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-
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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. experiences and is saying that if animals have the capacity to suffer—that is to experience pain, distress, or other negative Moral Considerability: What Is It? feelings—then the animals also should be taken into considera- Moral considerability, or moral consideration for an entity, tion in our moral judgments. means that the entity has the right for its interests to be taken into Sentientism is intuitive for many people: if another entity is account when a decision is made that will affect that entity.22 We capable of consciously experiencing pain and distress, there is will also use the term moral standing to indicate those animals that something wrong with disregarding that capability when we are due moral consideration. Having moral standing or moral make moral judgments. And, conversely, if an entity completely considerability can be thought of as a minimal threshold that, lacks consciousness, then for many it sounds strange to say that when reached, ensures that the entity’s interests will at least be we can morally wrong that entity. For the sentientist, it only given some weight in moral deliberation. However, as will be seen makes sense to claim that we can harm another entity if that later, merely saying that an entity is morally considerable does not entity can experience the harm done to them. determine how much weight is assigned to the entity’s interests; Others, however, disagree that knowledge of whether other additional considerations are needed to make this determination. beings are conscious is necessary for concluding that those Generally speaking, there is consensus that all humans are beings can be harmed. Marian Stamp Dawkins,15 for example, morally considerable. When decisions may cause harm to a has argued that too much emphasis is placed on the idea of person or persons, we think that harm should be taken into consciousness and that we can still talk about promoting animal account during decision making, and the harm(s) often will welfare by learning about animals’ preferences. If an animal has be enough to rule out certain possible choices. Conversely, a strong preference for a certain outcome (which we can test by most people would agree that inanimate objects such as rocks giving the animal choices between various options), then we are not morally considerable; we don’t tend to worry about have moral reasons to take the preferences into consideration whether our decisions will be harmful to rocks themselves. On independently of whether the animal has conscious experiences. this spectrum, nonhuman animals occupy a space somewhere Along different lines, David Degrazia,16 although emphasizing in between people and rocks. Most agree that we have some the importance of sentience for moral standing, has put forward obligation to refrain from treating animals badly, but the precise an account that elucidates harms that can occur to animals that nature of those obligations and to which species they apply have nothing to do with their experiential wellbeing. Degrazia is often debated heatedly. We argue below that the notion of argues that killing a healthy dog painlessly while it is sleeping moral considerability, guided by appreciation of different ethical is still harming the dog, even if the dog doesn’t feel anything. perspectives, could be incorporated into IACUC discussions. Similarly, he suggests that we can cause harm to animals by To highlight how moral considerability can be relevant for depriving them of freedom and by impairing their functioning. IACUC discussions and introduce ideas that will be helpful Another common perspective is that we owe consideration for future discussions, we explore several aspects of the notion and respect to all living things. Respect is sometimes put forward
225 Vol 54, No 2 Journal of the American Association for Laboratory Animal Science March 2015 as an additional R to the original 3Rs. Respect is independent of used to help researchers protect themselves from acknowledg- an entity’s preferences or sentience. Most people who hold this ing the feelings of animals.37 view wouldn’t suggest that the lives of dandelions are due equal However, the later 20th century featured the ‘cognitive consideration as the lives of humans. Nevertheless, if all lives revolution,’ which was a growing understanding that the mind deserve respect, then respect is relevant in laboratory settings. could not be reduced to only overt behavioral patterns. New Many other more cognitively sophisticated capacities have also technologies allow researchers to examine the minds of humans been suggested to be relevant for moral concern. Some have stated and nonhumans during various tasks and this is revealing the capacity for language is necessary for moral considerability.14 the amazing complexity of the brains in many species. As this Others who see morality as a sort of mutual agreement have ar- research has progressed, it has become more and more clear gued that to be due moral consideration, one has to be capable of that many of the same brain regions that are active in humans acting morally toward others.12 This reasoning would imply that during pains, pleasures, and other valenced states also appear only animals that have the capacity to form some sort of mutual to be active in other species, particularly in vertebrates.1,44 agreements have moral standing. And still others have argued Sentience should not necessarily be viewed in a binary manner that moral standing depends on having a sense of self, which where an animal either has it or doesn’t. Rather, sentience can be refers to the notion of self-awareness above.21 Each of these views viewed as a continuum; perhaps a chimpanzee (Pan troglodytes) suggest more than sentience is necessary for moral standing. is more sentient than a mouse (Mus musculus) which is, in turn, Investigating which animals have the relevant features. Know- more sentient than a snail (genus Helix). Such a perspective isn’t a ing how to treat particular animals depends on more than just problem for the sentientist position; it simply suggests that moral having a theory of which features are relevant. It is notoriously considerability of animals could also exist on a continuum. Pos- difficult to determine the mental states and cognitive capacities sessing a limited amount of sentience could mean that an entity of animals given that they are, unlike most humans, incapable is also due a limited amount of moral consideration. of reporting on their experiences. Nevertheless, assessing which Although the sentientist approach is influential with regard to animals have the capacities noted earlier is critical to under- moral standing, another approach emphasizes the importance standing the significance of any research paradigm on animals. of desires or preferences. A ‘gold standard’ test of preferences It is a common belief that many animals have the capacity in animal welfare literature is simply to give animals choices to consciously experience pleasures, pains, fear, anxiety, and between multiple options. If they choose an option over the other positively or negatively valenced states.20 The presence of others to a statistically significant degree, then we can say they positively and negatively valenced states in some animals leads have a preference for that option. This preference is independent to additional moral obligations when we engage in research of any assumptions about whether the animal is ‘conscious’ or on animals compared with other species such as plants.34,43 ‘sentient.’ Based on notions of preferences, we might think moral However, the history of our interactions with animals has been considerability extends even to insects, despite little evidence complicated by fluctuating views on whether humans are the that insects have the neural machinery necessary to support only ‘truly sentient’ entities. Though many famous thinkers consciousness. More sophisticated concepts of desires might give have shared their opinions on nonhuman animals, two pre20th- more focused conclusions as to which animals truly have them. century scholars’ views, in particular, have had lasting legacies Many theorists, for example, think that behaviors that result from that are still influential to this day. Pavlovian conditioning should not be regarded as sufficient to Seventeenth-century philosopher René Descartes claimed that indicate the presence of true desires. For a detailed examination only humans possess ‘minds’ that are independent from bodily of which animals can be said to have preferences, see reference.43 states. Descartes believed that, in contrast to those of humans, For many more advanced cognitive capacities, such as self- animals’ behaviors could be explained entirely by reference awareness, the ability to use language, and the ability to be part to mechanical properties of the body. Descartes argued that of a moral community, these capacities are generally thought animals could not be conscious because they do not possess not to be present in most animals used in research, with a few the capacity for language and, as such, could best be thought possible exceptions. Gordon Gallup21 developed a “mirror of as bête-machine, or ‘animal machines.’26 Today most people self-recognition test” which he thought was a way of determin- recognize Descartes’ claims as erroneous; however, his work was ing which animals had a sense of self. Either paint or a sham often referenced in the 18th and 19th centuries as justification marking was placed on an animal in a location not directly for vivisection on animals. observable to the test animal. Then the animal was observed In the 19th-century, another giant of Western intellectual his- in front of a mirror. If the animal spent more time interacting tory emphasized, in contrast to Descartes, continuity between with the spot of the paint marking than with the sham mark- humans and other species. Charles Darwin reported a number ing in front of a mirror, the animal was assumed to recognize of similarities between humans and other animals in the experi- that the mirror was a reflection of itself. Human infants only ence of emotions and famously concluded that any difference pass the mirror recognition task at a certain age. Only a few between humans and “the higher animals” was “one of degree animal species have been shown to pass it thus far, including and not of kind.”13 Although the heavy reliance on anecdotal chimpanzees (Pan troglodytes), bottlenose dolphins (Turciops reports by Darwin and, especially, some of his followers in truncates),29 and Asian elephants (Elephas maximus),33 whereas making this argument has been criticized,1 his emphasis on many animals have failed the test. There is some controversy continuity between species is influential to this day. regarding whether passing the test should be considered either Many years later, the behaviorist movement that dominated necessary or sufficient for having a sense of self. Some animals, psychology in the United States in the early 20th century took for example, find eye contact aversive and may not ever look the position that sentience in animals could not be studied long enough at the mirror to recognize themselves (see refer- scientifically. According to behaviorism, psychology should ences 2 and 44 for more detailed discussion). be concerned only with the study of observable behaviors; Regarding communication abilities that might be precursors to therefore any debate on emotionality in animals was considered language, Cheney and Seyfarth demonstrated that vervet mon- unfounded. Bernard Rollin has argued that this perspective was keys (Chlorocebus aethiops) differentially responded to playbacks of
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alarm calls for leopards, eagles, and snakes.10 Chimpanzees have perspective, it is easy to think that human pain should be af- been taught to use American Sign Language as well as lexigraphs forded more weight in utilitarian calculations. Similarly, some (machines that speak words when corresponding symbols are would argue that humans are capable of experiencing additional pressed) to communicate effectively.2,3 And at least one African kinds of suffering beyond pain and distress due to their under- Grey Parrot (Psittacus erithacus) has shown an ability to label standing and worry about past, present, and future events such objects by name, shape, and color and to correctly describe novel as the death of a loved one, an upcoming surgery. or knowledge combinations.32 Nevertheless, many linguists, including Noam that one has cancer. There is currently no consensus on how to Chomsky,11 still claim that only humans use syntax, which they weigh the experiences of animals against those of humans (see, take to be a defining feature of language (see references 2 and 3 for example, Singer’s40 utilitarian position compared with that for helpful reviews of this literature). of Frey19), but this does not lessen our obligation to attempt to And finally, it is clear that most animals do not have the moral quantify or qualify the weight of a potential harm. frameworks that humans use to guide their actions. However, The ethical approach contrasted most frequently with utilitari- research has indicated that at least some animals have at least anism is known as deontology. According to deontological views, the precursors of moral emotions, such as empathy for other certain actions are always wrong, regardless of whether they animals,27 a sense of fairness,7 and even a system of rules that result in a better overall set of consequences. So, for example, if determines when group members should be punished for harming a person is wrong, according to a deontological view, transgressions.24 Although animals may have rudimentary it would be wrong even if harming that person brought about moral feelings or what is sometimes called “proto-morality,”2 better consequences on the whole. The American constitution is most theorists agree that they do not have a true morality in often thought to be based on deontological views. If we believe the sense that humans do. that someone has a right to life, liberty, and the pursuit of hap- For each capacity noted earlier (sentience, preferences, piness, this generally means that it is morally wrong to violate language-possession, self-awareness, moral emotions), the re- any of those rights, even in cases where doing so would result search is not conclusive as to precisely which animals possess in a greater amount of overall good. the capacities and which do not. Nevertheless, it is imperative The criterion for deserving consideration in deontological for anyone interacting with animals to attempt to stay current theories varies widely. Tom Regan is one noted ethicist operat- with discoveries relating to those capacities that confer moral ing within a deontological framework.35 Regan’s belief is that standing. We do not (and may never) have perfect knowledge being the experiencing subject of a life is sufficient to endow about the abilities of other animals, but we have an obligation an animal with rights and therefore means that we have strong to use the best knowledge available in our decisions. prohibitions against harming the animal, even if doing so could Obligations and other aspects of moral considerability. After benefit humans. Stated differently, whereas in utilitarian thought discussing what features are relevant to moral considerability an animal can be a means to an end, in Regan’s proposal, an and which animals have them, we can now turn to determining animal must be treated as an end in themselves and never a what our obligations are to beings that are morally considerable. means to an end. Although Regan’s position is based on the Two people might agree that the capacity of an animal to feel writings of Immanuel Kant, Kant himself believed that humans pain and distress means an animal is worthy of moral consid- did not have any direct moral obligations to nonhuman animals eration but nevertheless come to very different conclusions as because those animals lacked the capacity to reason.25 In Kant’s to the significance of this fact. Goodpaster22 has distinguished view, harming animals was wrong only insofar as it led people between the notions of moral considerability, which implies an to be crueler toward other humans, but strictly speaking the organism’s interests should be given some consideration, with animals themselves were not morally considerable. that of moral significance, which tells us how much weight we In addition to strict views about rights entailing particular should give to those interests. forms of behavior, we also might think of rights in a less-de- According to utilitarianism, the ethical theory developed manding sense, namely a right to be considered. Tannenbaum41 by Jeremy Bentham6 and John Stuart Mill30 and more recently for example, has argued that all animals have a right to be applied to animals by Peter Singer,39,40 right actions are those considered in our ethical deliberations and has put forward a that maximize happiness and minimize suffering. The happi- rights-based view supporting the 3Rs. ness maximized, in this context, is meant to include everyone Another relevant ethical tradition is known as the ethics of care.17 affected by the action. If an action is good for me but causes This tradition rejects rule-based perspectives on ethics in favor of greater harm to others, utilitarianism would deem the action an emphasis on relationships. Specifically in regards to animals, wrong. Standard utilitarianism also entails that if an action there is often an emphasis on empathy as a natural response to harms me but brings good to a greater number, that action is suffering. This tradition, by emphasizing personal interactions right. We therefore judge the rightness and wrongness of ac- with animals, perhaps most closely captures the important role tions in utilitarianism by weighing up the sum of all the goods that animal caretakers can play in the lives of research animals. (happiness) and harms (suffering) of all affected and choosing More than anyone else’s, caretakers’ compassion and interaction the option with the greatest balance of good over harm. can positively influence the quality of life of the animals. In stating that an animal has moral standing, a utilitarian Finally, the work of Bernard Rollin has emphasized another would claim that potential goods for the animal and potential important consideration for research with animals.36 Rollin cites harms to the animal should be included in our moral calculation. Aristotle’s notion of telos, the biologic essence of the animal, to It is not clear from this principle alone just how much weight argue that there is more than just positive and negative expe- should be given to the good or harm of nonhuman animals. riences for animals’ well-being. Rollin claims that depriving Does the pain of a rabbit count to the same degree as the pain animals of the ability to fulfill their natural biologic functions of a human? Should it count for less? If so, how much less? As is often a more significant harm than momentary interactions noted earlier, it is possible that there is a continuum of sentience like drawing blood. He repeatedly has emphasized the need to where nonhuman animals have some consciousness but not alter conditions to better allow animals to engage in species- the full spectrum of experiences that humans have. From this typical behavior.
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Our goal in this section was not to provide a comprehensive would help to reduce such violations. The emphasis on telos in review of all of the relevant ethical perspectives on animals particular, calls for providing animals with the ability to act on but rather to highlight the diversity of thought on this issue. their natural impulses; therefore, this theory encourages labo- We encourage readers interested in learning more about ad- ratories to provide animals with strong enrichment options and ditional approaches to explore some of the useful reviews in opportunities to express their natural behaviors. Accordingly, the footnotes.5,8,42 his view can be seen as specifically relevant for the notion of Putting It All Together: Ethical Frameworks and the 3Rs As refinement, and calls on researchers to pay close attention to the can be seen, the complexity of thought that can be applied natural inclinations of the animals involved in studies. to animals is significant. Decisions about which features are The ethics of care highlights another important considera- relevant for moral standing need to be combined with the best tion: the role of the caretaker in the lives of animals. More than current scientific knowledge of which species have those traits. that of anyone else, caretakers’ compassion and interaction can And, even after that’s done, no specific recommendations for positively influence the quality of life of the animals. Vigilant and animals are obtained until we consider what specific ethical caring laboratory professionals can make a huge difference in the views recommend in light of these traits. In this section, we go quality of life for laboratory animals and may provide access to into more detail about how all 3 considerations can be combined knowledge of how to improve conditions that is not available to form recommendations about the 3Rs. from anyone else. For this reason, Larry Carbone has noted that As stated earlier, although the philosopher most associated with there are good reasons to think that laboratory animal caretakers deontology, Immanuel Kant, did think humans hold a different should perhaps be given a designated spot on IACUC.9 place in the world order than animals, there are other deontolo- The major schools of philosophy of utilitarianism and de- gists (notably Tom Regan) who strongly believe it is wrong to ontology, although different, are not necessarily incompatible. treat animals as a means to an end. This stance means nonhuman For example, people may hold a view of rights for people and animals should be viewed in the same way Kant viewed human utilitarianism for animals. Therefore, we might think that strong animals in his second formulation of his Categorical Imperative, deontological considerations should protect humans from be- the “Formula of the End-in-Itself.”25To paraphrase, deontological ing subjected to harmful experiments against their will, but beliefs require that you do not treat others as simply a means to nevertheless believe that it is permissible to perform research an end but as the end. This is often distilled down to do not use on animals if such research results or is likely to result in gains others. If a person truly sees no difference between human and that outweigh the harms. nonhuman animals, application of Kant’s principles would mean Several influential theories, as typically formulated, have little that very little or perhaps no research would be acceptable. So a or no contribution to discussions on the 3Rs. One such theory is strong deontological view like Regan’s does not provide much contractualism.12 Contractualism holds that we only have obli- guidance about how to specifically apply the 3Rs. gations to fellow members (humans) of our moral community. Other deontological views are more closely aligned with the Barring other considerations, this view suggests that we have no 3Rs. Tannenbaum41 has an essentially deontological theory moral obligations to animals themselves. Similarly, views that stating that animals have at least one right: the right for their depend on animals possessing rationality or a robust sense of interests to be taken into consideration. In this view, the ca- self are likely to rule out any direct moral obligations toward pacities of animals mentioned above are relevant in researchers’ most animals currently used in research. Because the 3Rs are decisions about the design of experiments. based on our dependence and obligation to animals, we believe Although some deontological views are compatible with the that these views do not contribute to the focus of this article. 3Rs approach, the view most commonly associated with the 3Rs Current laboratory policies can be thought of as establishing is utilitarianism.45 According to utilitarianism, animal research a minimal level of protection for animals based on moral con- can be justified if the benefits to humans and animals outweigh siderability. Animals are due the protection of minimizing pain the harms caused to animals during research. The majority of and distress. Nevertheless, enhancing the 3Rs with recommen- utilitarian views are either hedonistic, emphasizing conscious dations from additional frameworks on top of this minimum experiences like pleasures and pains as benefits and harms, or level of protection is necessary to fully respect the welfare of preference–satisfaction views, which consider desire satisfac- the animals involved in research. tion and desire frustration as benefits and harms, respectively. Because utilitarian theories claim that right actions are those How Could This All Work? that maximize benefits and minimize harms, there is a strong We believe that IACUCs will be well served by applying the no- incentive to reduce harms as much as possible. So, to take an tion of moral considerability to evaluations of specific protocols in example of research involving mice, we would argue that the laboratories. To achieve additional dimensions to 3Rs discussions, best science available suggests that mice are sentient, and this a working knowledge of different ethical views would enhance must be taken into consideration. As such, a 3Rs approach the effectiveness of the process. Such discussions will also enable can follow straightforward from this framework. Reducing IACUC to more effectively communicate their decisions to the the number of animals to a statistically robust design reduces public. To illustrate the value of the notion of moral consider- the total amount of potential harm, as does replacing research ability, we put forward 2 examples where we contrast what we with animals with other nonsentient techniques. And refining have termed the checkbox approach with the considerability approach. experiments leads to changes to the harm–benefit ratio to favor For the first example, imagine a protocol on type 2 diabetes less harm per animal or more benefit per study. Therefore, this is submitted to the IACUC. The model is the Zucker Diabetic interpretation of utilitarianism, tied with moral considerability, Fatty Rat. Both male and female study rats are at 6 weeks of can be seen as the basis of discussions on the 3Rs. age at start of the protocol. A typical summary of this type of Rollin’s view of telos is also compatible with the 3Rs and can work might read as follows, “Prior to starting drug treatment be seen to place special emphasis on certain features.36 On his (day –1), body weight, blood glucose, and serum biochemistry view, thwarting animals’ natural inclination to escape harmful were measured in nonfasted rats for grouping allocation. Rats stimulation can be seen as a violation of their telos, so the 3Rs were dosed twice daily for 6 weeks with vehicle or compound.
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Blood glucose levels were measured on days 7, 14, 21, 28, 35, and after surgery. Both perioperative and postoperative analgesia 42. Samples for glycated hemoglobin (HbA1c) were collected is provided. Signs of heart failure occur in the first 24 h as well. on days 14, 28, and 42. Serum samples were collected on days After postoperative recovery, dogs will return to pair-housing, 7, 14, 21, 28, 35, and 42 for longitudinal evaluation of insulin, except for dogs showing signs of distress (cowering, hiding, glucose, triglycerides, nonesterified fatty acids, total and HDL shaking, decrease in appetite) caused by pair-housing. Any cholesterol, glycerol and β-hydroxybutyric acid. Body weights social anxiety can increase sympathetic stimulation resulting in were measured every other day.” decompensated heart failure. The protocol goes into detail on In the more typical checkbox approach to the 3Rs, the IACUC specific endpoints including biomarkers. A final procedure in- would confirm that the principal investigator has conducted a cludes full necropsy and histopathology of the heart. The timing search for alternatives (replacement) for this study. The number of of the terminal event depends on evidence of decompensated animals and number and size of groups would be noted (reduc- heart failure or after 3 mo, whichever comes first. tion), including input from a statistician. Scientific justification This description addresses many important aspects of the dogs’ and study design would be discussed for possible modifications welfare. IACUC discussions would likely include how to refine the of the protocol (refinement). The IACUC is not constituted to study, what type of training or acclimation is needed to decrease do scientific review, but discussion of the protocol may include stress in the dogs, and whether the study design is statistically aspects such as the scientific justification for the study, number robust so as to ensure a valid answer to the question being asked of time points, the rationale for the number of time points, and in this model. Nevertheless, we believe that additional important other topics. The IACUC may also request missing information, improvements could be made by incorporating a robust discus- such as amount of blood taken. Special housing conditions that sion of moral considerability. One such area may be in discussing could improve the wellbeing of the rats, such as increases in cage and examining the increase in the negatively valenced state of the changes per week due to the size of the animals and the disease dog. Researchers might prefer docile dogs that can be more easily symptomatology, would also likely be discussed. handled. But with dogs, we must always challenge ourselves and Incorporation of moral considerability into the IACUC 3Rs ask whether a dog is demonstrating learned helplessness, a con- discussion may or may not change the final design of the study. dition in which the dog loses the willingness or ability to escape The incorporation of moral considerability allows recognition aversive stimuli, as compared with acclimation. Does learned of the animal and its needs independent of the study design helplessness represent a negatively valenced state? If so, then and therefore expands the breadth of thought and discussion. simply choosing dogs that put up the least resistance may result in Inclusion of the notion of moral considerability can lead to ad- increasing the amount of negatively valenced states caused by the ditional questions that may be missed in the simple checkbox study design. Similarly, a quiet, docile dog may fare more poorly approach just described. For example, should the shipping route in social housing after surgery, its nature being one of submission be considered? To keep costs down, an institution may allow a and acquiescence. We do not mean to suggest that more aggressive longer route with multiple stops—would this increase poten- dogs should always be chosen over docile dogs but rather that tial for negatively valenced states in the animals? In relation to the individual characteristics of individual animals need to be uncrating and housing, we can ask whether there is any differ- given careful attention. However, important considerations may ence in the telos of a fatty rat and a normal lean rat. Would the be missed by simply following a standard template (checkbox) concept of telos lead to different refinements in environmental approach when discussing the 3Rs of a protocol. enrichment discussions? Are additional negatively valenced One author of the current article (MSL) is a firm believer that states caused by the genetic anomaly of the animal model? the 3Rs are tied to science and should not just be discussed at Are there ways to increase the ability to experience positively an IACUC meeting. Any chance for true change in scientific valenced states? Should preferences (desires) play a part in any design, peer review, and possibility for replacement must hap- housing or handling changes? We suggest that all of these ques- pen before a protocol is submitted to the IACUC. The author tions might be missed on versions of the checkbox approach. recognizes the difference in both practicability and possibility As an example, consider the following summary of an IACUC may depend on the type of institution, for example academia proposal with dogs, a species that garners more public atten- compared with industry. However, the author also recognizes tion than rats. Assume the IACUC receives a protocol to induce that science is not just the science of the model or knowledge arrhythmias in dogs by surgically creating both a myocardial of laboratory animal science but also the application of ethics infarct and mitral regurgitation. The overall intent of this heart that leads to understanding the animal itself. Ethical discussions failure model is to validate or invalidate that treatment with should not add to the burden of care but rather elevate any biophysiologic techniques (neuromodulation) can reverse the debate and review of an animal study or model to recognize symptomatology of heart failure. This study uses 26 dogs—adult the animal as an end in itself. males, approximately 9 mo of age, that are obtained from a li- We understand that institutional processes often arise to censed, commercial vendor. Dogs will be pair-housed in pens or ensure compliance with laws, regulations, policies, and institu- cages that meet or exceed all federally mandated requirements, tional expectations. Documentation provides the ‘proof’ needed including FDA, USDA, and PHS, as well as recommendations for monitoring and ensuring compliance. Making changes to of the Guide. Animal rooms will also meet or exceed mandated established ways of working is not easy, given that we often are requirements. Animal welfare is assured daily by the laboratory measured by findings from oversight or governance bodies. If animal sciences staff specifically trained to work with dogs. amalgamated into present practices for IACUC, the addition Surgical procedures (details provided to the IACUC but not out- of the concept of moral considerability during 3Rs discussions lined here) will result in myocardial infarction and mitral valve should not add negatively to responsibilities, as we have shown regurgitation. Dogs with this experimentally induced pathology in the preceding examples. will be singly housed during the postsurgical period, generally 7 to 14 d. Animals are checked the evening of surgery and then Conclusion at least once every 4 h for 24 h. Experience indicates that any The biomedical community should recognize the importance mortality, expected to be 15%, will occur during the first 24 h the 3Rs play in most discussions on animal protocols and proce-
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