Online Issues

ILAR Journal Vol 46(2)

Enrichment and Nonhuman Primates: "First, Do No Harm"

Randall J. Nelson and Timothy D. Mandrell

Randall J. Nelson, Ph.D., is a Professor in the Department of Anatomy and Neurobiology, College of Medicine, and Executive Director of Animal Welfare and Compliance, University of Tennessee Health Science Center (UTHSC). Timothy D. Mandrell, D.V.M., is an Associate Professor and the Chair of the Department of Comparative Medicine, College of Medicine, UTHSC.

Abstract

Since the 1998 publication of The Psychological Well-Being of Nonhuman Primates by the National Research Council, and the 1991 implementation of the 1985 Animal Welfare Act Amendment, many formal and informal nonhuman primate enrichment programs have been put into practice. Reports of their successes and failures, however, are few. All programs have at least two things in common: (1) They are best when designed and maintained by teams of individuals with species-specific expertise; (2) the members of those teams, the stakeholders, usually include principal investigators, animal care and use committee members, veterinarians, and animal care staff. Discussions in this article address general principles about enrichment, goals of such programs from the perspective of each of the major stakeholders, and recently published sources of related information. These discussions follow the central premise that enrichment should benefit all involved and "First, do no harm."

Key Words: animal care staff; attending veterinarian; enrichment programs; IACUC; nonhuman primates; principal investigators

Introduction

The phrase "Primun non nocere" or "First, do no harm" is commonly thought to be part of the Hippocratic oath and thus attributable to Hippocrates. Recently, however, it has been noted that the phrase was anglicized from the Latin, making it somewhat unlikely that it derives from Hippocrates. It is more likely that the physician Galen originated these words (e.g., http://www.geocities.com/everwild7/noharm.html). Nevertheless, despite its origin, the phrase is important not only for its value to clinical medicine but also for its application to scientific experimentation. It is incumbent upon scientists who are considering potential forms of enrichment for laboratory animals to be mindful of this phrase.

The development and implementation of enrichment programs for nonhuman primates surprisingly have a few things in common with the controversies surrounding "First, do no harm." All agree that the goal is laudable; programs should be beneficial regardless of which form they take. Second, it is often difficult to determine what aspects of the programs should receive credit for prospective progress. Finally, it is not always clear what constitutes benefit or progress because the process of measuring well-being may introduce stress that obliterates the positive qualities of any action.

Regulations Related to Enrichment

In 1985, Congress revised the Animal Welfare Act significantly, to include provisions for an environment adequate to promote the psychological well-being of nonhuman primates (PL 99-158 1985). The regulations that promulgated those changes were implemented in 1991 (APHIS 1991). In subsequent years, many publications have addressed psychological well-being, enrichment, and the normal behavior of nonhuman primates (e.g., Fortman et al. 2002; NRC 1998; Reinhardt and Reinhardt 2004).

During the approximately 6 yr since publication of The Psychological Well-Being of Nonhuman Primates (NRC 1998), institutions have begun to develop, or have further developed, many formal and informal enrichment programs. Indeed, " . . . about as many different strategies [have] emerged as there are situations that have nonhuman primates" (NRC 1998, p. viii). Undoubtedly, some of these strategies have been more successful than others. Young (2003) suggests that objective reporting of the benefits and detriments of such programs has lagged far behind these fits and starts.

Although it is beyond the scope of this article to explore the primary enrichment literature in detail, the publication of numerous historical, philosophical, psychological, and regulatory perspectives pertaining to enrichment and nonhuman primates is fortunate for those who seek guidance in these areas. Several volumes and websites are now available that are devoted specifically to nonhuman primates. We refer herein to some of the more recent additions to the literature and the Internet because they have extensive bibliographies from which readers can explore the primary literature. We also refer readers to the brief list of recommended reading that appears in Table 1.

Table 1

Common Goals of Enrichment

The major goals of enrichment programs should benefit the animals and the science alike. Each of the references listed in Table 1 stresses that all major stakeholders should take into consideration the ethical as well as the scientific ramifications of providing an appropriate environment for nonhuman primates. Young (2003) suggests that the goals of any enrichment programs "should be to: 1) increase behavioral diversity; 2) reduce the frequencies of abnormal behavior; 3) increase the range or number of normal (i.e., wild type) behavior patterns; 4) increase the positive utilization of the environment; and 5) increase the ability to cope with challenges in a more normal way" (p. 2). By improving nonhuman primate well-being, it may be possible to increase the amount of experimental data that can be collected and increase the validity of experimental results. Although these goals may be scientifically desirable, they should be balanced with the enrichment needs and preferences of the animals as well as their husbandry and nutritional requirements.

Nonhuman primate enrichment programs are of unique concern to four groups of stakeholders: principal investigators (PIs¹), institutional animal care and use committee(IACUC¹) members, laboratory animal veterinarians, and animal care staff members. In addition to these major stakeholders, the institutional official (IO¹) may become involved in the context of facility requirements. Based on the available literature, we define herein a set of six general premises that we believe are commonly accepted by these stakeholders.

Premise 1: Enrichment Should Do No Harm

It is paramount for any enrichment program to include constant evaluation of whatever strategies are used to provide enrichment because even seemingly innocuous enrichment practices, methods, and/or devices may have unexpected health consequences. Several authors note that many anecdotal reports of adverse outcomes from enrichment devices exist, and that only a few published reports are available (e.g., Baer 1998; Etheridge and O'Malley 1996; Hahn et al. 2000; Murchison 1993). Similarly, some enrichment strategies that utilize group housing have resulted in serious injury due to altercations between animals. Even food-based enrichment strategies can have negative health implications if the strategies are not carefully chosen and implemented. For example, some approaches that have appeared reasonable initially have been detrimental to research goals and objectives in practice. In other words, engineering standards sometimes fail to translate into acceptable performance standards.

Observation is perhaps the single most important tool for assessing the efficacy of nonhuman primate enrichment programs. Bloomsmith and colleagues (1991) categorize five major types of enrichment: social, occupational, physical, sensory, and nutritional. Although each type involves different implementation strategies, the outcomes are assessed by shared behavioral observations and comparisons with expected norms. Novak and coworkers (1998) suggest that close monitoring of animals that have experienced recent separation facilitates assessment of their well-being so that intervention can occur if necessary. Frequent monitoring allows for the re-evaluation of goals and objectives to promote the best interests of the animals involved. Thus, Novak and colleagues emphasize observation of animals' responses to changes in social environment; and similarly, observation is necessary for Bloomsmith and coauthors' five categories of enrichments.

Premise 2: Enrichment Should Reduce Distress in a Measurable Way as It Improves Nonhuman Primate Well-being

One method for assessing the efficacy of enrichment strategies is to document short-term reductions in abnormal behaviors. This documentation requires two equally important components. First, staff who are responsible for taking the measurements must have a certain degree of familiarity with the species and the individual animals being evaluated. An accurate and honest assessment of their expertise with nonhuman primates is critical for each stakeholder. This process will essentially eliminate some inaccuracies in approaches that arise from inappropriate assumptions and insufficient knowledge about the species for which the enrichment programs are designed. Second, careful thought should be given to what can and will be measured to determine beneficial outcomes. Despite careful planning, enrichment strategies are, at times, evaluated under conditions in which the number of animals from which measurements are being taken is limited. When numbers are small, the benefit of enrichment generally is difficult to document, and the validity of that benefit may be questionable statistically.

The report of Vick and coworkers (2000) is one exception to the general rule regarding the number of animals involved in experimental observations. These investigators provide statistically analyzed evaluations of response to enrichment in a zoo setting in which they consider only 15 animals. This study indicates that even in a limited setting, environmental enrichment may have significant benefit. In addition, methods of assessing the characteristics of nonhuman primate interactions with the environment and how to measure those interactions can be gleaned from behavioral observations of conducted in the wild (see, e.g., Menard and Vallet, 1997). The results of carefully conducted field studies may themselves be extrapolated in an attempt to understand behaviors of animals in more controlled environments, such as laboratories and zoos.

Premise 3: Strategies Should Enrich Both the Experimental Subject and the Experiment--The PI's Role and Concerns

In research laboratory settings, PIs should design programs with the same enthusiasm and care with which they convey their experimental results. Conclusions are only as cogent as the validity of the supporting data, and validity is directly related to both experimental and environmental stability. Proper experimental design usually necessitates rigid control over many independent variables so that the range of variance in the dependent variables can be assessed repeatedly and accurately. All too often, the emotional and psychological state of nonhuman primates is not controlled, either during experiments or during periods of extended housing. PIs may anthropomorphize in assessing the well-being of nonhuman primates because of the similarities in behavior among primates of all types. It has also been suggested that assessments of pain and distress are often subject to the biases of observers (NRC 2003, pp. 18-22). PIs should exercise caution when assessing nonhuman primate well-being because well-established experimental goals could obscure the assessment of nonhuman primate well-being. It is incumbent upon PIs to avoid bias toward completion of experiments, thus jeopardizing the maintenance of enrichment programs.

Some aspects of experiments involving nonhuman primates are, in themselves, enriching for the animals. Monkeys trained to retrieve food pellets from shallow wells refine and elaborate the neocortical representations of the digits they use to perform those behaviors (Xerri et al. 1996). The initial clumsiness that animals exhibit as they learn behavioral tasks eventually progresses to skillful and accurate manipulations that are performed stereotypically. Young (2003) suggests that unpredictable environments enhance psychological well-being because they provide novel behavioral opportunities, and that highly predictable environments may promote stereotypies, often considered to be abnormal behaviors. The author argues that trained behaviors that result in rewards may constitute enrichment in two ways: (1) They allow animals to obtain goals; and (2) goal attainment reduces unpredictability, thus giving animals control over their environments. Thus, although these suggestions initially appear to be contradictory, they are not. On one hand, the environment interacts with the animal, stimulating the animal to produce unique responses. On the other hand, the animal interacts with the environment and the control the animal exerts on it determines the behavioral outcome. Both situations engage the animal and are thus enriching.

There is a fine balance between reward predictability and behavior in nonhuman primates (Schultz 2004). Novelty of action and variable reward schedules may be enriching; however, alterations in reward predictability result in activity changes in the brains of rhesus monkeys that are similar in location and have some of the same temporal characteristics as those observed in human patients with disturbances in motivation and expectation, as in obsessive-compulsive disorder and drug abuse (Shidara and Richmond 2002). Rewards maintain a positive relationship with behavior when activity related to the reward and the action necessary to gain that reward are present in the brain at the same time (Schultz 2004). Perhaps it is the disruption of the association between normal actions and rewards that leads to abnormal behaviors.

It is important to approach all aspects of enrichment design with caution because although these aspects may be necessary to achieve scientific goals, they also can have psychological and physiological effects on experimental subjects. Examples include the transportation of animals from housing areas to the site of experiments and the chairing of animals during experiments involving sampling or a behavioral component. Monkeys can be acclimated to pole and collar systems for transport and chairs for experiments (Anderson and Houghton 1983). However, even monkeys that have been acclimated to restraint may show stress-like effects in several biological systems for some time after successful acclimation (e.g., Morrow-Tesch et al. 1993).

The PI's role on the enrichment team is to weigh carefully the benefits and possible detriments to the research when implementing any enrichment strategies. Enrichment devices and programs should be chosen to augment, rather than hinder, the scientific progress for which the animals are being kept. Despite this obvious statement, PIs often cite numerous reasons for not implementing enrichment programs. Young (2003) summarizes these reasons as increased cost, increased work, increased risk, increased variability, and lack of proven benefit. It is incumbent upon all involved in establishing and carrying out enrichment programs to be mindful of these factors and to minimize them while providing proof of effectiveness. Often, simple and innocuous solutions have demonstrable positive effects (Bayne 2000; Vick et al. 2000). It is also important to communicate enrichment strategies clearly to those charged with determining whether current welfare guidelines are being met. This responsibility often is the purview of the IACUC.

Premise 4: Strategies Should Adhere to and Satisfy Current Guidelines--The IACUC's Role and Concerns

The responsibility of the IACUC for ensuring that environmental enhancement promotes psychological well-being of nonhuman primates derives from several sources. Animal Welfare Act Regulations (AWAR¹ §2.31, c, 1) and Public Health Service Policy (PHS 1996, IV, B, 1) mandate semiannual program reviews of humane care and use of animals; the IACUC is responsible for ensuring that programs adhere to the Guide for the Care and Use of Laboratory Animals (Guide¹) (NRC 1996) and meet the requirements of the animal welfare regulations (Bayne 2000). The current edition of the Guide contains a section on Behavioral Management for all species, including nonhuman primates (NRC 1996, pp. 36-38). Along with Appendix A of the NRC document on nonhuman primate psychological well-being (NRC 1998), and section 3.81 of the AWAR (APHIS 1991), these guidelines form a basis for IACUC consideration of enrichment programs.

Bayne (2000) details a number of objects and strategies that can be used for nonhuman primate enrichment and evaluated by IACUCs as indicators of enrichment program status. Detailed discussions of some of these methods for assessing the efficacy of enrichment strategies are available (e.g., Crockett 1998; Morgan et al. 1998). The clearest indication of the role of the IACUC in assessing enrichment plans is reflected in the following statements in an opinion presented in Chapter 3 of the Animal Welfare Act Regulations: "To fully conform with AWAR and Guide recommendations, the IACUC should include an assessment of the enrichment plan and program in its semiannual review. The review should include an evaluation of the efficacy of the enrichment program and whether it is current with the literature" (Bayne 2000, p. 479).

In practice, the IACUC, the attending veterinarian (AV¹), or a designated individual or committee may assume the responsibility for overseeing enrichment programs. Both the IACUC and the AV are charged with ensuring the existence and efficacy of enrichment programs (AWAR §3.81). Exemptions from enrichment programs for particular animals may be granted by the AV as specified by the AWAR (§3.81, e). An individual nonhuman primate may be exempted "because of its health or condition, or in consideration of its well-being." The AV must document and review such exemptions every 30 days.

Because there are numerous ways to implement enrichment programs for nonhuman primates and because assessment depends on how they are implemented, we and others (e.g., Carbone 2004) recommend that IACUCs promote a team approach that tailors enrichment to the species in question and, at times, to the needs of individual animals and the experiments for which they are housed. Whereas the principles of Russell and Burch (1959)--refinement, reduction, and replacement (the 3Rs¹)--often guide experimental design, Hendriksen (2000) has also suggested that incorporating the three tenets of common sense, commitment, and communication (the "3Cs") should form the basis for applying the 3Rs to experimental implementation. Perhaps these same principles should be used to develop, implement, and evaluate nonhuman primate enrichment programs.

Premise 5: Strategies Should Safeguard, Not Jeopardize, Animal Health and Welfare--The AV's Role and Concerns

The AV is charged with providing adequate veterinary care for the animals in an institution in compliance with provisions in the AWAR (§2.33). The AWAR (§3.81) require that enrichment plans "be in accordance with the currently accepted professional standards." This charge may in practice include the AV's development and implementation of enrichment plans, and the documentation of respective outcomes. Most often, it is the AV or another veterinarian who has the necessary and sufficient expertise to determine which practices are most appropriate and consistent with current standards. This expertise is used, for example, when determining whether animals may be socially housed or whether social housing may be detrimental to individual nonhuman primates because of age, behavioral traits, health status, or other aspects of compatibility. The AV may determine that special enrichment considerations are warranted based on IACUC-approved experimental protocol requirements, observance of behavior, or conditions that may preclude animals from the benefits of implemented programs. Examples of special considerations may include restriction of movement or contact with conspecifics or caretakers.

The AV may be in a unique position to coordinate the development and implementation of enrichment strategies. Often the AV is most likely to have knowledge of species-specific considerations and is in a position to include or exempt individual animals from enrichment programs based on scientific, health, or behavioral contingencies. In addition, the AV is probably the person who should notify PIs of the necessity to consider additional or alternate enrichment for their animal subjects and, with the IACUC, ensure that the enrichment plans are implemented. Although provisions for training are the responsibility of an institution, this responsibility often falls to the AV (with the help of the IACUC) to train both scientific and animal care staff to implement enrichment programs and identify which individual animals require special consideration.

According to the AWAR (§2.33), each facility shall maintain programs for adequate veterinary care, which should include the daily observation of the health and well-being of all animals and the guidance of PIs and others involved in animal care and use. Thus, although the AV may delegate the responsibility for daily observation to other veterinarians and/or animal caretakers, the AV is the communication nexus for information about the health, well-being (including psychological well-being), and characteristics of individual animals. Furthermore, the AV has the responsibility for prescribing appropriate treatment and overseeing behavioral management, as well as for intervening when the psychological well-being of an animal is at risk. Despite the AV's significant role, it is often the caretakers who are the most familiar with the animals involved in enrichment programs.

Premise 6: Strategies Should Not Burden the Implementers--The Animal Caretakers' Roles and Concerns

Animal care staff should actively participate in developing and implementing nonhuman primate enrichment programs and should receive specific training about the nature and scope of the programs as well as their direct implementation. Care staff often have the greatest amount of contact with nonhuman primates because they provide care on a daily basis. They not only see to the needs of individual animals but also come to know them as individuals. Caretakers often develop fondness for the animals. They are generally the first to observe and perhaps the ones most qualified to determine whether specific facets of enrichment programs are actually having beneficial effects on the general health and well-being of the animals under their care.

The nature of care giving to nonhuman primates generates two concerns. First, as mentioned above, care givers often become attached to animals in their charge. Therefore, some issues of objectivity and conflicts with PIs over environmental enrichment and research goals may arise. Second, frequent close contact with nonhuman primates generates health and safety concerns for the care givers themselves. That close proximity, however, places them in an advantageous position to assess the animals.

Four criteria for assessing animal well-being are suggested in The Psychological Well-Being of Nonhuman Primates (NRC 1998). The criteria include determining the following: whether the animals cope with environmental change; whether the general behavior of the animals is appropriate; whether maladaptive or pathological behaviors are being exhibited; and whether, as a whole, animals have balanced temperaments. In many instances, it is the caretakers who have the most extensive contact with animals on a daily basis and are thus able to make these determinations. When possible, determinations may also be made by expert observers who specialize in species-specific behaviors. It is incumbent upon the PIs, the AV (or veterinary staff), and the IACUC to ensure that animal care staff members receive appropriate and sufficient training to evaluate the behavioral characteristics of the nonhuman primates in their charge. They should be encouraged to become knowledgeable about the behavior of individual animals, to be active participants in the implementation of enrichment programs, and to be made aware of the special role they play in communicating the successes and failures of enrichment strategies. Furthermore, the director of the animal care program should ensure that sufficient time and resources are available for the care staff to carry out the program optimally.

Enrichment programs should be planned carefully by all stakeholders to avoid overburdening those who have the most extensive contact with the animals, and to ensure effectiveness and seamless blending into the overall animal care and use program. Although the enrichment resources listed in Table 1 share several common points, the following points stand out: (1) Interaction by nonhuman primates with their caretakers is, in itself, enriching for the animals (Fa 1989). This tenet applies especially to animals housed individually for particular reasons. It can be argued that the quality of animal-caretaker interaction may be diminished when the implementation of enrichment strategies overburdens animal caretakers. (2) Performance-based standards should be adopted to the extent possible, and strict prescriptive standards should be avoided Caretakers must be free to adjust enrichment devices and strategies dynamically to correspond to the needs of the nonhuman primates under their care, and caretakers should communicate these changes to the rest of the enrichment team. The appropriateness and effectiveness of changes to devices and in strategies is best done after consultation with key laboratory personnel so that alterations do not introduce unacceptable variability into the research conditions.

Conclusions

We urge all those involved in laboratory animal research to share enrichment strategies. Current sites and publications in which sharing may take place include but are not limited to the following: on the Internet (e.g., http://pin.primate.wisc.edu/infoserv/forums/pef/; http://www.enrichment.org/), and in journals (e.g., Applied Animal Behavior Science, Journal of Applied Animal Welfare Science, and Animal Welfare).

It is important to share and document strategies that work as well as strategies that do not work. Observations must be able to withstand the rigor necessary to establish statistical validity. Anecdotal information should be avoided unless it is supported by data. Controlled observations at multiple sites provide usable data. We believe that many institutions would benefit from such documentation, which would in turn facilitate the establishment of best practices.

Although we value the principle of "First, do no harm," we do not advise inaction, either from an ethical or a regulatory standpoint. In addition, any action that is contemplated should be beneficial to both animals and experiments alike. We recommend using expert opinion when sufficient scientific evidence is not available to substantiate strategies (Nelson 2004).

Finally, we endorse the team approach--the active cooperation of investigators, IACUC members, veterinarians, and animal caretakers in establishing and maintaining nonhuman primate enrichment programs. Utilization of this approach will ensure that enrichment does no harm, is beneficial, and is tailored to each animal for which it is intended.

¹Abbreviations used in this article: 3Rs, refinement, reduction, replacement; AV, attending veterinarian; AWAR, Animal Welfare Act regulations; Guide, Guide for the Care and Use of Laboratory Animals; IACUC, institutional animal care and use committee; IO, institutional official; PI, principal investigator.

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