Primates

References and resources for this tutorial:

Jeffrey D. Fortman, Terry A. Hewett, B. Taylor Bennett, The Laboratory NonHuman Primate (A Volume in The Laboratory Animal Pocket Reference Series) (Boca Raton: CRC Press, 2002)

James G. Fox, Lynn C. Anderson, Franklin M. Loew, Fred W. Quimby, Editors, Laboratory Animal Medicine, 2nd Edition, (New York: Academic Press, 2002) chapter on “Nonhuman Primates” by Bruce J. Bernacky, Susan V. Gibson, Michale E. Keeling, and Christian R. Abee

F. Barbara Orlans, Tom L. Beauchamp, Rebecca Dresser, David B. Morton, John P. Gluck, The Human Use of Animals: Case Studies in Ethical Choice (New York: Oxford University Press, 1998)

Trevor Poole, Editor; Pauline English, Editorial Assistant, The UFAW Handbook on the Care and Management of Laboratory Animals, 7th Edition, (London: Blackwell Science, 1999)

Overview

Using primates as research subjects has a unique history in the topic of animals in science.  While their closeness to us (a range of 95-98% genetic similarity in the case of the Great Apes) is what makes them valuable biomedical research subjects it is also a cause for ethical discomfort. Some of the projects using primates have led to greater public argument over their role in research. Their value as research subjects has lead to increased legal protection for them. Some people say that the genetic closeness of the Great Apes should not only exempt them from use as research subjects, but also affect their moral standing. The Body Group Papers on The Use of Non Human Primates in Research in Research and Testing (2002) is an example of one of the current discussions concerning primates and research ethics.  

In 1994, Deborah Blum’s The Monkey Wars (Oxford University Press) was published and became a popular trade book. The author, a well-known science writer, had received the Pulitzer Prize for the series of articles she had written for the Sacramento Bee and these articles became the impetus for the book which is listed in the Science/Current Affairs titles for Oxford. The listing points out the public’s keen interest in matters of science, to the point that science is considered a topic in current events. Moreover, it indicates that concern for other species, especially primates, is increasingly a matter for general societal discussion.

As it stands now, Blum explains, the research community and its activist critics are like two different nations, nations locked in a long, bitter seemingly intractable political standoff…But if you listen hard, there really are people on both sides willing to accept and work within the complex middle. When they can be freely heard, then we will have progressed to another place, beyond this time of hostilities. In The Monkey Wars, Deborah Blum gives these people their voice. (Business Week, back cover of paperback edition, Oxford University Press, 1994) (For an interesting internet roundtable discussion with Deborah Blum see: Deborah Blum on “The Monkey Wars.”)

Adding to the complexity of the basic ethical questions about animal subjects in research is the different status of the varying primate populations world-wide in terms of their survival in native habitats, ranging from thriving to vulnerable to threatened to endangered to nearly extinct. For example, the rhesus macaque is a monkey with a wide range, thriving in their native habitat while the sooty mangabies are almost extinct in their native land.  The Duke Primate Center is one research center which works with the country of origin, in this case Madagascar, in prosimian conservation efforts. The goal of the Center is directed toward the primates themselves, not their use as biomedical subjects. The International Primate Protection League is a well known international organization with a wide range of activities. 

In response to this problematic status in their native habitats, almost all primates used in research are now from captive breeding programs. In addition, there are moratoriums on some breeding programs involving chimpanzees in this country due to the current large population of laboratory chimpanzees.

The use of chimpanzees (Pan troglodytes) in biomedical research has led to numerous medical advances, including the development of a vaccine for hepatitis B virus. In 1986, chimpanzees were thought to constitute the critical model for understanding the human immunodeficiency virus, and a breeding program was established to provide animals for the study of this virus. The breeding program was very successful, and the combination of an increase in chimpanzee numbers and less-extensive research use than was expected has created a surplus of chimpanzees and a substantial management problem. Although chimpanzees are available for research, there are also pressures not to use them, such as the high cost of housing and maintenance and their endangered status in the wild. Their close genetic relationship to humans, which makes them the appropriate surrogate for human-health research, also creates serious concerns about the ethics of their use by scientists and the public. The US federal government now owns or supports some 900-1000 chimpanzees at a cost of approximately $7.3 million per year, but government investigators pay "use fees" for using animals in government research. Each of those issues contributes to the cost to investigators and the complexity of using chimpanzees in research. (Executive Summary, p. 1,  Chimpanzees in Research: Strategies for Their Ethical Care, Management and Use, National Academies Press, 1997)

Another recent National Academies Press book, International Perspectives: The Future of Nonhuman Primate Resources, reports on an international workshop to discuss this complex problem.  A Few New Developments in Primate Housing and Husbandry, an online article by Steven J. Schapiro, discusses changes in the Rhesus macaque and chimpanzee breeding program at the MD Anderson Cancer Center in terms of specific pathogen free status.

Currently, according to the United States Department of Agriculture (2000), there are 57,000 non-human primates in research in this country. Although not every university research program uses primates, most major medical schools and research institutions do use primates to varying degrees. Due to various reasons, they are quite possibly the most complex animal subject used in research and as such, this tutorial is a summary of the major areas of interest including clearinghouse information. One of the most extensive resources for primates on the web is the Primate Info Net, managed by the Wisconsin Primate Research Center, one of the eight national primate centers in the United States.

As laboratory animals, primates are in a class by themselves. As the animals most closely related to humans, phylogenetically, physiologically and anatomically, they have important uses in research. However, this relationship is also the reason that there is currently much discussion about the use of primates and how they are maintained in captivity. They are also expensive, to breed, rear and buy. All primates are listed by CITES (Convention on International Trade in Endangered Species of Wild Flora and Fauna) (1975-1996), and trade is therefore controlled. Exportation of wild primates from habitat countries for research purposes causes a depletion of wild populations, and involves both conservation and welfare issues. A useful document covering the capture, transport and housing of primates has been prepared by the International Primatological Society (1993).  (The UFAW Handbook on the Care and Management of Laboratory Animals, 7th Edition, op.cit. p. 537)

Primates vary immensely according to genus and species (there are 233 different species of primates); those used in research are sub-order “Anthropoidea” the monkeys, which are usually divided up into two infra-orders, the Catarrhine, old world monkeys (from Africa and Asia), and the Platyrrhine, new world monkeys (from Central and South America). Although the common names are more familiar, data bases may use the latin names in their search engines so we include both of them here.

Old World Monkeys (OWM)

Monkeys in this group include guenons, macacques, baboons and mangabeys. Monkeys in this group are large (20 to 50 pounds), ground dwelling, omnivorous; they forage for food over wide open territories. Some, such as the Asian macaques  and African mangabeys are more tree-dwelling. Their tails are not prehensile, they have narrow noses, ischial callosities (an evolutionary development that helps them sit on surfaces for long periods of time), have sexual skin that changes color/shape, have opposable thumbs; they do not need supplemental vitamin D, often have cheek pouches and often the males and the females have different physical characteristics.  

The most common Old World Monkeys from Asia used in research are the macques. such as the crab-eating macaque, also called the cynomolgus monkey and Macaca mulatto or rhesus macaque.

The most common species of OWM from Africa used in research are the baboon (Papio anubis, Papio cynocephalus ) the guenons and the mangabeys. Guenons are smaller, tree-dwelling monkeys; the most common laboratory species is the African green monkey or Cercopitheecus aethiops. The mangabeys most used are sooty mangabeys, Cercocebus torquatus atys.

The larger primates used, such as chimpanzees, belong to the Pongidae family, the great apes.

New World Monkeys (NWM)

The NWM can be divided into two families, the Callitrichidae and the Cebidae. The former include marmosets and tamarins and the latter the howler, woolly, spider, owl, capuchins and squirrel monkeys. NWM have flat noses, all have tails of which some are prehensile, they are long limbed and lack ischial callosities—both characteristics of their tree-dwelling nature. They have long nails, do not have opposable thumbs or cheek pouches and require supplemental vitamin D. They do not show sexual skin changes and the males and females have similar physical characteristics.

The most common NWM used in research is the squirrel monkey, Saimiri sciureus. A recent issue of the ILAR journal (Volume 41, 2000) focused on The Squirrel Monkey in Biomedical and Behavioral Research.  

Both OWM and NWM share general characteristics such as being extremely dexterous, highly visual, with a long gestation and post-natal period. They have a long period of puberty due to the fact that much of their behavior is learned and not instinctive. They are social animals, with highly developed group dynamics. Housing and environment planning must take into account their need for interaction with conspecifics. Because they are highly intelligent and can be aggressive, they need careful and trained handling. Facial expressions are indicators of different states of arousal; for example, aggression is indicated via staring and open-mouthed teeth showing or yawn display. An open-mouthed “smile” is a sign of fear. Primates that turn their backs toward others are showing submission, whereas the shaking of bars, or bristling out of hair is a threat display. Staring directly at a primate should be avoided as it will be perceived as a threat. In any colony Zoonotic concerns, both to protect handlers from primates and to protect primates from handlers need to be addressed.

The Animal Welfare Institute’s Comfortable Quarters for Non-Human Primates in Research Institutions presents a good summary, with photos, of basic husbandry issues relevant to primates in general.  

Primates and science

Currently, there are eight National Primate Research Centers in the United States, as well as a number of other primate centers and colonies. A Brief History of the Regional Primate Research Centers is an historic overview of the founding of primate centers in the United States. For an overview of the range of current research using primates, see Primates in Biomedical Research.

An historical review of some of the major use of primates as research subjects is, in some cases, an example of the continuing argument over the use of animals, particularly primates, as research subjects. In reading through this selection of brief summaries of some of the more publicized use of primates in scientific research, ethical principles such as costs and benefits, who benefits, who decides, acceptable and unacceptable risk, vulnerable populations, and setting limits continually face us. There is also the dilemma of the incremental nature of scientific discovery where blind alleys and mistakes are part of the process; one can wonder if there is any way to include this reality in the ethical calculus. A recent policy statement from the European Union Scientific Commission comments on the complexity of using primates in research.

With the research into polio and the search for a vaccine, primates were in demand; during the period of most intense research, 1953-1960, mortality for monkeys used in vaccine development approached the 1 million mark. This included the numbers dying either in transit or shortly after, before being included in research protocols. (Rudacille, 2000 and Rowan, 1984) The high numbers concerned the government of India, the major exporter of the monkeys to the United States and it was at this time that the beginnings of captive breeding programs were begun in the countries of origin.

During this period of time, the rising expertise of biotechnology also had a role in polio research. The polio virus’ preferred place of growth was the primate kidney: labs began to produce cell lines of primate kidneys to grow the virus, thereby reducing the need for a “whole monkey.” There is currently a debate about the historic use of primates in polio research; those opposed to using animals as tools for biomedical research argue that using animal models for human diseases actually set the research back due to the difficulty of correctly extrapolating from an animal model.

Another area where Primates, due to their biological closeness to us, have been used extensively is in space research. A major project was the joint project of American/French and Russian scientists, the Bion project, which studied among other things, the phenomenon of weightlessness. In 1997, NASA suspended its part in the Bion primate research program, in large part due to public concern and ethical questions about the use and welfare of the rhesus monkeys in the program.

In the 1980s, the use of primates in nerve studies, particularly the research by Dr. Edward Taub became highly publicized. Dr. Taub was using the deafferentation, a procedure that severed nerve connections, to study the ability of nerves to regenerate. The Silver Springs Monkey Case, gave PETA, a newly formed animal rights group at the time, a large public hearing. There is no question that spinal cord research is ethically troublesome and that the animals used are paying a high cost.

There is no question that Primates have a unique place in brain research, again, due to the genetic closeness to humans. Questions such as how to conduct ethical research in areas that involve the nervous system are very challenging. How far should we go? How do we (and who should the “we” be?) decide what limits should be set, both in terms of the questions we ask, and the difficulties the animals undergo?

Primates, again, due to their phylogenetic closeness to humans, have been used extensively in behavioral research. One of the kinds of studies have been maternal deprivation studies—such work has also been done with rats and dogs--the work of Harry Harlow is probably the best known. Harlow was working in the 1950s; one of his goals was to show scientific “proof” of the critical nature of the maternal-infant bond on future psychological development. His work with rhesus monkeys, along with other scientists on attachment studies were major developments in the field of psychology.  Although the work he did obviously caused great suffering for the monkeys used—nobody questions this either now or then—it did help revolutionize child care in this country. Harlow was also one of the first researchers to experimentally show the high level of intelligence and learning ability in primates.

The historical context in which Harlow’s work proceeded is also important. He was an early soldier in the profession of experimental psychology’s campaign to be acknowledged as a natural science. This acknowledgement was judged to require the adoption and application of a strictly scientific methodology, then widely interpreted to mean the explicit use of experiment and controlled observation. …Harlows hypothesis was controversial for a number of reaons….the typical learning experiment required that the animals be placed on some form of deprivation (e.g. food or water) so that the learning would take place. …He described monkeys as having complex cognitive abilities that involved the existence of intentions, curiosity, and solution plans…Harlow’s experiments have also revealed a great deal about the cognitive and emotional life of monkeys. …When reviewing Harlow and his work we should recall the assumptions of the period in which the work was done. The Animal Welfare Act did not exist until 1966 and did not directly influence experimental designs until 1985. (“Monkeys Without Mothers, in Orlans, et. al. op. cit. pp. 174-185)

There have been critiques of the primate attachment studies over the years, another example of the ongoing debate over primates as scientific research subjects.  Deborah Blum has recently authored, Love at Goon Park and the Science of Affection, a biography of Harry Harlow that discusses this question of the ethical problems when the research is in question is attempting to prove a new hypothesis.

During the 1970s to 1980s chimpanzees and Bonobos were research subjects in language and cognition studies, many of them ongoing today. Beginning in the 1970s, R. Allen Gardner and Beatrix T. Gardner, a research team at the University of Nevada were involved with teaching ASL language to Washoe, a chimpanzee. Roger Fouts, who had begun work with the Gardner’s as a graduate student later moved Washoe to Central Washington University where a colony of chimpanzees still live; the public has become involved via the Friends of Washoe organization, providing financial support and publicity. The Chimpanzee and Human Communication Institute was founded in 1992.

Continuing work on ape language by Sue Savage-Rumbaugh, Duane Rumbaugh as well as others goes on at the YerkesPrimateCenter and at the Georgia State Language Research Center. The level of achievement by the primates raises ethical questions regarding their treatment by us and their moral standing.

Do the great apes’ apparently exceptional capacities for thought and emotion justify conferring higher moral value on them than on other nonhuman species? One response is that the richness of the apes’ mental lives makes them more aware of and more distressed by the pain, suffering, or discomfort they experience from being confined in a sterile environment or deprived of opportunities to form relationships than is experienced by less cognitively complex creatures kept in such conditions. Members of the US Congress seemed to rely on a version of this position when they enacted a statutory provision that laboratory primates (and no other species) must be given “a physical environment adequate to promote [their] psychological well-being. (Orlans, op.cit. p. 151)

The question of ongoing studies in primate intelligence continue to raise ethical questions that are difficult to resolve. One such current project involves cross-fostering of chimpanzees at the University of Louisiana, Lafayette by Daniel Povinelli.

The Great Ape Project

As research with primates continues, particularly in the area of intelligence and language acquisition, a movement to give great apes some form of legal protection by virtue of their intelligence has come about.

This year, "The Great Ape Project," edited by Paola Cavalieri and Peter Singer was published. It is more than a collection of essays by 34 psychologists, biologists, philosophers, ethicists, and anthropologists. It is also the launching of the Great Ape Project which hopes to begin a movement with the purpose of giving apes the same legal rights as children and mentally retarded adults.

Apes would no longer be objects, things, or chattel, but considered as persons. The argument is that apes have both the ability to relate with others and to demonstrate consciousness. For example, DNA studies show that a chimpanzee's closest relative is not the gorilla, but the human. Humans share 98.4% of their DNA with the two living species of chimpanzees. Studies of the great apes have shown emotional and social lives similar to humans, for example, lifelong ties with family members. Washoe, the chimpanzee and Koko, the gorilla have shown capacity for speaking English and using abstract concepts through sign language and have demonstrated self-consciousness and abilities previously thought to only be present in humans. (The Great Ape Project)

Interestingly enough, a case could be made that the Great Ape Project is yet another stage in the evolving ethical thinking about animals, a direct result of the scientific research that has demonstrated the high level of cognition that the Great Apes are capable of.

Biology and Husbandry

Old World Monkeys (Macaques, Baboons, African Grey Monkeys)

OWM are both terrestrial and tree dwelling; in the wild they sleep in the trees but roam on the ground. Laboratory housing should provide both extended floor space as well as perches. Optimum temperatures are 15-24 Centigrade with humidity at 45-65% and 12-15 air exchanges per hour. Their natural instinct is to go up and look down on “intruders;” caging should be tall enough with high perches to allow for this normal behavior pattern.

Biological and chemical perimeters vary widely between species and individuals. For example, the heart rate for a Rhesus macaque can vary between 120-180 while the Cynomolgus macaque’s heart rate measures 240 bpm (data from Wolfensohn & Lloyd for anesthetized animals). Primates show great variety between species (e.g. the Cynomolgus will be easily stressed by routine events where the Rhesus will be less traumatized) and between individuals of the same species. Any housing situation needs to take into account this range of personalities. In the group housing situation hiding places, perches and visual barriers should be available to allow for subordinate animals to avoid direct confrontation. Likewise, food items should be placed in different areas to allow lower ranking animals to eat without having to compete. If J-feeders are used, they should be inspected to be sure any biscuit food drops down; if any of the primates are debilitated or less dexterious they may be unable to remove food from these feeders.

Some form of group housing is preferable; even quarantined animals should be pair housed if at all possible. If a primate needs to be singly housed some form of contact, e.g. adjacent caging to enable pairs to groom each other, should be attempted. Macaques are often caged in large groups, indoors or out. All primates have specific social hierarchies; the exact patterns vary with species but care must be taken in introducing new individuals.  Macaques can be group housed with several males and females with offspring, while Baboons do better grouped per family, with one male and one to four females with offspring. The young stay with their parents until adults since there is a prolonged period of juvenile learning and socialization.

Commercial pelleted feed is usually supplemented with a variety of items, for example, fresh fruit, nuts in the shell, seeds, boiled eggs in the shell and/or pine kernels. Primates need supplemental vitamin C. Food should be offered at least twice daily to avoid bloat; since in the wild primates spend the majority of their time foraging for food, it is preferable to provide some sort of foraging experience. Methods to do this vary, from presenting “foraging trays”, shavings mixed with food items, to providing shavings as bedding with food items randomly placed in the bedding. Foods and treats can be placed in containers or hidden in “puzzle boxes." Using Inexpensive Feeding Equipment and Techniques for Primate Enrichment, an online article, has some concrete suggestions. An added advantage is that the increased foraging gives the primates a sense of control over their environment, as well as providing a greater degree of variability to their day. Baboons will also eat small insects, grasses, roots and lizards. Cynomolgus macaques (often called crab eating macaques) also eat crustaceans. Water should be freely available.

New World Monkeys (Marmosets, Owl monkeys, Tamarins, Squirrel monkeys)

Since these primates are arboreal in the wild, caging needs to be tall with an emphasis on quality vertical space rather than floor space with room for normal postures, e.g. perching with the tail extended down naturally instead of draped on the floor. As with the OWM, their instinct is to go up and look down. Since their wild habitat is the rainforest, temperatures should range between 20-28 degrees Celsius with humidity at 55-65%. Either ultraviolet lighting should be available for them to convert vitamin D2 to D3 or they need to have supplemental vitamin D3 added to the diet. If they are overcrowded, they are highly susceptible to disease. Marmosets do best housed in family units, an adult pair with offspring.

Nesting boxes are important for body heat conservation, especially with the smaller primates; metal caging will predispose them to heat loss. The boxes should be made of wood to conserve body heat. PVC for perches and caging materials is preferable to metal. Marmosets and Tamarins scent mark their territory; this is normal behavior so cleaning schedules should take this into account, since removing the territorial markers will be stressful to the primates, and cleaning should be done on a rotating basis so as to leave some of the marked areas untouched. Nest boxes in particular should remain as undisturbed as possible, e.g. rotating only some of the wooden perches for cleaning at a time. In many cases these boxes can be used as transfer “cages.”

Squirrel monkeys do better with a harem system of caging since the males are interested in the females only during breeding and both sexes prefer same sex same age conspecifics. They do not engage in mutual grooming as do most other primates but they do sleep together in a huddle. One method of housing is to allow the males to join the females and offspring during breeding periods; the rest of the time, the males are caged with conspecifics and the females kept with their offspring. Stable hierarchies form quickly with Squirrel monkeys but they still need to be checked frequently for fighting in the first few days they are placed together until the hierarchy is clear. It is important to provide areas for them to withdraw from each other.

As with OWM, pelleted feed is common with supplements of fruits, nuts and seeds.  For NWM, the feeding stations should be elevated, since a behavioral trait is to inspect the food, drop it down and then go and retrieve it to eat. Again, flooring should allow for this. If feces and debris are not cleaned at least once daily, the dropped food will be contaminated and remain uneaten—in cages with wire bottoms the food will drop through and the monkeys’ health will be compromised due to inadequate amounts of food eaten. Since they have need of a high calorie diet and are prone to hypoglycemia, they should be presented with food at least twice daily.

The National Academies Press has an online book, Nutrient Requirements of Non-Human Primates, 2nd Edition.

General issues of primate well-being

Nonhuman primates have extremely complex social needs and foraging behaviors and housing should allow for species specific behaviors such as mutual grooming. Special attention needs to be paid to the specific groupings; e.g. they do better if housed with unfamiliars since this reduces the cliques and tendency to form groups against “outsiders.” They should be monitored closely until the social hierarchy is established, crush and bite wounds may not be readily apparent. Any individuals that seem depressed or solitary should be immediately removed and checked for wounds. Even after the hierarchy is stable, they should all be checked to be sure the nutritional status is satisfactory for even the low ranking individuals. Pair housing needs to be done carefully; the usual method is to allow possible pairs to familiarize with each other via open mesh screening for a period of time before grouping together. The key is to identify a pair that is comfortable together. If for any reason pair housing is not possible, then visual and auditory contact should be maintained and if at all possible, mutual grooming through cage openings should be facilitated. Often primates are shipped in pairs so that quarantine periods are not solitary.

They require significantly more enrichment than other species. According to the Research Animal Resources Website from the University of Minnesota, a primate enrichment program should consist of the following components:

1. Opportunities for social interaction, including housing in compatible pairs, visual contact with other nonhuman primates and socialization with the animal care technician and veterinary technician.
2. Foraging opportunities, such as provision of special "food treats", use of puzzle feeders and foraging boards.
3. Environmental manipulanda such as toys, chew sticks, perches, swings and an exercise cage.
4. Visual and auditory stimuli through videos and television

Enrichment procedures are varied regularly with nonhuman primates to ensure that the activity is novel. Investigators are encouraged to participate in the enrichment program. However, they should consult with the veterinary staff to ensure that efforts are coordinated and that animals do not receive articles that may be dangerous or excessive amounts of "treats" that could interfere with their normal diet. (http://www.ahc.umn.edu/rar/acservices.html#Routine

The use of wood chips for enrichment has several benefits. The use of bedding increases sanitation and makes cleaning easier; the animals are also able to keep themselves cleaner, dryer and warmer if provided with bedding. Also, increased opportunities for foraging reduces stress and thus experimental variability is decreased.

This study shows that when deprived of the opportunity to forage, monkeys compensate by increasing other behaviours; our young group showed increases in play, aggression, manipulation of the environment, and abnormal behaviours, primarily self-aggression. A litter substrate reduces these behaviours and encourages foraging, even in the absence of grain. In another study we have also shown that the beneficial effects of deep litter:

a. generalize to other primate species, and

b. that the litter is inhibitory to the growth of several types of bacteria (Chamove et. al., 1982, Allowing Captive Primates to Forage)

Environmental Enrichment for Primates an Annotated Database on Environmental Enrichment and Refinement of Husbandry for Nonhuman Primates is available and contains 477 online articles.

In general, primates are either purchased from vendors who have their own breeding programs here in the United States or are bred in the institutions doing the research. One of the issues here is how best to maintain them since in the wild they live in family units long after the neonates are grown. Artificial Weaning of Old World Monkeys: Benefits and Costs, addresses this procedure of weaning the young from their mothers.

The topic of psychological well-being is complicated with discussion over what is the proper definition.

Psychological well-being refers to mental state. It cannot be defined in terms of the environment, although environments certainly influence individual well-being. It cannot be equated with an activity or behavioral profile, although individual status influences behavior. It is not synonymous with any physiological state, although physiological condition and psychological well-being interact. Psychological well-being is influenced by meeting the needs of an individual animal that are based on its species, sex, age, and developmental experiences. Its assessment must be based on multiple indexes:

The animal's ability to cope effectively with day-to-day changes in its social and physical environment (with reference to meeting its own needs).

The animal's ability to engage in beneficial species-typical activities.

The absence of maladaptive or pathological behavior that results in self-injury or other undesirable consequences (see Bayne 1996 for a discussion of the normal and abnormal behaviors).

The presence of a balanced temperament (appropriate balance of aggression and passivity) and absence of chronic signs of distress as indexed by the presence of affiliative versus distress vocalizations, facial expressions, postures, and physiological responses (e.g., labored breathing, excessive cardiac response, and abnormal hormonal concentrations).

The assessment should be based on the behavior of an individual animal …

(National Academies Press: The Psychological Well-Being of Non-Human Primates, 1998)

Major illnesses

An index from the Wisconsin PrimateResearch Center lists articles on different illnesses of primates. A sample vaccination schedule has been published by the Primate Research Center, University of Washington.

Zoonotic diseases

Due to the phylogenetic closeness, disease risks go in both directions, non-human primates to people and vice versa. Primates are at risk for many of the same diseases that we are, e.g. colds, flu, tuberculosis, mumps, herpes simplex and hepatitis. If a worker has a cold they should wear a face mask and check with the veterinary office as to any other precautions. Primates, especially OWM, are extremely susceptible to measles; if workers have been exposed (e.g. their children are ill with measles or are in school with classmates who have become ill) then they should check with their veterinary office as to the correct protection for the colony. Salmonellosis is another illness of concern, as are Shigella and Campylobactger yersinia.

Tuberculosis testing is routine for monkeys; it is highly contagious within a colony and a sick individual, monkey or person is a potential carrier to others.

The disease of most concern in terms of spread from primate to person is Herpes B; (Cercopithecine Herpesvirus 1) it is so common among Macaques that most institutions consider all Macaques to be potential carriers, shedding the virus in mucous membrane secretions. Mouth lesions are the most common symptom of this illness in primates. This illness has a fatality rate of 70% for people. Purpose bred primates are preferable, from a known vendor; this is why many institutions also have their own breeding programs. A common behavior of primates is to spray their saliva as an aggressive display: this is one of the reasons protective clothing is standard for those working with primates. The risk of Herpes B is one of the reasons primates are not handled directly.

Other viruses have been well publicized; primates can carry viruses such as Marburg and Ebola.

Handling and procedures

Because of their phylogenetic closeness to us, zoonotic concerns are paramount, both from primates to us and from us to primates. It is standard procedure that animal caretakers wear protective clothing including masks and gloves to prevent disease transmission. Yet, primates, both human and non-human rely on facial visual cues for communication. For monkeys, a masked human being is frightening since they cannot see visual cues. The benefits of acclimating and training primates to participate in simple, common procedures are many, e.g. reduced stress will standardize chemical panel perimeters. Increasingly, there are protocols to train primates to cooperate for simple procedures such as injections and medication. http://www.brown.edu/Research/Primate/current.html#syringe

Before many procedures though, most primates are sedated. For OWM, chemical immobilization with ketamine is normally used. Injections can be given to a confined animal with the help of a squeeze cage. Once sedated, the monkey can be held by the upper arms, facing away from the handler. Small NWM can be caught and hand restrained (by personnel wearing protective gloves and clothing) and then sedated, usually with alphaxolone/alphadolone. Physical restraint of a conscious animal should only be attempted by trained, experienced personnel. Animals may be pole and collar trained if they will be handled frequently. Tether systems are recommended if animals must be administered drugs or if blood must be collected frequently. The University of Minnesota Research Animal Resources has posted their procedures to follow in case of a bite or scratch as well as specific instructions concerning handling at http://www.ahc.umn.edu/rar/handling.html#PRIMATE.

Nonhuman primates present a variety of challenges for human handlers. Nonhuman primate behavior is extremely complex. Proper behavioral and handling techniques are essential to prevent excessive stress to the animal that can be manifested violently. In addition, because of the close phylogenetic relationship between human and nonhuman primates, a variety of diseases can be transmitted back and forth. To protect both the animal and the handler, as well as other humans the handler may contact, proper preventative protocols must be followed. These include semi-annual tuberculosis screening, use of protective clothing and familiarity with procedures to follow in case of contact between nonhuman primate body fluids and exposed human tissue, such as with a bite or scratch, or an eye splash. Training in these biosafety procedures and in proper handling and behavioral techniques is required before nonhuman primates may be used. (University of Minnesota: http://www.ahc.umn.edu/rar/vetservices.html#Training)

"Working Safely with Nonhuman Primates" was produced by the NIH Office of Animal Care and Use in 1999 for training staff in the NIH intramural research program. This video has a strong emphasis on proper use of personal protective equipment combined with understanding nonhuman primate behavior, and the general principals are applicable to any program that houses nonhuman primates.

Monitoring

As with all animals, hiding pain and discomfort is instinctive. Monitoring should be done on a daily basis, ideally several times a day, by people familiar to and with the monkeys so that a change from normal will be quickly perceived. It is best to view the colony out of sight at first to view their appearance and behavior when they think they are unobserved. Then follow a standard inspection procedure, checking for signs of weight loss (or gain), for a normally groomed coat and for abnormal discharges. A monkey that is isolated, less active or unusually quiet should be removed from the group for a thorough medical check. A monkey in pain will have a sad look on his/her face, sometimes the eyes may appear glassy. They will clench their teeth, grimace or be unusually restless. Alternatively, they can be less active, huddling with their arms across their bodies. Sometimes the others will give an ill monkey increased attention and grooming and at other times, attack. Thus, an ill monkey should be removed promptly from the group. They usually do not vocalize when ill or hurt; vocalization is usually a sign of anger and/or aggression, not pain. All facilities will have their own health monitoring protocol for colonies.

Current research using primates

Marmosets are susceptible to oncological viruses and infectious hepatitis. They are used in immune system research.

Monkeys are used for malaria research.

They are used in HIV and AIDS vaccine research.

Squirrel monkeys are the most commonly used of the NWM; for many studies they are considered the representative model for primate biology. They are used in vaccine and general pharmacological research, malaria research and toxicology studies. They are susceptible to Creutzfeldt-Jakob disease and other transmissible spongiform encephalopathy illnesses. They have a hyperactive sympathetic nervous system and are often used to study atherosclerotic disease.

Primates have historically been used for both toxicology studies and for pharmacological work, particularly in the development of vaccines. Increasingly, they are the final step for much of the testing with rodents used in the earlier stages as a general biological model and the monkeys used as a primate model, prior to clinical trials with people.

Given the ethical issues which surround animal experimentation, it is important to be aware that due care for the biostatistical aspects of experiments can contribute greatly to the humane conduct of research, by minimizing the exposure of animals to harm. Suppose that an experiment is planned which would incontestably settle a physiological point having great bearing on the relief of human suffering. Suppose further that there really were no scientifically valid substitutes for animal testing in that particular case, and that the animals were truly to be treated as well as possible given the experimental protocol. This may indeed be a lot to suppose. But would it necessarily follow that the experiment would be as ethical as possible? No, because an experiment, to be ethical, must be adequate to test the hypothesis of interest. In particular, the sample size must be neither wastefully large nor so small that important findings are likely to be missed.  (“Chimps, Ethics and Numbers: Appropriate Sample Sizes for Tests of Vaccines" from Laboratory Primate Newsletter, Volume 28, No. 2, April 1989)

Primates are also used in aging studies.

Heart research, particularly atherosclerotic disease is another area where primates are utilized.

With genetic similarity to humans of approximately 89% and a relatively large size capable of providing ample fluid and tissue samples, the baboon has served as an ideal experimental model for over 3 decades…. Known as the laboratory model for coronary heart and chronic lung diseases, the baboon has also been used extensively in research involving atherosclerosis, hypertension, and osteoporosis. (Bernacky, et. al., al.cit., p. 711)

Cynomolgus monkeys (crab eating macaques or Macaca fasicularis) are the second most used species of primates, after the Rhesus macaque; they are common in reproductive biology studies as well as work with diseases such as cancer, atherosclerosis, tuberculosis and viral illnesses.

Chimpanzees occupy a unique place in scientific research due to their 98% genetic similarity to human primates.

Chimpanzees are expensive and difficult to manage in a biomedical setting….However, because of their phylogenetic similarities to humans, chimpanzees have been attractive animal models for limited, sophisticated, nonconsuming types of research. Their use in biomedical research has always evoked public concern and continues to challenge our evolving ethical, legal and social perspectives. Their significant contributions to biomedical research are undeniable, as is our obligation to maintain these research veterans in a high-quality life setting for their lifetime of 40-50 years…….The unique ability of chimpanzees to resist or develop a milder form of some human diseases like hepatitis, HIV, malaria, and Alzheimer’s, as well as the question of why chimpanzees rarely develop cancer, has made the chimpanzee an attractive comparative research subject. (Bernacky, et.al., al.cit.p. 715)

An 80 page report on xenotransplantation research in the United Kingdom focuses on the many complex ethical issues with this sort of work.

Primates in Biomedical Research is an online database search via the Info Net from the Wisconsin Primate Research Center.

Additional resources and data bases

A major resource is PrimateLit, a bibliographic site sponsored by NIH and maintained by the Wisconsin Primate Center.  Their Veterinary Resources listing has extensive online articles on a wide variety of husbandry and health issues. 

The Primate Information Network is a web resource from the Wisconsin Primate Research Center.

The Journal of Medical Primatology has an online search site.

Another web resource, NetVet, contains extensive links for Primates.

For those in the primate laboratory community, see the Laboratory Primate Newsletter.

A clearinghouse for Training in Primatology is maintained by the International Primatological Society

The National Academies Press has an online book, Occupational Health and Safety in the Care and Use of Non-Human Primates.

The National Academies Press has an online book, The Psychological Well-Being of Non-Human Primates.

Study Questions:

1. The practice of euthanizing research animals when they are no longer needed is common. This practice has been questioned in the case of chimpanzees. After reading Appendix A, A Minority Statement, from the NAP online book, Chimpanzees in Research: Strategies for Their Ethical Care, Management and Use (1997) would you support euthanasia or not for retired chimpanzees? Why or why not?

2. Do you think the ethical questions over using primates in research depend on the specific primate species being used? Why or why not?