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RECOMMENDATIONS Current and anticipated shortages of wild-caught primates for biomedical programs are such as to justify the development of a national plan that will incorporate the following features: 1. An adequate, assured supply of animals derived primarily from the establishment of self-sustaining domestic breeding colonies, but augmented by breeding colonies and production centers in countries of origin and also supported by the application of wildlife management techniques to natural populations. 2. Reduction of wastage in international primate trade by the adoption of sound managerial procedures--e. g. , closer supervision of trapping, holding and shipping operations; and sponsorship of trapping expeditions in which all aspects of collection and transport are monitored. 3. Establishment of a computerized users' service that would encourage and facilitate multiple use of primates by rapidly matching available surplus animals to existing needs, and would permit accurate estimates of national needs based on usage data. The overall administration of the proposed national plan should be under- taken by the National Institutes of Health (NIH), with the advice of a committee representative of the national biomedical community. Among the explicit responsibilities of NIH would be-- Administration of contracts in support of domestic breeding colonies. Establishment and operation of a computerized users' service. Management of "Certificate of Need" programs. Development and distribution of guidelines for commercial trapping, hold ng, and shipping of primates, based on best available information. Coordination of methods and locations of trapping expeditions. Support of cooperative field studies on population dynamics of wild populations as they relate to the potential for sustained-yield harvesting. ⢠Development of contingency plans to deal promptly with shortages and to allocate resources when shortages develop. It is essential that the plan look to meeting the needs of all major bio- medical programs and be fully operative within a decade. Stabilization of Supply Achievement and maintenance of a dependable supply of primates for research and related needs will require a vigorous, balanced effort and support in four distinct areas outlined in the following sections. Self-Sustaining Domestic Breeding Programs Generally, the primate species now widely used in biomedical research, and doubtless others now relatively unknown, will rapidly become less 3
available from naturally occurring populations. In no cases are wild popula- tions adequate to provide the numbers and the quality of animals needed in the United States and other countries on a sustained basis. Hence, despite the possible application of artificial insemination, sperm banks, fertility drugs, or drugs that regulate reproductive cycles, there are no shortcuts or feasible alternatives to the development of large-scale breeding pro- grams that depend on normal reproductive behavior. Indeed, even if fertility regulating techniques were to become feasible, it is likely that the costs would outweigh the potential benefits--costs of trained staff, nurseries for hand-rearing multiple and premature infants, and technical work. Breeding colonies should be stocked with animals originating from known geographic localities. Blood samples should be taken from all members of the founding stock since their progeny will be used to stock future production colonies. Frozen samples of serum and cells should be retained. Various tests should be run on the serum and red cells to define the genetic consti- tution of the individuals and of the founding stock. All government supported Requests For Proposals (RFP's) for primate breeding should require the submission of a breeding plan with an identified portion of the progeny to be retained as replacement breeding stock. If domestic breeding programs are to be successful they must be planned and funded on a long-term basis and must consist of colonies that are sufficiently large to assure adequate genetic diversity. Various political, economic and ecological forces are such that self-sufficiency for the United States within 15-20 years is essential. In moving toward this goal, certain priorities as to species that merit emphasis can be established: Group 1--Species currently used in numbers that exceed long-term re- sources and for which, in fact, breeding programs should have been estab- lished several years ago. These include rhesus macaques (Macaca mulatta), squirrel monkeys (Saimiri sciureus), marmosets (e.g., Saguinus mystax and S-. fuscicollis), and night monkeys (Aotus trivirgatus). Chimpanzees (Pan troglodytes) fall into this same group, but need be bred only on a substantially smaller scale. It is essential that support be provided for breeding programs in this group. Group 2-- Hardy species for which sufficient information is already in hand on which to develop breeding programs and for which efforts to increase their use in research are justified, especially as they might replace species in Group 1. In this category are baboons (Papio sp. ), vervets (Cercopithecus aethiops), any other macaque species, particularly long-tailed macaques (M. fascicularis), Japanese macaques (M. fuscata), and pigtail macaques (M. nemestrina), and capuchins (Cebus apella). Substantial support for breeding programs in this group is highly recommended. Group 3-- Species that, if they could be obtained, are potentially useful, but about which more information is needed. These might best be bred in pilot colonies while their usefulness is evaluated. This group includes gibbons (Hylobates sp. ), talapoins (Cercopithecus talapoin), and tree shrews (Tupaia sp. ). Modest support for breeding programs in this group is highly recommended. It cannot be overemphasized that the research potential of a large number of species is entirely unexplored and that information obtained on the proper husbandry of any species is likely to be applicable to breeding programs generally. Hence, species not explicitly cited in the three groups named
above should by no means be ignored. Research data on primate repro- duction, wherever obtained, will contribute to biomedical knowledge. Breeding in Countries of Origin Governmental actions in the countries from which primates of biomedical importance come indicate not only that animals for research and testing will become increasingly difficult to obtain in adequate numbers but that it maybe difficult in certain species, to obtain sufficient breeding stock to establish large-scale domestic production units. Despite the uncertainties, it is essential to support the establishment and operation of breeding colonies and production centers in countries of origin. These enterprises would have the advantage of generally lower costs than in the United States and would to a degree relieve the pressure on wild populations. At the same time, they would act to stabilize the overall supply. It should be feasible, also, to augment the number of species involved and to achieve a greater genetic diversity. Harvesting of Managed Wild Populations Of approximately 201 species of nonhuman primates in 56 genera (Napier and Napier, 1967), a mere dozen species in 8 genera have been sufficiently studied to warrant their production in the United States. If the gene pools of the remaining 94 percent are to be assured for the future, it is necessary to provide encouragement and financial support for conservation and study of the habitats in which they are to be found, whether these habitats be un- altered or under some degree of management. As matters now stand, there are laws in some countries (e.g. , Colombia) providing that private lands not being utilized will be confiscated for agricultural development. In other areas (e.g., Kenya) primates are regularly shot or poisoned as agricultural pests. To improve the situation it is proposed that a sustained market for primates harvested from wild populations be developed and support be provided for the management of these populations on a sustained-yield basis. By so doing, it might be possible to make privately owned forest lands eco- nomically productive and thereby justify their preservation in essentially their natural state. A further move would be to explore, with appropriate governmental departments, mechanisms whereby trapped animals that would otherwise be destroyed as pests could be purchased for biomedical use. In this way, overall income to the landowner would be increased and the supply of primates somewhat augmented. Improvement in the Primate 1 rade Despite the fact that there have been improvements during the last 10 years, far too many animals are still lost through wasteful capture practices, careless handling prior to export, and destruction as forest and plantation pests. It seems clear that these losses can be appreciably reduced if scien-
tifically sound practices are introduced and if all aspects of collection and transport are monitored by informed officials. Several specific measures are recommended here. ⢠When animals are needed for specific research projects or as breeding stock, collecting expeditions should be organized and supported that are manned by local trappers but supervised by zoologists and veterinarians. Thus managed, these expeditions should incur a minimal loss of animals and the quality of the animals should be enhanced, particularly as regards information on origin and genetic relationships. ⢠When feasible, collecting expeditions should be so timed and managed as to capitalize on situations where habitat destruction already dooms the natural populations or where they are being destroyed as pests. ⢠Losses in holding areas and in transport can be minimized by encour- aging and supporting dealers who provide well-cared-for animals of known origin and by paying higher prices for healthy animals. Conversely, ad- verse publicity should be given to instances where the stock received is of poor quality. It would be well, also, to develop regulations that prohibit shipments on other than a prepaid basis. ⢠The physiological characteristics of relatively little-known species should be investigated, so that their potential usefulness in research can be assessed. When populations of these species face destruction as the result of habitat alteration, it would then be possible to harvest the animals for breeding and scientific research programs. Maximum Utilization of Current Resources Certain economies in the number of animals used can be realized by the establishment of a computerized users' service that would match availability to need and, overall, provide information for making sound estimates of annual needs. Such an information network would not only provide rapid information on available animals, or, conversely, the need for specific animals, but also facilitate the exchange of biological materials derived from primates. It would have the valuable ancillary advantage of making known to the medical community instances of the discovery of animals with spontaneous diseases or congenital defects, animals that would in the usual course of events be destroyed. Once identified, these animals could be transferred to the appropriate research laboratory for study. Obviously, an effective information and exchange system must provide for the costs of holding animals for a reasonable time while a suitable arrangement for transport is being worked out. Still further economies could be obtained by critical attention to the validity of choosing primates as laboratory animal models in each instance. Through various media â periodic workshops, symposia, critical review articles--the biomedical use of primates and other taxa should be reviewed, and primates replaced, whenever possible, by faster-breeding, more readily obtainable species. Where legislative or regulatory actions are proposed that would hamper ready access to suitable and easily bred nonprimate species (e.g. , dogs and cats), appropriate measures should be taken to discourage their enactment. In a similar sense, the fact that measures to prevent or inhibit ethical utilization of human fetuses or tissues will
almost certainly augment the demand for primates as substitute experi- mental material must be faced. The research community, and scientific editors, should be urged to reject any proposal or manuscript that does not include precise information as to the species, sex, size (or age), and source of any primate used in the experiment. Only by such strictures can it be assured that an informed decision has been made as to the choice of research material and that primates are essential in preference to any other species to achieve the results sought. If reliable estimates of future needs are to be made, data must be collected more accurately and consistently than is now the case. A simplified permit system, similar to that proposed by the U.S. Depart- ment of the Interior (USDI) for dealing with injurious species, would do much to improve the situation and would provide more reliable data on numbers of animals imported and the reasons therefore. Data on repro- ductive rates and losses from deaths could well be required from all insti- tutions holding primates, whether exhibitors or research establishments. Administration by the National Institutes of Health A national program of the kind recommended here would best be adminis- tered by NIH under the guidance of an advisory committee representative of the biomedical community. In so doing, it would be necessary for NIH to assume several discrete functions, each related directly to the key recom- mendations brought out in preceding sections of this report. Support of Breeding Programs In the overall process of initiating and enlarging self-sustaining breeding colonies, funding mechanisms should be devised that eventually shift the cost burden to the user, although this is not likely to be feasible in certain cases. There should be provision primarily for colonies of outbred animals and also for production of inbred lines selected for specific physiologic and immunologic characteristics, where it has been demonstrated that primate models are essential. A number of activities and responsibilities are called for: ⢠Review of proposals to breed primates. ⢠Administration of contracts for domestic breeding of primates for intramural and extramural programs. ⢠Preparation of guidelines for commercial primate breeders both with- in the United States and in countries of origin. These guidelines should specify methods for monitoring genetic heterozygosity as well as standards of nutrition, housing, and sanitation for individual species. ⢠Increase in breeding capacity of the Regional Primate Research Centers (RPRC) so that they become self-sufficient. ⢠Support of basic colonies of selected species, primarily as a resource from which to initiate production centers as the need arises. (This support might be provided through a competitive program open to any facility having colonies with F-, or beyond, generations. Maintenance
8 of core breeding stocks is essential to ensure the integrity of established colonies with known genetic histories and social relationships and to make possible long-term reproductive studies. In this connection, the potential role of exhibitors, especially zoos, should be evaluated. ) ⢠Encouragement of new designs for laboratory holding cages that will accommodate the changing patterns of primate research, particularly the increased length of time for which animals are held and the increased fre- quency with which both long-tailed and arboreal species are utilized. (For example, sliding doors between compartments would provide convenient means for isolating individual animals for examination, false floors of proper height above the substrate could prevent the tails of long-tailed species from becoming soiled with water or feces, and the addition of perches would allow for normal foot and tail postures. ) Maximal Utilization of Available Resources In establishing a computerized users' service, several existing information programs should be evaluated with a view to adapting certain features to facilitate exchange of primate material. There is, for example, a computer- ized tissue typing registry of potential kidney transplant patients developed at the University of California, Los Angeles (Opelz and Terasaki, 1974). The 9th edition of Animals for Research (ILAR, In press) will provide information on commercial sources of many species. The Division of Computer Research and Technology, NIH, is developing programs to make this current information on suppliers of animals available more rapidly. Computerized bibliographic services that might be expanded to incorporate information on available experimental material include Medline (National Library of Medicine-NLM) and Current Primate References (Washington Primate Center). The Animal Resources Branch, Division of Research Resources, NIH, has administered the India Rhesus Monkey Certification Program since 1955. This agreement with the Indian government stipulates that rhesus macaques exported from India will be used in a humane manner only for medical research and vaccine production. In order to administer this Certificate of Need program properly, match production capacity to research need, and implement an allocation system in time of shortages, it is essential to know the volume of imports, the output of captive-reared animals, and the level of use in biomedical programs. This information should be compiled either through the users' service noted above or in cooperation with other programs having similar responsibilities. The U.S. Depart- ment of Agriculture (USDA), for example, monitors primate usage annually; if these data were computerized and augmented through a more specific program of data gathering, the end product might be wholly adequate. Annual reports, such as those provided by the University of Michigan and Tulane University to USDA in 1972, stand as models for large institutions that have worked out a suitable methodology for record- keeping, by species. A proposed USDI permit system for all imported animals, if implemented, would provide valuable information. Finally, an International Species Inventory System is being developed (Makey et al. , 1974) to collect data on vital statistics and reproduction, as well as inventory, in zoological parks.
Improvement of Wild-Caught Primate Programs A number of steps can be taken by NIH that should improve the situa- tion as regards wild-caught primates used in U.S. biomedical programs. Among these are the following: ⢠Coordination of Certificate of Need programs with comparable agencies in other nations and extend the program to include species other than rhesus macaques. This would eliminate the conflicting and competing estimates that now confront the governments of several countries. Scientists in the United States would then be in a position to set forth their own priorities rather than relying on a competitive acquisition procedure that is filled on a first-come, first-served basis. ⢠Enlargement of the Certificate of Need program to provide an evalu- ation of the need for the species selected at the national level in addition to the review of the choice of animal model at the institutional level or during the funding process for the study. ⢠Fostering of international coordination of captive breeding programs and trapping operations through established international scientific channels. The International Council of Scientific Unions, the World Health Organiza- tion, the Pan American Health Organization, the International Union for the Conservation of Nature and Natural Resources, and the International Pri- matological Society should be encouraged to facilitate the translation and implementation of these recommendations by assisting foreign governments to take appropriate actions. ⢠Working to minimize duplicative expeditions for trapping primates and assure priority assignment of females to breeding colonies, rather than to direct biomedical use. ⢠Development of guidelines for trapping operations that take advantage of good wildlife management techniques, with a view to sustained yields from habitats that are to remain intact and animal salvage from habitats that are being destroyed. ⢠Withholding of funds from investigators shown to knowingly purchase primates that were trapped or exported in violation of the laws of the country of origin. ⢠Development of guidelines for improving compounds for holding animals trapped seasonally. ⢠Cooperation with air carriers and regulatory agencies, directly and through the National Council on Animal Transportation, to improve the methods, supervision, and scheduling of all shipments. ⢠Training workshops for local wildlife management personnel who can then assist trapping expeditions, or supply professional assistance through the mechanism of travel grants to U.S. specialists. ⢠Provision of funds for studies of population dynamics that will identify factors affecting the carrying capacity of different habitats and the geographical distribution of primate species, and monitoring of the impact of trapping in areas managed for sustained yield. It seems likely that costs for monitoring wild populations will have to be borne by the user community through various bilateral and multinational projects until effective methods are worked out. Data from studies of local populations will be essential as a basis for regulation of export and habitat conser- vation by the country of origin.
10 ⢠Provision of support for immediate implementation of improved techniques for capturing primates, including use of anesthetizing drugs, that will replace the slaughter method whereby adult female chimpanzees, gibbons, and leaf monkeys are killed to obtain dependent young. Allocation in Time of Shortage Despite any precautions that may be taken, it is likely that there will be shortages of primates in the years just ahead. There must be, then, an allocation plan in readiness that will assign priorities for the distribution of imported and captive-bred animals from biomedically supported breeding centers to the most appropriate biomedical uses, thereby minimizing the undesirable impact of shortages on research programs and other important activities. It is likely, for example, that production and safety-testing of polio vaccines would be accorded priority over research needs. It can be anticipated that export restrictions in countries of origin will be enforced with a measure of irregularity in the next few years, which will lead, in turn, to wide fluctuations in availability and price of wild-caught animals. It would be most unfortunate if these uncertainties were permitted to discourage the development of domestic captive-breeding ventures. Improved Specifications for Research Animals Much is to be gained by making the specifications for research animals as rational and precise as possible. When this is not the case, females that should be held for breeding will undoubtedly be used in research programs and thereby lost; a shift to specifications that call for more male animals is clearly indicated where otherwise acceptable. In other cases, specifications do not allow for acceptable alternative species or, conversely, unwittingly call for rare or endangered species where they are not in fact essential. For example, attention might well be directed to including acceptable alternate species such as Macaca fascicularis in the current federal requirement that presently permits the use of only rhesus macaques in neurovirulence testing for polio vaccines. Where possible, specifications should permit the adaptation of procedures to accommodate fluctuations in supply and take advantage of changing techniques; in addition, they should not lay excessive stress on the existence of accumulated baseline data, however convenient the latter may be. For the protection of endangered species, the biomedical community should recognize the provisions of the U.S. Endangered Species Act (1970) and the Convention on International Trade and Endangered Species of Wild Fauna and Flora (1973) and fully support these instruments by sharply restricting, or prohibiting, any biomedical use that interferes with the normal reproduction and socialization of wild-trapped or F-^-laboratory born females of the species listed.
