Use of primates in research: a global overview

We assessed the use of nonhuman primates and nonhuman primate biological material in research by reviewing studies published in 2001 in peer-reviewed journals. The number and species of primates used, the origin of the animals, the type of study, the area of research of the investigation, and the location at which the research was performed were tabulated. Additionally, factors related to the animals that may have affected the outcome of the experiments were recorded. A total of 2,937 articles involving 4,411 studies that employed nonhuman primates or nonhuman primate biological material were identified and analyzed. More than 41,000 animals were represented in the studies published in 2001. In the 14% of studies for which re-use could be determined, 69% involved animals that had been used in previous experiments. Published studies most commonly used nonhuman primates or nonhuman primate biological material from the species Chlorocebus aethiops (19%), Macaca mulatta (18%), M. fascicularis (9%), and Papio spp. (6%). Of these studies, 54% were classified as in vitro studies, 14% as noninvasive, 30% as chronic, and 1% were considered acute. Nonhuman primates were primarily used in research areas in which they appear to be the most appropriate models for humans. The most common areas of research were microbiology (including HIV/AIDS (26%)), neuroscience (19%), and biochemistry/chemistry (12%). Most (84%) of the primate research published in 2001 was conducted in North America, Europe, and Japan. The animals and conditions under which they were housed and used were rarely described. Although it is estimated that nonhuman primates account for an extremely small fraction of all animals used in research, their special status makes it important to report the many husbandry and environmental factors that influence the research results generated. This analysis has identified that editors rarely require authors to provide comprehensive information concerning the subjects (e.g., their origin), treatment conditions, and experimental procedures utilized in the studies they publish. The present analysis addresses the use of primates for research, including the effects of a shortage of suitable nonhuman primate subjects in many research areas.     

Primate Communication: By Nature Honest, or by Experience Wise?

We review evolutionary views on honesty and deception and their application to studies of nonhuman primate communication. There is evidence that some primate signals are likely to be accurate on the basis of costliness. They appear most often in contexts that include overtly competitive interactions in which unrelated individuals have limited access to information about one another. However, both game theoretic models and most empirical work suggest that costly signals are not often likely to be the basis for honest communication in nonhuman primates. Inexpensive signaling can exist in contexts wherein communication occurs among related animals, something common among many nonhuman primate societies. Another condition in which inexpensive signaling is possible and that is also typical of nonhuman primates, is when sender and receiver both benefit from coordinated interactions. Additionally, when individuals interact repeatedly and can use past interactions to assess the honesty of signals and to modify future response to signals, low-cost signals can evolve. Nonhuman primates appear to deal with the problem of deception via skeptical responding, which can be largely accounted for by learning rules and the fact that they live in stable social groups and can recognize one another and recall past interactions.     

Advantages and limitations of nonhuman primates as animal models in genetic research on complex diseases

Abstract: The genetic similarity between humans and nonhuman primates makes nonhuman primates uniquely suited as models for genetic research on complex physiological and behavioral phenotypes. By comparison with human subjects, nonhuman primates, like other animal models, have several advantages for these types of studies: 1) constant environmental conditions can be maintained over long periods of time, greatly increasing the power to detect genetic effects; 2) different environmental conditions can be imposed sequentially on individuals to characterize genotype-environment interactions; 3) complex pedigrees that are much more powerful for genetic analysis than typically available human pedigrees can be generated; 4) genetic hypotheses can be tested prospectively by selective matings; and 5) essential invasive and terminal experiments can be conducted. Limitations of genetic research with nonhuman primates include cost and availability. However, the ability to manipulate both genetic and environmental factors in captive primate populations indicates the promise of genetic research with these important animal models for illuminating complex disease processes. The utility of nonhuman primates for biomedical research on human health problems is illustrated by examples concerning the use of baboons in studies of osteoporosis, alcohol metabolism, and lipoproteins.     

Nonhuman primate IgA: genetic heterogeneity and interactions with CD89

Nonhuman primates are extremely valuable animal models for a variety of human diseases. However, it is now becoming evident that these models, although widely used, are still uncharacterized. The major role that nonhuman primate species play in AIDS research as well as in the testing of Ab-based therapeutics requires the full characterization of structure and function of their Ab molecules. IgA is the Ab class mostly involved in protection at mucosal surfaces. By binding to its specific Fc receptor CD89, IgA plays additional and poorly understood roles in immunity. Therefore, Ig heavy alpha (IGHA) constant (C) genes were cloned and sequenced in four different species (rhesus macaques, pig-tailed macaques, baboons, and sooty mangabeys). Sequence analysis confirmed the high degree of intraspecies polymorphism present in nonhuman primates. Individual animals were either homozygous or heterozygous for IGHA genes. Highly variable hinge regions were shared by animals of different geographic origins and were present in different combinations in heterozygous animals. Therefore, it appears that although highly heterogeneous, hinge sequences are present only in limited numbers in various nonhuman primate populations. A macaque recombinant IgA molecule was generated and used to assess its interaction with a recombinant macaque CD89. Macaque CD89 was able to bind its native ligand as well as human IgA1 and IgA2. Presence of Ag enhanced macaque IgA binding and blocking of macaque CD89 N-glycosylation reduced CD89 expression. Together, our results suggest that, despite the presence of IgA polymorphism, nonhuman primates appear suitable for studies that involve the IgA/CD89 system.     

Modeling Social Dominance: Elo-Ratings,Prior History,and the Intensity of Aggression

Among studies of social species, it is common practice to rank individuals using dyadic social dominance relationships. The Elo-rating method for achieving this is powerful and increasingly popular, particularly among studies of nonhuman primates, but suffers from two deficiencies that hamper its usefulness: an initial burn-in period during which the model is unreliable and an assumption that all win–loss interactions are equivalent in their influence on rank trajectories. Here, I present R code that addresses these deficiencies by incorporating two modifications to a previously published function, testing this with data from a 9-mo observational study of social interactions among wild male chimpanzees (Pan troglodytes) in Uganda. I found that, unmodified, the R function failed to resolve a hierarchy, with the burn-in period spanning much of the study. Using the modified function, I incorporated both prior knowledge of dominance ranks and varying intensities of aggression. This effectively eliminated the burn-in period, generating rank trajectories that were consistent with the direction of pant-grunt vocalizations (an unambiguous demonstration of subordinacy) and field observations, as well as showing a clear relationship between rank and mating success. This function is likely to be particularly useful in studies that are short relative to the frequency of aggressive interactions, for longer-term data sets disrupted by periods of lower quality or missing data, and for projects investigating the relative importance of differing behaviors in driving changes in social dominance. This study highlights the need for caution when using Elo-ratings to model social dominance in nonhuman primates and other species.     

Control, choice, and assessments of the value of behavioral management to nonhuman primates in captivity

Many people have devoted considerable effort to enhancing the environments of nonhuman primates in captivity. There is substantial motivation to develop experimental, analytical, and interpretational frameworks to enable objective measurements of the value of environmental enrichment/behavioral management efforts. The consumer-demand approach is a framework not frequently implemented in studies of nonhuman primate welfare but profitably used in studies of the welfare of nonhuman animals in agriculture. Preference studies, in which primates can voluntarily choose to socialize or to participate in training, may be the best current examples of a consumer-demand-like approach to assessing the effects of captive management strategies on primate welfare. Additional work in this area would be beneficial; however, there are potential ethical constraints on purposefully subjecting primates to adverse circumstances to measure their demand for a resource. Primate welfare researchers need to design consumer-demand studies with obstacles that will help measure the relative value of resources to captive primates without compromising the welfare they are attempting to evaluate and enhance.     

Control,Choice, and Assessments of the Value of Behavioral Management to Nonhuman Primates in Captivity

Many people have devoted considerable effort to enhancing the environments of nonhuman primates in captivity. There is substantial motivation to develop experimental, analytical, and interpretational frameworks to enable objective measurements of the value of environmental enrichment/behavioral management efforts. The consumer-demand approach is a framework not frequently implemented in studies of nonhuman primate welfare but profitably used in studies of the welfare of nonhuman animals in agriculture. Preference studies, in which primates can voluntarily choose to socialize or to participate in training, may be the best current examples of a consumer-demand-like approach to assessing the effects of captive management strategies on primate welfare. Additional work in this area would be beneficial; however, there are potential ethical constraints on purposefully subjecting primates to adverse circumstances to measure their demand for a resource. Primate welfare researchers need to design consumer-demand studies with obstacles that will help measure the relative value of resources to captive primates without compromising the welfare they are attempting to evaluate and enhance.     

非人灵长类的亲缘选择

亲缘选择是动物进化的重要研究领域之一,非人灵长类因具有丰富的社会网络,是亲缘选择研究领域的重要类群。动物进行亲缘选择的前提是亲缘识别,并常通过社会行为的亲缘偏向表现。因此,本文从非人灵长类的亲缘识别机制和亲缘关系对其社会行为的影响两方面进行了综述:熟悉性和表现型匹配是目前普遍认同的非人灵长类亲缘识别机制,同时这两种机制并不相互排斥,它们可能共同在灵长类的亲缘识别中起作用;在非人灵长类中,亲缘关系是影响社会行为模式的主导因子,它影响着多种灵长类个体的友好行为、攻击行为和性行为的选择,同时亲缘偏向行为在不同物种中表现不尽相同,说明亲缘选择理论可以部分解释灵长类的行为,但存在一定的局限性。本文分析了两种亲缘识别机制的异同以及在实际研究中利用亲缘选择理论解释非人灵长
类社会行为的局限及可能原因。目前,对非人灵长类社会中的亲缘选择研究正逐步深入,其中分子遗传学技术的应用是重要的推动力量。同时,依然存在诸如汉密尔顿规则参数估计和新大陆猴的亲缘选择研究案例的难点,有待研究者进一步探究。     

Understanding emotions in primates: in honor of Darwin's 200th birthday

In the bicentenary year of Darwin's birth, the American Society of Primatologists honored his memory by convening a symposium entitled "Understanding emotions in primates: In honor of Darwin's 200th birthday." The four articles in this special section, excepting this introduction, derive from that symposium. The section confirms that the topic of emotion is once again, as in Darwin's lifetime, the subject of wide-ranging, theoretically exciting research, and that studies with nonhuman primates are at the leading edge of a rapidly changing field.     

In vitro manipulation of nonhuman primate gametes for embryo production and embryo transfer.

Since nonhuman primates are closely related to humans and share many physical similarities, they are important for use in research areas such as human infectious diseases, reproduction, physiology, endocrinology, metabolism, neurology and longevity. To develop and maintain these animals, we must establish techniques for in vitro manipulation of spermatozoa and eggs. For a decade my research group has been conducting basic research to establish embryo manipulation techniques and to clarify the reproductive phenomena in nonhuman primates. This article summarizes the past research on in vitro manipulation of nonhuman primate gametes, from collection of reproductive cells and in vitro fertilization to the birth of offspring after embryo transfer, as well as the current status of these research areas. The studies summarized here will directly lead to the development of standard techniques for practical and comprehensive use in nonhuman primates.     

Optimization of a Novel Non-invasive Oral Sampling Technique for Zoonotic Pathogen Surveillance in Nonhuman Primates

Free-ranging nonhuman primates are frequent sources of zoonotic pathogens due to their physiologic similarity and in many tropical regions, close contact with humans. Many high-risk disease transmission interfaces have not been monitored for zoonotic pathogens due to difficulties inherent to invasive sampling of free-ranging wildlife. Non-invasive surveillance of nonhuman primates for pathogens with high potential for spillover into humans is therefore critical for understanding disease ecology of existing zoonotic pathogen burdens and identifying communities where zoonotic diseases are likely to emerge in the future. We developed a non-invasive oral sampling technique using ropes distributed to nonhuman primates to target viruses shed in the oral cavity, which through bite wounds and discarded food, could be transmitted to people. Optimization was performed by testing paired rope and oral swabs from laboratory colony rhesus macaques for rhesus cytomegalovirus (RhCMV) and simian foamy virus (SFV) and implementing the technique with free-ranging terrestrial and arboreal nonhuman primate species in Uganda and Nepal. Both ubiquitous DNA and RNA viruses, RhCMV and SFV, were detected in oral samples collected from ropes distributed to laboratory colony macaques and SFV was detected in free-ranging macaques and olive baboons. Our study describes a technique that can be used for disease surveillance in free-ranging nonhuman primates and, potentially, other wildlife species when invasive sampling techniques may not be feasible.     

Nonhuman primate transgenesis: progress and prospects

The nonhuman primate is used extensively in biomedical research owing to its close similarities to human physiology and human disease pathophysiology. Recently, several groups have initiated efforts to genetically manipulate nonhuman primates to address complex questions concerning primate-specific development and physiological adaptation. Primates pose unique challenges to transgenesis and, although this field is still in its infancy, the potential for obtaining new insights into primate physiology and gene function is unprecedented. This review focuses on the methods and potential applications of genetically altered nonhuman primates in biomedical research.     

Lineage-specific loss of function of bitter taste receptor genes in humans and nonhuman primates

Since the process of becoming dead genes or pseudogenes (pseudogenization) is irreversible and can occur rather rapidly under certain environmental circumstances, it is one plausible determinant for characterizing species specificity. To test this evolutionary hypothesis, we analyzed the tempo and mode of duplication and pseudogenization of bitter taste receptor (T2R) genes in humans as well as in 12 nonhuman primates. The results show that primates have accumulated more pseudogenes than mice after their separation from the common ancestor and that lineage-specific pseudogenization becomes more conspicuous in humans than in nonhuman primates. Although positive selection has operated on some amino acids in extracellular domains, functional constraints against T2R genes are more relaxed in primates than in mice and this trend has culminated in the rapid deterioration of the bitter-tasting capability in humans. Since T2R molecules play an important role in avoiding generally bitter toxic and harmful substances, substantial modification of the T2R gene repertoire is likely to reflect different responses to changes in the environment and to result from species-specific food preference during primate evolution.     

Primates--requirements by the pharmaceutical industry

The use of primate animals by the pharmaceutical industry, emphasizing the species and number employed in the production and testing of biologics, is reviewed. The impact of the embargoes imposed by the resource countries is discussed, as well as the alternatives to the use of primates that are available to the pharmaceutical manufacturer. The paper concludes by considering the likely long-term effect of the curtailment of the supply of nonhuman primates from feral sources.     

Patterns of lateralized hand use in an arboreal primate, Simias concolor

Studies of hand use in nonhuman primates suggest that several species exhibit hand preferences for a variety of tasks. The majority of studies, however, focus on the lateralized hand use of captive nonhuman primate populations. Although captive settings offer a more controlled environment for assessing hand preferences, studies of wild populations provide important insights into how handedness is affected by natural environmental conditions and thus potential insights into the evolution of handedness. To investigate handedness in a population of wild nonhuman primates, we studied patterns of lateralized hand use during feeding in four simakobu monkeys (Simias concolor), an arboreal species inhabiting the Mentawai Islands, Indonesia. Our data show that individual variation in hand preferences for feeding existed among our study animals. In addition, each simakobu expressed a significant hand preference for supporting itself on a branch during feeding, an uncoordinated bimanual task. This bias was most prevalent when the branch used for support was a main branch rather than a terminal branch. When both hands were employed in a coordinated bimanual feeding activity (bimanual manipulation), only two subjects showed a significant bias for feeding. Our data suggest that these individuals are more likely to express significant hand preferences when feeding from stable, rather than precarious, positions within the canopy.     

Brief communication: Effect of size biases in the coefficient of variation on assessing intraspecific variability in the prosimian skeleton

Lack of independence of data points or the pooling fallacy has been suggested as a potential problem in the study of handedness in nonhuman primates, particularly as it relates to whether hand use responses should be recorded as individual events or bouts of activity. Here, I argue that there is no evidence that the concept of statistical independence of data points or the pooling fallacy is a problem in the evaluation of population‐level handedness in previous studies in nonhuman primates. I further argue these statistical concepts have been misapplied to the characterization of individual hand preferences. Finally, I argue that recording hand use responses as bouts rather than events has no significant effect on reports of hand use in nonhuman primates and, in fact, may unintentionally bias hand use toward the null hypothesis. Several suggestions for improvement in the measurement and statistical determination of individual handedness are offered in the article. Am J Phys Anthropol 151:151–157, 2013. © 2013 Wiley Periodicals, Inc.     

Nonhuman primate infections after organ transplantation

Nonhuman primates, primarily rhesus macaques (Macaca mulatta), cynomolgus macaques (Macaca fascicularis), and baboons (Papio spp.), have been used extensively in research models of solid organ transplantation, mainly because the nonhuman primate (NHP) immune system closely resembles that of the human. Nonhuman primates are also frequently the model of choice for preclinical testing of new immunosuppressive strategies. But the management of post-transplant nonhuman primates is complex, because it often involves multiple immunosuppressive agents, many of which are new and have unknown effects. Additionally, the resulting immunosuppression carries a risk of infectious complications, which are challenging to diagnose. Last, because of the natural tendency of animals to hide signs of weakness, infectious complications may not be obvious until the animal becomes severely ill. For these reasons the diagnosis of infectious complications is difficult among post-transplant NHPs. Because most nonhuman primate studies in organ transplantation are quite small, there are only a few published reports concerning infections after transplantation in nonhuman primates. Based on our survey of these reports, the incidence of infection in NHP transplant models is 14%. The majority of reports suggest that many of these infections are due to reactivation of viruses endemic to the primate species, such as cytomegalovirus (CMV), polyomavirus, and Epstein-Barr virus (EBV)-related infections. In this review, we address the epidemiology, pathogenesis, role of prophylaxis, clinical presentation, and treatment of infectious complications after solid organ transplantation in nonhuman primates.     

New approaches to tuberculosis surveillance in nonhuman primates

Despite significant progress in reducing the incidence of tuberculosis in nonhuman primates (NHPs) maintained in captivity, outbreaks continue to occur in established colonies, with potential serious consequences in human exposures, animal losses, disruption of research, and costs related to disease control efforts. The intradermal tuberculin skin test (TST) using mammalian old tuberculin (MOT) has been the mainstay of NHP tuberculosis surveillance and antemortem diagnosis for more than 60 years. But limitations of the TST, particularly its inability to reliably identify animals with latent TB infections, make it unsuitable for use as a single, standalone test for TB surveillance in nonhuman primates in the 21st century. Advances in technology and the availability of Mycobacterium spp. genomic sequence data have facilitated the development and evaluation of new immune-based screening assays as possible adjuncts and alternatives to the TST, including in vitro whole blood assays that measure the release of interferon gamma in response to stimulation with tuberculin or specific mycobacterial antigens, and assays that detect antibodies to highly immunogenic secreted proteins unique to M. tuberculosis, M. bovis, and other species belonging to the M. tuberculosis complex. It is becoming apparent that no single screening test will meet all the requirements for surveillance and diagnosis of tuberculosis in nonhuman primates. Instead, the use of several tests in combination can increase the overall sensitivity and specificity of screening and surveillance programs and likely represents the future of TB testing in nonhuman primates. In this article we describe the characteristics of these newer screening tests and discuss their potential contributions to NHP tuberculosis surveillance programs.