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International Perspectives: The Future of Nonhuman Primate Resources Keynote Speaker

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International Perspectives: The Future of Nonhuman Primate Resources This page in the original is blank.

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International Perspectives: The Future of Nonhuman Primate Resources Primate Priorities— An International Perspective John P. Hearn, MSc, PhD INTRODUCTION It is a real pleasure and privilege to open this conference on the future of primate research and the resources required. The challenges and scientific opportunities are enormous and the resources are limited. The study of nonhuman primate systems at all levels, from molecular through systemic, social through environmental, is the closest we can come to experimental investigation of many of the fundamental factors that influence human biology. In the past 50 years, there have been enormous advances in our understanding of primate biology. We now have an array of new research tools and technologies. The rich scientific agenda that we are about to enjoy at this symposium, replete with new data, is proof of these capacities. It is timely to ask how we should set course for the future and what the priorities should be in investing the sparse resources to the best advantage. Without being overly dramatic, it is fair to say that most of us in this company would not be alive, or would be debilitated, if it were not for the improvements in health that have resulted from primate research. A few simple examples include polio and other vaccines, antibiotics tailored to protect against specific diseases, transplantation and surgical technologies. Some argue that the needs for primate research are now met so that Australian National University, Canberra, ACT 0200, Australia

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International Perspectives: The Future of Nonhuman Primate Resources our level of knowledge is adequate. In this address, I will argue that the knowledge imperative is never sated, nor the applications exhausted. The more fundamental the question, the wider are the potential applications. Future challenges are just as demanding as those of the past. One core theme of this conference focuses on the critical situation that is developing globally over the current shortage of rhesus monkeys, exacerbated in recent years by the research needs of the AIDS plague. In aiming to set a framework for the meeting, I will consider briefly a few examples of the continuing research imperatives that require such resources. I will then comment on the requirements for rhesus monkeys, some of the species that might provide alternative model systems, the need for real partnerships between biomedical and conservation research programs, and the ethical essentials in this complex area. Finally, I will suggest a few issues and areas for action. In doing so, I ask how can we make the best use of these few days to influence the future of primate research and resource development, since many of the human primates who will make the decisions are here. RESEARCH IMPERATIVES This is a great time in primate biology, when basic and strategic research can often be translated quickly to new applications and solutions that are relevant to health and society. The biotechnologies that are being developed now will fundamentally affect the quality and sustainability of life and biodiversity. Availability of and access to many of these technologies are not universal, however, and differences exist between less developed and developed countries. There are also differences and disagreements due to cultural, religious, and ethical considerations. A few examples of areas where basic and strategic primate research is now helping to transform our expectations include AIDS and our understanding of infection immunology, stem cells and the knowledge of development and transplantation therapies, and gene therapy based on new functional genetics. The avoidance of age-related debilities based on molecular and cellular health and the enhancing of our understanding of neuroscience, behavior, and learning through imaging provide further exciting options. The opportunities arising from the genomics-proteomics-phenomics sequences are among the most exciting in the history of biomedicine. The monitoring of emerging diseases and their transition between animals (including primates) and humans is of special interest. All of these and many others will depend to an extent on rigorous primate research and validation. The resources to achieve such an ambitious agenda are limited. Therefore we must invest these limited primate resources strategically to deliver the widest possible benefit.

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International Perspectives: The Future of Nonhuman Primate Resources THE RHESUS MONKEY Due principally to the boost given to rhesus monkey research 50 years ago during the polio pandemic, this species has become the generalized laboratory primate of choice, especially in the United States. Information on the biology of the species is the broadest of any primate other than the human. Due to the lack of availability and relative expense of rhesus monkeys, the cynomolgus macaque has replaced the rhesus in areas such as applied drug development, toxicology, and teratology. These two are the species of choice for much of biomedical and behavioral research as it applies to human health. In some respects this is surprising since aspects of the biology of the rhesus, including its reproductive seasonality, are not similar to the human pattern. Surveys of rhesus monkeys in their home countries over the past 10 years, including India, reveal increases in numbers. I request respectfully that the Indian government might consider allowing limited access to their country’s rhesus resources by their own scientists and by the international community. Even if this access is restricted to the provision of breeding nuclei from which second generation animals can be available for research, it could make a significant difference. Some of the emerging challenges and diseases, including HIV-AIDS, are likely to affect the subcontinent. It may be wise to have the necessary scientific and animal resources to participate in the global response. The rhesus monkeys available from China appear to have variations in their immunology and endocrinology from the Indian animals, making comparisons difficult. The National Institutes of Health (NIH), and in particular the National Center for Research Resources (NCRR), have given long-term leadership in the development of global primate research. The eight National Primate Research Centers, with 20,000 animals of 20 species, have the largest and most comprehensive program of self-sustaining breeding colonies and specialized research programs in primate biology. This long-term approach is of enormous value and has contributed spectacularly to the advancement of knowledge and the improvement of human and animal health. One factor in this success is the availability of animals of high quality with known pedigrees, and sometimes known immune characteristics, that are available for a very wide range of biomedical and behavioral research, including neurobiology, behavior, genetics, aging, development, reproduction, and many diseases. The potential for accelerating the breeding of primate stocks, if necessary using assisted reproductive techniques, could be given support within the centers and in collaboration with those in source countries. Greater national and international collaboration among universities, special research centers, and industry could make more efficient use of scarce

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International Perspectives: The Future of Nonhuman Primate Resources materials. An expansion of the World Directory of Primatologists and Primate Infonet could improve the level of communication and provide a greater knowledge of resources and opportunities for collaboration worldwide. This in turn could reduce the overall numbers of primates required in research and assist in the conservation of the species. The Institute for Laboratory Animal Research (ILAR) of the National Academies has played a major role in developing the norms and standards for animal research, including primates, to the world’s best practice. This continuing role is vital into the future if the challenges currently facing us and the constantly changing research needs, including those due to the shortage of rhesus monkeys, are to be overcome. ALTERNATIVE OPPORTUNITIES For the historical reasons alluded to above, the rhesus monkey has been established as the major species of choice for biomedical research, with the cynomolgus a substitute for aspects of toxicology. There are other species that hold particular advantage in niche areas of biomedicine and behavior research. Among these, the nearest genetic relatives to the human are the great apes, but their size and sensibility make them unavailable except to a very few researchers, and their use must be restricted to only the most essential applications under stringent controls. The baboons have proved of great value in areas that include surgery, parasitology, and cardiology, but they are large and expensive to keep, as well as being dangerous except under carefully managed conditions. The South American species utilized in biomedicine, including the marmosets, tamarins, owl, and squirrel and cebus monkeys, have particular attributes. The common marmoset is perhaps the most widely used general laboratory primate after the macaques, but this is more evident in Europe than in the United States. New advances in noninvasive technologies are providing more efficient and rapid ways to develop some biomedical programs. The ability to monitor aspects of the genetics, nutrition, endocrinology, reproductive status, and general health of an animal or human through the analysis of small samples of urine, feces, or blood facilitates the transitions and comparisons between primate and human research. In addition, the great advances in noninvasive sensing, tomography, and imaging technologies now allow repeated studies with minimal stress and damage. CONSERVATION AND COLLABORATION An important consideration is that almost all of the primate species studied in biomedical research are not endangered. Many of them, in

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International Perspectives: The Future of Nonhuman Primate Resources cluding the rhesus, cynomolgus, baboon, and marmoset, are common or even pests in areas of their ranges. Studies on these species can benefit humans in the understanding of systems and the avoidance and treatment of disease. In many ways, these same studies and those on humans can also benefit the nonhuman primates through a greater knowledge of their genetics and reproduction, nutrition and disease, ecology and social organization. Biomedical and behavioral research accounts for a majority of the rhesus monkeys bred and managed in captivity. Of approximately 20 species, the other species studied are investigated in a wide range of research. In my opinion, it would be of benefit to all of those engaged in these studies and uses, and to the agencies who support them, if 2% of the budget were put toward conservation in captivity and in the wild. Benefits from such an investment would include a greater appreciation of the behavioral and ecological requirements of primates, together with more enlightened methods for maintaining them in captivity. Other benefits should include an increase in field studies, under competitive and well-supervised conditions, which would enable improved conservation, survival, and habitat protection in the wild. These arrangements could be managed jointly with conservation organizations and zoos to obtain best critical mass in meeting biomedical and conservation goals. In a conference such as this, with representatives from all of the major countries engaged in captive and field primate research, there is no better time or opportunity to establish such a principle and to build such networks. Time is not on our side. ETHICAL ESSENTIALS The human species faces severe challenges over the next 50 years. The way in which these challenges are approached will determine the survival of many animal and plant species, including primates—and perhaps of the human primate. They include an increase in the human population from the current 6 billion to between 10 and 12 billion by 2050, having already increased from 1.2 billion in 1850 and 2.5 billion in 1950. The forward projections may be affected by AIDS and other emerging diseases, or by famine and disorder, each of which also has an impact on biodiversity. There is an accelerating pace of habitat destruction, overfarming, habitat islanding, exotic species introductions, and pollution and environmental chemicals that can affect the development, reproduction, fertility, and health of humans and animals. At the same time, our ability for learning and advancing knowledge holds the opportunities for overcoming many of these constraints. We must harness and invest the available

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International Perspectives: The Future of Nonhuman Primate Resources resources to best effect. The global approach argued for above, with research and training collaborations that include the developed and less developed countries, is essential for human and nonhuman primates. An ethical and suitably regulated framework for primate research is welcomed and supported by all responsible researchers. ILAR has proven world leadership in aspects of these developments and in appreciation of the needs for a continuing dialogue between all concerned, including the public. This small and select conference, open to all stakeholder organizations including representatives of “animal rights” groups, is an example of such foresight. As a strategic reality check of the field, it could be repeated to monitor progress and the achievement of goals every 2 to 4 years, perhaps in conjunction with other primate society meetings including the International Society of Primatologists. ACTIONS ARE URGENT In closing, this must not be just another conference that raises issues without looking to actions. The presence of decision makers from around the world makes this an unusual opportunity to find solutions. Let me select and suggest, with respect, the following 10 candidate areas for consideration during the meeting: Global collaboration—Explore all possible ways to develop research and resource networks that ensure value for investment and economy of materials. Engage researchers especially from nonhuman primate source countries. Basic and strategic research—Give priority to at least a 30% of budgets investment toward long-term, basic, and strategic research that will fuel the next era of innovation. Emerging issues—Maintain a strategic involvement as new scientific opportunities and challenges arise. Current examples include emerging diseases and transmission between human and nonhuman primates, microbiology and biodefense, stem cells, and cell therapies. Animal care and welfare—Adopt policies for continuous improvement in standards, as pioneered and developed by ILAR, but with appropriate adaptations for country conditions. The conservation cycle—Build synergies and critical mass between captive and field studies in biomedicine and conservation that will benefit both human and nonhuman primates. Funding—Dedicate 2% of funding toward both captive and field research that advances our knowledge of the primate species most studied in biomedicine and health. Internet development—Seek innovative ways to make relevant

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International Perspectives: The Future of Nonhuman Primate Resources information in primate biomedicine and conservation available in developed and less developed countries. Expand the activities of Primate Infonet and the World Directory of Primatologists. National primate research centers—Maintain these centers as a national treasure and as a hub for national and international research and development in primate biology, health, and conservation. Infrastructure—Where possible, facilitate arrangements for sophisticated analytical equipment, laboratory resources, and information and communications technologies to be available for joint projects between developed and less developed countries. Communication—Engage in a positive dialogue with all relevant constituencies, explaining the vital need and value of primate research and the advances that are benefiting human and animal health. ACKNOWLEDGMENTS I thank Professor John VandeBerg and the organizing committee for inviting me to address this important conference, considering the future of primate research and resources. I thank the NAS, NCRR, and ILAR (especially Joanne Zurlo and Kathy Beil) for supporting my attendance. The opinions expressed in this address are mine and not necessarily theirs. I also thank the American primatologists, many of them present, with whom I have worked on the issues and toward many of the objectives noted above: David Abbott, Chris Abee, Dick Dukelow, Andy Hendrickx, Ron Hunt, Lorna Johnson, Fred King, Jerry Robinson, Judy Vaitukaitis, John VandeBerg, David Watkins, and Leo Whitehair. I acknowledge my own mentors, Hugh Tyndale-Biscoe and Roger Short. I dedicate this address to Leo Whitehair in recognition of his leadership, humanity, and friendship, much appreciated by all primate biologists.

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