Use of Animals

The merits of animal research are widely accepted by scientists and largely appreciated by the general public. Major biomedical research institutions, professional societies, and research scientists have a shared understanding of the tremendous value gained from studies using animal subjects. Similarly, polls of the general public repeatedly show strong support for biomedical research, and an acceptance of the need to perform studies using animals. However, the apparent support for biomedical research is tempered by widespread misunderstanding about the nature of research as well as an impassioned opposition to any use of animals by some vocal action groups.

Opposition to the use of animals in research is well funded and has had a significant impact on biomedical research. Some in the animal rights movement rely on carefully reasoned, philosophical arguments that humans do not have the right to use animals for experiments, despite the fact that such studies might contribute important new knowledge about physiology and the mechanisms of disease in both humans and animals (Singer 1975, Regan 1983). Other animal rights organizations bypass these philosophical arguments and instead focus on claims that animals suffer needlessly in research, that current medical advances were or could have been derived without the use of animals, and that animal research has provided no useful data.

Except for a set of guidelines for animal use recommended by the National Institutes of Health (NIH) in 1935, animal research in the United States was conducted with relatively little furor and virtually no oversight until the 1960's. A report entitled "Concentration Camps for Dogs", published in Life magazine in 1966, documented brutal conditions and lack of care by suppliers of dogs to research laboratories. Within the year, the first Animal Welfare Act was written and approved, calling for regulatory oversight of the suppliers of some animals. Within the next few years, the government and researchers approved further guidelines and regulations to reduce the risk that the privilege of working with animal subjects would be abused. One of the most important outcomes was the NIH Policy for Animal Care and Use for institutions supported by the Public Health Service (PHS).

Most, but not all, researchers recognize the need to employ animal subjects responsibly. Yet some investigators perform studies that deviate from approved protocol, some provide inadequate care or feeding for animal subjects, and some leave animals poorly attended during recovery from anesthesia and surgery. None of these lapses is acceptable, and while it is hoped that they happen only rarely, they can occur at the hands of a poorly trained or inexperienced investigator. Unfortunately, some instances of animal abuse have been far worse.

In 1984, head injury studies conducted with baboons at the University of Pennsylvania were found to exemplify the worst fears of those opposed to animal research. Apparently conscious baboons were restrained to test the effects of rapid, traumatic head injury. Surgery was performed under nonsterile conditions. Researchers working with the baboons made comments suggestive of a callous, if not sadistic, attitude toward the experimental subjects. Videotapes documenting these abuses were obtained by an animal rights organization and were aired on national television.

Despite the potential importance of studies on traumatic injury, such incidents reflect badly not just on one group of researchers, but on all of research. Investigators who are irresponsible risk not just their own research project, but also the research of others at the same institution. Potentially, they also risk the public's willingness to support or allow research with animal subjects.

Rules and Regulations

The use of animal subjects is covered by numerous regulations. Although many federal agencies have relevant regulatory controls, the two most important for biomedical research are the Public Health Service (PHS) and United States Department of Agriculture (USDA). Institutions are given the responsibility to implement federal regulations primarily through the Institutional Animal Care and Use Committee (IACUC). The roles of these federal agencies and the institutional committee are summarized below.

Public Health Service

The Health Research Extension Act of 1985 ('Animals in Research') is the legislative basis for PHS policy on use of animal subjects. The policy covers uses of living vertebrate animals for any PHS-supported research, research training, and biological testing. In addition to the NIH, PHS agencies include the Centers for Disease Control and Prevention (CDC), Food and Drug Administration (FDA), and several others.

United States Department of Agriculture

Animal Welfare Regulations, and specifically the Animal Welfare Act (AWA), are implemented by the Animal and Plant Health Inspection Service (APHIS) of the USDA. The AWA, first enacted in 1966 and amended periodically, covers the sale, handling, transport, and use of warm blooded, vertebrate animals. At present, birds, rats (genus Rattus), and mice (genus Mus) that are bred for research, but not those that are wild, are specifically exempted from the Animal Welfare Regulations. The AWA, as amended in 1985, incorporates a variety of requirements designed to promote animal welfare. These include minimization of pain and distress, consideration of alternative procedures, definitions of institutional responsibilities, and the establishment of IACUCs. In addition, institutions, businesses, or individuals covered under the AWA must be licensed or registered with APHIS. Facilities are inspected on an unannounced basis, and if deficiencies are not corrected by the subsequent inspection, consequences could include fines, or the suspension or revocation of licensing to use animals.

Institutional Animal Care and Use Committee

Although institutions are subject to federal oversight and inspection, the daily responsibility for complying with federal regulations is largely the responsibility of the IACUC. Under U.S. Public Health Service (PHS) Policy the IACUC must be comprised of at least five people. One of the members must be a doctor of veterinary medicine with training or experience in laboratory animal science and medicine. This individual must have direct or delegated authority and responsibility for the research activities involving animals at the institution. The committee must also include one practicing scientist with experience in animal research, one individual whose primary concerns are in a nonscientific area (e.g., clergy member, lawyer, ethicist), and one individual who is not affiliated with the institution in any way (other than as an IACUC member).

Under PHS policy, institutions are granted the provisional responsibility for self-regulation after approval of an Animal Welfare Assurance by the Office of Laboratory Animal Welfare (OLAW). If the institution fails to meet its regulatory responsibilities, then OLAW can restrict or withdraw the assurance.

Principles

Living creatures deserve respect. There is no presumption that animals may be sacrificed for research. Animals should only be harmed if there is a legitimate scientific advantage to doing so, and even then the harm should be as little as possible. Russell and Burch (1959) proposed three specific strategies for minimizing the pain and distress to animal subjects:

  • Replacement: Has a few meanings depending on the type of research you are doing. From a biomedical research perspective you are expected to, whenever possible, replace the use of live vertebrates with species lower on the phylogenetic scale or to replace the use of living creatures with computer models, cell culture techniques, or cadavers. Another component of replacement or the use of alternatives is tied in with "refinement". Whenever possible, you are expected to replace painful procedures that may cause animal suffering with non-painful procedures.
  • Reduction: Where it is without a loss of significance or precision, fewer animals should be used. This is primarily aimed at using the fewest number of animals necessary to obtain statistically valid results. However, use of too few animals is also considered a waste of animal life.
  • Refinement: Procedures used on live vertebrates should be the most current and should be designed so as to minimize the incidence and severity of harm to the animal subjects. For example, you may no longer immobilize wildlife using paralytics - there are currently much better methods to capture wildlife.

Reduction, Replacement, and Refinement are ethical principles, but they also have practical advantages. Research with animal subjects is expensive. If experiments can be conducted, for example, with mice rather than monkeys, with fewer animals, or without animals, then the cost of those studies will generally be reduced.

The scientific enterprise and the integrity of research depend on the responsible, humane treatment of animal subjects. Animal research has tremendous utility because an understanding of the complex interactions of molecular, biochemical, and physiological mechanisms ultimately depends on studies in intact, living organisms. To be performed, such studies depend on many genetic and environmental controls that are difficult, if not impossible, to achieve in studies with humans-- yet the studies only have value if these controls are carefully maintained. Furthermore, an experimental design that results in pain or suffering often decreases, if not eliminates, the scientific value of the experiment. Finally, irresponsible or inhumane treatment of animals harms the reputation of scientific institutions, endangers funding, and threatens the public image of science.

Guidelines

The PHS, USDA, and IACUCs are the key components of a regulatory environment that promotes the principles described above. However, the ultimate responsibility for the ethical and legal use of animals in research rests with those who conduct the research. The following are guidelines for responsible conduct of such research:

  • Comply with regulations: Any use of animals for the purposes of research, teaching, or testing is subject to regulation. Before such use, knowledgeable individuals should be asked about any obligations to be met by users of animals. This begins with the assumption that no procedure or study should be performed that is not explicitly part of an approved protocol.
  • Critically evaluate the use of animals: The responsible use of animals requires much more than complying with regulations. The spirit of the regulations and good science both require that individuals give thoughtful consideration to what defines an acceptable use of animals. This consideration is necessarily an ongoing and evolving process. Factors to be considered include new understandings of the science involved, potential benefits of the use of animals, possible alternative methods of study, etc. Such issues should be considered by individuals as well as in discussions that involve co-workers, other researchers, and/or the public.

    A prerequisite for the responsible use of animals is a realistic examination of the intended and likely benefits of that use. Does the benefit warrant the cost to animal subjects?
  • Protect animal welfare: The decision to use animals in research and teaching carries a responsibility for the welfare of those animals. That responsibility includes, but is not limited to: ensuring the use of appropriate and adequate anesthesia and analgesia; providing of appropriate feeding, care, and protection from infection, pain, or suffering; selecting humane methods for euthanasia; and obtaining adequate training to fulfill responsibilities for animal welfare.

    If you are responsible for training others or if you observe indifference to considerations for animal welfare, you should make attempts to initiate discussion, to identify relevant regulations, and to promote responsibility in studies involving animal subjects.

    If significant violations of animal welfare regulations are observed, then those observations should be reported to the appropriate people in the institution. This obligation is certainly for the sake of the animals, but it also helps to protect the integrity of the research, the status of the institution, and the institution's privilege for self-regulation.

ÃÛÌÒÓ°Ïñ Specific Information

ÃÛÌÒÓ°Ïñ Policies. ÃÛÌÒÓ°Ïñ researchers must be familiar with the following ÃÛÌÒÓ°Ïñ Policies (available on the Research Policy page) related to the use of animals in research. These policies combine the requirements and expectations issued by various regulatory agencies (including PHS and USDA) and scientific organizations into a single high standard to be applied to all activities involving live vertebrates. Other ÃÛÌÒÓ°Ïñ policies (i.e. Biosafety Policy or the Radiation Use & Safety Policy) may also apply depending on the specific research design and methodology.

Specific information is available on the ÃÛÌÒÓ°Ïñ Institutional Animal Care and Use Committee (IACUC) website and from the ÃÛÌÒÓ°Ïñ Office of Research Integrity. Contact information for ÃÛÌÒÓ°Ïñ Animal Facility Managers and ÃÛÌÒÓ°Ïñ Veterinary Services is also available on the IACUC website.

Protocol Review. All uses (including teaching) of live vertebrates must be approved by the IACUC. Collecting animals by a method that results in their death is considered use of live vertebrates. The only exceptions to this requirement are if the animals are being harvested as part of a legal hunt/fishery or if they are being collected as part of another approved protocol and you will be given subsamples (there are limits to this exception). If you think your use of animals may be exempt from the requirement for an IACUC protocol contact the ORI for a determination.

Key elements of IACUC review:

  • Has the PI adequately addressed the three Rs (replacement, refinement, reduction)?
  • Are the procedures described in sufficient detail so that the IACUC is clear on what will be done and in what time frame?
  • Is the sample size appropriate?
  • Has the PI minimized stress/distress and considered alternatives to painful procedures?
  • Is the research team knowledgeable about animal subject protections, the species proposed, and the techniques employed.
  • Are there any plans for dealing with unexpected outcomes?
  • Are personnel appropriately trained and qualified?

Works Cited

  • Regan T (1983): The Case for Animal Rights. University of California Press, Berkeley, CA.
  • Russell WMS, Burch RL (1959): Principles of Humane Animal Experimentation. Charles C. Thomas, Springfield, IL, 238 pp.
  • Singer P (1975): Animal Liberation. Distributed by Random House, New York.