RAR Home

RAR Home



Directory
Link to U of M homepageLink to the U of M homepage
Sub-Topic

Experiment Guidelines

IACUC Animal Care Veterinary Care Experiment Guidelines Surgery Anesthesia Euthanasia Safety Training

Ethics

Alternatives

 

Replacement

Reduction

Refinement

Resources for alternatives searches
 

 


 

Copyright 2003, University of Minnesota Board of Regents.

The University of Minnesota is an equal opportunity educator and employer.

Ethics and Alternatives

Ethics

The use of animals in research, teaching and testing is an important ethical and political issue. Much of the discussion about this issue revolves around the relative value, often referred to as 'moral value', of humans and animals. When the needs of animals and humans come into conflict, which takes precedence? Today there exists a wide spectrum of views on this subject, ranging from those concerned with animal 'rights' to those who view animals only as a resource to be exploited. All of these viewpoints have contributed to the development of ethical principles of animal use. These in turn have shaped animal use regulations promulgated by the USDA and the PHS, and echoed by organizations such as AAALAC, AALAS and the AVMA. These regulations embody principles summarized in statements by the Public Health Service Policy and by NASA. These issues are discussed below.

From the dawn of time, when the first human killed an animal for food, or drove it from a berry patch so that he could eat instead, there has been competition with animals for basic resources. Likewise, over the ages, humans have contemplated their relationship with animals. Ancestral societies worshipped the animals they used, recognizing that the lives they took fueled their own lives. As societies became more agrarian, reverence for wild animals waned, and thanks and worship were given instead to the crops and the sun and the livestock that sustained these early humans. Further introspection on humanity's place in the world resulted in the development of codes of morality and ethics and subsequently the first modern religions. While biblical views of animals are primarily those of utility rather than of moral value, early scholars argued that animals should be treated kindly because animal cruelty represented a flawed morality and was ultimately detrimental to the moral development of humans. This view that humans may ultimately be judged based on their treatment of other lives exists to this day, and for many, is a strong argument for stewardship toward animals.

The early Greek philosophers valued reason above all else, and ascribed little moral value to animals and even to other humans that did not possess this attribute. While this viewpoint might be viewed as extreme, from a biological perspective this might be seen as competition. Using the survival advantage given to us by our capacity for reason is no less moral or ethical than another animal using its adaptations to survive. However, it should be obvious that by allowing unrestricted human exploitation of animals, there is great potential for extirpation of species. Thus, we utilize animals for food and clothing; we keep them as pets or as livestock; we plant our crops, harvest wild plant products, and build our cities and highways where animals might otherwise have lived, but we do so with restrictions on our activities, if only to conserve our resources.

Interestingly, advances in biology that began in the 1800's have provided some of the strongest arguments for imbuing animals with an enhanced moral value. By recognizing that the nervous systems of all vertebrate animals are very similar, it is assumed that activities that will cause a human pain or distress, will likewise cause pain or distress to other animals. It is for this reason that current animal use regulations require the use of analgesics, anesthetics and sedatives for any procedures on animals that may cause more than momentary pain or distress.

Animals with advanced nervous systems, such as nonhuman primates, carnivores and marine mammals, have also demonstrated other abilities that humans can relate to and value, such as advanced social behavior, the ability to react to both positive and negative stimuli, intelligence and even self-awareness. What once had been a clear physical and mental distinction between humans and animals, has become much fuzzier with this new understanding that evolution represents a continuum. Likewise, the assumption that there is a clear moral distinction between humans and animals also has become fuzzier, and it suggests that perhaps gradations in moral value should be applied to animals. This thought is also reflected in modern thinking. Current legislation on animal use emphasizes the idea of replacement of 'higher' animals with 'lower' animals, and requires environmental enrichment or human contact for intelligent, social animals such as nonhuman primates, or dogs and cats, but not for vertebrates like amphibians.

Current legislation also recognizes that there are diverse viewpoints about the moral value of animals. Thus, all live animal use in research, teaching or testing must be reviewed by a committee (the IACUC) with diverse membership. There is also an emphasis on minimizing the overall use of animals. Proposals for animal use are reviewed based on the potential for learning new information, or for teaching skills or concepts that cannot be obtained using an alternative. There are also provisions for ensuring that animal use is performed in as humane a manner as possible, minimizing pain, distress or discomfort. These provisions include a requirement for a veterinarian to be employed at each institution, so that the needs of the animals are looked after by someone trained in, and sympathetic toward animals' needs. In addition to the requirements for analgesics, anesthetics and sedatives to be used where needed, it is also required that all personnel with animal contact be trained in appropriate handling techniques and that they be skilled in any experimental procedures that will be performed. Finally, basic husbandry requirements are specified, ensuring that an animal's food, water and shelter will be provided for in an optimal manner. Deviations from the numerous requirements are rarely granted by the IACUC, and then only if adequate justification is given that the proposed experiment is scientifically and socially important, and that any methods to alleviate pain or distress would frustrate the experimental objectives.

 

Alternatives

An important ethical principle of animal use in biomedical research is that alternatives to live animals should be used whenever possible. There is a legal requirement for documentation of a search for alternatives and an explanation for why these alternatives were not found to be suitable or how alternatives were incorporated into the experimental design.. While some may simplistically view alternatives in the classic Webster's sense, of a choice between two or more things, implying that good medical research may be performed with no use of live animals, a more sophisticated concept of alternatives has been put forth by Russell and Burch in their book, The Principles of Humane Animal Experimental Techniques, Charles Thomas, Springfield, IL, 1959. They promote a definition of alternatives as "the three Rs-replacement, reduction, and refinement" which has become a pervasive theme in biomedical research today.

The American College of Laboratory Animal Medicine Foundation funds grants to study alternative methods of animal use. All animal users are encouraged to explore this and other means of improving animal welfare while still accomplishing our research mission.

Replacement means replacing 'higher' animals with 'lower' animals. Microorganisms, plants, eggs, reptiles, amphibians, and invertebrates may be used in some studies to replace warm-blooded animals. [NIH website on Model Organisms for Biomedical Research] Alternately, live animals may be replaced with non-animal models, such as dummies for an introduction to dissection for teaching the structure of the animal or the human body, mechanical or computer models, audiovisual aids, or in vitro modeling. The Animal Care and Use Protocol (ACUP) asks about the alternatives that have been considered, why they were rejected and how the Principal Investigator searched for these alternatives.

Advantages to replacement include utilizing pre-existing knowledge for teaching, applying known principles to new systems to look for similarities, and using less expensive animals or models to screen large numbers of agents for toxicity or mutagenicity.
Disadvantages to replacement chiefly stem from the fact that any models are dependent on pre-existing information. In a system as complex as a live organism, all of the variables in physiology and pathology are not known. Thus, any research on new biological processes must utilize a living organism at some point.

Reduction means minimizing the number of animals needed to perform an experiment or teach a concept. This alternative is addressed in Appendix A, but also in the ACUP form which asks for justification of the species to be used and the numbers needed for each experimental group. By examining these parameters, the IACUC can determine if thoughtful experimental design was employed to minimize overall animal use. Methods to achieve this include:

  • Performing pilot studies to determine some of the potential problems in an experiment before numerous animals are used
  • Designing a study to utilize animals as their own controls
  • Gathering a maximum amount of information from each animal, perhaps gathering data for more than one experiment concurrently
  • Consulting with a statistician to use only the numbers of animals required to achieve significance [Link to on-line statistical resources] [ILAR Journal Statistical Approach to Calculating the Minimum Number of Animals Needed in Research]
  • Minimizing variables such as disease, stress, diet, genetics, etc., that may affect experimental results
  • Performing appropriate literature searches and consulting with colleagues to ensure that experiments are not duplicated
  • Using the appropriate species of animal so that useful data is collected
  • Replacement whenever possible.

Refinement means refining experimental protocols to minimize pain or distress whenever possible. This concept is addressed in numerous questions throughout the Animal Care and Use Protocol Form. Examples of refinement include:

  • Identifying pain and distress and making plans for preventing or relieving it.
  • Setting the earliest possible endpoint for the experiment. That is, if the necessary information can be gathered before the animal experiences any ill effects from the experiment, this should be defined as the endpoint and the animal subsequently euthanized. For example, if measuring toxicity of a compound or survival following implantation of a neoplasm, a pilot study may determine that once certain clinical signs are seen, or a tumor achieves a certain size, the time course until debilitation or death are predictable. Subsequent experiments may then utilize the earlier endpoint of tumor size or clinical signs of toxicity, rather than death as the endpoint.
  • Receiving adequate training prior to performing a procedure.
  • Using proper handling techniques for animals.
  • Ensuring that drug doses are correct and that the drugs used are not expired.
  • Ensuring that procedures to be performed on the animal are reasonable for that species.
  • Using appropriate anesthetics and analgesics for potentially painful procedures.
  • Performing surgeries and procedures aseptically to prevent infection.
  • Performing only a single major survival surgery on any one animal, whenever possible.
  • Performing appropriate post-surgical care, including thermoregulation and fluid balance.
  • There are several specific research techniques in common use that are often criticized for their potential for causing pain or distress to animals. The IACUC has established policies on some of these techniques. These include the use of Freund's Complete Adjuvant for antibody induction; foot pad injections; blood collection; ascites production for production of monoclonal antibodies; tumor induction; survival surgery; euthanasia; the use of the lethal dose 50 (LD 50), or other death as an endpoint studies, Animal Care and Use Protocol Form. Beside the information in the appendices, information on possible alternatives for these procedures is available from RAR.
 In some cases, application of one alternative concept may have an adverse effect in another area (i.e using a "lower" animal or minimizing pain or distress may require using more animals.)  These issues are discussed by the IACUC and depending on the circumstances different priorities may be set.

Searching for Alternatives

 

Appendix A of the Animal Usage Form asks for the methods used to search for alternatives to procedures that may cause more than slight pain or distress to animals. Examples of these methods would be a literature search (indexes searched and keywords used should be listed), consultation with peers in the field, and consultation with the National Agricultural Library's Animal Welfare Information Center (described below) or the Johns Hopkins Center for Alternatives to Animal Testing (see below).  [Guidance document from USDA on alternatives searches]

Some resources available to assist in searching for alternatives are listed below.


Top of page

 



 

The information contained in this site is intended as a reference for University of Minnesota investigators, and animal husbandry and veterinary staff. Drug information and dosages are derived from a variety of sources and do not necessarily guarantee safety or efficacy. Information obtained through this site should not be relied upon as professional veterinary advice. Any medications administered or procedures performed on animals should only be performed by or under order of a qualified, licensed veterinarian.