The welfare of animals used in science: How the “Three Rs” ethic guides improvements

The term “animal welfare” is widely used to refer to an animal’s quality of life. It encompasses the following: animals should be healthy, well fed, and housed in an environment that they might themselves choose; animals should be relatively free from negative states, such as pain, fear and distress, and capable of enjoying life; and animals should be able to carry out behaviors and activities that they are strongly motivated to do (1). The public has long been concerned about the welfare of animals as illustrated by our laws to prevent animal cruelty, the existence of humane organizations funded by charitable donations, and the use of public money to fund animal use oversight bodies. Public concern for animal welfare extends to animals used for science: although studies show that the public supports animal-based research, people also want animal pain and distress to be minimized (2).

In Canada, continuing improvements to the welfare of animals used in science have occurred over the past few decades partly because of the explicit adoption of a set of principles to guide the ethical evaluation of animal use. This is the “Three Rs” tenet — Replacement, Reduction and Refinement (3). The tenet is grounded in the premise that animals should be used only if a scientist’s best efforts to find a nonanimal alternative have failed, and that when animals are needed, only the most humane methods should be used on the smallest number of animals required to obtain valid information (4). Specifically, “Replacement alternatives” refers to methods that avoid or replace the use of animals in an area where animals would otherwise have been used, including both absolute replacements (replacing animals with inanimate systems, such as computer programs) and relative replacements (replacing more sentient animals, such as vertebrates, with animals that current scientific evidence indicates have a significantly lower potential for pain perception, such as some invertebrates). “Reduction alternatives” refers to any strategy that will result in fewer animals being used to obtain sufficient data to answer the research question, or in maximizing the information obtained per animal and thus potentially limiting or avoiding the subsequent use of additional animals, without compromising animal welfare. “Refinement alternatives” refers to the modification of husbandry or experimental procedures to minimize pain and distress, and to enhance the welfare of an animal used in science from the time it is born until its death (5). Today in Canada and internationally, the Three Rs ethic of animal use is an accepted part of the culture of animal-based science.

In Canada, the Canadian Council on Animal Care (CCAC) is the national organization that has the responsibility for overseeing the care and use of animals in science. Through the overarching CCAC policy statement on: Ethics of animal investigation (4), the CCAC has incorporated adherence to the Three Rs tenet as the fundamental basis for the ethical oversight of scientific animal care and use. Briefly, the oversight process requires that use of animals for a scientific purpose (research, teaching, testing) is subject to review and approval by an animal care committee located at the institution where the animal use is proposed. To reflect the broader public, animal care committees are composed of not only scientists and veterinary professionals, but also non-users of animals from the local institution and community representatives.

The CCAC also has a strong mandate to communicate with the Canadian public and to provide information to scientists to enable compliance with accepted standards. The CCAC has developed a new internet resource to communicate how the Three Rs tenet is implemented and to distribute related science-based resources: the “Three Rs Microsite” (5). The Microsite offers information on a wide range of topics related to Three Rs-Alternatives, for example Experimental Design, Telemetry, and Humane Killing; information on special topics such as Agricultural Research and Three Rs and Genetically Engineered Animals; plus a section with Additional Resources, including Species Specific Resources and a list of Three-Rs related journals.

How do the Three Rs assist scientists in improving the welfare of animals used in science?

The Three Rs tenet is applied by scientists as they prepare written descriptions of their proposed animal-based studies and by animal care committees during their ethical review of the proposed work. Use of the Three Rs tenet assists in improving the welfare of animals used in science in several ways: it addresses a range of concerns about scientific animal use; it places a focus on individual animals; it adapts and responds to new information; it balances the needs of science and the needs of the animals; and it unites disparate groups with an interest in the welfare of animals used in science.

A range of different types of concerns related to animal use in science, both ethical and “cage-level” are addressed by using the Three Rs to evaluate use of animals in science. The requirement for Replacement, Reduction and Refinement, as described earlier, results in fewer animals being used in total, preference for the use of nonanimal methods or less sentient animals, and in procedures that minimize pain and distress for those animals that are used in science. In addition, the ability of the Three Rs to address the range of concerns about the use of animals in science also rests on the foundation that equal consideration of each “R” must occur in order to assert that the Three Rs tenet has been applied. Therefore, if animals are used when an acceptable nonanimal substitute exists, then no matter how well the numbers are statistically justified or how well the animals are cared for, use of those animals still violates this ethic. In practical terms this means that partial implementation of the Three Rs tenet is not enough to justify approval of an animal-based study (6).

The Three Rs tenet also provides a way to focus on the welfare of individual animals rather than solely considering welfare indicators at the level of groups or populations. Importance of the individual is acknowledged through the requirement to use as few individual animals as possible and to justify how numbers were selected. Similarly, to properly implement Refinement the experience of an animal during proposed procedures and in the housing environment must be carefully examined to identify and mitigate potential harms.

The Three Rs also provides a set of principles that are responsive to new information. This flexibility allows the scientific community to reflect on new empirical knowledge, for example from animal welfare science. Similarly, as ethical values evolve, the Three Rs can respond to such evolution. For example, the principle of Refinement has developed from its original scope of minimizing “harms” to animals only during experimental procedures. It now includes both minimization of negative states (harms) and promotion of positive states, during the entire lifespan of an animal used in science. This ethical reflection is an important feature of the Three Rs tenet as it allows practices to be revisited and reassessed in order to continuously improve welfare standards.

The Three Rs tenet also provides a way to balance the needs of science and the needs of animals. The Three Rs framework of utilitarian ethics allows for recognition and acceptance of both the expectations of scientists and the cage-level welfare requirements of the animals. The Three Rs tenet has been successful because many aspects of the Three Rs are essential to good science and good animal welfare. For example, the principle of Reduction has long been closely tied to good experimental design and proper use of statistical methods to determine sample sizes that provide the most scientifically meaningful results (7). More recently, providing improved housing conditions for rodents (Refinement) has been shown to result in experimental data with greater scientific validity (8–10).

Lastly, the Three Rs tenet assists in improving welfare through its role in uniting disparate groups who have an interest in the welfare of animals used in science, including scientists, veterinary professionals, humane organizations, policy makers and the general public. Within these groups there are varied points of view concerning the acceptability of scientific use of animals; however, the Three Rs tenet provides an approach that is supported by a broad cross-section of opinion, and thus is a uniting ethical concept. On a practical level, the Three Rs also provides a common language with which to discuss the use of animals in science. This is important both within the scientific community (for scientists, veterinary, and animal care professionals) with its varied research, teaching and testing animal uses, and also between the scientific community, policy makers, the general public, and humane organizations. The accessibility of the Three Rs tenet is demonstrated by its widespread use in publications from humane organizations, the policies of scientific funding groups, and in regulations and law.

Limitations of the Three Rs tenet

Although the Three Rs tenet has achieved some success in improving animal welfare, it has also been criticized for its limitations.

1. The Three Rs tenet has been criticized for the underlying premise that the use of animals for scientific purposes is acceptable: providing the criteria for animal use but not allowing for examination of the assumption that use is acceptable (11).

2. The Three Rs tenet does not provide a way to give special consideration for certain species. Therefore species with the least public support for their use in science (nonhuman primates and western companion animal species) cannot be exempt from scientific use by solely applying the Three Rs tenet in the ethical evaluation process (12). In these cases, local institutional policy or legislation are often used to prohibit or limit use of these species, thus bypassing consideration under a Three Rs process. One example is the ban on the use of chimpanzees in science in the United Kingdom, New Zealand, the Netherlands, and Sweden (13).

3. Conflicts between each “R” have also been identified as a limitation, such as the conflict between the goal of reducing overall numbers and the goal of minimizing pain and distress for individual animals (Refinement) (14). The advent of newer and less invasive methods of data collection such as telemetry and imaging technologies makes it possible to re-use animals; however, this reduction strategy has the potential to increase harm to individual animals, and so must be carefully balanced.

4. There can be conflicts between the Three Rs tenet and the goals of certain types of scientific animal use. For example, in some research, such as studies of wildlife populations, Replacement may not be a valid goal (15). In addition, in some research and testing the creation of a poor welfare state is the aim of the use (as opposed to a consequence of the use). This is clearly in conflict with Refinement and goal of improving welfare.

5. The full potential of the Three Rs tenet to improve animal welfare has not yet been reached and has been identified as an area for renewed focus for the scientific community. Some suggestions to overcome this limitation include increasing efforts to share knowledge through more complete publication of Three Rs-related information in published scientific papers (11,16) and increasing funding for the development of viable Replacement alternatives (11).

What can others take from use of the Three Rs tenet in animal-based science?

In North America there are some strong parallels between the use of animals in science and use of animals for food production (agriculture or aquaculture). Both require a steady supply of animals, house animals in intensive environments, use genetic technologies to enhance animal strains, strive to use humane killing methods, and use some of the same species. In addition, agriculture has recently come under greater public scrutiny and criticism regarding the welfare of animals used for food production, reminiscent of the criticisms of use of animals in science that started in the 1970s (17).

By using the Three Rs tenet to guide the ethical evaluation of animal use, the scientific community has been able to achieve improvements in animal welfare. Today the welfare of animals used in science is often substantially better than animals used in other ways. For example, a pig used in biomedical research is most likely housed with some type of bedding, will receive anesthesia and analgesics before surgical procedures, and will have individualized veterinary care (18). In contrast, a typical grower pig will be housed on slatted floors without bedding, be castrated without anesthesia or analgesics, and will receive veterinary oversight only at the herd level. Therefore, the experiences of the scientific community and its use of the Three Rs tenet may be informative for other uses of animals such as their use in agriculture and aquaculture.

1. To achieve public support for use of animals, it is necessary to address the full range of concerns related to the use. In science, the ethical evaluation process and use of the Three Rs tenet is a clear acknowledgment by the scientific community that it does not have blanket permission to use animals for this purpose. In addition, to ensure equal consideration of concerns scientists are required to apply all 3 “Rs.” A similar model of ethical evaluation guided by clearly articulated principles could be adopted for other uses of animals to address concerns related to the use. In some sectors, an ethic of use may already be in place, but economic and other pressures may have resulted in an acceptance of incomplete implementation of possible welfare improvements. For example, in agriculture, aquaculture, and even in zoos, the nutritional status of animals may be high and parasitic disease states are minimized but animals may not be kept in environments where they can carry out strongly motivated behaviors. Consequently, overall welfare is diminished and the full range of welfare concerns remains unresolved.

2. In some areas of animal use, the welfare of individual animals may need to be re-prioritized. Current emphasis on group measures of health and welfare in large managed populations of animals does not go far enough to address the welfare needs of all animals in the group. For example, recent UK research found that 27% of broiler birds had some form of gait defect that impaired walking (19). In Canada, where over 611 million broiler birds are processed annually (20), this would translate into approximately 165 million individual birds experiencing a physical debilitation and the accompanying pain and distress.

3. Balancing the needs of use and animal welfare requires the establishment and promotion of an ethic of animal use that both recognizes and accepts the expectations of users, but also seeks to align these with the needs of animals. In effect, an ethic that finds common ground. Therefore an ethic of zoos might require use of animals only for education with demonstrated pedagogical merit (not entertainment), humane zoo practices, including evaluation of whether it is appropriate to maintain some species at all, given complex housing and environmental needs; and a requirement for conservation efforts to maintain species in the wild. An ethic of animal agriculture may translate to acceptance of the need for food production balanced against a requirement for humane farming practices, including those aspects which clearly minimize pain and distress. For example, use of fewer cows to produce greater milk yield per cow, may not be acceptable because of the additional physical burden on individual animals.

4. A common set of principles across various types of animal use could assist in unifying groups that are facing similar animal welfare challenges and criticisms. In the scientific community this has been accomplished through the Three Rs tenet, supported by scientists from different areas of animal use (including research and teaching and testing), veterinary professionals, and community representatives. Thus it may be useful for all sectors of the animal agriculture community, (veterinary professionals, and dairy, egg and meat producers) to develop and promote implementation of a common ethic of animal use.

Conclusion

With the Three Rs tenet the scientific community has been able to address animal welfare in a meaningful way for animals. The success of the Three Rs is demonstrated by its acceptance and recognition by the scientific community, humane organizations, policy makers, and the general public. As the public eye turns further towards examination of other uses of animals, it may be necessary for these other users to consider an ethic of animal use relevant to their particular area. While the Three Rs tenet may not fit all situations perfectly, other ethics of animal use could be developed and applied in a similar manner to the Three Rs with the goal of improving animal welfare.