Chimpanzees in Research

CHIMPANZEES IN RESEARCH

STRATEGIES FOR THEIR ETHICAL CARE,
MANAGEMENT, AND USE

COMMITTEE ON LONG-TERM CARE OF CHIMPANZEES

INSTITUTE FOR LABORATORY ANIMAL RESEARCH

COMMISSION ON LIFE SCIENCES

NATIONAL RESEARCH COUNCIL

NATIONAL ACADEMY PRESS
WASHINGTON, D.C., 1997

NATIONAL ACADEMY PRESS • 2101 Constitution Avenue, NW • Washington, DC 20418

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, National Academy of Engineering, and Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.

This report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sciences, National Academy of Engineering, and Institute of Medicine.

This study was supported under contract NO1-OD-4-2139, T.O. 17, from the National Institutes of Health. Core support is provided to the Institute of Laboratory Animal Resources by the Comparative Medicine Program, National Center for Research Resources, through grant 5P40RR0137; by the National Science Foundation through grant BIR-9024967; by the US Army Medical Research and Development Command, which serves as the lead agency for combined US Department of Defense funding, also received from the Human Systems Division of the US Air Force Systems Command, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, and US Naval Medical Research and Development Command, through grant DAMD17-93-J-3016; and by research project grant RC-1-34 from the American Cancer Society.

Any opinions, findings, and conclusions or recommendations expressed in this publication do not necessarily reflect the views of the Department of Health and Human Services or other sponsors, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. government or other sponsors.

Cover photograph by Susanna Berdecio, Primate Foundation of Arizona

Additional copies of this report are available from the Institute for Laboratory Animal Research, 2101 Constitution Avenue, N.W., Washington, D.C. 20418.

Printed in the United States of America.

COMMITTEE ON LONG-TERM CARE OF CHIMPANZEES

Dani P. Bolognesi

Chair

Thomas M. Butler,

Phillip Davies,

Neal L. First,

Nathan R. Flesness,

Jo Fritz,

Patricia Fultz,

Peter Theran,

Sarah Williams-Blangero,

Lilly-Marlene Russow

Staff

Thomas L. Wolfle,

Carol M. Rozmiarek,

Cheryl Mitchell,

Norman Grossblatt,

INSTITUTE FOR LABORATORY ANIMAL RESEARCH COUNCIL

John L. VandeBerg

Chair

Christian R. Abee,

Muriel T. Davisson,

Bennett Dyke,

Neal L. First,

Gerald F. Gebhart,

James W. Glosser,

John P. Hearn,

Margaret S. Landi,

Charles R. McCarthy,

Robert J. Russell,

John G. Vandenbergh,

Richard C. Van Sluyters,

Peter A. Ward,

Thomas D. Pollard

Staff

Thomas L. Wolfle,

Tania Williams,

Mara L. Glenshaw,

Carol M. Rozmiarek,

Cheryl Mitchell,

COMMISSION ON LIFE SCIENCES

Thomas D. Pollard

Chair

Frederick R. Anderson,

John C. Bailar III,

Paul Berg,

John E. Burris,

Sharon L. Dunwoody,

Ursula W. Goodenough,

Henry W. Heikkinen,

Hans J. Kende,

Susan E. Leeman,

Thomas E. Lovejoy,

Donald R. Mattison,

Joseph E. Murray,

Edward E. Penhoet,

Emil A. Pfitzer,

Malcolm C. Pike,

Henry C. Pitot III,

Jonathan M. Samet,

Charles Stevens,

John L. VandeBerg,

Paul Gilman,

PREFACE

The use of chimpanzees (Pan troglodytes) in biomedical research has led to numerous medical advances, including the development of a vaccine for hepatitis B virus. In 1986, chimpanzees were thought to constitute the critical model for understanding the human immunodeficiency virus, and a breeding program was established to provide animals for the study of this virus. The breeding program was very successful, and the combination of an increase in chimpanzee numbers and less-extensive research use than was expected has created a surplus of chimpanzees and a substantial management problem. Although chimpanzees are available for research, there are also pressures not to use them, such as the high cost of housing and maintenance and their endangered status in the wild. Their close genetic relationship to humans, which makes them the appropriate surrogate for human-health research, also creates serious concerns about the ethics of their use by scientists and the public. The US federal government now owns or supports some 900-1000 chimpanzees at a cost of approximately $7.3 million per year, but government investigators pay "use fees" for using animals in government research. Each of those issues contributes to the cost to investigators and the complexity of using chimpanzees in research.

The cost, ownership, and complex genetic management requirements of chimpanzees so greatly affect US policy regarding the use of chimpanzees in research that in 1994 the National Institutes of Health (NIH) requested advice from the National Research Council on

• The size of the breeding colony required to support the need.

• Issues of ownership, long-term care, and use in research.

• Mechanisms by which nongovernment organizations could assist in achieving appropriate goals and solutions for the long-term care of chimpanzees.

To address these issues, the National Research Council appointed a committee of experts. The committee convened four public meetings and communicated with chimpanzee-colony directors and behaviorists in each of the six major chimpanzee facilities and with the administrators and scientists who use chimpanzees in research. The public meetings provided opportunities for scientists, members of the public, and representatives of animal-protection societies to voice their concerns. One of the meetings was held in the form of a seminar at the joint meeting of the American Society of Primatologists and the international Primatological Society and was attended by many of the world's leading chimpanzee biologists and conservationists. Brief questionnaires were also sent to all grantees listed in the NIH Computer Retrieval of Information on Scientific Projects (CRISP) database who use chimpanzees in research. The public meetings and questionnaires all yielded information that was used in the preparation of this report.

The committee was faced with conflicting scientific, financial, and ethical situations. Euthanasia and cost were the chief contentious issues and led to a minority opinion (see Appendix A). The committee, like the public, found it difficult to agree on a single approach that embraces both euthanasia and cost. Euthanasia is common in veterinary medicine to alleviate uncontrollable suffering and for population control, but it is not easy to decide when it is acceptable for chimpanzees. Nor is it easy to address the expenditure of public funds for the "retirement" of chimpanzees that perhaps have never been used in government research, although they were bred for this purpose. The committee provides recommendations on these and other issues, but putting the recommendations into practice will require as much diligence and soul-searching as the committee itself used in developing the recommendations.

Presenting the population numbers and costs clearly and unambiguously has been a difficult task. It is largely because of the difficulty of accounting for sizes of the various subpopulations of chimpanzees (such as, those used in infectious research, available for research, and not needed for research) and the funding to support the research and the not-needed-for-research populations that the National Research Council was asked to prepare these recommendations. Great care has been used in collecting accurate information, but different sources of the same information often differed because of overlapping distributions. For example, surveys of chimpanzee facilities of the numbers of animals available for research and the number posing a public health threat, revealed 360 and 260, respectively (table 3.2). However, when asked just about the numbers of animals posing a public health threat they report 350. One might conclude from this that there are 360 animals available for research and 350 posing a public health threat, but to do so would double-count some animals. The difference is due to the fact that in the former case some of the animals posing a threat are also available for research. Such overlap exists in every subpopulation. The numbers presented in the text and tables are accurate to the best of the committee's ability. When the numbers are approximate or the populations overlap, they are so labeled. With this in mind, careful reading of the text in conjunction with the tables should yield an accurate picture, but, it is because of the difficulty in understanding these issues that the report addresses a need for an autonomous, high-level management and oversight structure with funding from increased appropriations to avoid reducing support for biomedical research.

We believe that our recommendations are sound, justifiable, cost-effective—although not inexpensive—and ethically responsible. We anticipate that they will meet with the approval of scientists, chimpanzee-colony directors, animal protectionists, the public, and members of Congress. We also strongly believe that NIH must work hard to achieve that breadth of approval.

This report would not have been possible without the information and advice provided by those who wrote to and met with the committee. All the chimpanzee-colony directors participated in conference calls and responded to questionnaires, for which the committee is most grateful. The NIH Interagency Animal Models Committee was helpful and frank in assisting the committee; its breadth of experience and its records were invaluable. The committee appreciated the opportunity to tour and have discussions with the staff of the Southwest Foundation for Biomedical Research and the University of Texas M.D. Anderson Cancer Center Science Park.

Equally important were the people who came to the public meetings or wrote to the committee because they cared. They came or wrote to share their concerns for chimpanzees and to seek assurance of their appropriate long-term care. Members of humane, protectionist, and antivivisectionist groups came to public meetings and gave testimony of their sincerity in seeking partnerships with the government for the long-term care of chimpanzees no longer needed in research. Among these were Nancy Blaney, American Society for the Prevention of Cruelty to Animals; Peggy Cunniff, Donald J. Barnes, and Claire Haggarty, National Anti-Vivisection Society; Tina Nelson, American Anti-Vivisection Society; Alan Berger, Animal Protection Institute; Holly Hazard, Doris Day Animal League; Anne Kleiman, In Defense of Animals, People for the Ethical Treatment of Animals, and the New England Anti-Vivisection Society; Carole Noon, International Primate Protection League; Valerie Stanley, Animal Legal Defense Fund; Martin Stephens, Humane Society of the United States; and Christine Stevens, Animal Welfare Institute. We are indeed grateful to the reception and informative tours provided to members of the committee by Wally Swett, Primarily Primates, and Martine Colette, Wildlife Waystation. The committee was saddened by the death of Michael McGehee during the course of this study. He was a strong spokesman for the National Chimpanzee Sanctuary Task Force, and the committee members appreciated the time that he took to inform them of the task force and for his dedication on behalf of chimpanzees. We thank all for their time and for their expressions of concern for this unique species. They are strong allies of the goals of this report and should be consulted in the implementation of its recommendations.

Naming people who assisted the committee risks errors of omission, yet some must be acknowledged. The work in the field by Jane Goodall and others has greatly assisted in the understanding of appropriate captive management and housing of chimpanzees. Their work contributes substantially both to the well-being of chimpanzees in captivity and to our recommendations. We appreciate the time and thoughtfulness of Donald Buford, Jane Goodall Foundation; Joseph Erwin; William I. Gay; Travis Griffin, Coulston Foundation; and Barbara Orlans, Kennedy Institute of Ethics. We also thank three staff behaviorists from chimpanzee colonies who briefed the committee on the physical and social structures of captive facilities that contribute to well-being: Mollie Bloomsmith, University of Texas M.D. Anderson Cancer Research Center; Linda Brent, Southwest Foundation for Biomedical Research; and Sue Howell, Primate Foundation of Arizona. Finally, we wish to acknowledge Lilly-Marlene Russow's contribution. Her thoughtful assertiveness stimulated discussion and resolution of difficult ethical issues. Her choice of wording throughout the text attests to her commitment to the animals and to her profession. We thank her.

We also want to acknowledge the contribution of the many individuals who agreed to review our work. Their labor improved the quality of the report. Readers who detect errors of omission or commission in this report are encouraged to send their suggestions to the Institute for Laboratory Animal Research, National Academy of Sciences, 2101 Constitution Ave., NW, Washington, DC 20418.

The committee extends its appreciation to the sponsor of this report; to Norman Grossblatt for editing the manuscript; to Carol Rozmiarek and Cheryl Mitchell for their skillful support at each of the committee's meetings and for coordinating the great flow of information to and from committee members; and to Tania Williams for her skillful assistance in the coordination and planning of two meetings. The committee reserves special thanks for Thomas Wolfle, expressed by the following quotation: "Working with Dr. Wolfle has been an enriching experience for the committee. His insistence on continuous progress toward the resolution of the complex issues facing the committee was always tempered by patience, professionalism, and the warmth of his genuine and unassuming personality. The ability of the committee to reach consensus was due, in no small part, to his unusual skill in bringing people of diverse backgrounds together for a common purpose. We are grateful for his guidance."

CONTENTS

EXECUTIVE SUMMARY

1 INTRODUCTION

2 RESEARCH NEEDS

3 LONG-TERM CARE

4 DEMOGRAPHY, COST, AND GENETIC MANAGEMENT

5 CENTRALIZATION OF RESEARCH CHIMPANZEE MANAGEMENT AND DEVELOPMENT OF A NATIONAL CHIMPANZEE RESOURCE

REFERENCES

APPENDIX A: MINORITY STATEMENT

EXECUTIVE SUMMARY

Chimpanzees in biomedical and behavioral research constitute a national resource that has been valuable in addressing national health needs. Facilities that house chimpanzees owned and supported by the National Institutes of Health (NIH) have successfully met the research requirements of the scientific community. The captive chimpanzee population in the United States has grown substantially, particularly over the last decade. That growth is due primarily to the success of the NIH-sponsored Chimpanzee Breeding and Research Program, which achieved the birth numbers thought necessary to meet the projected needs of biomedical research. However, the expected level of use of the chimpanzee model in biomedical research did not materialize, and that has created a complex problem that threatens both the availability of chimpanzees for research in the future and the infrastructure required to ensure the well-being of captive chimpanzees used in biomedical research.

Because the present system is fragmented, it is impossible to formulate an accurate overview of the size and nature of the chimpanzee population. But, if the chimpanzee is to continue to be used in biomedical research responsibly, effectively, and cost-effectively, we must be able to oversee, track, and coordinate the maintenance and use of chimpanzees and to control the size of the population. To assess the long-range situation and to develop, implement, and monitor the application of policies for the proper use and care of chimpanzees, an authoritative, centralized oversight structure is imperative. Once it is in place, it will be possible to refine and implement this report's recommendations, which are summarized here.

The existing chimpanzee population is more than adequate to meet research needs for at least five years. Moreover, increasing the number of chimpanzees maintained in the major NIH-supported biomedical chimpanzee facilities would risk eroding the quality of their care as a result of overcrowding, pressure on limited resources, and contamination of breeding and other research-naive animals by those used in infectious-disease studies. Therefore,

(1) A breeding moratorium should be imposed for at least five years (1997-2001).

Such a moratorium, necessary to prevent additional strain on the system, will not itself create more housing space or improve the housing of many animals now in the research population, but it will reduce operating costs by about 15% from present costs by year five. Decisions about acceptable means of population maintenance and control in a setting of scarce resources are inordinately complex and involve both scientific and ethical questions; there are no simple solutions.

The committee has been made aware that both the NIH National Center for Research Resources (NCRR) and the Interagency Animal Models Committee have orally communicated to breeding colony managers and researchers that euthanasia as a means of population control is not desirable. The committee agrees with those groups and with members of the public with whom these issues were discussed and recommends that this position be formalized and communicated to all government-supported chimpanzee managers and researchers. Therefore,

(2) Euthanasia should not be endorsed as a general means of population control.

The committee fully recognizes the implications of that recommendation in regard to lifetime funding for all animals and the need for additional space and facilities for an aging population, the third fundamental issue addressed in this report. There are about 1,500 US biomedical chimpanzees. The committee examined in detail the trend of reduced use of the chimpanzee model in biomedical research. Chapter 2 discusses this topic by first reviewing the past use of chimpanzees and their major contributions to the understanding and alleviation of human health problems. New developments in biomedical research and threats to society from emerging and re-emerging infectious microorganisms are expected to contribute to future demands for chimpanzees. However, several barriers prevent or reduce the use of the chimpanzee model. One expressed by scientists is that the chimpanzee is not now a good research model, for three reasons: the availability of government-supported chimpanzees is not well advertised, use fees for non-government animals are often over $50,000 per animal, and government protocol-review procedures inhibit the use of chimpanzees in NIH-sponsored research and by commercial institutions. Because the importance of chimpanzees in biomedical science has been amply demonstrated—for example, in the development of vaccines for hepatitis B—and equally important uses in the future are likely,

(3) A core population of approximately 1,000 chimpanzees should be assured lifetime support by the federal government, and ownership of these animals should be transferred to the government.

Government ownership of animals used in federally-funded studies will be critical for ensuring the long-term care of this important bio-medical resource. The scientists' concerns will be addressed by reducing the cost of using chimpanzees (through elimination of use fees), thereby increasing the opportunity to improve understanding of the chimpanzee's biology and behavior, which is essential for its proper characterization as a research model. Government ownership, as detailed in chapter 5, should be carefully designed to sustain a captive population, provide animals for research, and protect human health through the provision of lifetime care, in existing biomedical chimpanzee facilities, of animals thought to constitute a human health hazard.

To facilitate developing its recommendations, the committee divided the chimpanzee population into five components: the present breeding population supported by NCRR, animals now on research protocols, animals available for research (both naive and those used in prior studies), animals used in previous government-sponsored research that are no longer needed for research and pose a risk to human health, and animals that are no longer needed for research or breeding and pose no risk to human health. Each component presents unique opportunities and problems and is more fully addressed in chapter 2.

Not all of the initial core population recommended for government ownership is likely to be needed, and options should be sought for nongovernment support of animals that are no longer needed for research and breeding and are not thought to constitute a human health hazard. Cost savings and more effective use of the current overcrowded facilities could be achieved by transferring such animals to appropriate public (nongovernment) sanctuaries. That would save money by reducing the number of animals for which long-term maintenance is required in research facilities and reducing the requirements for expansion of current facilities. Properly designed, such sanctuary facilities should provide lower-cost maintenance of the animals than is possible in existing research facilities. Therefore,

(4) The concept of sanctuaries capable of providing for the long-term care and well-being of chimpanzees that are no longer needed for research and breeding should become an integral component of the strategic plan to achieve the best and most cost-effective solutions to the current dilemma.

The most obvious deficiency in present population management is the absence of a central coordinating program responsible for balancing the need to advance scientific knowledge relevant to human health with the short-term and long-term needs of the chimpanzee population. Rather, there is a system driven by fragmented approaches that primarily react to immediate needs. The committee believes that many of the scientific and ethical problems addressed in this report are a consequence of the general lack of coordination. Therefore,

(5) A single multiagency organizational unit, the Chimpanzee Management Program (ChiMP), should be established within the office of the director of the National Institutes of Health, or as described below, and be given direct administrative and fiscal responsibility for government-owned animals that are considered necessary to meet current and long-term national needs.

ChiMP should be an autonomous body with sole responsibility and authority for coordinating the management and use of a US-government-owned population of chimpanzees for use in biomedical research by any government agency or department, irrespective of whether an investigator is employed by the government, receives research funding from a government source, or represents private enterprise. The committee believes that ChiMP, housed within the office of the Director of NIH (or a suitable alternative that has the autonomy, infrastructure, and expertise to manage the program), should serve as the leader of a consortium of government agencies that would include the Centers for Disease Control and Prevention, the Food and Drug Administration, and the Department of Defense, all of which need chimpanzees to fulfill their missions. Substantial cost savings will be achieved if participating agencies pool existing resources allocated to chimpanzees and jointly develop procurement plans for the long-term care of government-owned animals. Because the animals constitute a national resource that benefits all of society, they should not have to compete for funds for their long-term care with other entities that need resources that are already overextended for current and future biomedical research. The committee urges that the ChiMP office encourage and assist in efforts now being led by private initiatives and animal-protection organizations to develop sanctuary facilities for chimpanzees that are no longer needed for research or breeding.

The committee views development of a centralized management structure as the only rational vehicle for implementing its recommendations. It also recognizes that the breadth of expertise needed for oversight of the chimpanzee resource is not likely to exist in a single office or agency. Therefore,

(6) An appropriate advisory council of nongovernment experts should be created as a chartered committee for the purpose of establishing policies of ChiMP and for monitoring the short-term and long-term implications of the foregoing recommendations, including implications for research use, breeding-colony size, demography, genetics, and long-term care.

The need for combined centralization of management and oversight is so obvious that the last two recommendations of the Committee on the Long-Term Care of Chimpanzees represent platforms for carrying out its core recommendations. If the committee's recommendations are followed, biomedical and behavioral research using chimpanzees can continue to thrive in a productive, ethically responsible, and cost-effective manner. If, however, the current lack of long-range planning and coordination continues, the combination of excess captive chimpanzees in the US biomedical population and lack of facilities and resources to care for increasing numbers adequately will soon become an insurmountable problem of enormous complexity, cost, and ethical concern. Lacking the ability to relocate their animals to acceptable alternative facilities, colony managers will be forced to reduce population numbers through euthanasia. The likelihood of this "train wreck" scenario must be considered in light of the broader issues surrounding the well-being of chimpanzees. In the final analysis, it is difficult to conceive that our society would accept a system that deteriorated to the point where euthanasia of chimpanzees became the best or only humane option.

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