Vol. 437|1 September 2005 COMMENTARY The ethics of research on great apes J. MCDONALD/CORBIS In the wake of the chimpanzee genome publication, Pascal Gagneux, James J. Moore and Ajit Varki consider the ethical and scientific challenges for scientists who work on captive great apes. Most captive great apes were born in captivity and returning them to the wild is not feasible. ublication of the draft sequence of the chimpanzee genome is an exciting event; it opens the door to learning a great deal about our closest evolutionary cousins — and about ourselves in the process. But unlike the human genome project, the chimpanzee sequencing effort was not accompanied by studies addressing ethical, legal and social issues1. Meanwhile, there is continuing debate over the future of captive ‘great apes’ (chimpanzees, bonobos, gorillas and orang-utans)*. What does the publication of the chimpanzee genome mean for the thousands of great apes in captivity in the United States? Some fear the potential for increased invasive research on these individuals. Others are concerned that our limited knowledge of chimpanzee physiology and biology will constrain the usefulness of the chimpanzee sequence for understanding both humans and great apes. P For example, critical resources required for comparative genetic and biological studies, such as messenger RNA or complementary DNA libraries, are almost non-existent for great apes. Here, we advance a proposal that addresses these and related issues, to lead, we hope, to a mutually beneficial outcome for all, including the great apes (see Box for a summary of proposed goals and objectives). We emphasize that this article relates only to great apes, and not to other primates, nor other animals. Also, this piece is not about animal ‘rights’ but about ethical and scientific challenges specific to great apes in captivity. Born in captivity Opinions and attitudes regarding captive great apes span from the view that they are just expensive research animals to the idea that they should be accorded equal ‘rights’ with humans. Such views are in the minority, but there is need for continued dialogue among the majority spanning the middle ground. The current ethical status of the great apes also varies among nations. US research on great apes is regulated by local ‘animalsubjects’ committees. And although national guidelines for breeding and long-term care have been proposed2,3, there is still much disagreement. Some believe that our close similarity to the great apes means that they should never be kept in captivity, but for the ones now living in US facilities, it is too late. While great ape numbers in the wild have fallen to tens of thousands, captive populations have expanded, especially in the United States, where past government support for breeding programmes was aimed at producing subjects for research into the human immunodeficiency virus (HIV). Today the United States is *Footnote: ‘Great apes’ is used here in its colloquial sense. In the commonly used classification, these species are grouped alongside humans in the family Hominidae, and humans belong to the tribe Hominini, along with chimpanzees and bonobos. 27 ©2005 Nature Publishing Group COMMENTARY home to roughly 3,000 captive great apes (mostly west African chimpanzees) in research institutions, sanctuaries, zoos, private hands or the entertainment industry. Most of these individuals were born in captivity and never learned how to forage for survival or avoid predators. Thus, with few exceptions, attempts at returning captive great apes to the wild have proven extremely demanding — logistically and financially. Regardless, we agree with those who say the biomedical-research community has special ethical responsibilities towards captive great apes. In our view, the great apes share traits — including, but not limited to, their genetic similarity to humans, the ability to use and modify tools and a sense of ‘self ’ — that collectively justify this special status. (Individually, such traits are not unique to great apes; for example, bottle-nosed dolphins may also have a sense of self.) Pause for thought But there are other reasons to re-evaluate the situation for captive great apes. Their current medical care often assumes physiological and pathological identity with humans. But despite genetic and biological similarities, humans and apes differ markedly in their susceptibility to some major diseases, including AIDS (ref. 3). Working out the reasons for such biomedical differences will benefit all concerned, including the great apes, by allowing more speciesappropriate medical care. Understanding how our genetic differences give rise to these and other biological differences has been a longterm interest of some researchers. Sequencing of the chimpanzee genome is likely to motivate many further studies of ape biology and physiology. But how such research should proceed needs careful thought. Given the diversity of opinions (including among the three of us), it is impossible to define a single A summary of proposed goals and objectives Community issues ● Promote funding for an ELSI (ethical, legal and social issues) component of the chimpanzee genome project, as was done with the human genome project. ● Encourage dialogue on ethical standards and guidelines for research on great apes, following principles generally similar to those used in research on humans. ● Promote institutional and individual recognition of, and support for, the connection between the care and use of captive apes and their conservation in the wild. Research issues ● Encourage exploration of genetic, biological and medical similarities and differences between great apes and humans, especially in the context of providing medical care. ● Promote development of standardized databases of individual genotypic and phenotypic information about all captive great apes. NATURE|Vol 437|1 September 2005 clear-cut principle that can guide this discus- biomedical studies on great apes be carried sion. We do suggest, however, that the study of out in a manner that supports further great apes should follow ethical principles gen- improvements to their care. The time has come to establish broadly erally similar to those currently used in studies on human subjects who cannot give informed accepted guidelines for systematic, humane and ethical studies of captive consent. Of course, many great ape populations. These complex questions arise, such “Our ability to care studies should be carried out as who acts as the advocate for wild populations at all levels, from genetics for a great ape in agreeing on to biochemistry to physiolwhat are appropriate studies? could benefit from an And there are many grey increased understanding ogy to behaviour and culture. A previous US National areas. For example, is it of great ape medicine.” Research Council report2 acceptable to do reversible harm, such as causing a mild treatable infection addressed many issues regarding the care of (as is done with adult human volunteers), or to captive chimpanzees, and a follow-up 2005 sedate a chimpanzee (as you would a child) to Federal Register Notice emphasized that they allow a therapeutic or research procedure? deserve the best and most humane care possiCaptive great apes have been subject to ble. For example, they should be maintained in experimental procedures with the potential for groups that respect existing social bonds, with irreversible damage or death, such as infec- opportunities for physical, intellectual and tions with human pathogens, vital-organ biop- social activities. Moreover, euthanasia is specifsies, multiple inoculations for vaccine testing, ically excluded as a means of population contransfections for virus production and so on. trol2. Although opinions vary about the Development of the widely used hepatitis B benefits of contact with human caretakers, vaccine and understanding of the hepatitis C there is generally wider agreement regarding virus would not have been possible without human intervention for the control of escalatthe use of captive chimpanzees — and may still ing aggression within or between groups. not be possible using other technologies. In retrospect, however, many of these expensive Precious resource studies (for example, on HIV/AIDS, Plasmod- There is currently a moratorium on the breedium falciparum malaria and influenza A) ing of chimpanzees at facilities funded by the turned out to have limited benefits for improv- National Institutes of Health (NIH). Although ing human health. this may seem inhumane to some, it must be We suggest that alternatives to the use of remembered that each birth in captivity can whole chimpanzees be sought as soon as pos- represent a 50-year or longer commitment on sible, and that substantial new funding be the part of human society. Facilities that do directed towards finding such alternatives. allow great apes to breed should avoid large And, as with humans, we believe that the numbers of births, as well as inbreeding and newly emerging genomic data should never the mixing of subspecies. be used to attempt germline genetic modifiAs long as great ape facilities provide a safe, cations in great apes (to produce ‘transgenic’ healthy and humane environment, it seems apes, as is routinely done with mice). reasonable that captive great apes should Additionally, we recommend that any new remain a source of basic knowledge — which, in turn, may benefit both them and us. Understanding the normal biology, physiology and behaviour of the great apes provides a unique ● Encourage funding for standardized approach to understanding ourselves, even if collection and banking of tissues, fluids, imaging we do not suffer from all the same diseases. and biometric data obtained during medical Much of this can be accomplished through care and autopsies. And make such data simple observational studies and by giving available to the scientific community for high-quality medical care to diseased individgenetic, biochemical, histological and morphological studies. uals, as occurs routinely in human medicine. ● Encourage funding for the production of high Experiments involving physical intervention quality cDNA libraries. with no long-term consequences could also be ● Encourage funding for expanded programmes considered, provided that there is due considfocused on understanding cognitive functions in eration to the individual personalities of each great apes. ape, and that comparisons to normal humans ● Encourage development of mechanisms for are made wherever possible. sharing data, while respecting individual and When a captive ape dies of natural causes institutional privacy concerns. (or is humanely killed to end incurable suffering), a thorough autopsy and rapid collection Care issues of organ samples for genomic, transcriptomic ● Encourage greater fiscal support to ensure (gene expression), proteomic, biochemical optimal living conditions for captive great apes. and histological studies should be done, to ● Suggest mechanisms to ensure and support generate an extremely valuable and sorely the best possible medical care for captive great needed resource. There is also much to learn apes. by careful preservation and analysis of the 28 ©2005 Nature Publishing Group COMMENTARY NATURE|Vol 437|1 September 2005 Mutual gains In 2000, the US Congress passed a Chimpanzee Health Improvement, Maintenance, and Protection Act mandating the establishment of the NIH Chimpanzee Management Program4 (ChiMP) and federal funding of sanctuaries for chimpanzees from research institutions, such as Chimp Haven (www.chimphaven.org). We suggest that these and many other ongoing efforts be bolstered by a federally and philanthropically supported collaborative network in which facilities housing captive great apes could choose to participate. This would generate interactions among interested scientists from fields such as comparative biomedicine, psychology or biological anthropology. Already, leaders from US institutions holding most chimpanzees have come together to establish a National Chimpanzee Resource Committee, which meets regularly to discuss issues of mutual interest. The increased cost of supporting all such facilities will be more than justified by the knowledge gleaned from the study of healthy, socially integrated great apes — information that could potentially contribute to the ultimate survival of some of these species in their natural habitat. Such a national network could also help train and support scientists interested in the standardized accumulation of all relevant biological information on healthy captive great apes. Each great ape should continue to be accounted for, by a name and unique identifier. Complete medical records should be collected in a standardized fashion into electronically searchable databases, in a way that maintains the privacy of researchers and institutions. Samples, such as body fluids, taken from live apes during routine physical examinations should also be collected and archived. In this way, we can create a great ape tissue bank of flash-frozen and archived samples for use by the scientific community — which could eventually result in (among other payoffs) the production of high quality cDNA libraries. In some cases, therapeutic medical care could be extended to include data collection J. BALOG/GETTY remaining musculoskeletal system. Partly due to inadequate funding, personnel, and facilities, many great ape deaths now occur without such analysis, translating into numerous wasted opportunities to learn more about their biology. Being responsible for great ape captivity, we must maximize the information from them, rather than treating them as single-use, disposable tools. Likewise, body fluid and tissue samples that are collected during routine medical care are often discarded or inadequately archived. Such detailed studies of living and deceased humans have long benefited our species by providing valuable medical and scientific knowledge. Indeed, some humans approve postmortem donation of their entire bodies to science. Fast learner: tool use is one of the traits that sets the great apes apart from most other research animals. for research purposes (for example, standardized brain magnetic resonance imaging protocols appended to diagnostic imaging procedures). Increased funding will be needed to enhance existing medical facilities and expertise, and the ability to perform complete autopsies with tissue collection. As for newly proposed research studies on live great apes, we suggest that these be reviewed and approved by specialized ethical oversight groups that incorporate appropriate aspects of the separate human-subject and animal-subject committees found at most institutions. Cooperation by the great ape research subjects will be critical for many studies, and will only be possible if there is also adequate funding for behavioural training of the animals. We fully recognize that our proposal is unlikely to please everyone interested in great apes, and that this is only an initial contribution to a much-needed dialogue among all interested parties. Many changes and adjustments will be required to develop a mutually acceptable solution for all concerned, including the great apes. Meanwhile, there is a deep irony in the fact that the sequencing of the chimpanzee genome coincides with the potential demise of great apes in the wild. We urge all scientists studying great apes, or tissues and samples derived from them, to contribute not only to the care of captive apes, but also to develop mechanisms by which studies of captive great apes would help generate a revenue stream to support the conservation of populations in the wild. While recommending improved care of captive great apes, we recognize that the remaining wild great apes may end up living in strictly managed reserves, depending on increased human intervention for their survival. In the long run, even our ability to care for wild populations could benefit from an increased understanding of great ape cognition, behaviour, physiology, biology, pathology and medicine. ■ Pascal Gagneux is at Conservation and Research for Endangered Species, Zoological Society of San Diego, San Diego, California, USA; James J. Moore is in the Department of Anthropology, and Ajit Varki is in the Department of Medicine and Cellular & Molecular Medicine, University of California, San Diego, La Jolla, California, USA. 1. Human Genome Project Information www.ornl.gov/ sci/techresources/Human_Genome/elsi/elsi.shtml (2004). 2. The National Academies Press http://books.nap.edu/catalog/5843.html (1997). 3. Olson, M. & Varki A. Nature Rev. Genet. 4, 20–28 (2003). 4. National Center for Research Resources www.ncrr.nih.gov/compmed/cm_chimp.asp Acknowledgements: We are grateful to the following readers for very helpful comments and suggestions: A. Zihlman, C. Tutin, D. Povinelli, D. Rumbaugh, F. B. M. de Waal, J. Goodall, J. Allman, K. Semendeferi, K. Benirschke, M. Goodman, O. Ryder, R. Wrangham, S. Boysen, S. Blaffer Hrdy, S. Savage-Rumbaugh, T. Matsuzawa, T. Murray, and W. McGrew. We also gratefully acknowledge the support of the G. Harold and Leila Y. Mathers Charitable Foundation. 29 ©2005 Nature Publishing Group