By considering reduction before refinement, we risk allowing some animals to experience greater pain and distress. A variety of approaches can help balance reduction and refinement while promoting the welfare of individual animals
Nicole Fenwick and Gilly Griffin
The classic Russell & Burch 1 sequence of applying the Three Rs first examines how to replace the use of the animal, followed by how to reduce numbers through good experimental design. Then ways to minimise pain and distress (and improve animal welfare) through refinements are considered. If this sequence is followed slavishly, there is a risk that the drive to reduce animal numbers will overshadow the goal of minimising pain and distress for each individual animal.
Conflict between reduction and refinement arises when “procedures can be performed such that they either inflict less harm on more animals or inflict more harm on fewer animals”2 (p. 334), as has been recognised in the more-recent literature.2–5 It has also been addressed in animal use policy. For example, the UK Animals (Scientific Procedures) Act 1986 states “the use of fewer animals in each experiment” must occur “…without compromising animal welfare”.6
Similarly, the International Council for Laboratory Animal Science states that the use of genetically-altered animals “may be a Refinement due to the increased accuracy of the animal model, [but] a significant number of animals are required to generate a new animal line, thus bringing the principles of Refinement and Reduction into conflict” 7 (p.3). In addition, Policy #14 of the United States Animal Welfare Act prohibits the use of an animal “in more than one major survival operative procedure, unless the multiple procedures are required to meet the objective of a single animal study activity”.8 The difficulties of balancing reduction and refinement are routinely faced by animal ethics committees (AECs). A study of Canadian AECs found that, when evaluating studies, members often disagreed about whether animal numbers are an important consideration and whether harm from routine housing and husbandry should be considered.9 The original definition of refinement referred only to experimental procedures, not husbandry. However, refinement is now usually taken to embrace the entire lifetime of the animal.10–12 Conflict between reduction and refinement was also identified as a source of “tension” for AECs in the United States.13
Reduction–refinement conflicts appear before AECs in a variety of forms. One form, related to quality of life or the animals’ welfare from birth to death, encompasses concerns about housing and husbandry (not just experimental procedures). One example might be the maintenance of a colony of immunecompromised mice, where the condition of the mice requires they be housed without bedding (to avoid skin irritation) in ventilated cages (where they are exposed to continuous draughts and noise). The colony is maintained while the research is temporarily suspended, because animals will be needed again in the near future. It can be argued that fewer animals are used in the maintenance of the colony than if the colony were euthanised and rederived from frozen embryos when subsequently needed. However, focusing on minimising animal numbers means that debilitated mice continue to experience a poor quality of life, unable to perform the full repertoire of mouse behaviour, such as nest building14 and subject to distress from noise and draughts.14, 15
Animal re-use, defined as sequential use of the same animal for unrelated experiments,16 highlights a further reduction–refinement conflict. One example involves dogs maintained for pharmacokinetic studies in drug research. They are trained to co-operate with the administration of novel drugs and repeated blood sampling, and are housed in an enriched environment. However, the same dogs are re-used many times in order to keep numbers low, so the procedures are experienced repeatedly by the animals, presenting challenges to AECs regarding how to establish limits.
Determining the value of a study is a key factor for AECs, who must weigh harms and benefits. In some cases, they must evaluate how a reduction–refinement conflict might influence experimental outcomes, and therefore the value of the study.
Consider the example of wildlife research on freeliving animals to understand the species biology and inform conservation, where the use of telemetry devices and recapture often allows for fewer animals to be used. However, these individuals may be subjected to harms from capture, wearing tracking devices, biological sampling, and multiple recapture,17–19 leading to concerns that their welfare is compromised and that they no longer represent the typical individuals of their species.
How can reduction and refinement be successfully balanced? Russell and Burch prioritised the experience of the individual animal over reduction. Therefore, when AECs identify a reduction–refinement conflict, they may choose to address it by applying reduction and refinement in conjunction, rather than independently,4 or by considering refinement before reduction. In addition, they may consider that weighing harms and benefits — a utilitarian framework — may not be the best approach for tackling reduction–
Policymakers might address the reduction–refinement conflict by adopting expanded definitions
for refinement that apply to the lifetime experiences of animals. The recent EU Directive 2010/63/EU places conditions on animal re-use, which focus on assessing cumulative severity. Re-use is dependent on the “actual severity of the previous procedures” and the “lifetime experience of the animal” (Article 16).20 The assessment of cumulative suffering, through the use of extended welfare assessment grids,21 should provide more-objective information on whether refinement for individual animals is being achieved. Policymakers can also draw attention to the reduction–refinement conflict by counting and reporting animal re-use and breeding colony animal numbers.
When reduction is prioritised or given equal importance to refinement, greater harms may occur to individual animals. Conversely, when refinement is prioritised, more animals must be used. Arguably, if it is possible to eliminate any pain and distress, then reduction of animal numbers becomes less important.22 To minimise pain and distress and improve animal welfare, a variety of approaches by AECs and policymakers that focus on experiences of the individual animal, will be needed.
Thanks to Dr Andrew Winterborn and the Queens University Animal Care Committee, for discussions on this topic.
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