Theor Med Bioeth (2014) 35:143–156 DOI 10.1007/s11017-014-9288-2
Harms and deprivation of benefits for nonhuman primates in research Hope Ferdowsian • Agustı´n Fuentes
Published online: 14 March 2014 Ó Springer Science+Business Media Dordrecht 2014
Abstract The risks of harm to nonhuman primates, and the absence of benefits for them, are critically important to decisions about nonhuman primate research. Current guidelines for review and practice tend to be permissive for nonhuman primate research as long as minimal welfare requirements are fulfilled and human medical advances are anticipated. This situation is substantially different from human research, in which risks of harms to the individual subject are typically reduced to the extent feasible. A risk threshold is needed for the justification of research on nonhuman primates, comparable to the way risk thresholds are set for vulnerable human subjects who cannot provide informed consent. Much of the laboratory research conducted today has inadequate standards, leading to common physical, psychological, and social harms. Keywords Risk Harm Threshold Nonhuman primates Animal research Risk-benefit analysis
Introduction The main problem explored in this paper is whether risk in nonhuman primate research should be modeled on the thresholds of risk used in human research. The risks of harm to nonhuman primates and the relative absence of direct benefits to H. Ferdowsian (&) Department of Medicine, The George Washington University, 2150 Pennsylvania Avenue, Washington, DC 20037, USA e-mail: [email protected] A. Fuentes Department of Anthropology, University of Notre Dame, 648 Flanner Hall, Notre Dame, Indiana, USA e-mail: [email protected]
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these individuals are critical ingredients in ethical decision making about their use in research, though these are not currently central considerations in research review, just as thresholds of harm are not typical. We argue that the threshold of risk of harm to nonhuman primates ought to be comparable to the risk threshold set for humans who are particularly vulnerable to physical, psychological, and social harms. Specifically, we recommend that nonhuman primates should not be exposed to risks that exceed those posed in the normal daily lives of healthy primates living in species-appropriate, safe environments. This standard should generally protect nonhuman primates from conditions and interventions that pose more than a low probability of serious physical, psychological, or social harm. We conclude that available empirical evidence indicates that invasive biomedical and behavioral research conducted in nonhuman primates living in captivity generally exceeds an acceptable threshold level.
Inadequate attention to harm-causing activities and their limits in animal research The roots of the failures in current animal research can be teased out by analysis of current human research standards, where risks of harm to individual subjects are monitored so that risks are minimized and benefits maximized [1]. Within human research, the nature and scope of physical, psychological, social, and other harms and benefits are considered. Even when conflicts occur between commitments to the production of societal benefits and risks of harms to individuals, standards exist to protect human subjects from significant levels of harm [1]. Human research protections pay special attention to individuals who cannot protect their own interests from being exposed to the types and degrees of physical, psychological, and social harms that individuals who can protect their own interests would characteristically refuse. Vulnerable human populations should not, with rare exceptions, be exposed to more than minimal risk—that is, to risks that exceed those encountered during daily life by normal, average, healthy individuals living in safe environments or during the performance of routine physical or psychological examinations or tests [1, 2]. United States regulations allow institutional review boards to approve human pediatric research that does not offer subjects a prospect of direct benefit only when the risks are minimal or a minor increase over minimal and several additional protections are satisfied. In some situations, individuals are excluded from research situations that may harm them, as a result of their particular vulnerabilities [1, 2]. These standards prevent populations such as children and prisoners from being coerced or subtly manipulated into harmful research [2]. These standards prevent the most severe harms from being unjustly inflicted on the most vulnerable subjects and reflect a common morality to avoid harm, particularly in populations at risk for coercion [1, 2]. By contrast, animal research guidelines typically do not reflect the attention to harm avoidance so fundamental to human research. It is basically assumed that nonhuman animals can be exposed to levels of harm without compensating benefits
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as long as there is a degree of anticipated benefit for humans [3]. No clear moral justification is offered for this situation within any laws, policies, and guidelines that present themselves as comprehensive ethical approaches to animal research. For example, the majority of international guidelines reflect a position expressed in the preamble of the International Guiding Principles for Biomedical Research Involving Animals, first published in 1985 and revised in 2012 by the Council for International Organizations of Medical Sciences (CIOMS): The use of animals in research, education, and testing is an essential component of the advancement of our understanding about human and animal function. This knowledge is important for advancing human and animal health and welfare through disease prevention and cures, new treatments, and drug and device development. The scientific community, understanding that using animals is a privilege entrusted by society, remains committed to ensuring the health and welfare of animals as an integral consideration when animals are used for these purposes. [4] The premise that nonhuman animals can be used and harmed for human benefit sidesteps questions of both the moral status of nonhuman animals and the justification of particular research protocols. The importance of nonhuman animals’ interests and choices, the moral relevance of harms, and whether there should be a harm or risk threshold that cannot be exceeded do not receive attention in the process. Many have justified the use of nonhuman animals in research by citing their similarities to humans, rather than considering how the common potential for vulnerability and mental and physical suffering influences moral considerations regarding nonhuman animals. However, humans and other animals have common interests in self-preservation, living free of unnecessary constraints, and meeting their basic needs. If human and nonhuman animals have similar (or shared)1 capacities for pain, distress, and suffering and similar interests in avoiding these harms, general moral duties to not harm should cover humans and nonhuman animals in relevant similar ways. It is morally suspect to have different sets of ethical norms in similar situations. In the case of invasive and potentially damaging research, it would be prejudicial and ethically problematic to discount serious harms to one species when the same or similar harms are considered to be of serious import in another species. Current laws, policies, and guidelines governing animal research demonstrate the deficiencies within animal research standards. These standards implicitly recognize the importance of animals’ welfare interests and harms associated with research 1
Increasingly, research suggests that highly social mammals, including primates, have psychological and behavioral systems that detect and respond to inequity and even perceived social injustice [5, 6]. This suggests more substantive overlap than is generally assumed between human and nonhuman primate perceptions of ethical landscapes, and thus, calls for more homology in the impositions of ethical standards and moral justifications for their use. If some core perceptions of fairness and inequity overlap between human and other primates (even to a general extent), then those other primates should be granted minimally an awareness of social justice and recognition of their endangerment and potential harm by being the focus of human experimentation and manipulation.
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protocols and conditions by regulating breeding, transportation, housing, husbandry, and the technical aspects of research, including the use of tranquilizers, analgesics, anesthetics, paralytics, and euthanasia; peri-operative care; the composition and operation of animal care committees; and accreditation of laboratory facilities [7– 10]. Researchers and reviewers are also asked to follow the ‘‘Three Rs’’ principles, by reducing the number of animals used, refining or limiting the pain and distress to which animals will be exposed, and replacing the use of animals with nonanimal alternatives when possible or using a species believed to be less sentient [11]. In effect, these standards acknowledge and sanction a range of types and degrees of harm. Attention is given to risk mitigation and management but less, if any, attention is given to harm avoidance. The acceptable levels of harm and risks of harm are inadequately addressed in these highly general standards, though some animal care committees may independently accept a responsibility for more specific and higher levels of protections. ‘‘Harms’’ involve a setback to welfare interests, of which pain, fear, distress, psychological suffering, and death are all examples [12–14]. Other setbacks to wellbeing, a concept that extends beyond an absence of fear, pain, distress, and disease, broaden the scope of harms. Primate well-being depends on whether physiological needs, such as water, nutrition, sex, sleep, and homeostasis are met, as well as whether psychological needs such as safety, security, sociality, self-determination, freedom to express a wide-range of natural behaviors, and cognitive stimulation are realized [15, 16]. Sources of cognitive stimulation range from simple task completion to problem solving, complex decision making, and dynamic social exchanges. Basic primate sociality includes creating and maintaining bonds among friends, families, and sexual partners. Primates require a broad and rich scope of social attachments, and the patterns for these social attachments are often specific to the evolution of the species and individual experiences [17]. As with humans, the social needs of nonhuman primates are determined by complicated interactions between genetic, developmental, and environmental factors. Primate well-being is also determined by opportunities to attain levels of esteem and respect of others. These constituent features of primate well-being are common in native habitats but less common or absent in artificial captive environments such as research laboratories. During the course of research, blocking or seriously obstructing interests such as those in developing social attachments and in maintaining mental and physical health and self-determined choice and movement are all harmful. Although harms intrinsic to research protocols and the research enterprise are sometimes reduced in accordance with existing laws, policies, and guidelines, the likelihood of serious harm to these social dimensions remains high. Newer animal research guidelines promote the inclusion of a risk-benefit analysis for nonhuman animal use, suggesting that the benefits derived from the research activity should be balanced with the potential for pain or distress experienced by the nonhuman animal [4, 10]. However, the assumption remains that presumed benefits to humans justify risks of serious harms to nonhuman animals. Further, there is little guidance offered for how to assess benefits and risks. Risk has two dimensions: the probability or possibility of harm and the magnitude of harm that is expected. In
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many instances, the probability of harm in animal research is purposely high; experimental protocols are specifically designed to test harmful substances or understand disease in ways that set back welfare interests. ‘‘Magnitude’’ refers to scope or intensity (i.e., severity) of harm. Standards to evaluate the severity of laboratory procedures are commonly used and, in some instances, legally required [18]. Although the most severe experiments require specific justification, they are not uncommon and there is no established severity threshold. Existing guidelines for review also make it difficult for reviewers to consider the cumulative scope of harms experienced by individual subjects. Authorized protocol reviewers are asked to focus primarily on the treatment of harms generated during the exercise of an experiment (e.g., exposure to electric shock or pain produced by an implanted tumor) rather than the harms created during animal acquisition, transportation, and housing or the harms animals endure after completion of an experiment [11, 19]. This situation contrasts with human research, wherein risks of harm are minimized. With nonhuman animals used in research, harmful conditions and interventions are intentionally inflicted, resulting in repeated, high, certain, or severe risks for harm. Regardless of their positive intent, current animal research standards do not establish a harm or risk threshold or offer meaningful guidance for how to balance the risks and benefits of research. The assumption appears to be that if a good faith attempt at satisfying current standards has been made, residual pain and distress are justified. This perspective is morally unacceptable, whatever its legal standing. Researchers should provide ethical justification for causing harm, particularly harms that seriously compromise well-being.
Setting a risk threshold for research involving nonhuman primates Nonhuman primates are vulnerable to many of the same harms as humans, and nonhuman primates’ abilities to protect their own interests in research are hampered by intrinsic and extrinsic factors beyond their control. It would therefore be prudent to establish a standard risk threshold for nonhuman primates comparable to standards that protect vulnerable human subjects from more than minimal risk of serious harm. Nonhuman primates have all of the requisites for experiencing pain, including suitable receptors and nervous systems, physiological changes due to noxious stimuli, protective motor reactions, intrinsic analgesic responses, stimulus avoidance, and avoidance learning. Additionally, nonhuman primates experience pain and discomfort associated with disease, which can result in lethargy, anorexia, sleep disturbances, and enhanced sensitivity to pain [20]. Fear, distress, and induced psychopathology are sometimes as harmful as physical pain for primates [21, 22]. In this regard nonhuman primates are vulnerable to many of the same physical and psychological harms to which humans are vulnerable. Like children and other vulnerable human populations, nonhuman primates cannot always protect their own interests in achieving well-being or avoiding fear, pain, and distress while confined as research subjects. Nonhuman primates are unable to provide informed consent or otherwise to protect themselves from harms
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that informed, competent human adults typically avoid or refuse. Owing to their lack of linguistic capabilities and the absence of advocates within their own species in roles of power, nonhuman primates are often more vulnerable than human children in research, thus calling for a conservative standard for their use. Whereas a parent or guardian who represents a child’s best interests can provide permission on his/her behalf (sometimes with a child’s assent), it is virtually impossible for a human to represent the interests of a nonhuman primate as well as a human could represent the interests of another human, because we cannot understand the minds of other animals as well as we can understand human minds [23]. Nonhuman primates are also vulnerable to being selected as subjects for harmful research, similar to the ways in which some humans are vulnerable to harms as a result of personal, political, social, economic, and environmental constructs [24].2 Since there is a lack of convincing arguments for why nonbeneficial research is acceptable in those who cannot provide consent, current practice relies on a standard in which humans who are unable to provide consent cannot be exposed to risks that exceed those encountered during normal daily life in safe environments.3 An analogous standard for nonhuman primates would be that nonhuman primates should not be exposed to risks that exceed those posed in the normal daily lives of healthy primates living in species-appropriate, safe environments. ‘‘Speciesappropriate environments’’ would include settings like those in the wild, which have not been significantly distorted by humans, or environments such as sanctuaries that promote the well-being of nonhuman primates who cannot live in the wild. A criterion of ‘‘species-appropriate environments’’ accounts for the needs of diverse species of primates and upholds an analogy to human children, who are allowed to live their lives outside of their involvement in research protocols in their normal, free-living environments. A risk threshold standard that includes criteria for ‘‘species-appropriate environments’’ and ‘‘normal’’ lives would likely exclude typical laboratory and zoo settings.4 The specification for ‘‘healthy’’ primates living in ‘‘safe’’ environments would exclude researchers inflicting diseases or other disabilities on individuals, even if similar harms occur in the wild. Permitted research would include (1) observational behavioral research in an individual’s natural (i.e., wild) environment, which has no significant physical, social, psychological, or epidemiological impact on the individual, conspecifics, or co-inhabitants, and (2) the collection of biological specimens, such as urine, feces, skin, and hair samples, for research purposes by noninvasive means in wild or sanctuary environments. Use of 2
For example, nonhuman primates have no political power; they cannot advocate for themselves. Legally, they are property; they can be bought and sold. Nonhuman primates are easily trapped, restrained, and transported by physical force. In captive and some field settings, nonhuman primates are in totally dependent relationships with humans. For more on this topic, see [24, 25].
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For more on this subject, see [26]. Also see [1, 27].
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Although primate well-being might be a concern for some zoo caretakers and officials, the primary purpose of zoological parks is exhibition rather than promotion of animal well-being. Nonhuman animals used in zoo displays are often captured from the wild, confined, and exposed to harms associated with captivity and transport. Although there have been claims that zoos are agents of public education and species preservation, these claims have been challenged by Marino and colleagues; see [28].
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tissue that has been stored in a tissue bank and poses no new risks to individuals or groups of animals would also be permitted. Obviously permissible research would include noninvasive procedures that do not involve general anesthesia, sedation,5 aversive reinforcement contingencies, or physical or chemical restraint, because these interventions involve setbacks to primates’ basic interests. In wild or captive environments, such as sanctuaries, research involving materials collected for nonresearch purposes (e.g., medical diagnosis or treatment) would be permitted, because these interventions would serve the interests of the individual. According to the standard we propose, clinical monitoring of medications already approved for veterinary use, and in which a medication or device is being used in accordance with its approved labeling (clinical use) or professionally established off-label clinical uses, would also be permitted if the research itself would not introduce additional harm to the individual. The level of risk we suggest provides some estimate of the levels of risk nonhuman primates would otherwise face in wild or similar environments, either in the course of daily life or during the course of medical treatment conducted for the benefit of the animal. If nonhuman primates were not exposed to risks that exceed those posed in the daily lives of healthy primates living in species-appropriate, safe environments, the research would not generally increase the risks to which primates are already exposed. Our proposal would, with rare exception, restrict research involving nonhuman primates to observational field research and medical research in which nonhuman primates receive direct benefits of the research. We have not addressed here the question of whether humans have a right to use nonhuman primates at all, even if the harms are minimal to nonexistent. This question deserves further consideration but falls outside the scope of this paper. We have merely argued that nonhuman primates should not be exposed to more than minimal risk. Questions will undoubtedly be raised about whether more than minimal risk should be incorporated into decisions about nonhuman primate research. Although human children can be exposed to a minor increase over minimal risk [2], such interventions or procedures must, by law, hold out the prospect of direct benefit for the individual subject or meet all of the following requirements: (a) The intervention or procedure presents experiences to subjects that are reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social, or educational situations; (b) The intervention or procedure is likely to yield generalizable knowledge about the subjects’ disorder or condition that is of vital importance for the understanding or amelioration of the subjects’ disorder or condition; and (c) Adequate provisions are made for soliciting assent of the children and permission of their parents or guardians [2]. These provisions are specifically constructed to protect the interests of children enrolled in research and balance a minor increase over minimal risk with benefit to the individual or his/her class of subjects. Because nonhuman primates generally do not directly or indirectly benefit 5
There may be some instances in which interventions such as general anesthesia and sedation are beneficial to nonhuman primates. In these cases, benefits could exceed risks and provide justification for these types of interventions.
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from biomedical and behavioral research conducted on them, and there is no way of obtaining permission from nonhuman primates or appointed guardians, they cannot be compared to human children in these ways. Opposition to the threshold analysis we propose will likely stem from two main areas: concerns about limiting access to nonhuman primates in research to the potential detriment of human health; and perceived differences in the moral relevance of harms to vulnerable human and nonhuman primate populations. On the first point, we concede that, based on this threshold analysis, most research involving nonhuman primates that is practiced today would not continue. It is unclear how restricting nonhuman primate research would affect human health outcomes, and it is an area that could be explored further in another paper. On the second point, we have treated the moral relevance of harms equivalently across humans and other primate species.
Permissibility of certain types of harm in nonhuman primate research The standard we recommend is in stark contrast with the risks incurred by nonhuman primates currently used in invasive biomedical and behavioral research. As we discuss below, the most common uses of nonhuman primates in invasive biomedical and behavioral research involving nonhuman primates living in captivity exceed our proposed threshold for physical, psychological, and social harm. The probability, scope, and magnitude of physical harms experienced by nonhuman primates used in laboratory research today are high, yet fully compatible with existing laws and guidelines. Nonhuman primates are most commonly used in microbiology (including HIV/AIDS), neuroscience, biochemistry, and pharmacology experiments, primarily in North America, Europe, and Japan [29]. During these experiments they are deliberately exposed to diseases, invasive procedures, and harmful substances not normally encountered in their free-living environments. In addition, nonhuman primates have long lives in research, and have typically been re-used throughout much of their life span [30, 31]. These interventions exceed the risks posed in the daily lives of healthy primates living in species-appropriate, safe environments. The introduction of toxic chemicals, diseases, unnecessary drug exposure, device implantation, and other surgical interventions are all clear setbacks to the interests of nonhuman primates to avoid pain and discomfort and remain healthy. The likelihood of physical harm to individual subjects is high because infection, illness, and injury are commonly the intended consequences of experiments. Nonhuman primates used in invasive laboratory research also experience the chronic effects of experimental exposure or manipulation, including the intended and unintended physical consequences of harmful substances and diseases, such as organ damage and physiological derangements. Additionally, access to basic needs such as adequate water, food, sunlight, and sleep are often influenced by experimental participation and remain outside of their control. Living in laboratories deprives nonhuman primates of their natural habitats and normal amounts of physical activity. Subsequent to their use in research, nonhuman
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primates are frequently killed.6 These research interventions are all significant setbacks to the physical welfare of nonhuman primates and exceed the standard risk threshold we recommend. Conditions in which nonhuman primates are kept for laboratory research also exact acute, recurrent, or chronic social and psychological harms on nonhuman primates. Social and psychological harms frequently experienced by nonhuman primates living in laboratories include social deprivation and undue social pressures from conspecifics or laboratory personnel; social and physical isolation or the inability to seek solitude or socially secure contexts; sensory deprivation or overstimulation; deprivation of the ability to participate in normal activities of daily living and to exhibit naturalistic behaviors; threats to physical and psychological integrity from laboratory staff and other animals; and the witnessing of painful or distressful interventions conducted on others [19]. In preparation for research, nonhuman primates are commercially bred or removed from their wild environments and traded internationally, disrupting normal maternal-infant and other conspecific relationships. International trade of primates from source countries in Asia, Africa, and South America to North America and Europe involve long-distance transportation, resulting in considerable stress on the animals [29]. Nonhuman primates are often confined and housed in socially deprived laboratory environments [33]. Multiple studies show that adverse rearing conditions such as premature maternal separation, social isolation, prolonged confinement, and sensory deprivation lead to developmental and behavioral pathology in nonhuman primates [34–40], which impair psychological well-being. One of the most harmful conditions of research is the lack of socialization experienced by nonhuman primates. More than half of macaques being used in research in the United States are singly caged, and, on average, macaques and baboons spend more than half their lives living alone in cages.7 Normally, social bonding and the development and negotiation of social bonds are characteristic of all gregarious primate societies, and complex sociality is arguably the core primate adaptation and directly related to mental and physical well-being [6, 45–47]. A recent review [48] also suggests that nonhuman primate species’ preferences for fairness and the development of social cooperation, and even altruistic behavior, are related to the social and environmental contexts experienced by primates. Most captive contexts harm or severely restrict the development of central aspects of core social tools, such as inequity aversion, cooperation, and even types of ‘‘fairness’’ assessments. Substantial inter-population and intra-specific analyses of social behavior in primates show that complex and variable patterns of networks and the ability to 6
In the United States, euthanasia of chimpanzees is allowed only to alleviate suffering [32].
7
A 2003 survey encompassing almost 36,000 macaques in 22 U.S. primate laboratories found that 54% of animals used in research were singly caged [41]. A nonexhaustive survey by USDA Animal Care field inspectors between October 2000 and August 2001 determined that 35% of surveyed animals kept in research facilities were single-housed [42]. Between 2004 and 2006, at the National Primate Research Center in Seattle, Washington, 63% of monkeys were singly caged [43]. Individual monkeys spend an average of more than 3 years alone [33]. Other surveys indicate that macaques and baboons spend more than half of their lives caged alone [44].
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construct and manipulate social niches are the center of primate social organization [49]. For example, Jessica Flack and colleagues [50] argue for social niche construction in monkeys where social networks constitute the essential social resources in gregarious primate societies. They suggest that the structure of social networks can play a critical role in infant survivorship, cooperative behavior, social learning, and cultural traditions [15]. This socially constructed niche is intertwined with behavioral components of relationships (e.g., affiliative, agonistic, and sexual), and it is the dynamics of these patterns and processes that affect the overall psychological and physiological health of primates [51]. Conditions of captivity, especially changes to social contexts and networks, can therefore adversely influence the basal psychological and behavioral profiles and experiences of primates. Removing animals from stable social groups can have profound impacts on the lives and health of the remaining group members, which can have dramatic effects on the well-being of primates, as indicated by behavioral and physiological changes. Despite the harmfulness of creating socially impoverished conditions, it is a common practice within laboratory research and compliant with existing laws and regulations [7, 10]. Current research standards do not prevent some of the most severe harms to nonhuman primates. This is surprising since the association of pathological behaviors with adverse physical, psychological, and social conditions in nonhuman primates has been investigated for decades [52–60]. Research protocols designed to understand psychopathology in nonhuman primates have deliberately inflicted severe, acute, recurrent, or chronic harm on research subjects. Research subjects rarely, if ever, benefit from these types of research. Even if the subjects had benefited from the research, it would be difficult to justify the level of maleficence fundamental to these protocols because of the severity and chronicity of harms the subjects incur. The unintended psychological harms, via disruption and inhibition of social processes, associated with living in a laboratory and a variety of other captive contexts need to be included in ethical assessments of primate research. These are sometimes differentiated as incidental harms, though the origin of the harm is irrelevant to the experience of the individual and when considering harms from a moral perspective. Although the potential for psychological harm is addressed in the Animal Welfare Act and the Guide for the Care and Use of Laboratory Animals [7, 10], efforts to reduce psychological harm are focused on structural aspects, including toy and tool procurement, cage size, temperature control, and noise levels. Such measures may not take into account the centrality, or functional significance, of social context and processes in primates. Post-traumatic stress disorder, depression, generalized anxiety, and compulsive disorders have been described in nonhuman primates used in research [61–64]. Even in captive settings that are not research oriented, nonhuman primates display significantly more abnormal behaviors detrimental to individual welfare than their counterparts in the wild [65]. Collectively, these findings show that conditions of captivity alone can be harmful to well-being. The harms are likely a result of the loss of autonomy, sociality, and cognitive stimulation, which are critical to primate well-being. Processes and events that disrupt, destroy, or limit the range of social relationships core to well-being are
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ubiquitous aspects of captivity and contribute to the scope and magnitude of harms experienced by nonhuman primates used in laboratory research.
Conclusion Currently, laboratory research involving nonhuman primates pervasively involves elevated risks of severe harm, including but not limited to mental and physical suffering, with minimal to no benefit for research subjects. Similar or shared perceptions and sensations of harm suggest that the threshold for risk of harm to nonhuman primates should be comparable to that of humans who are at increased risk for physical, psychological, and social harms. Nonhuman primates should not be exposed to more than a low risk of serious physical, psychological, and social harm. Under our proposal, much of the invasive biomedical and behavioral research involving nonhuman primates conducted today should be discontinued. Acknowledgments This material is based upon work supported by the National Science Foundation under Grant No. 1058186. Any opinion, findings, and conclusions or recommendations expressed in this article are those of the authors and do not necessarily reflect the views of the National Science Foundation. The authors thank Tom Beauchamp, John Gluck, and David Wendler for helpful comments on previous versions of this article.
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13. Harman, Elizabeth. 2011. The moral significance of animal pain and animal death. In The Oxford handbook of animal ethics, ed. Tom L. Beauchamp and R.G. Frey, 726–737. New York: Oxford University Press. 14. Feinberg, Joel. 1984. Harm to others: Moral limits of the criminal law. New York: Oxford University Press. 15. McCowan, Brenda, Kristen Anderson, Allison Heagarty, and Ashley Cameron. 2008. Utility of social network analysis for primate behavioral management and well-being. Applied Animal Behaviour Science 109: 396–405. 16. Nash, Leanne T. 2005. Studies of primates in the field and in captivity: Similarities and differences in ethical concerns. In Biological anthropology and ethics: From repatriation to genetic identity, ed. Trudy Turner, 27–48. Albany: SUNY Press. 17. Fuentes, Agustı´n. 2010. Social systems and socioecology: Understanding the evolution of primate behavior. In Primates in perspective, ed. Christina Campbell, Agustı´n Fuentes, Katherine MacKinnon, Simon Bearder, and Rebecca Stumpf. Oxford: Oxford University Press. 18. United States Department of Agriculture. 2011. Animal care policy #11: Painful and distressful procedures. http://www.aphis.usda.gov/animal_welfare/policy.php?policy=11. Accessed March 3, 2013. 19. Ferdowsian, Hope R., and Debra Merskin. 2012. Parallels in trauma, pain, distress, and suffering in humans and nonhuman animals. Journal of Trauma and Dissociation 13: 448–469. 20. Dantzer, Robert, and Keith W. Kelley. 2007. Twenty years of research on cytokine-induced sickness behavior. Brain, Behavior, and Immunity 21: 153–160. 21. Rowan, Andrew N., Martin L. Stephens, Francine Dolins, Adrienne Gleason, and Lori Donley. 1998. Animal welfare perspectives on pain and distress management in research and testing. In Proceedings for Pain Management and Humane Endpoints. http://altweb.jhsph.edu/pubs/proceedings/pain/rowan. html. Accessed March 3, 2013. 22. Malone, Nicholas Martin, Agustı´n Fuentes, and Frances White. 2010. Subjects of knowledge and control in field primatology. American Journal of Primatology 72: 779–784. 23. Nagel, Thomas. 1974. What is it like to be a bat? The Philosophical Review 83: 435–450. 24. Satz, Ani. 2009. Animals as vulnerable subjects: Beyond interest-convergence, hierarchy, and property. Animal Law 16: 1–50. 25. Rogers, Wendy, Catriona Mackenzie, and Susan Dodds. 2012. Why bioethics needs a concept of vulnerability. International Journal of Feminist Approaches to Bioethics 5: 11–38. 26. Wendler, David, Leah Belsky, Kimberly Thompson, and Ezekiel Emanuel. 2005. Quantifying the federal minimal risk standard. Journal of the American Medical Association 294: 826–832. 27. Bartholome, William. 1977. The ethics of non-therapeutic clinical research on children. In Research involving children: Report and recommendations, appendix 3. Washington, DC: US Department of Health, Education, and Welfare. 28. Marino, Lori, Scott Lilienfield, Randy Malumud, Nathan Nobis, and Ron Broglio. 2010. Do zoos and aquariums promote attitude change in visitors? A critical evaluation of the American zoo and aquarium study. Society and Animals 18: 126–138. 29. Carlsonn, Hans-Erik, Steven J. Schapiro, Idle Farah, and Jann Hau. 2004. Use of primates in research: A global overview. American Journal of Primatology 63: 225–237. 30. National Primate Research Center, University of Wisconsin–Madison. 2008. The life spans of nonhuman primates. Primate Info Net. http://pin.primate.wisc.edu/aboutp/phys/lifespan.html. Accessed May 25, 2013. 31. Johnsen, Dennis, David Johnson, and Robert Whitney Jr. 2012. History of the use of nonhuman primates in research. In Nonhuman primates in biomedical research: Biology and management, vol. 1, ed. Christian Abee, Keith Mansfield, Suzette Tardif, and Timothy Morris, 1–34. London: Elsevier. 32. National Research Council. 1997. Chimpanzees in research: Strategies for their ethical care, management, and use. http://books.nap.edu/catalog.php?record_id=5843. Accessed May 25, 2013. 33. Balcombe, Jonathan, Hope Ferdowsian, and Debra Durham. 2011. Self-harm in laboratory primates: Where is the evidence that the Animal Welfare Act amendment has worked? Journal of Applied Animal Welfare Science 14: 361–370. 34. International Primatological Society. 2007. IPS international guidelines for the acquisition, care and breeding of nonhuman primates. http://www.internationalprimatologicalsociety.org/docs/IPS_ International_Guidelines_for_the_Acquisition_Care_and_Breeding_of_Nonhuman_Primates_Second_ Edition_2007.pdf. Accessed September 14, 2012.
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35. Baker, Kate. 2005. Enrichment for nonhuman primates: Chimpanzees. NIH Publication No. 05–5748. Washington, DC: Department of Health and Human Services. http://grants.nih.gov/grants/olaw/ Chimpanzees.pdf. Accessed March 4, 2013. 36. Bellanca, Rita U., and Carolyn M. Crockett. 2002. Factors predicting increased incidence of abnormal behavior in male pigtailed macaques. American Journal of Primatology 58: 57–69. 37. Lutz, Corrine, Arnold Well, and Melinda Novak. 2003. Stereotypic and self-injurious behavior in rhesus macaques: A survey and retrospective analysis of environment and early experience. American Journal of Primatology 60: 1–15. 38. Novak, Melinda. 2003. Self-injurious behavior in rhesus monkeys: New insights into its etiology, physiology, and treatment. American Journal of Primatology 59: 3–19. 39. Hook, Melinda A., Susan Lambeth, Janice E. Perlman, Ronda Stavisky, Mollie A. Bloomsmith, and Steven Schapiro. 2002. Inter-group variation in abnormal behavior in chimpanzees (Pan troglodytes) and rhesus macaques (Macaca mulatta). Applied Animal Behavior Science 76: 165–176. 40. Rommeck, Ina, Kenneth Anderson, Allison Heagerty, Ashley Cameron, and Brenda McCowan. 2009. Risk factors and remediation of self-injurious and self-abuse behavior in Rhesus macaques. Journal of Applied Animal Welfare Science 12: 61–72. 41. Baker, Kate. 2007. Enrichment and primate centers: Closing the gap between research and practice. Journal of Applied Animal Welfare Science 10: 49–54. 42. United States Department of Agriculture. 2002. Fall 2000 NHP housing survey for animal care. Unpublished report. 43. Thom, Jinhee, and Carolyn Crockett. 2008. Managing enrichment plans for individual research projects at a National Primate Research Center. Journal of the American Association of Laboratory Animal Science 47: 51–57. 44. Balcombe, Jonathan, and Kathleen Conlee. 2011. Primate life in two American laboratories. Paper presented at the Eighth World Congress on Alternatives and Animal Use in the Life Sciences, Montreal, Quebec, Canada, August 21–25. 45. Dolhinow, Phyllis (ed.). 1972. Primate patterns. New York: Holt, Rinehart and Winston. 46. Kappeler, Peter M., and Carel P. van Schaik. 2006. Cooperation in primates and humans: Mechanisms and evolution. Berlin: Springer. 47. Silk, Joan B. 2007. Social components of fitness in primate groups. Science 317: 1347–1351. 48. Price, Jessica, and Sarah Brosnan. 2012. To each according to his need? Variability in the responses to inequity in nonhuman primates. Social Justice Research 25: 140–169. 49. Fuentes, Agustı´n. 2011. Social systems and socioecology: Understanding the evolution of primate behavior. In Primates in perspective, ed. Christina Campbell, Agustı´n Fuentes, Katherine MacKinnon, Simon Bearder, and Rebecca Stumpf, 500–511. New York: Oxford University Press. 50. Flack, Jessica, Michelle Girvan, Frans de Waal, and David Krakauer. 2006. Policing stabilizes construction of social niches in primates. Nature 439: 426–429. 51. MacKinnon, Katherine C., and Agustin Fuentes. 2012. Primate social cognition, human evolution, and niche construction: A core context for neuroanthropology. In The encultured brain, ed. Daniel H. Lende and Greg Downey, 67–102. Cambridge: MIT Press. 52. Brent, Linda, Rick Lee, and J.W. Eichberg. 1989. The effects of single caging on chimpanzee behavior. Laboratory Animal Science 39: 345–346. 53. Capitanio, John P. 1986. Behavioral pathology. In Comparative primate biology, volume 2, part A: Behavior, conservation, and ecology, ed. Gary D. Mitchell and Joseph M. Erwin, 411–454. New York: Alan R. Liss. 54. Davenport, Richard K., and Charles M. Rogers. 1970. In Immunology, infection, hormones, anatomy, and behavior, vol. 3 of The chimpanzee, ed. Geoffrey H. Bourne, 337–360. Baltimore: University Park Press. 55. Harlow, Harry. 1986. From learning to love: The selected papers of H.F Harlow. New York: Praeger Publishers. 56. Nash, Leanne T., Jo Fritz, Patricia L. Alford, and Linda Brent. 1999. Variables influencing the origins of diverse abnormal behaviors in a large sample of captive chimpanzees (Pan troglodytes). American Journal of Primatology 48: 15–29. 57. Ridley, Rosalind M., and Harry F. Baker. 1982. Stereotypy in monkeys and humans. Psychological Medicine 12: 61–72. 58. Tinklepaugh, Otto L. 1928. The self-mutilation of a male Macacus rhesus monkey. Journal of Mammalogy 9: 293–300. 59. Yerkes, Robert M. 1943. Chimpanzees: A laboratory colony. New Haven: Yale University Press.
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60. Nelson, Eric E., and James T. Winslow. 2009. Nonhuman primates: Model animals for developmental psychopathology. Neuropsychopharmacology 34: 90–105. 61. Bruene, Martin, Ute Bruene-Cohrs, William C. McGrew, and Signe Preuschoft. 2006. Psychopathology in great apes: Concepts, treatment options and possible homologies to human psychiatric disorders. Neuroscience and Behavioral Reviews 30: 1246–1259. 62. Bradshaw, Gay A., Theodora Capaldo, Lauren Lindner, and Gloria Grow. 2008. Building an inner sanctuary: Complex PTSD in chimpanzees. Journal of Trauma and Dissociation 9: 9–34. 63. Ferdowsian, Hope R., Debra Durham, Charles Kimwele, et al. 2011. Signs of mood and anxiety disorders in chimpanzees. PLoS ONE. doi:10.1371/journal.pone.001985519855. 64. Ferdowsian, Hope R., Debra Durham, Cassie M. Johnson, et al. 2012. Signs of generalized anxiety and compulsive disorders in chimpanzees. Journal of Veterinary Behavior: Clinical Applications and Research 7: 353–361. 65. Birkett, Lucy P., and Nicholas E. Newton-Fisher. 2011. How abnormal is the behavior of captive, zoo-living chimpanzees? PLoS ONE. doi:10.1371/journal.pone.0020101.
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Harms and deprivation of benefits for nonhuman primates in research Hope Ferdowsian • Agustı´n Fuentes
Published online: 14 March 2014 Ó Springer Science+Business Media Dordrecht 2014
Abstract The risks of harm to nonhuman primates, and the absence of benefits for them, are critically important to decisions about nonhuman primate research. Current guidelines for review and practice tend to be permissive for nonhuman primate research as long as minimal welfare requirements are fulfilled and human medical advances are anticipated. This situation is substantially different from human research, in which risks of harms to the individual subject are typically reduced to the extent feasible. A risk threshold is needed for the justification of research on nonhuman primates, comparable to the way risk thresholds are set for vulnerable human subjects who cannot provide informed consent. Much of the laboratory research conducted today has inadequate standards, leading to common physical, psychological, and social harms. Keywords Risk Harm Threshold Nonhuman primates Animal research Risk-benefit analysis
Introduction The main problem explored in this paper is whether risk in nonhuman primate research should be modeled on the thresholds of risk used in human research. The risks of harm to nonhuman primates and the relative absence of direct benefits to H. Ferdowsian (&) Department of Medicine, The George Washington University, 2150 Pennsylvania Avenue, Washington, DC 20037, USA e-mail: [email protected] A. Fuentes Department of Anthropology, University of Notre Dame, 648 Flanner Hall, Notre Dame, Indiana, USA e-mail: [email protected]
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these individuals are critical ingredients in ethical decision making about their use in research, though these are not currently central considerations in research review, just as thresholds of harm are not typical. We argue that the threshold of risk of harm to nonhuman primates ought to be comparable to the risk threshold set for humans who are particularly vulnerable to physical, psychological, and social harms. Specifically, we recommend that nonhuman primates should not be exposed to risks that exceed those posed in the normal daily lives of healthy primates living in species-appropriate, safe environments. This standard should generally protect nonhuman primates from conditions and interventions that pose more than a low probability of serious physical, psychological, or social harm. We conclude that available empirical evidence indicates that invasive biomedical and behavioral research conducted in nonhuman primates living in captivity generally exceeds an acceptable threshold level.
Inadequate attention to harm-causing activities and their limits in animal research The roots of the failures in current animal research can be teased out by analysis of current human research standards, where risks of harm to individual subjects are monitored so that risks are minimized and benefits maximized [1]. Within human research, the nature and scope of physical, psychological, social, and other harms and benefits are considered. Even when conflicts occur between commitments to the production of societal benefits and risks of harms to individuals, standards exist to protect human subjects from significant levels of harm [1]. Human research protections pay special attention to individuals who cannot protect their own interests from being exposed to the types and degrees of physical, psychological, and social harms that individuals who can protect their own interests would characteristically refuse. Vulnerable human populations should not, with rare exceptions, be exposed to more than minimal risk—that is, to risks that exceed those encountered during daily life by normal, average, healthy individuals living in safe environments or during the performance of routine physical or psychological examinations or tests [1, 2]. United States regulations allow institutional review boards to approve human pediatric research that does not offer subjects a prospect of direct benefit only when the risks are minimal or a minor increase over minimal and several additional protections are satisfied. In some situations, individuals are excluded from research situations that may harm them, as a result of their particular vulnerabilities [1, 2]. These standards prevent populations such as children and prisoners from being coerced or subtly manipulated into harmful research [2]. These standards prevent the most severe harms from being unjustly inflicted on the most vulnerable subjects and reflect a common morality to avoid harm, particularly in populations at risk for coercion [1, 2]. By contrast, animal research guidelines typically do not reflect the attention to harm avoidance so fundamental to human research. It is basically assumed that nonhuman animals can be exposed to levels of harm without compensating benefits
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as long as there is a degree of anticipated benefit for humans [3]. No clear moral justification is offered for this situation within any laws, policies, and guidelines that present themselves as comprehensive ethical approaches to animal research. For example, the majority of international guidelines reflect a position expressed in the preamble of the International Guiding Principles for Biomedical Research Involving Animals, first published in 1985 and revised in 2012 by the Council for International Organizations of Medical Sciences (CIOMS): The use of animals in research, education, and testing is an essential component of the advancement of our understanding about human and animal function. This knowledge is important for advancing human and animal health and welfare through disease prevention and cures, new treatments, and drug and device development. The scientific community, understanding that using animals is a privilege entrusted by society, remains committed to ensuring the health and welfare of animals as an integral consideration when animals are used for these purposes. [4] The premise that nonhuman animals can be used and harmed for human benefit sidesteps questions of both the moral status of nonhuman animals and the justification of particular research protocols. The importance of nonhuman animals’ interests and choices, the moral relevance of harms, and whether there should be a harm or risk threshold that cannot be exceeded do not receive attention in the process. Many have justified the use of nonhuman animals in research by citing their similarities to humans, rather than considering how the common potential for vulnerability and mental and physical suffering influences moral considerations regarding nonhuman animals. However, humans and other animals have common interests in self-preservation, living free of unnecessary constraints, and meeting their basic needs. If human and nonhuman animals have similar (or shared)1 capacities for pain, distress, and suffering and similar interests in avoiding these harms, general moral duties to not harm should cover humans and nonhuman animals in relevant similar ways. It is morally suspect to have different sets of ethical norms in similar situations. In the case of invasive and potentially damaging research, it would be prejudicial and ethically problematic to discount serious harms to one species when the same or similar harms are considered to be of serious import in another species. Current laws, policies, and guidelines governing animal research demonstrate the deficiencies within animal research standards. These standards implicitly recognize the importance of animals’ welfare interests and harms associated with research 1
Increasingly, research suggests that highly social mammals, including primates, have psychological and behavioral systems that detect and respond to inequity and even perceived social injustice [5, 6]. This suggests more substantive overlap than is generally assumed between human and nonhuman primate perceptions of ethical landscapes, and thus, calls for more homology in the impositions of ethical standards and moral justifications for their use. If some core perceptions of fairness and inequity overlap between human and other primates (even to a general extent), then those other primates should be granted minimally an awareness of social justice and recognition of their endangerment and potential harm by being the focus of human experimentation and manipulation.
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protocols and conditions by regulating breeding, transportation, housing, husbandry, and the technical aspects of research, including the use of tranquilizers, analgesics, anesthetics, paralytics, and euthanasia; peri-operative care; the composition and operation of animal care committees; and accreditation of laboratory facilities [7– 10]. Researchers and reviewers are also asked to follow the ‘‘Three Rs’’ principles, by reducing the number of animals used, refining or limiting the pain and distress to which animals will be exposed, and replacing the use of animals with nonanimal alternatives when possible or using a species believed to be less sentient [11]. In effect, these standards acknowledge and sanction a range of types and degrees of harm. Attention is given to risk mitigation and management but less, if any, attention is given to harm avoidance. The acceptable levels of harm and risks of harm are inadequately addressed in these highly general standards, though some animal care committees may independently accept a responsibility for more specific and higher levels of protections. ‘‘Harms’’ involve a setback to welfare interests, of which pain, fear, distress, psychological suffering, and death are all examples [12–14]. Other setbacks to wellbeing, a concept that extends beyond an absence of fear, pain, distress, and disease, broaden the scope of harms. Primate well-being depends on whether physiological needs, such as water, nutrition, sex, sleep, and homeostasis are met, as well as whether psychological needs such as safety, security, sociality, self-determination, freedom to express a wide-range of natural behaviors, and cognitive stimulation are realized [15, 16]. Sources of cognitive stimulation range from simple task completion to problem solving, complex decision making, and dynamic social exchanges. Basic primate sociality includes creating and maintaining bonds among friends, families, and sexual partners. Primates require a broad and rich scope of social attachments, and the patterns for these social attachments are often specific to the evolution of the species and individual experiences [17]. As with humans, the social needs of nonhuman primates are determined by complicated interactions between genetic, developmental, and environmental factors. Primate well-being is also determined by opportunities to attain levels of esteem and respect of others. These constituent features of primate well-being are common in native habitats but less common or absent in artificial captive environments such as research laboratories. During the course of research, blocking or seriously obstructing interests such as those in developing social attachments and in maintaining mental and physical health and self-determined choice and movement are all harmful. Although harms intrinsic to research protocols and the research enterprise are sometimes reduced in accordance with existing laws, policies, and guidelines, the likelihood of serious harm to these social dimensions remains high. Newer animal research guidelines promote the inclusion of a risk-benefit analysis for nonhuman animal use, suggesting that the benefits derived from the research activity should be balanced with the potential for pain or distress experienced by the nonhuman animal [4, 10]. However, the assumption remains that presumed benefits to humans justify risks of serious harms to nonhuman animals. Further, there is little guidance offered for how to assess benefits and risks. Risk has two dimensions: the probability or possibility of harm and the magnitude of harm that is expected. In
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many instances, the probability of harm in animal research is purposely high; experimental protocols are specifically designed to test harmful substances or understand disease in ways that set back welfare interests. ‘‘Magnitude’’ refers to scope or intensity (i.e., severity) of harm. Standards to evaluate the severity of laboratory procedures are commonly used and, in some instances, legally required [18]. Although the most severe experiments require specific justification, they are not uncommon and there is no established severity threshold. Existing guidelines for review also make it difficult for reviewers to consider the cumulative scope of harms experienced by individual subjects. Authorized protocol reviewers are asked to focus primarily on the treatment of harms generated during the exercise of an experiment (e.g., exposure to electric shock or pain produced by an implanted tumor) rather than the harms created during animal acquisition, transportation, and housing or the harms animals endure after completion of an experiment [11, 19]. This situation contrasts with human research, wherein risks of harm are minimized. With nonhuman animals used in research, harmful conditions and interventions are intentionally inflicted, resulting in repeated, high, certain, or severe risks for harm. Regardless of their positive intent, current animal research standards do not establish a harm or risk threshold or offer meaningful guidance for how to balance the risks and benefits of research. The assumption appears to be that if a good faith attempt at satisfying current standards has been made, residual pain and distress are justified. This perspective is morally unacceptable, whatever its legal standing. Researchers should provide ethical justification for causing harm, particularly harms that seriously compromise well-being.
Setting a risk threshold for research involving nonhuman primates Nonhuman primates are vulnerable to many of the same harms as humans, and nonhuman primates’ abilities to protect their own interests in research are hampered by intrinsic and extrinsic factors beyond their control. It would therefore be prudent to establish a standard risk threshold for nonhuman primates comparable to standards that protect vulnerable human subjects from more than minimal risk of serious harm. Nonhuman primates have all of the requisites for experiencing pain, including suitable receptors and nervous systems, physiological changes due to noxious stimuli, protective motor reactions, intrinsic analgesic responses, stimulus avoidance, and avoidance learning. Additionally, nonhuman primates experience pain and discomfort associated with disease, which can result in lethargy, anorexia, sleep disturbances, and enhanced sensitivity to pain [20]. Fear, distress, and induced psychopathology are sometimes as harmful as physical pain for primates [21, 22]. In this regard nonhuman primates are vulnerable to many of the same physical and psychological harms to which humans are vulnerable. Like children and other vulnerable human populations, nonhuman primates cannot always protect their own interests in achieving well-being or avoiding fear, pain, and distress while confined as research subjects. Nonhuman primates are unable to provide informed consent or otherwise to protect themselves from harms
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that informed, competent human adults typically avoid or refuse. Owing to their lack of linguistic capabilities and the absence of advocates within their own species in roles of power, nonhuman primates are often more vulnerable than human children in research, thus calling for a conservative standard for their use. Whereas a parent or guardian who represents a child’s best interests can provide permission on his/her behalf (sometimes with a child’s assent), it is virtually impossible for a human to represent the interests of a nonhuman primate as well as a human could represent the interests of another human, because we cannot understand the minds of other animals as well as we can understand human minds [23]. Nonhuman primates are also vulnerable to being selected as subjects for harmful research, similar to the ways in which some humans are vulnerable to harms as a result of personal, political, social, economic, and environmental constructs [24].2 Since there is a lack of convincing arguments for why nonbeneficial research is acceptable in those who cannot provide consent, current practice relies on a standard in which humans who are unable to provide consent cannot be exposed to risks that exceed those encountered during normal daily life in safe environments.3 An analogous standard for nonhuman primates would be that nonhuman primates should not be exposed to risks that exceed those posed in the normal daily lives of healthy primates living in species-appropriate, safe environments. ‘‘Speciesappropriate environments’’ would include settings like those in the wild, which have not been significantly distorted by humans, or environments such as sanctuaries that promote the well-being of nonhuman primates who cannot live in the wild. A criterion of ‘‘species-appropriate environments’’ accounts for the needs of diverse species of primates and upholds an analogy to human children, who are allowed to live their lives outside of their involvement in research protocols in their normal, free-living environments. A risk threshold standard that includes criteria for ‘‘species-appropriate environments’’ and ‘‘normal’’ lives would likely exclude typical laboratory and zoo settings.4 The specification for ‘‘healthy’’ primates living in ‘‘safe’’ environments would exclude researchers inflicting diseases or other disabilities on individuals, even if similar harms occur in the wild. Permitted research would include (1) observational behavioral research in an individual’s natural (i.e., wild) environment, which has no significant physical, social, psychological, or epidemiological impact on the individual, conspecifics, or co-inhabitants, and (2) the collection of biological specimens, such as urine, feces, skin, and hair samples, for research purposes by noninvasive means in wild or sanctuary environments. Use of 2
For example, nonhuman primates have no political power; they cannot advocate for themselves. Legally, they are property; they can be bought and sold. Nonhuman primates are easily trapped, restrained, and transported by physical force. In captive and some field settings, nonhuman primates are in totally dependent relationships with humans. For more on this topic, see [24, 25].
3
For more on this subject, see [26]. Also see [1, 27].
4
Although primate well-being might be a concern for some zoo caretakers and officials, the primary purpose of zoological parks is exhibition rather than promotion of animal well-being. Nonhuman animals used in zoo displays are often captured from the wild, confined, and exposed to harms associated with captivity and transport. Although there have been claims that zoos are agents of public education and species preservation, these claims have been challenged by Marino and colleagues; see [28].
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tissue that has been stored in a tissue bank and poses no new risks to individuals or groups of animals would also be permitted. Obviously permissible research would include noninvasive procedures that do not involve general anesthesia, sedation,5 aversive reinforcement contingencies, or physical or chemical restraint, because these interventions involve setbacks to primates’ basic interests. In wild or captive environments, such as sanctuaries, research involving materials collected for nonresearch purposes (e.g., medical diagnosis or treatment) would be permitted, because these interventions would serve the interests of the individual. According to the standard we propose, clinical monitoring of medications already approved for veterinary use, and in which a medication or device is being used in accordance with its approved labeling (clinical use) or professionally established off-label clinical uses, would also be permitted if the research itself would not introduce additional harm to the individual. The level of risk we suggest provides some estimate of the levels of risk nonhuman primates would otherwise face in wild or similar environments, either in the course of daily life or during the course of medical treatment conducted for the benefit of the animal. If nonhuman primates were not exposed to risks that exceed those posed in the daily lives of healthy primates living in species-appropriate, safe environments, the research would not generally increase the risks to which primates are already exposed. Our proposal would, with rare exception, restrict research involving nonhuman primates to observational field research and medical research in which nonhuman primates receive direct benefits of the research. We have not addressed here the question of whether humans have a right to use nonhuman primates at all, even if the harms are minimal to nonexistent. This question deserves further consideration but falls outside the scope of this paper. We have merely argued that nonhuman primates should not be exposed to more than minimal risk. Questions will undoubtedly be raised about whether more than minimal risk should be incorporated into decisions about nonhuman primate research. Although human children can be exposed to a minor increase over minimal risk [2], such interventions or procedures must, by law, hold out the prospect of direct benefit for the individual subject or meet all of the following requirements: (a) The intervention or procedure presents experiences to subjects that are reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social, or educational situations; (b) The intervention or procedure is likely to yield generalizable knowledge about the subjects’ disorder or condition that is of vital importance for the understanding or amelioration of the subjects’ disorder or condition; and (c) Adequate provisions are made for soliciting assent of the children and permission of their parents or guardians [2]. These provisions are specifically constructed to protect the interests of children enrolled in research and balance a minor increase over minimal risk with benefit to the individual or his/her class of subjects. Because nonhuman primates generally do not directly or indirectly benefit 5
There may be some instances in which interventions such as general anesthesia and sedation are beneficial to nonhuman primates. In these cases, benefits could exceed risks and provide justification for these types of interventions.
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from biomedical and behavioral research conducted on them, and there is no way of obtaining permission from nonhuman primates or appointed guardians, they cannot be compared to human children in these ways. Opposition to the threshold analysis we propose will likely stem from two main areas: concerns about limiting access to nonhuman primates in research to the potential detriment of human health; and perceived differences in the moral relevance of harms to vulnerable human and nonhuman primate populations. On the first point, we concede that, based on this threshold analysis, most research involving nonhuman primates that is practiced today would not continue. It is unclear how restricting nonhuman primate research would affect human health outcomes, and it is an area that could be explored further in another paper. On the second point, we have treated the moral relevance of harms equivalently across humans and other primate species.
Permissibility of certain types of harm in nonhuman primate research The standard we recommend is in stark contrast with the risks incurred by nonhuman primates currently used in invasive biomedical and behavioral research. As we discuss below, the most common uses of nonhuman primates in invasive biomedical and behavioral research involving nonhuman primates living in captivity exceed our proposed threshold for physical, psychological, and social harm. The probability, scope, and magnitude of physical harms experienced by nonhuman primates used in laboratory research today are high, yet fully compatible with existing laws and guidelines. Nonhuman primates are most commonly used in microbiology (including HIV/AIDS), neuroscience, biochemistry, and pharmacology experiments, primarily in North America, Europe, and Japan [29]. During these experiments they are deliberately exposed to diseases, invasive procedures, and harmful substances not normally encountered in their free-living environments. In addition, nonhuman primates have long lives in research, and have typically been re-used throughout much of their life span [30, 31]. These interventions exceed the risks posed in the daily lives of healthy primates living in species-appropriate, safe environments. The introduction of toxic chemicals, diseases, unnecessary drug exposure, device implantation, and other surgical interventions are all clear setbacks to the interests of nonhuman primates to avoid pain and discomfort and remain healthy. The likelihood of physical harm to individual subjects is high because infection, illness, and injury are commonly the intended consequences of experiments. Nonhuman primates used in invasive laboratory research also experience the chronic effects of experimental exposure or manipulation, including the intended and unintended physical consequences of harmful substances and diseases, such as organ damage and physiological derangements. Additionally, access to basic needs such as adequate water, food, sunlight, and sleep are often influenced by experimental participation and remain outside of their control. Living in laboratories deprives nonhuman primates of their natural habitats and normal amounts of physical activity. Subsequent to their use in research, nonhuman
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primates are frequently killed.6 These research interventions are all significant setbacks to the physical welfare of nonhuman primates and exceed the standard risk threshold we recommend. Conditions in which nonhuman primates are kept for laboratory research also exact acute, recurrent, or chronic social and psychological harms on nonhuman primates. Social and psychological harms frequently experienced by nonhuman primates living in laboratories include social deprivation and undue social pressures from conspecifics or laboratory personnel; social and physical isolation or the inability to seek solitude or socially secure contexts; sensory deprivation or overstimulation; deprivation of the ability to participate in normal activities of daily living and to exhibit naturalistic behaviors; threats to physical and psychological integrity from laboratory staff and other animals; and the witnessing of painful or distressful interventions conducted on others [19]. In preparation for research, nonhuman primates are commercially bred or removed from their wild environments and traded internationally, disrupting normal maternal-infant and other conspecific relationships. International trade of primates from source countries in Asia, Africa, and South America to North America and Europe involve long-distance transportation, resulting in considerable stress on the animals [29]. Nonhuman primates are often confined and housed in socially deprived laboratory environments [33]. Multiple studies show that adverse rearing conditions such as premature maternal separation, social isolation, prolonged confinement, and sensory deprivation lead to developmental and behavioral pathology in nonhuman primates [34–40], which impair psychological well-being. One of the most harmful conditions of research is the lack of socialization experienced by nonhuman primates. More than half of macaques being used in research in the United States are singly caged, and, on average, macaques and baboons spend more than half their lives living alone in cages.7 Normally, social bonding and the development and negotiation of social bonds are characteristic of all gregarious primate societies, and complex sociality is arguably the core primate adaptation and directly related to mental and physical well-being [6, 45–47]. A recent review [48] also suggests that nonhuman primate species’ preferences for fairness and the development of social cooperation, and even altruistic behavior, are related to the social and environmental contexts experienced by primates. Most captive contexts harm or severely restrict the development of central aspects of core social tools, such as inequity aversion, cooperation, and even types of ‘‘fairness’’ assessments. Substantial inter-population and intra-specific analyses of social behavior in primates show that complex and variable patterns of networks and the ability to 6
In the United States, euthanasia of chimpanzees is allowed only to alleviate suffering [32].
7
A 2003 survey encompassing almost 36,000 macaques in 22 U.S. primate laboratories found that 54% of animals used in research were singly caged [41]. A nonexhaustive survey by USDA Animal Care field inspectors between October 2000 and August 2001 determined that 35% of surveyed animals kept in research facilities were single-housed [42]. Between 2004 and 2006, at the National Primate Research Center in Seattle, Washington, 63% of monkeys were singly caged [43]. Individual monkeys spend an average of more than 3 years alone [33]. Other surveys indicate that macaques and baboons spend more than half of their lives caged alone [44].
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construct and manipulate social niches are the center of primate social organization [49]. For example, Jessica Flack and colleagues [50] argue for social niche construction in monkeys where social networks constitute the essential social resources in gregarious primate societies. They suggest that the structure of social networks can play a critical role in infant survivorship, cooperative behavior, social learning, and cultural traditions [15]. This socially constructed niche is intertwined with behavioral components of relationships (e.g., affiliative, agonistic, and sexual), and it is the dynamics of these patterns and processes that affect the overall psychological and physiological health of primates [51]. Conditions of captivity, especially changes to social contexts and networks, can therefore adversely influence the basal psychological and behavioral profiles and experiences of primates. Removing animals from stable social groups can have profound impacts on the lives and health of the remaining group members, which can have dramatic effects on the well-being of primates, as indicated by behavioral and physiological changes. Despite the harmfulness of creating socially impoverished conditions, it is a common practice within laboratory research and compliant with existing laws and regulations [7, 10]. Current research standards do not prevent some of the most severe harms to nonhuman primates. This is surprising since the association of pathological behaviors with adverse physical, psychological, and social conditions in nonhuman primates has been investigated for decades [52–60]. Research protocols designed to understand psychopathology in nonhuman primates have deliberately inflicted severe, acute, recurrent, or chronic harm on research subjects. Research subjects rarely, if ever, benefit from these types of research. Even if the subjects had benefited from the research, it would be difficult to justify the level of maleficence fundamental to these protocols because of the severity and chronicity of harms the subjects incur. The unintended psychological harms, via disruption and inhibition of social processes, associated with living in a laboratory and a variety of other captive contexts need to be included in ethical assessments of primate research. These are sometimes differentiated as incidental harms, though the origin of the harm is irrelevant to the experience of the individual and when considering harms from a moral perspective. Although the potential for psychological harm is addressed in the Animal Welfare Act and the Guide for the Care and Use of Laboratory Animals [7, 10], efforts to reduce psychological harm are focused on structural aspects, including toy and tool procurement, cage size, temperature control, and noise levels. Such measures may not take into account the centrality, or functional significance, of social context and processes in primates. Post-traumatic stress disorder, depression, generalized anxiety, and compulsive disorders have been described in nonhuman primates used in research [61–64]. Even in captive settings that are not research oriented, nonhuman primates display significantly more abnormal behaviors detrimental to individual welfare than their counterparts in the wild [65]. Collectively, these findings show that conditions of captivity alone can be harmful to well-being. The harms are likely a result of the loss of autonomy, sociality, and cognitive stimulation, which are critical to primate well-being. Processes and events that disrupt, destroy, or limit the range of social relationships core to well-being are
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ubiquitous aspects of captivity and contribute to the scope and magnitude of harms experienced by nonhuman primates used in laboratory research.
Conclusion Currently, laboratory research involving nonhuman primates pervasively involves elevated risks of severe harm, including but not limited to mental and physical suffering, with minimal to no benefit for research subjects. Similar or shared perceptions and sensations of harm suggest that the threshold for risk of harm to nonhuman primates should be comparable to that of humans who are at increased risk for physical, psychological, and social harms. Nonhuman primates should not be exposed to more than a low risk of serious physical, psychological, and social harm. Under our proposal, much of the invasive biomedical and behavioral research involving nonhuman primates conducted today should be discontinued. Acknowledgments This material is based upon work supported by the National Science Foundation under Grant No. 1058186. Any opinion, findings, and conclusions or recommendations expressed in this article are those of the authors and do not necessarily reflect the views of the National Science Foundation. The authors thank Tom Beauchamp, John Gluck, and David Wendler for helpful comments on previous versions of this article.
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