Journal of the American Association for Laboratory Animal Science Vol 54, No 2 Copyright 2015 March 2015 by the American Association for Laboratory Animal Science Pages 224–230 Consideration and Checkboxes: Incorporating Ethics and Science into the 3Rs Margaret S Landi, 1,* Adam J Shriver, 2 and Anne Mueller 3 Members of the research community aim to both produce high-quality research and ensure that harm is minimized in animals. The primary means of ensuring these goals are both met is the 3Rs framework of replacement, reduction, and refine- ment. However, some approaches to the 3Rs may result in a ‘check box mentality’ in which IACUC members, researchers, administrators, and caretakers check off a list of tasks to evaluate a protocol. We provide reasons for thinking that the 3Rs approach could be enhanced with more explicit discussion of the ethical assumptions used to arrive at an approved research protocol during IACUC review. Here we suggest that the notion of moral considerability, and all of the related issues it gives rise to, should be incorporated into IACUC discussions of 3Rs deliberations during protocol review to ensure that animal wellbeing is enhanced within the constraints of scientific investigation. Conflicting feelings about conducting experiments in animals lead to suboptimal reviews and missed opportunities for im- have existed for more than 4 centuries.28 The ‘father of physiol- proving welfare. Why do we think that standard practices for ogy,’ Claude Bernard (1813–1878) recognized this polarization in IACUC could be enhanced? his statement that “the science of life is a superb and dazzlingly First, the checkbox approach can limit critical thinking about lighted hall which may be reached only by passing through a long reviews by making the process more about following a set of and ghastly kitchen.”18 In fact, Dr. Bernard’s wife, Marie Francoise instructions than about holistically considering how the pro- Martin, established the first antivivisection society in France.18 cedures might affect the welfare of animals. New procedures The conflict, concern, and debate continue into the present time. and technologies are developed continuously, and different One major step forward was taken with Russell and Burch’s experimental designs might introduce novel considerations seminal book on animal research. Russell and Burch developed that were not present when the checklist was developed. A rote what is known as the 3Rs approach more than 50 years ago with following of instructions could lead IACUC members to miss the intention of balancing the advancement of knowledge in sci- potential changes that would enhance the welfare of the animals. ence with respect for the lives and experiences of animals.38 The Second, the checkbox approach can lead to a bias in favor of three principles arose from recognition that harm to animals in the status quo. If older approaches or technologies have been ap- studies could be prevented or minimized without compromis- proved in the past, an approach with an emphasis of checking off ing the quality of the scientific investigation. This prevention of requirements that meet a minimal threshold likely would lead to harm could be achieved by replacing potentially harmful research bias of past approaches and technologies, even if new (and poten- on sentient organisms with nonsentient material (replacement), tially better) approaches and technologies have been developed. planning carefully to establish smaller group sizes or fewer study Thus, the checkbox approach might act as a barrier to progress. groups (reduction), and fine-tuning animal care and experimen- Third, the checkbox approach may make it possible for mem- tal designs to reduce unnecessary pain or distress (refinement). bers to conduct reviews without seriously considering all ethical Although the 3Rs approach has led to valuable progress, the and scientific assumptions underlying different approaches. If 3Rs are sometimes treated as a bureaucratic hurdle. Assessment a reviewer knows that a certain approach has been approved of the 3Rs frequently is accomplished by review of a set of before, the reviewer may simply move forward to approval, prompts or boxes to check off by using standardized procedures in light of past practices. However, ultimately many of the that can bypass in-depth discussions and full consideration of challenges of IACUC reviews require careful and thoughtful enhancement guided by knowledge of various ethical views consideration of protocols and an understanding of the specific on animals. A checklist way of working, when not bolstered by animals being studied, so a system structured in a manner where additional discussion, might minimize the true nature and value such critical thinking is not rewarded or valued could lead to of the 3Rs and can work to circumvent in-depth discussions. important improvements being missed. Our view is that many IACUC do an excellent job of carefully As a supplement to the checklist approach, we argue that the considering all of the relevant information and synthesizing rich body of thought on animal ethics can and should inform this information into an optimal set of recommendations. Some IACUC discussions and continuously move the 3Rs framework IACUCs may use checkboxes extremely effectively. However, forward. We center our discussion of animal ethics on the we suggest a few reasons by which a checkbox approach could notion of moral considerability and argue that including discus- sions of moral considerability in IACUC assessments will help ensure that assessment of the 3Rs for a protocol or study are an Received: 28 Sep 2014. Accepted: 8 Jan 2015. intellectually engaging process that continuously evolves and 1 GlaxoSmithKline Office of Animal Welfare, Ethics and Strategy, King of Prussia, Pa and responds to new research. Although we do not offer a formal 2University of Pennsylvania Department of Medical Ethics and Health Policy 3Applied Bioethics, Philadelphia, PA proposal here for IACUC evaluation, we outline how we believe *Corresponding author. Email: [email protected] a discussion of moral considerability can be valuable and sug- 224 Ethics and science in the 3Rs gest why we think such discussions could be important in the of moral considerability: 1) What features contribute to moral IACUC protocol review process. considerability? 2) Which animals have those features? and 3) As we soon describe, there are a variety of perspectives on What do those features entail in terms of treatment? We do not which animals have moral considerability, on how to best as- expect that readers will find all approaches equally useful for sess moral significance in animals, and on the implications of IACUC review, but we aim to provide a range of options to help possessing these capacities. Although US Government Principles,4 enhance IACUC discussions. The Guide for the Care and Use of Animals (the Guide),23 and other What features contribute to moral considerability? The most policy documents and publications provide guidance, we en- common basis for granting moral considerability to nonhuman courage each IACUC to come to their own conclusions about animals is the view that animals are sentient: that is, capable of how they can best enhance the 3Rs perspective with discussion experiencing pleasure, pain, and other feelings. Because there of moral considerability. Not all IACUC will reach the same are many definitions of sentience, we want to be clear about the conclusions about which ethical theories are relevant; however, definition we are using. We will use sentience interchangeably what is important is that careful consideration is given to both with consciousness and conscious awareness. To say that an animal the ethical assumptions and scientific knowledge that underlie is sentient, in our use of the term, means that the animal has the ultimate decision. conscious experiences of pleasures, pains, and other emotions Finally, some may ask why we should think about ethics at all and that the animal can be directly aware of such feelings. To during IACUC evaluations. Good research should be objective say that an animal is consciously aware of pain is different from and unbiased; why would particular ethical theories play a role? claiming the animal is self-aware. Being self-aware implies the This stance, we believe, relies on a mistaken understanding of animal has a conception of itself as a being having a type of the application of ethics in science. Science, of course, needs to be experience, but the awareness of sentience just refers to being as objective as possible, and steps should be taken to ensure that capable of having the experience. Likewise, sentience is often results are evaluated without prejudice. Nevertheless, the choice contrasted with the notion of cognition, which refers to certain of any particular research design will, by necessity, depend in part complicated forms of information processing. For our purposes, on the ethical assumptions of the researchers. Avoiding discussion cognition can be thought of as thinking and sentience as feeling. of the ethical principles at work in research design is not truly We see an early example of recognition of the importance avoiding subjective value judgments; rather it is relying on hid- of sentience for moral standing in Jeremy Bentham’s famous den and unexamined value judgments to do the work. Although quote, “a full-grown horse or dog is beyond comparison a more we recognize that IACUC are not tasked by law to conduct harm/ rational, as well as a more conversable animal, than an infant 4,31 benefit analyses, we nevertheless believe that understanding of a day or a week or even a month old. But suppose the case the notion of moral considerability can be useful in determining were otherwise, what would it avail? The question is not, Can the best way to apply the 3Rs to a particular research design. That they reason? Nor, Can they talk? But, Can they suffer?”6 In this is, deliberation about moral considerability may expand or offer quote, Bentham is emphasizing the importance of animals’ new opportunities for the application of the 3Rs.