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The Washington Regional Primate Research Center

The seven regional primate research centers were established by congressional mandate during the 1960s and are now funded by the National Institutes of Health (NIH) through the National Center for Research Resources (NCRR). The primate centers are distributed throughout the United States, and together they maintain more than 18,000 nonhuman primates representing 32 species. The following objectives were specified by Congress:

  1. To develop nonhuman primate models for basic and clinical research and to examine the underlying mechanisms and processes of human health problems and diseases.
  2. To pursue basic and applied biomedical nonhuman primate research directed toward solving human health and social problems.
  3. To establish a resource for scientists from many disciplines who are trained in the use of primates and who maintain both the continuity and the high quality of scientific research.
  4. To develop improved breeding practices that more adequately meet the overall research demands of the centers for high-quality, disease-free primates.
  5. To continue efforts to preserve primate species threatened with extinction.
  6. To provide opportunities for research experience to graduate students; postdoctoral fellows; visiting scientists; faculty members; and medical, dental, and veterinary students.
  7. To identify and develop nonhuman primate models of human diseases.
  8. To develop new methods and equipment for primate studies.


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--> 5 The Washington Regional Primate Research Center The seven regional primate research centers were established by congressional mandate during the 1960s and are now funded by the National Institutes of Health (NIH) through the National Center for Research Resources (NCRR). The primate centers are distributed throughout the United States, and together they maintain more than 18,000 nonhuman primates representing 32 species. The following objectives were specified by Congress: To develop nonhuman primate models for basic and clinical research and to examine the underlying mechanisms and processes of human health problems and diseases. To pursue basic and applied biomedical nonhuman primate research directed toward solving human health and social problems. To establish a resource for scientists from many disciplines who are trained in the use of primates and who maintain both the continuity and the high quality of scientific research. To develop improved breeding practices that more adequately meet the overall research demands of the centers for high-quality, disease-free primates. To continue efforts to preserve primate species threatened with extinction. To provide opportunities for research experience to graduate students; postdoctoral fellows; visiting scientists; faculty members; and medical, dental, and veterinary students. To identify and develop nonhuman primate models of human diseases. To develop new methods and equipment for primate studies.

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--> To study natural diseases of primates and techniques of importation conditioning, housing, and management, which improve the well-being and suitability of the research primate. To supply biological specimens to biomedical investigators. To disseminate findings of center-supported studies to the biomedical research community. The primate centers have 190 core scientists who receive part or all of their salary and research support through the primate center grant. The core scientists, in turn, work with 924 collaborators, affiliates, or visiting scientists and have 276 graduate students. During 1994, they produced 1,200 scientific publications and books, and more than 450 are in press. These scientists are assisted by more than 1,000 support staff at the primate centers. All but one of the primate centers is directly affiliated with a university, but most of them are not located on the main campus of the affiliated institution. When the primate center program began, each new center had an identifiable focus, which often was linked to a particular species of primate. As the centers have matured, there is increasing overlap among them in regard to the focus of their research. Despite this merging of some activities, each primate center still maintains some of its original orientation. Perhaps the major influences on the scientific programs of a primate center are the research interests of the director and core faculty, the research strengths of the institution, and the availability of funding for particular types of research. Facilities and Programs The Washington Regional Primate Research Center (WRPRC) is an integral part of the University of Washington research community. The central campus facility is part of the Warren G. Magnuson Health Sciences Center in Seattle, which houses the schools of medicine, dentistry, nursing and public health; several other research centers; and the university medical center. The 45,000-square-foot, three-story building, dedicated in 1964, is designed specifically for primate housing and research; it houses about 500 primates: baboons (Papio papio), and monkeys, primarily pigtailed and cynomologus macaques (Macaca nemestrina and Macaca fascicularis). In addition to conventional laboratories and associated facilities for animal housing, cage washing, food preparation, and veterinary care, the building contains fully equipped surgical and radiological suites for experimental and clinical use and an automated quantitative microscopy system. Additional features are facilities for covertly observing and recording the behaviors and social interactions of groups of nonhuman primates, as well as certified biological safety level 3

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--> (BSL-3) facilities for studying hazardous viruses and other pathogens. The WRPRC staff is composed of eight doctoral-level researchers. They are joined by approximately 300 other scientists and graduate, medical, dental, and veterinary students in a wide array of research projects. In recent years the center's principal research efforts have focused on neuroscience, cardiovascular physiology and pathology, hemorrhagic shock, complications of metastatic cancer, and viral diseases, including AIDS. Like the other centers, WRPRC has always supported the research and development of animal housing facilities and of breeding, rearing, and management techniques that maximize the health and well-being of laboratory primates. WRPRC operates several additional facilities. The Infant Primate Research Laboratory, located in the health sciences complex at the Center on Human Development and Disabilities provides lab space and housing for 125 animals and a 24-hour-a-day intensive care unit for low birth weight animals, animals rejected by their mothers, or primate infants assigned to studies of developmental problems such as fetal alcohol syndrome or respiratory distress syndrome. The Primate Field Station is located on the grounds of Eastern State Hospital at Medical Lake, Washington. Its principal function is breeding animals for research (about 350 annually). A small program in southern Russia maintains a breeding colony of pigtailed macaques (Macaca nemestrina ), and a major breeding and research program at Tinjil Island, Indonesia, produces Macaca fascicularis. The latter is a cooperative program of the WRPRC, Bowman Gray School of Medicine, and Institut Pertanian Bogor, Indonesia. This new program is designed to produce healthy research animals in a free-ranging natural habitat at relatively low costs. It provides scientific training in an underdeveloped country as well as helping the country benefit from its natural resources. The Primate Information Center of the WRPRC maintains three national information systems. One of these is a very comprehensive bibliographic database on nonhuman primates (35,000 post-1984 references). Current Primate References is a monthly bulletin that lists new publications on primates from all around the world. The center also publishes a number of specialized kinds of bibliographies, particularly the topical bibliography, and has a very well developed primate database that can be leased by investigators with special needs. The Primate Supply Information Clearinghouse was set up in 1977 specifically to provide information for the sharing of primates; it not only serves primate centers but is a nationwide effort to facilitate efficient use of nonhuman primates by collecting and listing offers from laboratories with available primates and requests from laboratories that need specific primates. Its primary purpose was conservation; because of the inability to exchange this kind of information in the past, many primates were being euthanized when

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--> they could have simply been used in other research programs. In recent years the database has expanded to include information on available facilities and services and on regulatory requirements. This information is disseminated through a series of publications, which include weekly and annual bulletins. The Primate Supply Information Clearinghouse has been very successful in disseminating information about the availability of primates for all kinds of primate-using facilities including primate centers, zoos, biotech companies, government agencies, and others. Any facility licensed with the U.S. Department of Agriculture (USDA) can take advantage of the service. The Tissue Distribution Program is a spin-off of the clearinghouse. This program maintains a listing of scientists' needs and provides fresh, fixed, or frozen specimens prepared in a variety of ways to laboratories throughout the world. About 50 investigators are currently using this service, most of whom are from academic research institutions; about 3,000 tissues harvested from roughly 200 animals will be distributed this year. Ownership and Access Issues Although tissue specimens distributed through the Tissue Distribution Program become the property of the recipient, all living WRPRC monkeys are owned by the primate center regardless of their status as research subjects. Scientists with peer-reviewed, funded support, who have protocols approved by the University of Washington's Institutional Animal Care and Use Committee (IACUC), submit requests to the WRPRC's Research Review Committee to utilize monkeys. When the Research Review Committee approves the study, the scientist pays an acquisition fee and per diem for the duration of the study, but the ownership of the monkey is retained by WRPRC. This does not preclude terminal studies, nor does it necessarily prevent scientists from continuing their studies if they relocate to other institutions. Although typically the research is conducted within the primate center itself, this is not required, and significant parts of the research may be carried out elsewhere. The current review process provides extensive oversight of proposals, but it also creates at least two types of difficulties. First, the Freedom of Information Act of the State of Washington requires that all IACUC meetings be open to the general public, and animal rights activists have used this mechanism to harass individual scientists and members of the WRPRC faculty or staff. Second, although the strength of the Washington Regional Primate Research Center is in no small measure due to the strong scientific leadership it received from prior center directors Orville Smith and Douglas Bowden, and the strong research faculty at the University of Washington, the secondary

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--> review by the WRPRC Research Review Committee creates the potential for a real (or perceived) conflict of interest by members of the committee who might be reviewing competing scientists' proposals. For extramural scientists whose interests are similar to those of a core staff scientist at WRPRC, the easier route to access is often a collaboration, although in recent years even this arrangement has resulted in some intellectual property problems of the sort discussed in the previous case studies. William Morton pointed to his own work with a monkey AIDS model using a variant of human immunodeficiency virus (HIV) known as HIV-2287. The original HIV-2 strain or isolate was brought back from France years ago by an individual from what was then called Genetic Systems, a small biotech company in Seattle. The company evaluated a number of HIV-2 prototypes in vitro and finally chose several to study in vivo. WRPRC and Genetic Systems formed a collaborative arrangement and inoculated some of these strains into pigtail monkeys. After several years of whole blood transfusions to identify more virulent mutants, they defined a variant of HIV-2 they named HIV-2287, which can cause acute infection, CD4 cell decline within two to six weeks, and ultimately full-blown AIDS syndrome within six to nine months. Now, however, Genetic Systems no longer exists, having been acquired by Bristol Myers. Bristol Myers would like complete ownership of HIV-2287 and has drawn up and forwarded an agreement saying that Bristol Myers owns HIV-2287, that it has the right to tell WRPRC scientists when they can or cannot use this variant, and when they can publish, and that the company may invoke confidentiality about any or all communications concerning the strain. Dr. Morton believes he cannot sign such a document. Instead, WRPRC scientists will have to try to rederive and reisolate another strain to develop their own titered stock rather than using the HIV-2287 stock, which Bristol Myers now claims as its own. This will resolve the disagreement, but it will replace more productive research. Cost Issues Each regional primate research center operates under grant funds obtained from NCRR, and its program is reviewed every five years. In 1993, the seven regional primate research centers received $40.8 million (57 percent) of the $72.2 million budget of the Comparative Medicine Program of NCRR. In comparison, the Laboratory Animal Sciences Program, which support grants for research, other research resources, and training, received $22 million (30 percent) of the Comparative Medicine budget. WRPRC received $6.7 million in core funding from NCRR in 1995, allocated to four major categories: Basic Research ($1 million), AIDS-related Research ($1.6 million), Basic Services ($2.4 million), and AIDS-Related

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--> Services ($1.7 million). Additional sources of income are the State of Washington, which provides about $600,000 per year in the form of support for faculty salaries and indirect cost reimbursements, outside grant support for core staff and research affiliates ($22.5 million), and charges to users for animals and services ($3 million). As noted in the previous section, investigators are charged an acquisition fee for animals and a per diem charge for the duration of the study even though WRPRC maintains ownership. Medical and surgical procedures required by experimental protocol or clinical care are also billed to the investigator, as are clinical laboratory tests. Investigators receiving specimens through the Tissue Distribution Program are charged a fee (in this case ownership transfers with the specimen). In keeping with the WRPRC philosophy that promoting basic research should be one of its primary missions, noncommercial users are given a substantial discount on all of these charges (20–50 percent). Primate centers have high maintenance costs because nonhuman primates are extremely destructive and require high levels of containment. The costs of acquiring and maintaining the health of animals from these primate centers are significant, but the health status and welfare of the animals that they produce are certainly greater than could be obtained by trapping feral animals. Moreover, many countries no longer permit trapping or sale of monkeys. The increasing costs associated with raising the animals are forcing reevaluation of where the breeding colonies are located. To reduce the costs of maintaining breeding colonies, the old Medical Lake facility 300 miles from Seattle will be closed in the coming years. A new, smaller, and more efficient facility at American Lake will be constructed; this facility will be shared with the Oregon Regional Primate Research Center. In addition, some breeding animals will be moved to the Tulane Regional Primate Research Center in Louisiana, where they can be reared in outdoor corrals far less expensively, at perhaps one-tenth the cost of Medical Lake. The Indonesian facility, where the colony ranges freely about the small island of Tinjil and lives off the land, promises to be even less expensive. Other Issues and Problems The plans to breed healthy animals in a setting more analogous to their native habitat (such as the facility in Indonesia) may be a partial solution to the costs, This solution is, however, totally dependent on the availability of transportation for those animals. At present, virtually all international commercial airlines, under pressure from animal rights activists, have refused to transport nonhuman primates. To a much greater degree than with other

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--> laboratory animals, the transportation and handling of nonhuman primates may be associated with significant or potential biohazards such as Herpes B virus, filovirus, shigella, and others. Thus, even within the United States, transportation needs are the downside of any consolidated breeding plan. The costs of operating the Primate Center Program are also adversely affected by increasing regulatory activity by the USDA and the Public Health Service via the Office for Protection Against Research Risks (OPRR). It is not unusual for different federal agencies to have different requirements for the same species of animals. Regulations have been imposed requiring provisions for the psychological well-being of nonhuman primates and specifying precise cage sizes. Cages for monkeys commonly cost $8,000–$10,000 each. Many of these regulations have more to do with the perception of the individuals (many of whom were nonscientists) who proposed them than with scientific data. In addition, accrediting organizations such as the American Association for the Accreditation of Laboratory Animal Care (AAALAC), as well as federal agencies, are requiring increased recordkeeping and other types of documentation. All of these regulatory requirements are coming at a time when there is less and less core support from federal funding for the infrastructure for key laboratories and administrative personnel—a role that financially strapped academic institutions facing similar constraints are unable to assume. The political activities of animal rights organizations create major costs for a primate facility because nonhuman primates are typically perceived by the public as more sentient animals with a special bond with humans. By focusing on nonhuman primates, animal rights organization generate sympathy for animal rights, in general, and also often generate funds for the animal rights cause. The costs of animal rights activities to an institution take several forms and include the costs of security to protect the safety of employees and the investigators' research; the costs of security to prevent vandalism by committed animal rights terrorist groups; the costs of litigation instigated as a form of harassment by animal rights activists; and the costs of staff time to investigate and respond to allegations by animal rights activists of violations of animal welfare regulations. Federal regulations require that all allegations of improper care of animals reported to internal (IACUC) and external (OPRR and USDA) oversight bodies be investigated. Therefore, even frivolous complaints must be fully investigated and documented, and the findings must be reported to the appropriate agencies.

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