and Public Policy, National Academy of Sciences, National Academy of Engineering, Institute of Medicine.
Includes bibliographical references and index.
1. Human cloning. 2. Human reproductive technology. 3. Cloning. I. Committee on Science, Engineering, and Public Policy (U.S.)
RG133.5 .S385 2002
Funding: The development of this report was supported by the National Research Council.
Scientific and Medical Aspects of Human Reproductive Cloning is available from the
National Academy Press,
2101 Constitution Avenue, NW, PO Box 285, Washington, DC 20055 (1-800-624-6242 or 202-334-3313 in the Washington metropolitan area; Internet http://www.nap.edu). Additional information on this report, the panel membership, and its study is available at www.nationalacademies.org/humancloning.
Copyright 2002 by the National Academy of Sciences. All rights reserved. This document may be reproduced solely for educational purposes without the written permission of the National Academy of Sciences.
Printed in the United States of America.
THE NATIONAL ACADEMIES
National Academy of Sciences
National Academy of Engineering
Institute of Medicine
National Research Council
The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Bruce M. Alberts is president of the National Academy of Sciences.
The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Wm. A. Wulf is president of the National Academy of Engineering.
The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Kenneth I. Shine is president of the Institute of Medicine.
The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Bruce M. Alberts and Dr. Wm. A. Wulf are chairman and vice chairman, respectively, of the National Research Council.
PANEL ON SCIENTIFIC AND MEDICAL ASPECTS OF HUMAN CLONING
IRVING L. WEISSMAN (Chair), Karel and Avice Beekhuis Professor of Cancer Biology,
Stanford University School of Medicine, Stanford
ARTHUR L. BEAUDET,
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
PATRICIA K. DONAHOE, Chief,
Pediatric Surgical Services, Massachusetts General Hospital, Boston
DAVID J. GALAS,
Keck Graduate Institute of Applied Life Science, Claremont, California
JUDITH HALL, Professor of Pediatrics and Medical Genetics,
University of British Columbia, Vancouver, Canada
BRIGID L.M. HOGAN, Hortense B. Ingram Professor,
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee
ROBERT B. JAFFE, Fred Gellert Professor of Reproductive Medicine and Biology,
University of California, San Francisco, School of Medicine
EDWARD R.B. McCABE, Physician-in-Chief,
Mattel Children’s Hospital at UCLA, University of California, Los Angeles, School of Medicine
The Wellcome Trust and Cancer Research Campaign, Institute of Cancer and Developmental Biology, University of Cambridge, England
GERALD M. RUBIN, Vice President for Biomedical Research,
Howard Hughes Medical Institute, Chevy Chase, Maryland
MARK SIEGLER, Lindy Bergman Distinguished Service Professor of Medicine and Director,
MacLean Center for Clinical Medical Ethics, University of Chicago, Illinois
Principal Project Staff
DEBORAH D. STINE, Study Director
WILLIAM WELLS, Consultant Science Writer
SUSAN A. DANIELS, Consultant Research Associate
ROBERT COOK-DEEGAN, Senior Program Officer, IOM
REBECCA BURKA, Administrative Associate
KEVIN ROWAN, Project Assistant
NORMAN GROSSBLATT, Editor
COMMITTEE ON SCIENCE, ENGINEERING, AND PUBLIC POLICY
MAXINE F. SINGER (Chair), President,
Carnegie Institution of Washington, Washington, D.C.
BRUCE M. ALBERTS,* President,
National Academy of Sciences, Washington, D.C.
ENRIQUETA C. BOND, President,
The Burroughs Wellcome Fund, Research Triangle Park, North Carolina
R. JAMES COOK, R. James Cook Endowed Chair in Wheat Research,
Washington State University, Pullman
GERALD DINNEEN,* Retired Vice President,
Science and Technology, Honeywell, Inc., Edina, Minnesota
JAMES J. DUDERSTADT, President Emeritus and University Professor of Science and Engineering,
Millennium Project, University of Michigan, Ann Arbor
MARYE ANNE FOX, Chancellor,
North Carolina State University, Raleigh
RALPH E. GOMORY, President,
Alfred P. Sloan Foundation, New York, New York
RUBY P. HEARN, Retired Senior Vice President,
The Robert Wood Johnson Foundation, Baltimore, Maryland
SAMUEL PRESTON, Dean,
University of Pennsylvania School of Arts and Sciences, Philadelphia
GERALD M. RUBIN, Vice President for Biomedical Research,
Howard Hughes Medical Institute, Chevy Chase, Maryland
EDWARD H. SHORTLIFFE, Professor and Chair,
Department of Medical Informatics, Columbia University, New York, New York
KENNETH I. SHINE,* President,
Institute of Medicine, Washington, D.C.
HUGO F. SONNENSCHEIN, Charles L. Hutchenson Distinguished Service Professor,
Department of Economics, University of Chicago, Illinois
PAUL E. TORGERSON, John W. Hancock, Jr. Chair and President Emeritus,
Virginia Polytechnic Institute and State University, Blacksburg
IRVING L. WEISSMAN, Karel and Avice Beekhuis Professor of Cancer Biology,
Stanford University School of Medicine, California
SHEILA E. WIDNALL, Abbey Rockefeller Mauze Professor of Aeronautics,
Massachusetts Institute of Technology, Cambridge
WM. A. WULF,* President,
National Academy of Engineering, Washington, D.C.
BOARD ON LIFE SCIENCES*
COREY S. GOODMAN, (Chair), Evan Rauch Professor of Neuroscience, Director,
Wills Neuroscience Institute, Department of Molecular and Cell Biology, University of California, Berkeley
MICHAEL T. CLEGG, Distinguished Professor of Genetics,
University of California, Riverside
R. ATLA CHARO, Professor of Law and Medical Ethics,
University of Wisconsin at Madison, Wisconsin
JOANNE CHORY, Associate Investigator, HHMI and Professor Plant Biology Laboratory,
The Salk Institute for Biological Studies, La Jolla, California
ED HARLOW, Professor and Chairman Department of Biological Chemistry and Molecular Pharmacology,
Harvard Medical School, Boston, Massachusetts
BARBARA GASTEL, Associate Professor,
Department of Journalism, Texas A&M University, College Station
JAMES M. GENTILE, Dean for Natural Sciences and Kenneth G. Herrick Professor of Biology,
Natural Science Division, Hope College, Holland, Michigan
LINDA E. GREER, Senior Scientist,
Natural Resources Defense Council, Washington, D.C.
ELLIOTT M. MEYEROWITZ, Professor of Biology,
California Institute of Technology, Pasadena
ROBERT T. PAINE, Professor Emeritus,
Department of Zoology, University of Washington, Seattle
GREGORY A. PETSKO, Tauber Professor of Biochemistry and Molecular Pharmacodynamics and Director,
Rosentiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts
STUART L. PIMM, Professor,
Center for Environmental Research and Conservation, Columbia University, New York
JOAN B. ROSE, Professor of Marine Science,
University of South Florida, St. Petersburg
GERALD M. RUBIN, Vice President for Biomedical Research,
Howard Hughes Medical Institute, Chevy Chase, Maryland
BARBARA A. SCHAAL, Spencer T. Olin Professor of Biology,
Department of Biology, Washington University, St. Louis, Missouri
RAYMOND L. WHITE,
DNA Sciences, Inc., Freemont, California
Advances in animal reproductive cloning methods have encouraged some practitioners to attempt human reproductive cloning to produce newborn humans from a predetermined donor. The decision as to whether the self-proposed practitioners of human reproductive cloning should be allowed to proceed is most properly a societal decision, and likely one that will be made by the government. An informed decision requires two kinds of inputs, medical-scientific and ethical. It is the responsibility of the scientific and medical community to inform society if current methods are scientifically feasible and reproducible, and medically safe; and to provide guidelines to assure that if human reproductive cloning is carried out, the human participants involved are adequately advised and protected. Once society is so informed, it will be in a position to determine whether an attempt to use reproductive cloning methods with humans is acceptable in any circumstance. The scope of this report is limited to informing society by providing an assessment of the medical and scientific aspects of human reproductive cloning.
The public debate on the possible reproductive cloning of humans is often linked to the debate on human embryonic stem (ES) cells. Because one proposed method to establish new human embryonic stem cell lines uses a process very similar to the first steps in the reproductive cloning of complete humans, it is easy to understand how even a scientifically literate society could become confused about these issues. Clarity on these matters is vitally important since these issues involve both medical risk
and opportunity, and the government is considering the use of sanctions on the free inquiry that normally characterizes effective research.
The present panel was charged to consider the biomedical issues surrounding the question of reproductive cloning of human beings, including making clear the distinctions between reproductive cloning and the related methods used to derive new ES cells.1 As biomedical scientists and physicians it is our job to seek new scientific principles, and from them new therapies to ameliorate the personal tragedies brought on by disease. And we must do so without subjecting patients and society to unwarranted medical experimentation. Medical progress requires clinical experimentation, but that process must go forward with the highest ethical standards—and only when the risks and potential benefits are understood and agreed on by patient, physician, scientist, and participating institution.
Last year, at least three groups declared that they not only were in the process of modifying the methods used first to produce a cloned living lamb (Dolly) in order to apply them to humans, but that they intended to carry out the reproductive cloning of human beings in the near future. In response to the prospect of those medical experiments, the presidents of the National Academies convened a joint panel of the Committee on Science, Engineering, and Public Policy (COSEPUP) and the Board on Life Sciences (BLS) to examine the scientific and medical issues relevant to human reproductive cloning and to consider the ethical issues that apply specifically to the participation of human subjects in cloning research. The purpose of this undertaking is to clarify and provide as much understanding as possible of these issues in order to inform the much broader debate that will be carried out by a larger cross section of society.
The method used to initiate the reproductive cloning procedure is called nuclear transplantation, or somatic cell nuclear transfer (SCNT). It involves replacing the chromosomes of a human egg with the nucleus of a body (somatic) cell from a developed human. In reproductive cloning, the egg is then stimulated to undergo the first few divisions to become an aggregate of 64 to 200 cells called a blastocyst. The blastocyst is a preimplantation embryo that contains some cells with the potential to give rise to a fetus and other cells that help to make the placenta. If the blastocyst is placed in a uterus, it can implant and form a fetus. If the blastocyst is instead maintained in the laboratory, cells can be extracted from it and grown on their own. Those cells will grow indefinitely without becoming
Stem cells are the subject of a complementary report from the National Academies entitled Stem Cells and the Future of Regenerative Medicine, which was released to the public in September 2001. The full text of that report is available at http://www.nap.edu/catalog/10195.html
specialized, and each blastocyst may give rise to a continuously growing cell line, known as an embryonic stem (ES) cell line. For reasons that are explained in Chapter 2, these cell lines cannot on their own implant or give rise to a fetus. The process of producing ES cell lines by using somatic cell nuclei is called nuclear transplantation to produce stem cells.
A potential benefit of reproductive cloning—producing a complete human being—is that it offers one solution for complete infertility. The potential benefit of using nuclear transplantation to produce stem cells is that it offers opportunities for medical research, medical discovery, and therapies. Both human reproductive cloning and nuclear transplantation to produce stem cells raise ethical, moral, and legal questions.2
The panel that produced this report was chosen to reflect expertise in the relevant scientific and medical disciplines, making it well equipped to explore the scientific literature and identify the current leaders in these fields. We were helped by a superb staff that was deeply experienced in matters of science, science policy, and medical ethics. The entire panel participated in 12 weekly conference calls to identify the key issues that would be the subject of our report and the people who would inform our deliberations, as well as to plan for a workshop wherein experts in the field could address the issues and present us with the appropriate data.
We soon concluded that it was not sufficient to understand the issues only from experiments in the cloning of animals combined with fundamental studies in mammalian embryogenesis. We also needed to inform ourselves concerning the principles and practices used by those clinical entities that provide assisted reproductive technology (ART) services, most often to assist sperm-egg fertilization and test-tube development of an embryo to the stage where it is ready to be placed into the uterus of a biological or surrogate mother. And we also needed to learn about the plans of those who would carry out the reproductive cloning of human beings and, more important, to have them learn, with us, of the scientific and medical results and experiences of those who had cloned animals. We therefore decided to place the three workshop participants who propose to clone humans in a setting where their clinical plans could be scrutinized. Although including them in the workshop provided a platform for the most vocal proponents and opponents, it also provided valuable input to members of our panel.
The report that follows reflects all the data that we have gathered concerning the animal reproductive cloning models used in the years since the cloning of Dolly. We have found that the efficiency of production of a blastocyst from an egg whose own chromosomes have been
removed and replaced by the nucleus of another cell is very low. Moreover, the efficiency of further development of such a blastocyst after transfer to a uterus in the same animal species is extremely poor. In view of these findings, it became clear that the number of human eggs needed for a single human reproductive cloning attempt could well reach several hundred. Most importantly, the animal models had an excess of fetal deaths throughout pregnancy. The late fetal deaths could cause excess maternal damage and possibly maternal deaths if the cloned fetus became too large, as was often the case in sheep and cows. And the risk of excess mortality of clones (compared with newborns from normal reproduction) continued in the neonatal and later stages. The experience in reproductive cloning of all animal species tested was of concern and provided powerful evidence of the potential problems with human reproductive cloning. A number of scientific studies on animals pointed to some likely causes of the failures, and these are described extensively in the report.
The panel examined closely the critiques and explanations offered by both those who wish to undertake human reproductive cloning and other participants in the workshop. We determined that the potential tests offered as preconditions to implant a blastocyst by those who wish to undertake human reproductive cloning were incomplete or, in one case, unlikely to be credible. The tests proposed to monitor an implanted fetus were also deemed by the panel to be incomplete and inadequate to protect either the fetus or the woman carrying it. Based on its evaluation of the evidence, the panel supports the proposal that the government enact a legally enforceable ban on the reproductive cloning of humans that remains in place for at least 5 years.
The panel also reviewed the potential of nuclear transplantation to produce stem cells for the development of therapies, for advancing fundamental biomedical knowledge, and for biomedical applications of this research. None of the scientific and medical considerations that led the panel to the above conclusion concerning human reproductive cloning apply to the production of stem cells by nuclear transplantation. The panel supports the conclusion of a recent National Academies report that recommended that biomedical research using nuclear transplantation to produce stem cells be permitted.3 We encourage a broad national dialogue on the relevant societal, religious, and ethical issues.
Our panel of 11 members has been unanimous in reaching the recommendations and conclusions presented in the Executive Summary and Chapter 6 of this report. In making our decisions, we carefully considered the results of the workshop, some of which have been outlined above. We
also read widely and extensively, consulted experts, and took into account the findings of the important recent report from the National Academies entitled Stem Cells and the Future of Regenerative Medicine.
This work would not have been possible without the dedication and skill of the lead staff member for this study, Deborah Stine. We are also deeply indebted to Maxine Singer and Corey Goodman, whose many contributions went far beyond those expected for ex-officio members responsible for institutional oversight.
The panel believes that all concerned segments of society should examine and debate the broad ethical issues associated with human cloning. Although we have only examined the scientific and medical aspects, we hope that our report helps to inform this broader consideration by society.
Irving L. Weissman, Chair
This report is the product of many people. First, we would like to thank all the speakers who attended our workshop on August 7, 2001. They were (in alphabetical order) Severino Antinori, Brigitte Boisselier, R. Alta Charo, Jose Cibelli, Alan Colman, Jay Cross, Peter Farin, Jonathan Hill, Rudolf Jaenisch, Peter Mombaerts, Virginia Papaioannou, Eugene Pergament, John Robertson, Eric Schon, Alan Trounson, Andre Van Steirteghem, Ian Wilmut, Ryuzo Yanagimachi, and Panayiotis Zavos. Without the input of each of these speakers, this report would not have been possible.
Next, we would like to thank the reviewers of this report. This guide has been reviewed in draft form by persons chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Council’s Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making the published report as sound as possible and to ensure that the report meets institutional standards of objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following for their participation in the review of this report:
George J. Annas, Boston University, Massachusetts
Paul Berg, Stanford University, California
Alexander Capron, University of Southern California, Los Angeles
R. Alta Charo, University of Wisconsin, Madison
Neal First, University of Wisconsin, Madison
Fred Gage, The Salk Institute for Biological Studies, San Diego, California
Barbara Gastel, Texas A&M University, College Station
Jeffrey Kahn, University of Minnesota, Minneapolis
Lori Knowles, Hastings Center, Garrison, New York
Mary Lake Polan, Stanford University, California
Micheline M. Mathews-Roth, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
John Robertson, University of Texas, Austin
Janet Rossant, University of Toronto, Canada
Lee M. Silver, Princeton University, New Jersey
Alan Trounson, Monash University, Melbourne, Australia
Harold Varmus, Memorial Sloan-Kettering Cancer Center, New York, New York
Bert Vogelstein, The Johns Hopkins University, Baltimore, Maryland
Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations nor did they see the final draft of the report before its release. The review of this report was overseen by Robert Frosch and M.R.C. Greenwood, appointed by the NRC’s Report Review Committee, who were responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.
In addition, we would like to thank Maxine Singer and Corey Goodman, the chairs of COSEPUP and BLS, respectively, and Kenneth Shine, president of the Institute of Medicine, who helped greatly with the panel’s deliberations.
Finally, we would like to thank the staff for this project, including Deborah Stine, associate director of COSEPUP and study director, who managed the project; William Wells, consultant writer, who worked with the panel to develop the text of the guide; Susan Daniels, who provided research support including the development of the bibliography and the tables and figures in Appendix B, and support in developing the glossary; Robert Cook-Deegan, who provided guidance to the panel on medical policy and ethics; Rebecca Burka, administrative associate, and Kevin Rowan, project assistant, who provided project support; Norman Grossblatt, editor; Fran Sharples, Director of the Board on Life Sciences; and Richard Bissell, executive director of COSEPUP and the Policy and Global Affairs Division.