Nonhuman Primates in Biomedical Research

Biology and Management

Christian R. Abee, Keith Mansfield, Suzette D. Tardif, Timothy Morris

• Publisher: Academic Press
• Year: 2012
• ISBN:
  9780123978370
• Edition: 2
• Topic: Ciencias biológicas
• Subtopic: Zoología

The 2e of the gold standard text in the field, Nonhuman Primates in Biomedical Research provides a comprehensive, up-to-date review of the use of nonhuman primates in biomedical research. The Biology and Management volume provides basic information on the natural biology of nonhuman primates and the current state of knowledge regarding captive management. Each chapter contains an extensive list of bibliographic references, photographs, and graphic illustrations to provide the reader with a thorough review of the subject.

• Now in four color throughout, making the book more visually stimulating to enhance learning and ease of use
• Fully revised and updated, providing researchers with the most comprehensive review of the use of nonhuman primates in biomedical research
• Addresses commonly used nonhuman primate biomedical models, providing researchers with species-specific information

Chapter 1

History of the Use of Nonhuman Primates in Biomedical Research

Dennis O. Johnsen^∗, David K. Johnson^† and Robert A. Whitney, Jr^‡

^∗Port Townsend, WA,^†Cascade Biosciences Consultants, Inc., Sisters, OR, ^‡RADM (0–8 Retired), US Public Health Service, Steilacoom, WA

Chapter Outline

Human and Nonhuman Primates to 1960

Roots of Modern Primatology

First Primate Centers

Soviet Institute of Experimental Pathology and Therapy

Robert Yerkes and the Primate Laboratory of the Yale Institute of Psychobiology

Cayo Santiago and the Caribbean Primate Research Center

Virological Research in Nonhuman Primates

General

Polio

Kuru

Virus (Herpes B Virus or Macacine Herpesvirus 1)

Other Contributions

The Work of Harry Harlow

Breeding and Reproductive Physiology

Establishment of the National Institutes of Health’s National Primate Research Centers Program in the USA: Crossing the Threshold

Initial Activity

Developing the Concept

Launching the New Program

National Primate Research Centers Program Today

1960–1980: Period of Growth in a World of Increasing Constraints

Emulation of the Center Concept

General

Southwest Foundation for Research and Education

Wake Forest University Primate Center

Duke Primate Center

Laboratory for Experimental Medicine and Surgery in Primates

Michale E. Keeling Center for Comparative Medicine and Research

Caribbean Primate Research Center

Department of Defense, Department of Health and Human Services’ Public Health Service, and other US Government Laboratories

Activities Abroad

Constraints

Regulation

1978 Indian Ban on Monkey Exports

Similar Actions in Other Countries

Responding to the Constraints

Rise of Domestic Breeding

Interagency Primate Steering Committee

Other Conservation Activities

Non-Governmental Organizations

Transition to the 1980s

Patterns of Usage

Retroviral Disease

1980S and 1990S: Progress Paying off in the Face of Serious Challenges

A Nobel Prize

Retroviral Disease and Simian Immunodeficiency Virus (SIV)

Emergence and Impact of the Animal Rights Movement

People for the Ethical Treatment of Animals

1985 Amendment of the Animal Welfare Act

Other Effects of AIDS Research

Chimpanzee Breeding and Research Program

Virus, Zoonotic Diseases, and AIDS Provide the Stimulus for Specific Pathogen Free Breeding

Ebola Virus and Interruption of Imports

Captive Breeding Goes Global

Primate Research Beyond the Year 2000

Significant Scientific Advances

Mapping the Chimpanzee and Rhesus Monkey Genome

Genomic Research

Infectious Disease

Growth in the Use of Nonhuman Primates

General

The NPRC Program

CDC Import Data, CRO, and Pharmaceutical Activity

International

Regulation and Review

Transportation

Animal Extremism and its Effects

Chimpanzees

Demand for Specific Pathogen Free and Genetically Defined Nonhuman Primates

Specific Pathogen Free (SPF) NHPs

Advances in Genetics and Genomics

Living in the 3R (Replacement, Refinement, and Reduction) World

Looking Toward the Future

General Trends

Pharmaceutical and Biotechnological Research

Conclusion

References

Human and Nonhuman Primates to 1960

Roots of Modern Primatology

Nonhuman primates probably first became valuable to humans as pets, but they are also the oldest recorded animal subjects for scientific research (Hill, 1977). Nonhuman primate pet trading is known to have occurred in Egypt as long as 5000 years ago (Morris and Morris, 1966); their use for medical purposes came somewhat later, although still in respectably ancient times. Galen (130–200 AD) did anatomical studies on animals including monkeys (Cohen and Loew, 1984) and Vesalius (1514–1564) used barbary apes (Macaca sylvanus) in his studies of circulatory anatomy (Morris and Morris, 1966; Kavanaugh and Bennett 1984; Loeb et al., 1989). Ruch (1941) has also documented that monkeys and apes were studied from ancient times through the middle ages by Hanno, Aristotle, Pliny the Elder, Pliny the Younger, Petrus, Candidus, and others.

Darwin’s research on evolution and particularly his notes on the behavior of the gorilla established his credentials as one of the first observational primatologists (Darwin, 1871). Also late in the 19th century, the British physician David Ferrier conducted comparative neuroanatomy studies of apes and monkeys (Morris and Morris, 1966). During the same time period, Pasteur discovered that the passage of the rabies virus through monkeys caused it to lose its virulence for dogs (Pasteur et al., 1884a, b). Some 20 years later, poliovirus was isolated by inoculating spinal cord material collected from fatal human cases intraperitoneally into monkeys (Landsteiner and Popper, 1908, 1909). The primatological knowledge that was generated came largely from relatively few behavioral and biomedical investigators working independently. With the institutionalization of nonhuman primate research, a profound change became possible.

First Primate Centers

Soviet Institute of Experimental Pathology and Therapy

According to Held and Gay (1983) and Lapin (1983), the first Commissar of Health in the USSR was persuaded by Mechnikov, a pioneer of modern Soviet experimental primatology, to establish a primate breeding station in 1923. Located in Sukhumi on the subtropical shores of the Black Sea in the then Soviet State of Georgia, the station was intended to be a quarantine, breeding, and holding center for nonhuman primates and to support a network of 50 medical and biomedical research institutions. It began operations in 1927 when it received the first shipment of hamadryas baboons (Papio hamadryas) and chimpanzees (Pan troglodytes) from Africa. At first, captive breeding was unsuccessful. However, there was improvement as experience in maintaining and breeding nonhuman primates was gained. Charting a course that has been followed elsewhere, activities of the Sukhumi station’s service gradually expanded to encompass initiatives in independent research. In 1957, now under the auspices of the Academy of Medical Sciences of the USSR, the station became the Institute of Experimental Pathology and Therapy (IEPT) in recognition of its status as a full-fledged research institution. By 1990, the IEPT had production colonies of over 7000 animals consisting primarily of baboon and macaque species, a staff of about 1000 people, and research programs focusing on oncology, physiology, biochemistry, infectious diseases, and the biology of nonhuman primates (B. A. Lapin, personal communication, 1990). The institute also served as a principal source of nonhuman primates for the Virology Institute in Moscow and the Russian space program. It was also an international resource with productive research links to medical scientists in the USA and elsewhere (Figure 1.1).

FIGURE 1.1 Drs Boris Lapin and Orville Smith at the IEPT in Sukhumi in 1987. Lapin, who became director of IEPT in 1958 and continued in that capacity after the move to Adler in 2010 had directed a major primate research center longer than anyone else. Smith was a longtime director of the Washington NPRC and studied the behavioral components of hypertension in baboons and collaborated extensively with investigators at IEPT and IMP.

The secession of Georgia from the former Soviet Union and the disturbances associated with the declaration of independence of Abkhazia seriously disrupted continued operations in Sukhumi. These problems forced completion in 1992 of a move of less than 100 miles to a satellite site in Russia near the city of Adler (D. M. Bowden, personal communication, 1993). Despite this adversity, the institute, now the Institute of Medical Primatology of the Russian Academy of Medical Sciences, remains not only one of the largest nonhuman primate research centers in the world but one of the most enduring as well.

Robert Yerkes and the Primate Laboratory of the Yale Institute of Psychobiology

Robert Yerkes, an accomplished comparative psychologist, had a vision for what the future held for nonhuman primate research and how to realize those dreams (Yerkes, 1916). Yerkes established the Primate Laboratory of the Yale Institute of Psychobiology at Orange Park, Florida, in 1930 (Bourne, 1971; Maple, 1979). His plan was to establish and develop “an institute of comparative psychobiology in which the resources of the various natural sciences should be used effectively for the solution of varied problems of life” (Yerkes, 1932). As early as 1919, he proposed the idea of establishing a nonhuman primate research institute for the systematic study of the “fundamental instincts” and “social relations” of nonhuman primates. Yerkes was a contemporary of other notable early investigators of the time such as Kohler and Kohts who were interested in nonhuman primate research (Maple, 1979). Interest in Kohts’ perceptual and sensory work with chimpanzees in the Soviet Union may have contributed to the initiative for the establishment of the Sukhumi station (Yerkes, 1943).

Yerkes established his Orange Park station in 1930 with funds from Yale University and the Rockefeller and Carnegie Foundations. He received an initial gift of 13 chimpanzees from a breeding facility belonging to Rosalia Abreu in Cuba (Maple, 1979). The colony was expanded during the next several years with 16 additional chimpanzees from Africa, a gift from the Pasteur Institute. Laboratory studies were multi-categorical, encompassing neurophysiology, anatomy, pathology, nutrition, growth, and development (Bourne, 1971). Orange Park was the first organization of its kind in the western hemisphere.

In 1965, the laboratories in Orange Park were moved to Atlanta, Georgia, and the animals were re-established in the new Yerkes Regional Primate Research Center of Emory University.

Cayo Santiago and the Caribbean Primate Research Center

Clarence Ray Carpenter, a student of Yerkes and an accomplished field primatologist (Maple, 1979), has as one of his most enduring accomplishments the establishment of the Cayo Santiago Colony of rhesus monkeys. Rawlins and Kessler (1986) and Kessler (1989; M. J. Kessler, personal communication, 2007) have provided extensive accounts of the history of the Cayo Santiago Colony. Much of the following historical information is derived from those accounts.

Carpenter formulated plans in the early 1930s for establishing a population of both gibbons and rhesus macaques on an island in the American tropics. The possibility of conducting both behavioral and biomedical research on an island colony was basic to those plans. He interested a number of people, including the staff of Harvard’s Museum of Comparative Zoology, the faculty of Columbia University’s College of Physicians and Surgeons, and the Columbia University/University of Puerto Rico’s (UPR) School of Tropical Medicine in San Juan (later to become the UPR School of Medicine), in a planning effort. He selected Cayo Santiago, a 15.2-hectare (approximately 38-acre) island one kilometer off Puerto Rico’s eastern coastal town of Humacao that was donated to the university by a wealthy Puerto Rican sugar cane and banking family.

With the help of a $60 000 grant from a private foundation, Carpenter set off for Indochina and India in 1938. He fared well in collecting the desired number of macaques. Survival of the 47-day sea voyage from Calcutta with the caged animals shipped as deck cargo was a testimonial to the enduring qualities of rhesus monkeys as well as to the care that they received. In late 1938, he released 409 rhesus monkeys, 14 gibbons, and three pig-tailed macaques on Cayo Santiago. Eventually only the rhesus monkeys remained.

Maintenance of the island and breeding were not without problems. Local fruits and vegetables did not provide an adequate diet and malnutrition was overcome only by feeding fox chow, the early precursor to monkey chow. Wells were dug, but the water was brackish. Cisterns and a system for collecting rainwater had to be constructed. A number of monkeys were lost through fighting or being denied access to feed by other animals. Under this pressure, some monkeys even escaped by swimming to the mainland. Various diseases also took their toll, but persistent efforts were successful in eventually eliminating tuberculosis.

Another problem was the lack of dependable financial support. In 1947, the UPR, which had assumed full responsibility for the project, actually offered it free to any institution that would support it. In 1948, ...

Table of contents

• Cover Image
• Content
• Title
• American College of Laboratory Animal Medicine Series
• Copyright
• Preface
• Acknowledgments
• Reviewers
• Contributors
• Chapter 1. History of the Use of Nonhuman Primates in Biomedical Research
• Chapter 2. Laws, Regulations and Policies Relating to the Care and Use of Nonhuman Primates in Biomedical Research
• Chapter 3. Taxonomy of Nonhuman Primates Used in Biomedical Research
• Chapter 4. Functional Morphology
• Chapter 5. Study of Nonhuman Primate Social Behavior
• Chapter 6. Behavioral Management, Enrichment, and Psychological Well-being of Laboratory Nonhuman Primates
• Chapter 7. Behavioral Disorders of Nonhuman Primates
• Chapter 8. Reproduction and Breeding of Nonhuman Primates
• Chapter 9. Laboratory Housing of Nonhuman Primates
• Chapter 10. Nutrient Requirements and Dietary Husbandry Principles for Captive Nonhuman Primates
• Chapter 11. Animal Identification and Record Keeping for Nonhuman Primates
• Chapter 12. Preventative Medicine in Nonhuman Primates
• Chapter 13. Clinical Techniques used for Nonhuman Primates
• Chapter 14. Surgery in Nonhuman Primates
• Chapter 15. Emergency Medicine and Critical Care for Nonhuman Primates
• Chapter 16. Xenotransplantation
• Chapter 17. Anesthesia and Analgesia in Nonhuman Primates
• Chapter 18. Biosafety in Laboratories using Nonhuman Primates
• Chapter 19. Safety and Efficacy Evaluation Using Nonhuman Primates
• Index