Balancing Animal Research with Animal Well-being:
Establishment of Goals and Harmonization of Approaches
James L. Weed and James M. Raber
Abstract
A resource is provided for the creation of an institutional
program that balances the scientific mission of an institution
with the well-being of the animals used in support of the
research. The concept of harmonizing scientific goals with
animal well-being was first suggested in the early part of the
twentieth century and later revitalized in the literature of the
1950s. Harmonization can best be achieved through the promotion of a team initiative. The team should include, at a
minimum, the scientist, veterinarian, institutional animal care
and use committee, and animal care staff. It is the responsibility of this animal research team to promote and balance
the generation of scientifically valid data with animal wellbeing. The team must strive to minimize or eliminate nonprotocol variables that could adversely affect the validity
and repeatability of the experimental data. Good experimental design coupled with excellent communication between
team members can often minimize or eliminate many variables and result in both better science and animal wellbeing. To ensure the scientific validity of experimental data,
scientists must be aware of the complex nature of the environment in which their animals are maintained. To ensure
repeatability of an experiment, scientists must document
and publish both the inanimate and social environments in
which their animals are housed. Better documentation of
environmental variables and their correlation with experimental results will promote critical knowledge about the
relationships between an animal’s environment, its wellbeing, and science.
Key Words: animal research; environmental enrichment;
experimental design; harmonization; research methods;
well-being; welfare;
Efforts to Define Animal Well-being
W
“ell-being” is a term used to describe the biological, physical, and mental aspects of animals
maintained for laboratory, zoological, or agricultural purposes (Clark 1998; Clark et al. 1997a; Ewing
James L. Weed, Ph.D., is Senior Behaviorist in the Division of Veterinary
Resources, Office of Research Services, NIH, Department of Health and
Human Services (DHHS), Bethesda, Maryland. James M. Raber, D.V.M.,
Ph.D., is Animal Program Director at the National Eye Institute and the
National Institute of Mental Health, NIH, DHHS, in Bethesda.
118
et al. 1999). Ewing and colleagues (1999) addressed the
common usage of the terms “welfare” and “animal wellbeing” as follows:
“Terms such as animal well-being and animal welfare are often used interchangeably. The term animal welfare, for some, has a broader meaning than
well-being. Use of the terms is intended to describe
a state in which an animal is existing within a
range of acceptable environmental specifications.
Biological scientists dealing with the physiological,
biochemical, and physical effects of an animal’s
surroundings are more inclined to use the term
well-being. Social-behavioral scientists appear to
favor the term welfare” (p. 3).
Scientists and laypersons might disagree on the precise
definition of animal well-being or welfare. Broom and
Johnson (1993) note that the biological implications of welfare are not well understood. They recommend defining
these terms within a logical and scientific framework to
make them usable. Others have echoed similar concerns and
contributed their own definitions of well-being or welfare
(Clark et al. 1997a; Dawkins 1997; Hewson 2003). King
(2003) reviews the concepts relating to animal use, particularly for behavioral evaluations of agricultural research animals; and Hetts (1991) has provided a similar review for
dogs. Nevertheless, a lack of consensus regarding the definition of animal well-being and welfare and its measurement persists.
In the United States, two documents introduced the contemporary approach to animal welfare: the Humane Slaughter Act of 1958 (PL 85-765), and the Animal Welfare Act
(AWA1) of 1966 (PL 89-544) (Guither 1998). Subsequent
revisions to the AWA have asserted the need to address the
psychological well-being of nonhuman primates and provide exercise for dogs (AWR 2002). The AWA refers to
animal welfare and well-being but does not provide definitions. Instead, the AWA refers to “humane care and treatment of animals.” The term well-being first appears under
the section on Standards, § 2143, as follows:
1
Abbreviations used in this article: 3Rs, refinement, reduction, and replacement of animals used in research and testing; AWA, Animal Welfare Act;
Guide, Guide for the Care and Use of Laboratory Animals; IACUC, institutional animal care and use committee; IO, institutional official; NK,
natural killer.
ILAR Journal
§ 2143 Standards and certification process for humane handling, care, treatment, and transportation
of animals.
Subsection (2) “The standards . . . shall include minimum requirements - (B) for exercise of dogs . . .
and for a physical environment adequate to promote the psychological well-being of primates.”
The term “animal welfare” is first mentioned in the section describing proposed functions of the animal care and
use committee. Committees should have sufficient ability to
assess animal care and treatment and “shall represent society’s concerns regarding the welfare of animal subjects used
at such facility.”
Although the AWA attempted to codify the term “psychological well-being”, it did not define it. Interested readers who wish to review the difficulties in defining the term
are guided to The Housing, Care and Psychological Wellbeing of Captive and Laboratory Primates (Segal 1989) and
Through The Looking Glass (Novak and Petto 1991).
One of the major challenges for the animal research
community is to establish criteria for the assessment of psychological well-being. Over the last decade, the presence or
absence of specific behavior patterns has been utilized as a
tool in many species to assess an animal’s well-being and
welfare (Young 2003). For example, the reduction or absence of stereotypies and injurious and aggressive behavior
has been viewed as an improvement in an animal’s welfare
and well-being. Alternatively, an increase in use and control
of the environment by an animal is also viewed as a positive
sign of increased animal welfare and well-being.
Specific criteria have been proposed as useful starting
points for the assessment of well-being in primates (NRC
1998). Many of these indices might be adaptable or modifiable for other laboratory, zoo, or farm animals. The recommended criteria are as follows: (1) Animals should be
able to cope effectively with daily changes in their environment; (2) animals should be able to engage in speciestypical behavior patterns which are beneficial to the animal;
(3) the display of maladaptive or pathological behavior
should be at a minimum; and (4) animals should display a
balanced temperament (i.e., neither too aggressive nor too
passive).
The components of well-being for each animal depend
on the circumstances under which the animal is maintained.
As discussed in this article and throughout this issue of
ILAR Journal, a comprehensive definition of well-being is
problematic at best (Duncan and Fraser 1997). When we
assess well-being in our respective programs, we commonly
look for signs that animals are physiologically and behaviorally well adapted to their environment. Animals that are
physiologically well adapted to their environment thrive and
demonstrate a normal appetite, growth rate, and breeding
performance (Crockett et al. 1995, 2000; Novak and Suomi
1988; Wallace 1900; Yerkes 1916). Animals that are behaviorally well adapted to their environment do not demonstrate maladaptive behavior patterns (e.g., self-directed
injurious behavior or stereotypies) but instead, display speVolume 46, Number 2
2005
cies-specific behavior as permitted by their physical and
social environment (Novak and Suomi 1988).
All animals have a wide range of species-specific behavior that can be displayed if they are provided with an
enriched environment that can facilitate the behavior and
potentially improve the animal’s well-being or welfare. The
assessment of an animal’s well-being, in turn, can be facilitated by the provision of an environment that supports a
wide range of behavior. It is not necessary for the environment to support the full spectrum of an animal’s speciesspecific behavior to provide for the animal’s well-being or
welfare. Observation of species-specific behavior can provide a valuable indication of the animal’s well-being. It is
important to understand that the absence of a behavior is
problematic only if an animal is adapted to an environment
that supports the behavior and yet the animal fails to exhibit
the behavior. Using the criteria outlined above as a starting
point, each program should develop performance standards
that balance scientific goals with animal well-being.
Efforts to Define Enrichment
Enrichment is another challenging concept to define precisely. Newberry (1995) has argued that the term “environmental enrichment” is a vague concept and is used
inconsistently in the welfare literature. Furthermore, Newberry notes that there is no clear conceptual framework
regarding environmental enrichment. A similar perspective
on enrichment and well-being is reflected elsewhere (NRC
1998). Standardization of methods and criteria for assessing
enrichment are also lacking.
Some definitions of environmental enrichment include
the following:
“Environmental enrichment is an animal husbandry
principle that seeks to enhance the quality of captive animal care by identifying and providing the
environmental stimuli necessary for optimal psychological and physiological well-being” (Shepherdson 1998, p. 1).
“[E]nrichment is an attempt to ameliorate problems
caused by containment, . . . the goals of enrichment are to alter behaviour so that it is within the
range of the animals’ normal behaviour” (Chamove 1989, p. 155).
“[E]nvironmental enrichment is ⱊa process for improving or enhancing . . . environments and care
within the context of the inhabitants’ behavioral
biology and natural history. It is a dynamic process
in which changes to structures and husbandry
practices are made with the goal of increasing behavioral choices to animals and drawing out their
species appropriate behavior and abilities, thus enhancing animal welfare’ ” (BHAG 1999, as cited in
Young 2003, p. 2).
“[E]nvironmental enrichment–that is, additions to an
animal’s environment with which it can interact”
(Beaver 1989, p. 6).
119
Although these definitions vary, the common emphasis is
on the provision of a more stimulating environment. Historically, Alfred Russel Wallace may have been one of the
first individuals to provide enrichment to captive animals
(Wallace 1869). Upon receipt of an orphan orangutan in his
camp, he fashioned an artificial mother from a buffalo skin
that appeared to comfort the animal, served as a surrogate
mother, and thereby enriched the animal’s environment.
Shortly afterward, Wallace received another animal in
camp, a cynomolgus monkey, and the two animals were
successfully paired. Thus, Wallace’s earliest attempts at enriching the animal’s environment included the provision of
both inanimate and animate exemplars of enrichment.
The Animal Welfare Regulations (AWR 2002) delineate
certain types of enrichments for some animals. For example,
each primary enclosure for cats must have elevated resting
surfaces. Parturient rabbits must be provided with a suitable
nest box. Dogs must be offered exercise opportunities or
adequate floor space as defined in the document. In addition, the regulations require an established plan for the provision of environmental enhancement that promotes
psychological well-being for nonhuman primates. One of
the goals outlined in the Guide for Care and Use of Laboratory Animals (the Guide,1 NRC 1996) is to promote the
humane care of animals, which will ultimately provide information to enhance the well-being of animals. The Guide
expands on the AWA requirements for enrichment of captive environments and includes the statement that animals
should be able to demonstrate or engage in species-typical
behavior. Additionally, animals should be afforded opportunities for motor and cognitive activity or social interaction
(NRC 1996).
Enrichment can be defined as the provision of inanimate
items (e.g., chew toys, nesting material, puzzle feeders, activity rooms) or social environmental factors (e.g., group
housing, grooming contact panels) (Crockett 1998), which
can facilitate and promote the display of species-specific
behavior. The observation of species-specific behavior,
coupled with the physiological assessment of the animal, is
a helpful tool when evaluating an animal’s well-being.
Desired Outcome of Animal Research
Identifying the desired outcome of animal research is complex and often depends on the perspective of the individual
queried. Ultimately, the generation of scientifically valid
data is the desired outcome of every research paradigm.
However, few individuals would disagree that the methods
used to generate the data are as important as the data itself.
One of the most important concepts of modern experimental design is the controlled experiment (Beveridge
1957). In a controlled experiment, two experimental groups
are randomly formed, with one as the control group and the
other as the test group. Both groups are treated equally,
except for the variable under study. The protocol must include procedural details and any environmental factors that
120
could lead to unwanted differences between the two study
groups. Clear delineation and communication of the conditions under which an experiment is conducted are critical to
the validity and repeatability of experimental results.
In addition to the generation of scientifically valid data,
scientists have recognized that the humane treatment of experimental animals is a prerequisite for successful animal
experimentation. The principles of refinement, reduction,
and replacement (the 3Rs1) (Russell and Burch 1959) have
become the cornerstone for most major animal welfare initiatives as well as a desired outcome for all well-designed
experiments using animals. Of the three principles, refinement relates directly to the well-being of the animals under
investigation. In this article, we define refinement as the use
of methods that lessen or eliminate pain and/or distress and
therefore enhance an animal’s well-being (NRC 2003).
Thus, we identify the desired outcome of animal research as the generation of scientifically valid data while
ensuring the humane treatment and promoting well-being of
experimental animals. It is to this end that many institutions
have developed multifaceted enrichment programs to address the well-being of animals used in research.
Impact of Animal Well-being
on Research Objectives
It has long been recognized that animals that are acclimated
and adapted to their physical environment make better test
subjects than animals under stress or animals that are maladapted to their environment (NRC 1996). As stated in the
Guide, “Animals should be housed with a goal of maximizing species-specific behavior and minimizing stress-induced
behavior” (NRC 1996, p. 22). This recommendation is also
consistent with the principles of humane experimental techniques presented by Russell and Burch (1959).
Animals can display a wide range of physiological and
psychological manifestations related to acute and chronic
stressors in their environment (Landi et al. 1982; Sanhouri
et al. 1989; Tuli et al. 1995; Webster 1998). In addition, the
response to a given stressor can be as varied as the stressors
themselves (Grandin 1997; Moberg 1985; Rushen 1986).
The presence of nonuniform, nonidentified stressors can
introduce unwanted variables into an experiment, resulting in increased variance and nonrepeatable data. Crockett
and colleagues (Crockett et al. 1995, 2000) examined the
influence of cage size and level, room change, ketamine
sedation, and other common laboratory procedures on the
behavioral and physiological responses of laboratory macaques. The results of their assessments of changes in
behavior, appetite, and urinary cortisol as indices of psychological well-being demonstrate that for female pigtail
macaques, ketamine sedation produced an unequivocal
stress response as measured by appetite suppression and
cortisol elevation. For the longtailed macaques, moving to a
new room, or into a new, clean cage, was associated with
changes in sleep patterns and suppressed behavioral activity
ILAR Journal
(i.e., decreased self-grooming the day after the move). The
authors (Crockett et al. 1995) suggest that disruption of
normal activity patterns can be used as a useful indicator of
disturbances to the psychological well-being of animals
housed in the laboratory environment.
It has been suggested that the psychosocial experiences
of an animal can negatively affect the survival of an animal
challenged with an immunodeficiency disease (Capitanio
and Lerche 1998). Nonhuman primates subjected to stressors at the time of simian immunodeficiency virus infection
had a decreased survival rate compared with control animals. The effect of animal well-being on research objectives
was further demonstrated by Riley (1981). In an effort to
study the effect of stress on latent oncogenic viruses, mice
were housed in either standard or “low-stress” facilities.
Plasma corticosterone levels in mice housed under standard
conditions were markedly higher than animals housed under
low-stress conditions. In addition, animals housed under
standard conditions developed mammary tumors by the
time they were 360 days old. Mice housed under low-stress
conditions reached a 50% tumor incidence within 560 days.
Based on these data, it can be concluded that the wellbeing of an animal directly affects the scientific validity and
repeatability of the data. For this reason, the systematic
identification and elimination of stressors from an animal’s
environment can lead to improved animal well-being, a reduction in experimental variation, and better science. In
light of the information described above, one must also
acknowledge that failure to acclimate an animal to the experimental environment can introduce confounding variables into an experimental paradigm. All members of the
research team must discuss and endorse environmental
changes such as the introduction of enrichment devices.
Establishment of Strategies That
Harmonize Research and Animal
Well-being: The Team Approach
It is unlikely that an individual can independently identify
and balance all of the issues required to ensure the scientific
integrity of a research paradigm in addition to the wellbeing of the animals used. The foundation of all animal care
and use programs rests in the strength of the animal research
team, which supports the program (NRC 2003).
Within an institution, it is possible to identify more than
one team. One team may establish global program goals and
ensure the availability of resources and funding required to
achieve the goals. A second team, which is closer to the
issues surrounding a given research project, may identify
and balance specific variables surrounding an animal research protocol. Although it is not necessary for the members of each team to meet formally to discuss and deliberate
issues, each team must have a clear understanding of their
responsibilities and objectives. The first team is composed
of one or more institutional officials (IOs1) and administrative and budgetary personnel. In our experience, the second
Volume 46, Number 2
2005
team is composed of the institutional animal care and use
committee (IACUC1,2), the scientist(s), the veterinarian(s),
animal management and care personnel, the animal behaviorist, and the institutional occupational safety consultant.
All team members share the goal of creating an environment
that minimizes or removes non-protocol-related variables
while striving to ensure the scientific validity and repeatability of the research.
In our program, it is common for environmental enrichment standards to be established at the facility level by the
veterinarian and management staff, in consultation with a
behaviorist. Minimum enrichment strategies for many of
our facilities include the following: (1) the use of nesting
material for mice, (2) virgin paper tubes for rats, (3) manipulanda and novelty food items for rabbits, (4) hiding
areas for aquatics, and (5) manipulanda, visualization of
other animals, and novelty food items for nonhuman primates. Intervention strategies for problem animals may include but are not limited to (1) provision of hiding areas for
mice, (2) chew toys for rats, (3) chew blocks for rabbits,
(4) novelty food for aquatics, and (5) foraging devices and
access to activity enclosures for nonhuman primates. These
strategies are in addition to the requirements of the AWA
(1966) for regulated species.
The IACUC responsible for the facility program reviews
the facility environmental enrichment plan before its implementation. Scientists are encouraged to communicate with
their veterinarian and facility personnel when developing
their animal study protocols. When reviewing a protocol
for activation in our facility, we have recently begun to
provide each scientist with a letter that outlines the approved facility policies for routine animal husbandry and
minimal environmental enrichment. Our letter includes a
detailed description of the enrichment devices and, when
available, manufacturing details and certification analysis.
In addition, the IACUCs of programs for which scientists
house animals in our facility are also provided with similar
information.
Current enrichment plans as well as standard operating
procedures describing the environmental enrichment programs and procedures are already in place in our facilities.
When justified, exceptions to the facility policy can be
granted by the facility veterinarian and, when appropriate,
approved by the IACUC that reviewed the original protocol.
In addition, changes in the facility policy or procedures
must be approved by the facility IACUC and communicated
to the research staff and IACUCs before their implementation. Smith and Hargaden (2001) advocate the use of an
enrichment authorization questionnaire to ensure communication with the investigator and provide documentation of
their approval.
2
Animal care and use committees outside the United States are typically
identified without the word “institutional,” therefore we urge readers to
apply the term as appropriate.
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Although program staff may decide to delineate the
tasks and responsibilities outlined below differently, the
over-riding objectives and goals remain the same. Descriptions and recommendations related to the roles of team
members are discussed below.
Role of the Institution and the IO
The institution is responsible for establishing the culture
that defines the care and use of animals within the organization. It must foster an environment that promotes quality
research and cultivates respect for animals simultaneously.
The foundation of the institutional program should be anchored in the Guide (NRC 1996), Public Health Service
Policy (PHS 2002), and Animal Welfare Regulations (AWR
2002). The institution must ensure the availability of the
resources necessary to accomplish established programmatic initiatives that promote quality science as well as
humane animal care and use. The institution must identify
an IO who is legally authorized to commit, on behalf of the
institution, institutional resources that will ensure compliance with all governing regulations and guidelines, as well
as those needed to meet established program initiatives. The
IO must have the authority to initiate and/or codify institutional initiatives, requirements, and policies designed to
promote high-quality science and animal well-being.
The IO must provide general oversight of the institutional program; take the lead in creating a dynamic, compliant, and responsible institutional culture; and establish an
expectation of quality scientific research while promoting
the humane use and well-being of animals used in research.
He or she must appoint and empower key personnel to
provide day-to-day oversight of the program as well as the
resources required to ensure quality science and promote
animal well-being. Finally, the IO should develop a team
approach, enhance consensus building, and encourage the
sharing of responsibilities and accountability. The IO
should establish a program of self-assessment to ensure the
fulfillment of all program goals.
Role of the IACUC
The IO appoints the IACUC, and the IACUC then has the
following responsibilities and authority: to view and approve animal study proposals; to evaluate unanticipated scientific outcomes that adversely affect animal well-being and
welfare; to ensure compliance with all policies and regulations; and to promote animal well-being and good science.
When necessary, the IACUC has the authority to approve
exceptions to guidelines and regulations. The IACUC must
approve the implementation of institutional initiatives to
address animal well-being. The IACUC should strive to
develop agreement between members of the animal research
team and harmonize program initiatives.
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Role of the Scientist
The scientist is the subject expert who develops the research
concept and experimental design. He or she must ensure that
the experimental design complies with all institutional programs, policies, and guidelines. The scientist is often highly
trained in the humane use of animals used in support of his
or her scientific discipline. The scientist must work closely
with other members of the animal research team, especially
the veterinarian, in the development of animal study protocols and to ensure that all team members have a clear understanding of the scientific goals and methodology.
Whenever possible, the scientist must strive to harmonize scientific requirements with animal well-being issues
and, when not possible, ensure that the animal research team
has a clear understanding of the issues that warrant an exception. The scientist must ensure that the animals are monitored closely for unexpected outcomes not delineated in the
approved animal study protocol and report any such outcomes to the veterinarian and IACUC. It is critical to the
repeatability of the experiment for the scientist to ensure
that the materials and methods used are clearly and accurately reported in the scientific literature. This documentation should include a concise description of the inanimate
and social environmental factors surrounding the use of animals under investigation.
Role of the Veterinarian
In addition to having legal accountability for animal care,
the veterinarian has the authority to make decisions on behalf of the animal on critical issues (NRC 1996). As the
expert in animal care and use and a key member of the
animal research team, the veterinarian must strive to balance
scientific goals with animal health and well-being. He or she
should participate in protocol development, approval, and
implementation. With regard to animal well-being, the veterinarian must convey to the scientist both the inanimate
(e.g., chew toys, nesting material, puzzle feeders, activity
rooms) and social strategies (e.g., group housing) used
within their program to address animal well-being.
The veterinarian must strive to identify and control environmental factors that could adversely affect study variability. When evaluating new strategies to address animal
well-being, he or she must balance the potential for an adverse effect on the animal’s health with the proposed benefit
of the new strategy. The veterinarian must ensure that animal care personnel understand how enrichment strategies
may adversely affect the science being conducted.
Role of Facility Management Staff
and Animal Care Personnel
The facility management and husbandry staff are critical
members of the animal research team. As experts in animal
ILAR Journal
care, they must know the normal, expected, species-typical
behavior patterns of the animals under their care and be
trained to recognize abnormal presentations. They have the
daily responsibility for assessment of animal well-being
throughout the institutional program. They must strive for
uniformity in animal care, and document and report departures from established policies and procedures.
When evaluating the management impact of new enrichment strategies, it is important to balance facility, staffing, and monetary issues with the potential benefit of the
new strategy. The IACUC, veterinarian, and scientist should
approve all changes in the use of enrichment before the
implementation of a new strategy. When using randomly
applied inanimate environmental enrichment strategies, it is
important to ensure that they are indeed randomly implemented. All unexpected or unwanted responses to enrichment strategies should be reported to the veterinarian,
scientist, and IACUC.
Role of the Animal Behaviorist
The animal behaviorist is one of the newest members of the
animal research team. Although many programs do not yet
have the benefit of a staff animal behaviorist, behavioral
consultants can be a valuable resource. Many behaviorists
are scientists themselves, and they are also veterinarians
in some situations. For the behaviorist to participate fully as
a member of the team, he or she must have a thorough
understanding of the scientific goal(s) and nature of the
science being conducted. The individual must be committed both to the promotion of quality science and to animal
well-being.
The behaviorist can participate on many different levels,
ranging from the provision of technical assistance to full
participation as a collaborator and colleague. In addition,
the individual with behavioral expertise can facilitate the
assessment of animal well-being, the documentation of program effectiveness and humane treatment of animals, and
protocol development. The animal behaviorist can help reduce experimental variability, enhance repeatability, and
provide improved animal models.
Measurements of Enrichment
Related to Animal Well-being
If the focus of enrichment is to provide environments that
enhance animal well-being by maximizing species-typical
behavior and minimizing stress-induced behavior (NRC
1996), then some reliable and valid measures of well-being
that assess these criteria are needed (Rushen 2003). All of
the following quantitative physiological measures have
been proposed as indicators of animal well-being under varied enrichment strategies: weight changes, heart or respiration rate, body temperature, increased or decreased cortisol
or corticosterone production, changes in endocrinological
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2005
parameters, and alterations in the immune system responsiveness (Bayne et al. 2002; Broom and Johnson 1993;
Capitanio 1998; Clark et al. 1997a,b; Marashi et al. 2003;
Moncek et al. 2004; Morrow-Tesch 2001; Schapiro et al.
2000).
Similarly, the level of natural killer (NK1) cell activity
has recently been observed to be higher in the spleens of
mice provided with environmental enrichment than in mice
housed under standard conditions (Benaroya-Milshtein
et al. 2004). The effect of enrichment on NK cell activity is
interesting because of the role of NK cells in host resistance.
It was also observed that environmental enrichment had a
beneficial effect by reducing anxiety-like behavior and
minimizing stress responses.
The problem encountered when attempting to measure
effective enrichment strategies is the lack of a unifying concept of well-being. The challenge for today’s animal research team is to avoid the “nominal fallacy” (Beach
1955)—that to name something (e.g., well-being or welfare)
is to assume that it has been explained. The members of
each team must develop performance standards that reflect
the effectiveness of their program in promoting the wellbeing of the animals used in research. The further development of quantitative measures of an animal’s physiological
and behavioral well-being will provide the data required to
determine ultimately whether an animal’s well-being can be
enhanced by enrichment strategies.
It should be noted that several examples of the potential
negative impact of enrichment on well-being have been reported. Problems have arisen when animals have found innovative ways to manipulate or get entangled with
enrichment items (e.g., nesting material, Bazille et al. 2001;
ring toys, Murchison 1993; whiffle balls, Shomer et al.
2001), or ingest material (sisal rope, Hahn et al. 2000; wood
pieces, Mätz-Rensing et al. 2004). A rebound effect, or a
return to baseline levels of behavioral pathology, was reported by Bayne and colleagues (1992) after the removal of
enrichment devices in their study. These authors cautioned
that removal of enrichment devices from nonhuman primates might have long-term detrimental effects on the research use of these animals. Jennings and coworkers (1998)
have noted the need for caution when a potential enrichment
device (e.g., cage additions) serves to stimulate increased
aggression among inhabitants.
Impact of Enrichment
on Research Objectives
The assumption that both the “control” and “treatment”
groups are similar, except for the variable under study, is
fundamental to the design of a controlled experiment (Beveridge 1957). The animal research team should strive to
identify, remove, and/or minimize the number of nonprotocol-related variables that could affect a study. When
non-protocol-related variables cannot be eliminated, the
animal research team should strive to ensure that those variables are uniformly present in both experimental groups.
123
The addition or application of enrichment into an already existing research program has the potential to alter the
experimental results significantly. Benefiel and Greenough
(1998) evaluated the results of experiments in which subjects experienced different enrichment conditions. They describe distinct neuroanatomical changes associated with
enriched housing conditions for rats. For example, compared with rats housed in standard laboratory cages, animals
raised in complex environments have shown an increased
number of synapses per neuron in the visual cortex (Jones
and Greenough 1996). Benefiel and Greenough (1998) suggest that assessment of studies in which enrichment was not
provided necessitates qualifying older results with more recent findings. They further state that consideration of an
animal’s well-being is as important as its nutrition, cage
sanitation, and health status.
When introducing new program initiatives or enrichment strategies, it is important to minimize the number of
variables changed at any given time. Ideally, all members of
the animal research team should agree with the change before implementation. Depending on the research being conducted, the introduction of new variables could adversely
affect the scientific validity of the research. Ultimately, it is
the role of the IACUC to balance the perceived potential for
an adverse effect with actual benefit. With new methodologies, wherein experience or published documentation is
lacking, it is always good practice to conduct pilot studies to
assess safety and applicability before implementation in the
general population. In all situations, the animal research
team must be aware of the methodologies used in an institute’s program. Communication between members of the
team is fundamental to meeting both scientific and animal
well-being goals. In most situations, the investigative staff
and animal care staff are in the best position to identify the
effect of enrichment strategies on both the animals and
research.
In some situations it is easy to assess the impact of an
enrichment strategy on research objectives when the approach leads to the removal of an animal from the study
(Bazille et al. 2001; Hahn et al. 2000; Mätz-Rensing et al.
2004; Murchison 1993; Shomer et al. 2001). However, even
under these situations, the animal research team must move
cautiously and weigh the magnitude of the actual and perceived risk to the research paradigm with the potential
for benefit to the animals. Although the loss of an animal
should be avoided whenever possible, the accidental loss of
an animal can occur in any situation or environment. In
most situations, good experimental design can compensate
for the unexpected and random loss of a valuable research
animal.
However, the description above may not apply in experiments with very small sample sizes. Although small
sample sizes should be avoided when possible, the scarcity
of appropriate subjects or the unique nature of an experimental paradigm may dictate smaller sample sizes. In these
situations, the accidental loss of a data point could be problematic. It is necessary to implement new enrichment ini124
tiatives under these situations with great caution to ensure
that the scientific goal of the study is addressed. Only methodologies with a proven track record and a wide margin of
safety should be utilized.
To summarize, when establishing new program goals
and initiatives, animal research teams must continually
evaluate the potential impact of program initiatives on the
animals as well as the research they support. Clough (1982)
has stated that the ideal laboratory animal should have standard, reproducible physiological responses. This ideal is
possible only when performance goals and assessment plans
are in place before the implementation of any new strategy.
In our experience, the majority of research paradigms are
not adversely affected by the careful, systematic implementation of inanimate and social environmental enrichment
strategies. When problems have occurred, they have been
secondary to failures in communication and, in many instances, a lack of understanding of the scientific goal by
some team members.
Potential of Positive Effects
The benefit of acclimating animals to their physical environment before their use in research has been established
(NRC 1996). Accordingly, one might argue that maximizing species-specific behavior and minimizing stress-induced
behavior promotes animal well-being and produces a less
“variable” animal for scientific research. However, it is important to recognize that the effect of outside variables on
the experimental result can be minimized as long as both the
control and treatment groups within a given experiment are
similarly housed and maintained.
Schapiro and colleagues (2001) have demonstrated that
positive reinforcement training of macaques can be used
both as a means to promote species-typical behavior and as
an important experimental manipulation to facilitate systematic analyses of the effects of psychosocial factors on
behavior and potentially even on immunology. Positive reinforcement techniques have been used to facilitate the administration of treatments (Laule et al. 1996; Reinhardt
et al. 1995) and the collection of blood samples without
anesthesia (Priest 1991; Reinhardt 1997; Reinhardt and
Cowley 1992). Chamove and coworkers (1982) established
that woodchip litter could be used as an enrichment device
for macaques. The primates in the study were more active,
had fewer periods of inactivity, and demonstrated decreased
aggression.
In studies with rodents, the animal’s ability to manipulate inanimate environmental objects (i.e., nesting material)
in a species-typical manner has been used as an indication
of well-being after experimental manipulation (T. Blankenship, National Institute of Environmental Health Sciences,
NIH, Research Triangle Park, NC, personal communication,
2004). We have observed the following effects after the
implementation of enrichment programs involving the use
of both inanimate and social environmental strategies in
ILAR Journal
both rodent and nonhuman primate colonies: a marked reduction in both animal-animal and animal-human aggression, a reduction in maladaptive behavior, and a concurrent
increase in species-specific behavior. Investigators within
our programs have reported that their animals are easier to
handle, less apprehensive, and in many instances appear less
stressed after experimental manipulations. All of these factors may have a positive effect on research by minimizing
study variability, promoting animal well-being, and preventing
injuries to both animals and humans. A useful compilation
of normal behavior patterns and abnormal/maladaptive behavior for various species can be found in Stewart and
Bayne (2004).
Potential of Negative Effects
The impact of environmental variables on a given study can
often, but not always, be minimized by the experimental
design of a study. Depending on the experimental paradigm
under consideration, changes in the inanimate or social environment of an animal can directly change the behavioral
and/or physiological parameter being studied (Landi et al.
1982; Sanhouri et al. 1989; Tuli et al. 1995; Webster 1998).
Studies designed to evaluate behavioral, anatomical, or
physiological parameters that are susceptible to stress or
distress may be most problematic. Studies have demonstrated the reorganization and plasticity of brain neurons in
response to chronic behavioral stress or environmental enrichment (Coq and Xerri 1998; Johannsson and Belichenko
2002; Radley et al. 2004). Radley and coworkers (2004)
observed neuroanatomical changes evident in the brains of
rats under chronic behavioral stress. These structural variations were characterized by decreases in the total length and
number of branches on apical dendrites of pyramidal neurons. Following the induction of focal brain ischemia, Dahlqvist and colleagues (1999) demonstrated earlier that the
presence of an enriched environment changed the functional
outcome of their experiment. Young (2003) has provided an
additional overview of the potential impact of environmental enrichment on neurological parameters. In these complex situations where there may be scientific justification
for exempting an animal from established enrichment strategies, the IACUC has the authority to make exemptions.
With regard to experimental repeatability, studies have
demonstrated that using the same strain and species as in a
previous experiment is not enough to guarantee that the
animals currently used are the same physiologically and
behaviorally as those utilized in the past (Crabbe et al.
1999). It is clear that both the inanimate environment and
social environment can influence the behavior and physiology of laboratory animals (Bohus and Koolhass 1991; Novak and Suomi 1991; Schapiro 2002). Therefore the careful
documentation and communication of both the inanimate
and social environmental parameters under which an animal
has been maintained are critical for future repeatability of
the experiment.
Volume 46, Number 2
2005
Facility Design Considerations
Animal facility design is typically guided by engineering
specifications and animal care guidelines (Curtis and Widowski 1991), rather than by data derived from animal behavior experiments that assess ways to provide enrichment
and address questions of welfare or well-being in a laboratory or zoological setting. Behaviorists or enrichment specialists are often asked to rectify animal management
problems created by poor zoo/facility design, which fails to
account for the behavioral propensities of the animals (Coe
2003). It is unfortunate that behavioral specialists are typically consulted after the design phase of a project, or only
after construction has been completed. However, one clear
exception is the work of Temple Grandin.
Grandin’s initial efforts were focused on determining
better ways to manage livestock through modifications of
standard housing and handling under a variety of circumstances (Grandin 1987, 1991). This approach has benefited
both the animals and the livestock handlers. Although the
approach is not specifically referred to as enrichment, Grandin’s work addresses the welfare of stock animals housed in
production facilities. The effects of improving the welfare
of the production animals maintained in these newly designed facilities have been decreased losses, better housing,
and increased productivity.
The laboratory animal community continues to conduct
research in facilities for which the design and construction
emphasis has been on air handling, sealed floors, direct
overhead lighting, and drainage. This design focus has a
direct impact on the daily management of enrichment programs in these facilities. Managers of enrichment programs
must address “worst-case scenarios” regarding potential
hazards to the facility and the animals (Young 2003). Facility managers face different challenges with enrichment
items (e.g., manipulanda or other materials), which can potentially obstruct drainage systems (Hill and Ambrose 2003).
Grandin (1991) suggests that designers and architects often
make the mistake of installing drainage systems that are too
small for the task within animal housing facilities. Engineering specifications typically do not address the potential
impact of enrichment devices on facility infrastructure.
Hill and Ambrose (2003) managed a sanitation and
drainage problem in a nonhuman primate facility with a
simple drain modification. In this example, a small section
of steel pipe with two zinc-coated bolts welded perpendicular to each other across the neck of the pipe replaced the
drain basket and slotted drain cover. When placed back into
the original drain, the bolts prevented larger manipulable
enrichment objects from entering the drain. In a similar
attempt to minimize problems caused by obstructions, drain
covers were modified at one of the NIH animal holding
facilities. The modification provided an opportunity for pigs
to forage for novel food items that were distributed in loose
straw. The modified drain covers allowed for the distribution of straw, and prevented soiled materials from entering
the drains and potentially obstructing the flow of wastewa125
ter. Modifications to the drain covers did not preclude their
removal by animal care personnel when necessary.
Curtis and Widowski (1991) have noted that buildings
designed for one species of primate may be inappropriate
for another when addressing species-specific behavior and
implementation of enrichment programs. They suggest that
facility design should provide some flexibility and allow for
easy retrofitting or redesign if the need arises (Curtis and
Widowski 1991). For example, over time, zoos have made
a transition from easily cleaned concrete enclosures to
stimulating exhibits that mimic naturalistic environments
wherever possible and promote well-being (Coe 2003).
A similar change in laboratory design may not be possible, yet examples of designs or enrichment methods are
available that take into account the natural history and propensities of the animals via installation or distribution of
simple devices (NRC 1998; Williams et al. 1988). Facility
managers who collaborate with enrichment specialists or
animal behaviorists thus encounter the following challenge:
to find the balance between providing the most stimulating
or enriching environments for animals while following the
recommendations of the Guide with respect to an appropriate physical environment for research animals (NRC 1996).
It is important to remember that the sensory world of
animals is different from that of humans (Ruys 1991; von
Uexküll 1934 as cited in Dewsbury 1978), and this knowledge should ideally be factored into the design of new facilities. It is stated in the Guide that an animal’s social
environment usually involves physical contact and communication among members of the same species through visual, auditory, and olfactory signals. We believe that the
challenge is to promote a flexible physical environment that
facilitates both physical contact and noncontact communication among individuals of the same species.
The animal facility design issues outlined above,
coupled with increasing construction costs, demonstrate the
importance of having scientists, veterinarians, husbandry
experts, and behaviorists as members of the facility design
team. The ideal facility design must be flexible and meet not
only current research requirements but also future research
programs and the animals required to support them. All
members of the facility design team must strive to harmonize scientific requirements and management issues, as well
as cost constraints and engineering requirements, with the
well-being of the animals being housed.
Summary
The need to address the well-being of animals in research is
not a new concept, but rather one that has been revitalized
and receiving renewed attention. Scientists themselves were
among the first to recognize that addressing the humane
treatment of animals could further their scientific goals
while promoting animal well-being. Institutions must establish a culture that promotes quality research and cultivates
respect for animals simultaneously. The harmonization of
126
the two goals is best achieved through the promotion of a
team initiative and ensuring that all members of the team
understand the institutional goals and objectives. We summarize the pertinent characteristics of the team approach
below.
Animal Research Team
Composition. Often multifaceted but at a minimum
composed of the scientist, veterinarian, IACUC, and animal
care staff. There are clear benefits in the addition of an
animal behaviorist to the team.
Responsibility. To promote and balance the generation
of scientifically valid data with animal well-being.
Goals. (1) To minimize or eliminate nonprotocol variables that could affect the validity of the experimental data.
Good experimental design coupled with high-quality communication between members of the team can often minimize or eliminate many variables, while promoting animal
well-being. This result will not be possible in some situations. In such situations, the IACUC must evaluate the issues, strive for harmonization and, if warranted, approve
exceptions to guidelines, regulations, institutional programs, or initiatives.
(2) To ensure the scientific repeatability of experimental
data. Scientists must be aware of both the animals’ inanimate and social environment, and must be proactive in
understanding housing and environmental conditions. Veterinarians, facility management personnel, and care staff
must ensure a stable, uniform environment for the housing
and maintenance of research animals. All parties must strive
for timely, clear, and concise communication throughout the
program.
(3) To consider carefully and approve all programs designed to address the well-being of experimental animals
before the programs are implemented. Consideration should
be given to pilot testing new methodologies before global
use. Methodologies designed to be randomly applied must
be implemented at the facility level in a random manner. In
addition, because investigators may have animals in more
than one facility at the same institution, all facilities within
an institution should ideally have a similar approach to addressing environmental enrichment and animal well-being.
(4) Finally, to provide detailed documentation of all
parameters under which an experiment was conducted. This
documentation is one of the best methods for ensuring the
repeatability of experimental data. Scientists must consider
the role that environmental variables may play in their experimental design and results. It may no longer be sufficient
to state only that animals were provided food and water ad
libitum and maintained on a 12:12 hr light cycle. Instead,
published materials and methods should include both the
inanimate and social environments in which the animals
were maintained. Through better documentation of environmental variables and their correlation with experimental results, we can better understand the relationships between an
animal’s environment, well-being, and science.
ILAR Journal
Acknowledgments
The authors participated equally and fully in the development of this article. Drs. Ginger Tansey, Tanya Burkholder,
Robert Wurtz, and Fred Miles reviewed earlier drafts of
this article and provided suggestions for its improvement.
Ms. Kathleen Burns provided expert editorial assistance.
Drs. T. Blankenship, M. Grant, and D. Forsythe suggested
the novel use of enrichment as a tool for the assessment
of animal well-being after experimental manipulation. The
input of the Behavior and Environmental Enrichment
technicians, both past and present, on issues germane to
animal well-being and programmatic goals is gratefully
acknowledged.
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