ILAR Journal Online, Volume 34(4) 1992: ILAR Reports

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ILAR Journal V34(4) 1992 [FORMERLY ILAR NEWS]
ILAR Reports

Special Article

Conservationally Sound Assurance of Primate Supply and Diversity
Douglas M. Bowden and Orville A. Smith

Douglas M. Bowden, M.D., is director of the Regional Primate Research Center (RPRC) of the University of Washington in Seattle. Orville A. Smith, Ph.D., former director of the RPRC, University of Washington, is a core staff scientist at this institution.

The rapid disappearance of the natural habitats of monkeys in Asia, Africa, and South America is forcing biomedical researchers to confront anew the question of laboratory primate supply. The search for a reliable supply of laboratory primates has evolved through 2 eras during the last 40 years, and has now entered a third.

The first era began in the 1950s, when the search for a polio vaccine required the biomedical community to use nonhuman primates as experimental animals. For the two decades that followed, U.S. researchers' need for primates was met largely by importation. When a particular primate species was found to have a characteristic of unique research value, researchers contacted an agent to obtain the necessary animals. The second era began in the mid-1970s, when many countries introduced rigid regulations or outright bans on the export of primates. In response, federal agencies such as the National Institutes of Health (NIH) and the Food and Drug Administration (FDA), which anticipated a long-term need for particular species, expanded breeding colonies at the Regional Primate Research Centers and established new ones at other sites. Since then, the need for the most commonly used species, such as rhesus macaques (Macaca mulatta), squirrel monkeys (Saimiri sciureus), and common marmosets (Callithrixjacchus), has been met to a significant extent by domestic breeding. Primates of other species have continued to be imported from countries such as Indonesia, where they remain populous and where the government recognizes their international importance in biomedical research. We are now entering a third era in which ensuring long-term access to a diversity of primate species is as important as access to a sufficient number of animals. Both challenges must be met without threatening the existence of the species in their natural habitats.

Since the 1950s, the use of primates has expanded into virtually every area of human biology and medicine. Since the early 1970s the number of full-length scientific publications based on primate studies has doubled from 2500 to 5000 per year (Primate Information Center, Regional Primate Research Center, University of Washington, Seattle). Fortunately, the dramatic increase in the number of studies has been accompanied by an even more dramatic decrease in the number of animals used. Whereas monkeys were imported into the U.S. at a rate of up to 127,000 annually during and for years after development of the polio vaccine (Mack, 1982), fewer than 20,000 have been imported annually in recent years, with a low of 13,000 in 1983 (Gray-Schofield and Chandler, 1984). This represents a remarkable decrease of almost 90 percent since 1968.

Many factors have contributed to the decline in number of monkeys imported and used in the U.S., not all of which are related to research. The importation of monkeys as pets, which may have accounted for as many as 40,000 to 50,000 per year between 1968 and 1972 (Mack, 1982), was outlawed in 1975. The need to import monkeys for research was reduced with the establishment of domestic breeding colonies. Currently more than 6000 animals are produced each year in colonies supported by the NIH and the FDA. Additional animals are produced in U.S. commercial colonies. Still more primates have been conserved through the efforts of the Primate Supply Information Clearinghouse, which facilitates the recycling of more than 3000 animals per year among investigators across the country (Jacobsen and Hearn, 1992). Nationwide tissue distribution programs by primate research centers have greatly enhanced the efficient use of animals, as have advances in brain stereotaxis, cell culture technology, and molecular biology.

Economics and regulation have also played a significant role in animal conservation. As institutions became reliant on large numbers of U.S.-bred animals, they found the cost per animal to be in the thousands, rather than hundreds, of dollars. Procedures and paperwork mandated by the 1985 amendment to the Animal Welfare Act and new macaque transport and quarantine requirements issued by the Centers for Disease Control in the course of the 1990 filovirus scare added significantly to the per-animal cost of primate research. All of these factors contributed to increased efficiency of animal use in primate research.

While the number of primates used in research has declined, the variety of species that have found an essential niche in biomedical research has expanded. Twenty years ago, some argued that the rhesus macaque was destined to become the "white rat of primate research" and that no other species was really necessary. However, the embargo on exportation of rhesus macaques from India triggered a shift in many labs to the longtailed macaque (M.fascicularis, also known as the Java macaque, crab-eating macaque, or cynomolgus monkey). The large populations of this species in many areas of southeast Asia and its similarities to the rhesus macaque in terms of size, fecundity, and hardiness make it a natural substitute for its close cousin the rhesus macaque. While primarily used in drug development and testing by pharmaceutical companies in the U.S., western Europe, and Japan, the longtailed macaque is now almost as widely used as the rhesus in some areas of academic research (Bowden, 1989).

With each passing year, a new species seems to be in the biomedical spotlight. For example, the sooty mangabey (Cercocebus atys) may be the only easily studied animal closer to human than the armadillo that is susceptible to the leprosy bacillus (Gormus et al., 1988; Martin et al., 1983). Owl monkeys (Aotus sp.) belong to one of only two genera that are susceptible to the same malaria species that infect humans (Mons and Sinden, 1990). The crested black macaque of Sulawesi (M. nigra, formerly "Celebes black ape") has found a special niche in diabetes research (Howard and Yasuda, 1990) and, most recently, the pigtailed macaque (M. nemestrina) has shown a susceptibility to HIV-1 infection that is not shared by the more common laboratory species (Agy et al., 1992).

The 1990s have suddenly marked a new era in the pattern of primate supply. In its new incarnation, the problem of ensuring adequate supplies of primates in the long term has expanded from simply providing enough animals to securing permanent access to an ever-expanding diversity of essential species. To this is added the inexorable challenge of supplying animals in a manner that does not threaten the future existence of any species. These kinds of challenges were foreseen for decades by the international conservation community, but until recently, appreciated by only a minority in the biomedical primate research community (Bermant and Lindburg, 1975; Smith, 1975).

The challenge was addressed to some extent in the 1970s when new regulations on primate exports from South America, designed to bring the pet trade under control, threatened the supply of squirrel monkeys, owl monkeys, marmosets, and other species used for biomedical research. The Pan American Health Organization, recognizing the legitimate long-term need for certain New World primate species in biomedical research, sponsored the establishment of a field station at Iquitos, Peru--the Centro de Reproduccion y Conservacion de Primates no Humanos (Jacobsen and Hearn, 1992)--to address those needs in a conservationally sound manner.

In no country today are the conflicting challenges of conservation and research needs being felt more acutely than in Indonesia. Indonesia is the fourth largest country in the world by population (Levy and Greenhill, 1983) and the fourteenth by area (Johnson, 1992). As the natural habitat of more species of Old World monkey than any other country in the world (more than 30 species of monkeys and apes), Indonesia has become the world's leading source of primates for research. For a variety of geographic and historical reasons, it was one of the few countries that was able to continue supplying primates for research through the late 1970s and 1980s. At the same time, Indonesia was taking major steps toward ensuring the conservation and preservation of its biological treasure.

The guiding principle in Indonesia has been to develop primates as a sustainable resource within a broader program to establish primatology as a component of a growing effort in national health research. The modes of implementation include natural-habitat breeding facilities (NHBFs) and compound breeding colonies for relatively plentiful species such as longtailed and pigtailed macaques, which are most in demand for research. These efforts are complemented by nature reserves, export embargoes, and proposals for special breeding programs for particularly vulnerable species such as the Sulawesi crested black macaque.

In 1982 and 1983, the Indonesian government met with a small team of consultants sponsored by the World Health Organization (WHO) to explore the feasibility of maintaining the supply of primates "for essential biomedical purposes" in a manner that would "ensure the permanent conservation of the various species" (Hiddleston and Smith, 1982; MacKinnon, 1983). The ensuing reports applauded the Indonesian government's recent steps toward conservation, such as the establishment of nature reserves exceeding 11.2 million hectares and setting export quotas on primates for use in research at about 16,000 per year (Hiddleston and Smith, 1982; MacKinnon, 1983), a level that has remained relatively stable since that time.

The team's recommendations focused on NHBFs as the most feasible approach to a sustainable resource capable of meeting the needs of both conservation and biomedical research. It noted a number of issues that certain members of the Indonesian government recognized must be addressed if any such approach were to succeed in the long run. These issues included training Indonesian professional personnel in such areas as primate medicine, population survey techniques, habitat monitoring, reproductive biology, and wildlife management, as well as training research scientists who planned to use primate models in biomedical research directed at health problems of Indonesians.

In 1986, three U.S. institutions whose research programs were particularly focused on primate species indigenous to Indonesia joined forces with a major Indonesian agricultural university, Institut Pertanian Bogor (IPB), in a series of programs to address these issues. The Regional Primate Research Center at the University of Washington was heavily committed to pigtailed macaques as the species of choice in many research areas including atherosclerosis, infant respiratory distress syndrome, fetal alcohol syndrome, early behavioral development, and aging. The Bowman Gray School of Medicine had built a wide-ranging atherosclerosis research program around longtailed macaques, and the Oregon Regional Primate Research Center had a major diabetes program based on crested black macaques. The three institutions had a vital interest in ensuring the permanent conservation and supply of those species. That concern became the vehicle, on the U.S. side, for implementing several joint resource and research projects with IPB, including the development of Tinjil Island (Pulau Tinjil in Indonesian) as the first island-based NHBF in a country where the animals were indigenous (Kyes, in press).

Tinjil is a tropical island located about 15 kilometers off the southwest coast of Java, the capital island of Indonesia. Six kilometers long and one kilometer wide, it is almost completely covered with vegetation, much of which is tree growth that is 20 to 30 meters high. A botanical survey has revealed many fruiting bushes and other plants known to be edible to macaques. Three natural water sources and a number of shallow wells provide water. Animal life on the island includes crabs and other seashore creatures; lizards, including some monitor lizards; a few snakes; and, of course, insects. There were no native primates before the introduction of the longtailed macaque colony that now inhabits the island.

Facilities and support equipment on the island include a house for the manager and visiting scientists, smaller houses for the caretaking families and security personnel, and several huts for workmen and students. In addition, 12 feeding-trapping cages are distributed about the island, where the animals are provisioned and captured periodically for health monitoring or transfer to research facilities.

Between 1988 and 1990, 475 longtailed macaques (10 to 1 ratio of females to males) were screened against tuberculosis and immunodeficiency viruses, cleared of common primate intestinal parasites, and released onto the island. A survey conducted in mid-1990 indicated that about 57 percent of the females produced offspring in a 10-month period (Kyes, in press). The total estimated population in 1990 was between 775 and 825. In 1991 the total estimate was about 1000, and in 1992, after export of 100 offspring, the population was greater than 1200.

The private sector played a crucial role in the rapid development of the NHBF on Tinjil Island. Chuck L. Darsono, D.Sc.(Hon.), a private entrepreneur whose business and avocational interests have ranged from construction engineering to primate export, established the facility. He identified the site, purchased and maintained the boats, and built the structures on the island necessary to maintain, monitor, and capture the animals and to train personnel in those procedures. He managed all aspects of the operation for the first 4 years of its existence.

During the time that the NHBF was under development, several young Indonesian veterinarians were studying at the collaborating U.S. institutions in fields necessary for them to assume long-term responsibility for the facility. To date, the consortium of U.S. primate centers (Bowman Gray, Oregon, Washington) has provided postdoctoral training to Indonesians in the fields of primate medicine, clinical laboratory technology, pathology, reproductive biology, virology, and atherosclerosis. Plans for the immediate future include the training of fellows in forestry wildlife management and other fields.

As the veterinarians trained in primate management returned to IPB, the university was able to establish a primatology program to offer training in pertinent aspects of primate biology and ecology to students and professional personnel of the IPB and governmental agencies involved in forestry management. Simultaneously, they began to set up the quarantine facilities, compound breeding facilities, and laboratories necessary to conduct primate research at the university. The Indonesian government provided funds to the university to establish a staging area at Muara Binuanguen, a fishing village on the Java mainland where the boats for Tinjil Island were based. The base camp includes a dock for two boats with inboard diesel engines to transport people, animals, and equipment between the island and the mainland, a covered dry dock for maintenance of the boats, and a quarantine facility for animals going to or from the island. With these accommodations as a focus, the university has built facilities where it will offer extension courses to residents of the village and surrounding area in subjects pertinent to their occupations, not only to those involved in the NHBF, but to local fishermen, farmers, and other community members.

In 1990, the primate program at IPB advanced to the status of a full-fledged primate research center, the Pusat Studi Satwa Primata (PSSP). With Dr. Dondin Sajuthi as director, the PSSP is a rapidly growing national resource for Indonesia. It is accumulating the professional personnel, laboratories, and primate colonies necessary to establish collaborative research programs in virology, cardiovascular pathology, and reproductive biology. Government agencies and commercial enterprises, with responsibilities that impinge on primate conservation and use, increasingly turn to the staff of PSSP for expert consultation on issues they face in those areas.

In early 1992, the PSSP assumed managerial responsibility for the NHBF on Tinjil Island. Thus, the island now serves as a source of income to the research center, a field station for testing ideas about optimal approaches to conservationally sound management, and a training site for university students in such areas as veterinary medicine, forestry, and primate biology.

The establishment of the Tinjil NHBF and the primate research center at IPB are not the only major developments occurring in Indonesia. Some government officials have predicted that within a few years Indonesia, in the interests of conservation, will cease to export wild-born primates. Both to ensure future supplies of healthy research animals and in anticipation of such a policy shift, a small but significant number of exporters have begun to establish breeding facilities for the most commonly used species. As the NHBF on Tinjil approached completion, Mr. Darsono established a second NHBF for longtailed macaques on Pulau Deli, a neighboring island. This commercial venture, which involves several thousand breeders, appears to be proceeding well; the first export of offspring took place in late 1992. The governmental agency responsible for forestry development is considering making other islands available for NHBFs patterned on the Tinjil and Deli operations. Other enterprises engaged in the export of primates for research are establishing breeding colonies consisting of open air compounds similar to the large U.S. breeding colonies.

With every passing year, the success of the Indonesian approaches to primate conservation and supply becomes more critical to the international biomedical research community. A decade ago, the number of dependable external sources of primates used in conventional laboratory research had dwindled to two countries, that is, Indonesia and the Philippines. With the political problems in the Philippines and the discovery in 1989 of a potentially virulent filovirus in some of the longtailed macaques coming from the Phillipines, the availability of animals from there has become problematic. Furthermore, the diversity of primate species in Indonesia, ranging as it does from the tiny nocturnal tarsier, a variety of species of leaf-eaters, macaques, and lesser apes to the gentle, majestic orangutan, is unmatched anywhere else in the world.

The exponential growth of human populations into the areas where monkeys live, combined with the massive expansion of technologies to exploit the natural resources of those regions, has accelerated the destruction of the natural habitats of nonhuman primates. While these trends are being addressed more effectively in Indonesia than in many similar countries of the world, they are having an impact both on the species currently in demand and on other species that may hold the key to solution of health challenges in the future. Institutions and individuals that are concerned with the problems of both human and nonhuman primate species are searching for a means to accommodate the human needs, while at the same time conserving the animals and their habitats. Thus, it behooves the scientific and conservation organizations outside Indonesia to support in every way possible the constructive path of development on which it has embarked.

References

Agy, M. B., L. R. Frumkin, L. Corey, R. W. Coombs, S. M. Wolinsky, J. M. Koehler, W. R. Morton, and M. G. Katze. 1992. Infection of Macaca nemestrina by human immunodeficiency virus type-1. Science 257:103-6.

Bermant, G., and D. G. Lindburg, eds. 1975. Primate Utilization and Conservation. New York: Wiley.

Bowden, D.M. 1989. Trends in species studied by neuroscientists, 1973-1988. Neurosci. Newsleu. 20:4-5.

Gormus, B. J., D. K. Ohashi, S. Ohkawa, G. P. Walsh, W. M. Meyers, P. J. Brennan, and C. Trygg. 1988. Serologic responses to Mycobacterium leprae-specific phenolic glycolipid I antigen in sooty mangabey monkeys with experimental leprosy. Int. J. Leprosy 56:537-45.

Gray-Schofield, L., and J. L. Chandler. 1984. Trends in primate imports into the United States, 1983, including a discussion on worldwide trade in primates. ILAR News 27(4):6-12.

Hiddleston, W. A., and O. A. Smith. 1982. Report of World Health Organization (WHO) mission to determine the feasibility of establishing a primate breeding programme in Indonesia. Unpublished.

Howard, C. F. Jr., and M. Yasuda. 1990. Diabetes mellitus in nonhuman primates: Recent research advances and current husbandry practices. J. Med. Primatol. 19:609-25.

Jacobsen, L., and J. Hearn. 1992. International Directory of Primatol-ogy. Madison: Wisconsin Regional Primate Research Center, Publication #32-010.

Johnson, O., ed. 1992. Information Please Almanac, 45th edition. Boston: Houghton and Mifflin.

Kyes, R. In press. Survey of the longtailed macaques on Tinjil Island, Indonesia. Am. J. Primatol.

Levy, J. S., and A. Greenhill, eds. 1983. The Concise Columbia Encyclopedia. New York: Columbia University Press.

Mack, D. 1982. Trends in primate imports into the United States, 198l. ILAR News 25:(4)10-13.

MacKinnon, K. S. 1983. Report of a World Health Organization consultancy to Indonesia to determine population estimates of the cynomolgus or longtailed macaque (Macaca fascicularis) and other primates and the feasibility of semi-wild projects of this species. WHO Primate Resources Program Feasibility Study: Phase 11. Bogor, Indonesia. Unpublished.

Martin, L. N., B. J. Gormus, R. H. Wolf, G. P. Walsh, W. M. Meyers, and C. H. Binford. 1983. Experimental leprosy in nonhuman primates. Adv. Vet. Sci. Comp. Med. 28:201-36.

Mons, B., and R. E. Sinden. 1990. Laboratory models for research in vivo and in vitro on malaria parasites of mammals: Current status. Parasitol. Today 6:3-7.

Smith, O. A. 1975. Production of specialized laboratory primates with consideration for primate conservation. Pp. 127-39 in Primate Utilization and Conservation, G. Bermant and D. G. Lindburg, eds. New York: Wiley.