Animal Research

Abstract

This chapter investigates whether animals used in research should be described as a particularly vulnerable group. First, it inquires whether research animals currently receive the protection they are due, and concludes that they do not. Indeed, it is shown that the research standards currently guiding animal research insufficiently protect animals’ basic claims. Consequently, many research animals can be considered particularly vulnerable, insofar as they run an increased risk of not receiving what they are due. Second, it argues that for animal research to be ethical, it must be made more similar to research with humans, and it is outlined what research respecting animals’ claims could look like in practice.

Millions of animals are used every year for research. In the European Union alone, for example, nearly 10 million animals are involved in research and testing on a yearly basis (European Commission 2020). Many studies inflict considerable harm on animals: they are bred with genetic modifications which impair their well-being; they are intentionally infected with diseases; they are handled during experiments in ways which may lead to considerable distress and suffering (e.g., biopsies); they are housed in small cages, which can severely restrict their agency and natural behavior; and in most cases, they are prematurely killed at the study’s end. This chapter discusses whether such harmful animal research practices can be justified from an ethical point of view, or whether animals used in research should be seen as a particularly vulnerable group in need of special protection and additional attention.

Humans’ using animals for research is a more puzzling case than humans’ eating animals and their products. What we lose when we refrain from eating animals is often rather trivial, such as a reduction in gustatory satisfaction, whereas the losses for the animals bred and raised to serve as food sources are often weighty, as they are frequently condemned to an existence full of suffering before being prematurely killed. The case presents itself differently for research with animals: it seems that more important claims of humans are at stake, namely, leading a long and healthy life. Thus, one may be tempted to regard harmful animal research as legitimate as long as it improves human health and increases human lifespan.

Animals’ vulnerability in research contexts is probably one of the most discussed topics in the animal vulnerability literature so far (see, e.g., Beauchamp et al. 2012; Johnson 2013; Johnson and Barnard 2014; Ferdowsian et al. 2020). The reason is likely that the bioethics literature about vulnerability in research with humans is already highly developed. Some philosophers have taken these writings as their starting point to argue that animals used in research share morally relevant features with vulnerable human research populations. Consequently—so the argument goes—vulnerable research animals should benefit from similar forms of protection (see, e.g., Beauchamp et al. 2012). That is, authors extending the concept of vulnerability to animals used in research demand more protection for these animals than they currently receive. In practice, this may mean that animals should not be involved in harmful research, that research should only be undertaken if the risk to the animals is minimal, or when the potential benefits far outweigh the risk of harming the animals (Ferdowsian and Choe 2013).

I proceed as follows: in a first step, I discuss the view that research animals are already sufficiently protected because animal research is highly regulated and research protocols have to be reviewed by Animal Ethics Committees (AECs). However, as I will show in a next step, currently implemented principles for animal research are insufficient from a moral perspective, for two reasons: first, because they fail to sufficiently respect animals’ basic claims in principle; second, because these claims are often not respected in fact. That is, I will argue that the claims of many laboratory animals are indeed frequently at higher risk of being unjustly considered by researchers and AEC members due to the speciesist prejudices still prevailing in current animal research practices. I do not mean that we should entirely abolish all research with animals; rather, I will suggest that animal research should be reformed. Animal research that respects animals’ most basic claims is possible. After all, we frequently conduct research with humans, including groups who cannot speak up for themselves or give informed consent. And such research can nonetheless be ethical if several strict conditions are fulfilled. Consequently, I argue that the ethical requirements in place for research with particularly vulnerable humans should be extended to animals in the research context, and I show how this can be done in practice.

Insofar as most current research practices fail to respect animals’ basic claims, we can deem many research animals particularly vulnerable. They are at an increased risk of having their interests unfairly considered because speciesist prejudices are currently deeply entrenched in the practice of animal research. However, this does not mean that all current research with animals is ethically problematic. Rather, the ethical acceptability depends on factors such as the specific study protocol, the evaluation by and composition of the Animal Ethics Committee, and the specific animal species.

6.1 The Ethics of Animal Research: Some Preliminary Remarks

Should we deem research animals a particularly vulnerable group? To answer this question, recall the definition of vulnerability presented earlier in this book. My definition of vulnerability reconciles general vulnerability with situational vulnerability: it accounts for the intuition that most individuals are generally vulnerable by their very nature; at the same time, it allows for situations or contexts of increased vulnerability for some individuals or groups, who then deserve special protection and additional attention. I defined as “particularly vulnerable” those who are at a comparatively higher risk of having their claims intentionally or unintentionally disregarded or unfairly considered by those who hold power over the satisfaction of these claims. Due to this increased risk, particularly vulnerable individuals or groups are more likely to incur wrongful harms or mere wrongs. On this reasoning, research animals should be regarded as a particularly vulnerable group to the extent that they face an increased likelihood of having their basic claims unjustly considered by moral agents. Is this the case?

To answer this question, it is useful to take a closer look at different types of animal research. In many cases—but not all—research with animals entails a violation of animals’ most basic claims. For example, research animals often are kept in cages, a practice which restricts their agency and thereby violates their claim to lead a self-determined life. Furthermore, research animals are often bred with diseases or other impairments (such as lameness), which is at odds with their claim to bodily integrity. At the same time, one may argue that more is at stake for humans compared to research animals: humans have greater potential for welfare, happiness, and a rich life than animals. For example, humans’ life plans and quality of life may be impaired if they do not receive the medical treatments they need. Given that most humans are more connected to their future than animals, their life may be considered a bigger loss than the loss of life of a laboratory mouse. The question then becomes: in what cases are such violations of animals’ most basic claims for humans’ benefit ethically justified?

One might be tempted to say that research with animals is justified in all cases where it saves human lives, increases our life expectancy, or improves our quality of life. But for animal research to be ethical, it is not enough that it be beneficial to humans. After all, it may be tremendously useful to force other human beings to participate in a harmful clinical trials or to use their organs against their will to save many individuals. Although such practices could be highly beneficial overall, we nonetheless refrain from undertaking them. This is because the claims of those individuals from whom the organs would be harvested, for example, are more fundamental than the claims of those who would benefit. In most situations, it is clearly unethical to sacrifice one human being to save many. Consequently, it is not solely medical and scientific benefits that matter—ethical considerations matter, too.

Furthermore, we must be careful not to overstate the benefits of animal research. Animal research certainly does not benefit all humans and all animals. Millions of humans die every year because of starvation, malnutrition, and lack of basic medical care. Their lives are not improved or saved thanks to animal research (Nobis 2012: 251). Thus, animal experimentation benefits some humans, but not all. Moreover, while some animal research is beneficial to some animals (e.g., when medication is developed to treat their ailments and diseases), not all animals benefit from such medical advancements. Rather, if animals do benefit from animal research, they are often members of certain species which are useful to or appreciated by humans, such as companion animals and farmed animals. Furthermore, not all animal research is directly beneficial to humans and animals. Much research is done without any aim or expectation of saving or improving human and animal life. An example is basic or fundamental scientific research, which aims to better understand natural phenomena as such. Its results may one day become useful and applicable, but the research is not mainly conducted with this aim in view. Another example is research undertaken for trivial purposes, such as to test the safety of cosmetic or cleaning products. While such tests are forbidden in the European Union (European Union 2009), they are still legally conducted in other parts of the world.

In this chapter, I will mostly pass over research for such futile goals, as the situation presents itself quite simply: the conflict resides between the vital and fundamental claims of animals, on the one hand, and the trivial interests of humans (in new cosmetic products and the like), on the other. It is hard to see how our non-vital interests or mere preferences for new cosmetics could override animals’ vital and fundamental claims. While research animals have claims to the absence of hunger and thirst, to the absence of suffering, to the pursuit of normal behavior, to be free from discomfort and distress, to lead a self-determined life and to continued existence (as argued in Chap. 4), humans merely have a preference interest in new cosmetic products—not a claim. Therefore, in the following discussion, I focus on scenarios in which animal research is conducted to improve human and animal health and quality of life.

One might wonder why I do not say that animal research is saving human lives (and sometimes animal lives, for that matter). Instead, I concentrate on animal research which extends lifetime and improves health, welfare, and quality of life. As Christine Korsgaard argues, the notion of “life-saving animal research” is, in many cases, inappropriate. After all, everyone will die at some point. Rarely is someone in a situation where she is saved from imminent death by an injection derived from animal research, for example. In most situations, medical treatments “tend to prevent certain kinds of emergency situations from arising at all, or simply to extend the life span” (Korsgaard 2004: 108). Admittedly, there are some scenarios in which a life is spared from premature death—notably the COVID-19 vaccines, which probably prevented millions of early deaths. Another example is chemotherapy to treat cancer: if successful, a person’s lifespan is often considerably extended. We have to be careful to neither overestimate nor underestimate the benefits of animal research. Nonetheless, in most cases, it is accurate to talk about medication healing certain conditions or improving quality of life, instead of talking about medication as “life-saving.” Neither is animal research equivalent to lifeboat scenarios—that is, scenarios in which the life of a human is directly opposed to the life of an animal in a lifeboat—as many studies and animals are needed in order to eventually develop a treatment for certain health conditions. That is, there is likely not one trial with a certain number X of animals that will save number Y of humans. Animal research is more complex than that.

Nonetheless, some research with animals certainly promotes human health, increases our well-being, and extends our lifespan. Furthermore, some studies conducted with animals benefit the animals’ own health, notably studies with animals which result in treatments and medication for their ailments. Finally, there is also behavioral research—that is, research which helps us to better understand the behavior of animals. In what follows, I focus on these types of research with animals: in what cases is such research ethically justified?

6.2 Is Animal Research Under Current Guidelines Morally Justified?

This section is partly based on Martin (2021). I thank Wiley for their permission to reuse the material.

One might argue that research animals’ claims are already fairly considered: enough protection and attention are applied to prevent unjustified forms of harm. After all, substantial ethical principles and legal guidelines are already in place to govern animal research. Furthermore, Animal Ethics Committees are meant to ensure that only those studies which are justified from an ethical perspective receive approval. In the following, I discuss whether this reasoning is sound.

What principles are currently in place to regulate animal research? While guidelines in various countries differ in their specific requirements, it is possible to identify some basic research principles that are mandatory for animal research in most countries. The first requirements are the “3Rs,” proposed in the late 1950 by William Russell and Rex Burch (Russell and Burch 1959). These 3Rs are: Replace (i.e., whenever possible, research animals should be replaced by an alternative non-animal method or model); Reduce (whenever possible, the number of research animals should be reduced, provided statistical validity can be guaranteed); and Refine (whenever possible, methods should be used which minimize the distress experienced by the research animals or which improve their welfare). Further requirements accepted by animal research guidelines, such as the American Animal Welfare Act, the research codes of the Canadian Council on Animal Care in Science, and the DIRECTIVE 2010/63/EU of the European Union, include social and scientific value, scientific validity, and review by an independent Animal Ethics Committee (European Union 2010; United States Code 2015; Canadian Council on Animal Care 2020).¹ Hence, the 3Rs, social and scientific value, scientific validity, and independent review by an Animal Ethics Committee currently constitute the basic requirements for animal research in most countries. But are they sufficiently protecting animals from unjustified harm in research, in practice?

First, let us discuss the 3Rs, which are probably the most widely accepted principles for limiting harm to research animals. Nowadays, they are implicitly or explicitly required by most animal research guidelines, regulations, and codes. The first R is replacement. Russell and Burch (1959: Chap. 5) distinguish between relative and absolute replacement. In absolute replacement, research is conducted without any sentient animals at all, at any stage. In the case of relative replacement, animals are still used in experiments, yet with as little distress as possible (e.g., their cells, tissues, or organs are used only after their death). Russell and Burch suggest hierarchizing the 3Rs: Replacement takes precedence over Reduction, and Reduction takes precedence over Refinement. Refinement should only be applied after it was ensured that replacement is not possible, and after the number of animals has been reduced to the strict minimum.

In practice, however, researchers often hierarchize the 3Rs differently. According to a study conducted by Nuno Henrique Franco et al. (2018), many researchers are skeptical of the idea that all animal research can be replaced by non-animal alternatives: non-animal methods are “mostly seen as complementary to animal use, or at best as potential alternatives to some steps in biomedical research” (Franco et al. 2018: 18). Furthermore, the participants in the survey—researchers undergoing training in laboratory animal science in four European countries—put Refinement first, and Replacement last, contrary to the hierarchy initially suggested by Russell and Burch.

Admittedly, one might argue that the replacement and further reduction of research animals is not possible, because animals are the best model for many diseases and conditions. However, such a view is flawed. If we assume that one of the ultimate aims of research with animals is to heal and improve conditions afflicting humans, then humans would naturally be better research subjects than animals.² After all, using humans in research instead of animals would avoid many problems related to the extrapolation of research results across species. Understandably, due to ethical issues, we refrain from conducting invasive and deadly studies with humans—a practice still widely accepted in the case of animals. It is undeniable that some experiments with animals have greatly contributed to medical progress in the form of treatments and therapies, such as vaccines. But as Robinson et al. (2019: 11) note in a review article on the current state of animal models in research, “[o]ver the past decade, however, it has become increasingly clear that conclusions drawn from animal studies cannot be simply transferred to human studies.” That is, animal models may not always be the most useful ones for studying diseases and conditions afflicting humans.

There are further issues regarding the implementation of the 3Rs. Reviews of animal studies showed that in many research areas—such as prolonged pain research—the numbers of animals used (such as mice) has been rising over the last 15 years, instead of falling (Balcombe et al. 2013). Generally, the number of animals used in research is holding steady or even increasing in most countries (Goodman et al. 2015; Taylor and Alvarez 2019). Therefore, one cannot say that the use of animals for research has been replaced or reduced overall, as demanded by the 3Rs. Admittedly, it is possible that the number of animals per experiment has been reduced while more animal experiments were conducted, which would explain this stagnation or even increase in numbers. Nonetheless, if a main aim of the 3Rs is the absolute or relative replacement of animals in research, then this goal has not yet been achieved.

Furthermore, reporting of the 3Rs in studies is often insufficient: many studies do not report whether and how the 3Rs were implemented in the study design (Taylor 2010; Balcombe et al. 2013; Bara and Joffe 2014). One may object here that researchers are obliged to adhere to research guidelines and thus indirectly respect the 3Rs, as the latter are prescribed by many guidelines and come under scrutiny during evaluation by AECs. However, as the authors of one study noted, “the growing proportion of the number of studies subjecting mice to prolonged pain and the lack of any change in the number of mice being subjected to prolonged pain reported elsewhere in this paper suggests that adherence to guidelines and/or animal use committee requirements is not translating into significant progress from a reduction or replacement perspective” (Balcombe et al. 2013: 17).³ All these problems have led some animal ethicists to call the practical and legal implementation of the 3Rs a “regulatory failure” (Blattner 2019: 168).⁴

Let us now turn to social and scientific value. As with research with humans, animal research should only be conducted if it generates new knowledge, is useful to society, or replicates and confirms previous results. However, even if one assumes that the expected value should only benefit humans (and not necessarily the individual animal or animal species in question), there are still—as outlined earlier—experiments which do not address any crucial human health problems but merely serve trivial purposes. Examples include the safety testing of new cosmetic products and cleaning detergents on animals, which is still permissible and conducted in some countries. Tests in these domains do not expand existing knowledge, nor do they serve any important scientific goal. Another example is research that is responsive to rather trivial health or welfare issues of only few humans, such as non-painful, non-harmful, and non-contagious skin irritations or fungal infections.

Research that does not respect the requirement of social and scientific value effectively gives trivial human interests priority over animals’ legitimate claims to be free from suffering and discomfort, to pursue normal and species-typical behavior, to live a self-determined life, and to enjoy continued existence. Those groups of animals likely to be involved in such research can be deemed particularly vulnerable insofar as they are at greater risk of not having their claims considered as they should.

A further animal research requirement endorsed by most countries is scientific validity. Studies should be conducted with clear scientific objectives and hypotheses in mind, the methodology should be appropriate and valid, the statistical analysis should be sound, and the study should be reported in a way that is comprehensible to other researchers, so that it can be replicated. Studies—whether conducted on humans or on animals—which fail to fulfill these conditions are unethical, as they are wasting precious resources, researchers’ time and animals’ welfare and possibly lives, and may result in harm for both humans and animals: “if poorly conducted studies produce unreliable findings, any suffering endured by animals loses its moral justification because their use cannot possibly contribute towards clinical benefit” (Pound and Bracken 2014: 3). If a study cannot be replicated or fails to generate reliable knowledge, then the death and suffering endured by its research animals becomes simply futile.

In the case of animal research, some studies are methodologically wanting or inadequately reported. As a consequence, the results are irreproducible and thus useless, which goes against the principles of evidence-based medicine. Problems include the use of an insufficient number of animals for yielding reliable and statistically sound results; lack of randomization and blinding; investigation of too many different and potentially interfering parameters at the same time; flawed design, methods, or statistics; and finally, poor reporting and insufficient description of the experiment (such as the sex, age, and health-status of the animals involved as well as the laboratory conditions) such that the study cannot be repeated or false-positive results are published (Hackam 2007; Kilkenny et al. 2009; van Luijk et al. 2014; Green 2015; Avey et al. 2016). This is why some researchers talk about a reproducibility crisis in different fields, including animal research (Baker 2016).

Once recognized, these methodological issues have led to the creation of various guidelines. The Planning Research and Experimental Procedures on Animals: Recommendations for Excellence PREPARE guidelines help researchers to plan their study adequately (Smith et al. 2018). Furthermore, the Animal Research: Reporting of In Vivo Experiments ARRIVE guidelines of 2010 provide researchers with a checklist designed to improve the reporting of animal research (Kilkenny et al. 2010). Yet despite the endorsement of these guidelines by over 100 academic journals and funding agencies, they are poorly known by researchers and are often not followed (Baker et al. 2014; Vogt et al. 2016). That is, the anticipated improvements in reporting animal research have not yet been achieved. Therefore, in 2020, the ARRIVE guidelines were updated and reorganized in order to simplify their use (Du Percie Sert et al. 2020). Time will tell whether the reporting of animal research will be substantially improved with the updated guidelines. In any event, animals who are likely to be involved in methodologically deficient studies can certainly be described as particularly vulnerable. Their claims to avoid unnecessary suffering and discomfort, their claim to express and pursue normal and species-typical behavior, their claim to lead a self-determined life, and their claim to continued existence were not given due weight when they were involved in studies that are problematic from a scientific perspective.

A final requirement for ethical animal research is independent review by an external committee. At first sight, one may think that Animal Ethics Committees fulfill the role of independent, unbiased, and fair reviewers—that is, that they actually serve as defenders and guardians of animals’ interests. Correspondingly, one might contend that research animals receive the consideration they are due. However, this is not necessarily the case: evaluation by an Animal Ethics Committee is not legally mandatory in all countries (Fakoya 2012). Furthermore, the composition of Animal Ethics Committees can be biased regarding animal research, which may result in an unfair consideration of animals’ interests. After all, Animal Ethics Committees often consist of animal researchers and veterinarians who themselves undertake animal research and depend on it for their own research (Schuppli and Fraser 2007; Hansen 2013). In such cases, it is unclear whether one can really speak of genuinely independent review, as there may be a bias toward and in favor of animal research: animals’ interests and the importance of the study’s aims may not be impartially assessed according to their respective importance. Additionally, there is disagreement amongst Animal Ethics Committees about key issues, such as what ethically acceptable and thus approvable animal research consists in, or what the exact role of the committee members should be (Plous and Herzog 2001; Ideland 2009; Varga et al. 2012). That is, judgements about the acceptability of animal research studies may vary from one committee to another and from one country to another: not only do the requirements differ between countries, but the composition of Animal Ethics Committees may also lead to different deliberations and outcomes.⁵ A further problem with current Animal Ethics Committees’ practices consists in the fact that they often do not predominantly discuss ethical issues, but rather focus on technical aspects such as experimental design and scientific validity (Houde et al. 2003; Ideland 2009; Varga et al. 2012). That is, many Animal Ethics Committees do not focus as much as they should on ethical issues—such as weighing the harms and benefits of a given study—but rather on the study design. Admittedly, as outlined earlier, scientific validity is a cornerstone of all empirical and experimental research. But ideally, studies submitted to Animal Ethics Committees should already be scientifically sound, for instance, because they have been controlled by a biostatistician and other experts. This way, Animal Ethics Committees could focus on their core task, namely, evaluating whether the study is permissible from an ethical perspective. In sum, there are no clear-cut agreements amongst Animal Ethics Committees and their members about what acceptable animal research amounts to. This is problematic for the animals involved in research studies: if Animal Ethics Committee members fundamentally disagree in most of the cases, are biased, or do not know what their role and task in the committee are, how can they then properly evaluate the studies?

So far, I have shown that currently implemented research requirements are often insufficiently respected: animals used in research are currently not, in fact, adequately protected from unjustified forms of harm. If the animals are involved in studies in which at least one of the above criteria—the 3Rs, social and scientific value, scientific validity, and independent review by an Animal Ethics Committee—is likely to be disrespected, then the animals concerned can be considered particularly vulnerable, inasmuch as their interests are not given the weight they are due, and they are at an increased risk of incurring unjustified harm or mere wrongs. Furthermore, even if currently implemented research standards were respected, a problem would remain. Currently implemented research standards do not take the moral worth and legitimate claims of animals seriously—that is, they are insufficient from an ethical perspective.⁶ I turn to this point now.

6.3 Just Animal Research: Extending Requirements for Research with Humans to Animals

This section is based on Martin (2022). I thank Cambridge University Press for the kind permission to reuse this article.

In the last section, I argued that many animals can be considered particularly vulnerable under current guidelines for animal research: their interests do not receive the protection they are due, since basic research requirements are often not respected. However, the situation is actually even more dire than suggested in the last section: currently implemented guidelines for animal research are insufficient from an ethical perspective as well. If we accept that animals count morally for their own sake, that they have basic claims, that similar claims should have the same weight, and that we should avoid speciesism, then we must rethink the conditions under which research with animals can be conducted.

Earlier, I defined as “particularly vulnerable” those beings who are at a higher risk of having their legitimate claims unjustly considered. To have one’s claims unjustly considered means, among other things, that they are not considered in an impartial way. From this perspective, speciesist considerations can be regarded as unjust: animals’ interests are more easily ignored or discarded precisely because they are the interests of animals. Animal research as laid out in the last section—even if all currently implemented research requirements are perfectly respected—is a deeply speciesist practice: animals are enclosed in cages, they are bred with diseases, and they are killed prematurely—practices we would not undertake with human research subjects. If we truly wanted to respect animals’ basic claims, we would thus be restricted in what we would be allowed to do with them before, during, and after research. Inducing diseases in animals, for example, would no longer be ethically permissible, nor would experiments which cause the animals substantial suffering or which inevitably lead to their deaths. The same consequence applies to experiments that severely restrict animals’ opportunity to pursue species-typical behavior, such as maternal deprivation studies.

Consequently, one might defend the view that research with animals should be entirely abolished on the grounds that it is highly unethical, exploitative, and incompatible with a commitment to non-speciesism. However, this is not the stance I am going to take here. The reason is that ethical research with animals is possible, in my view. Indeed, many groups of humans cannot consent to their participation in research because they lack the cognitive capacities required for informed consent. Examples are infants and cognitively disabled individuals. Nonetheless, research with them is, in many cases, permissible under certain conditions, and often highly desirable. We should not exclude these groups from research, since this would deprive them of all potential benefits from the research results (Shepherd 2016). Therefore, we do permit research with groups unable to consent under certain conditions: if the study involves little or no risk and is not at all or only minimally harmful; if the study cannot be undertaken with another population; if those involved in the study will benefit from the results and their participation is thus in their best interest, determined, for instance, via consent by proxy; and if the involvement of this specific group has been approved during independent review.⁷ The same reasoning can be extended to animals. Non-harmful and minimally harmful low-risk research with them should remain permissible, since a complete abolition of all animal research would deprive animals of research results that are beneficial to them individually, to their species, or to other species. If animal research is modeled in a way that respects animals’ basic claims, then it remains permissible from an ethical point of view. That is, current animal research requirements do not need to be complemented and refined by further principles. Rather, they need to be entirely remodeled: research with animals should be made more similar to research with humans.

And research with humans is strongly regulated. For example, we are not allowed to render humans sick so that they can serve as study subjects;⁸ we are not allowed to close them in without the option of leaving anytime they want; and most definitely, we are not allowed to kill them at the end of studies (e.g., to dissect their brains). Despite medical research’s goal to promote health, knowledge, and well-being at large, there are certain limits regarding research with humans. In order to avoid the exploitation of research participants, protective ethical requirements have been put in place.

These research requirements should be sensitive to humans’ basic claims, such as bodily integrity and respectful treatment (Tavaglione et al. 2015): it is impermissible to infringe upon or violate the claims of a few human research participants for the sake of health and knowledge of many individuals. In addition, formal requirements have to be respected. An example is scientific validity: research that does not meet this requirement is void, as the results are useless from a scientific perspective. The same applies to independent review by Institutional Review Boards (IRBs).⁹ Review by IRBs ensures that the study pursues an important aim, that the methodology is sound, and that research participants are chosen fairly.

In recent years, quite a few philosophers and bioethicists have suggested that we should render animal research more similar to research with humans. However, they have mostly focused on the extension of single requirements, and did not suggest comprehensive accounts.¹⁰ Nonetheless, two more complete accounts have been presented recently. In their article “A Belmont Report for Animals,” Hope Ferdowsian et al. (2020) argue that the key ethical principles of the Belmont Report—that is, respect for persons and their autonomy, beneficence, justice, and special protection for vulnerable individuals and populations—should be extended to animals used in research. In a similar vein, Lauren van Patter and Charlotte Blattner (2020) argue in favor of the extension of the principles of non-maleficence, beneficence, and voluntary participation to animal research. They assert that these “principles represent a starting point for developing more comprehensive ethics protocols for research with animals” (van Patter and Blattner 2020: 173). These are important and convincing contributions to the literature. Nonetheless, as I will show, they can and should be further refined and complemented. To do so, it is necessary to look more closely at requirements in place for research with humans. A fairly complete account has been suggested by Ezekiel Emanuel, David Wendler and Christine Grady (Emanuel et al. 2000). They examined different research guidelines and medical research codes, and established a list of seven requirements that should guide all research with humans:

• (1) social value,

• (2) scientific validity,

• (3) independent review,

• (4) favorable risk-benefit ratio,

• (5) fair subject selection,

• (6) informed consent, and

• (7) respect for research subjects.¹¹

To summarize these requirements, research with humans should be socially and scientifically useful, hence, it should address important societal and scientific questions, increase and foster knowledge, and yield valuable results for society. Studies should rely on accepted scientific principles and methods to produce reliable and statistically sound results, which must be described in a comprehensible manner so that the study can be replicated by others. Independent review requires review and approval of the study protocol by an independent committee. Fair subject selection demands that justice and fairness prevail when choosing the population with which the research will be conducted. This means that researchers should choose the research participants based on the study’s goals. In practice, this implies that researchers should, for example, refrain from enrolling individuals who are readily available to take high risks (e.g., due to terminal disease or because they are tempted by financial rewards or admission to medical care during the study), especially if the study can be carried out with other populations. Favorable risk-benefit ratio requires a just distribution of burdens and benefits: risks should be minimized, and be proportional to the expected benefits of the study (for the individual concerned, but also for society at large). Informed consent requires that research subjects consent to their participation after having been given all relevant information and that they understand their involvement in a clinical trial with its concomitant risks. However, some research subjects cannot consent, due to the nature of the study (e.g., research which focuses on unconscious patients in emergency rooms, or patients in a coma), or because they lack the required cognitive capacities for giving informed consent. In this case, consent by proxy is required in the participants’ best interest or in accordance with their presumed values. Furthermore, harm and risks should be minimized. Finally, respect for research subjects means that participants be permitted to withdraw from the clinical trial at any time, that their privacy be protected by confidentiality, that they be informed of newly discovered risks, benefits, and the study’s results, and that their welfare be maintained throughout the study.

In what follows, I argue that these requirements can and should be extended to animals used in research, and I show how this can be done in practice. Note that I discussed social and scientific value, scientific validity and independent review in the previous section, as they are already required for animal research in most countries. However, as outlined earlier, they are not always respected, and in what follows, I outline what their ideal application should look like.

Let us start with social and scientific value. As with research involving humans, research with animals should only be conducted if it addresses important societal and scientific issues, yields valuable results for society at large, generates new knowledge, or replicates and furthers previous results. The aim of most animal research studies nowadays is to eventually benefit and improve human health and welfare. However, if animals have basic claims, this aim is problematic: if studies are pursued on and with animals, then the benefits should also be useful to individual animals or their species, not solely to humans. If animal research is predominantly responsive to humans’ health priorities, then animals carry the undue burden of being used in research from which they do not benefit—which is speciesist. Many animals form part of a shared human-animal society, as humans live with them, and both sides can benefit from inter-species relationships. Furthermore, humans use or affect many animals directly or indirectly with their actions, for example, in the case of domesticated and wild animals. Correspondingly, these animals’ interests and health priorities should also be considered in the common good. In practice, this means that the beneficiaries of the study’s results must be identified when establishing animal research protocols. If they are solely a very small human group, or if the study serves to investigate or promote the trivial health issues of a small number of humans, then the study’s aims and the allocation of resources to this end should be reconsidered if animals are to be involved.

A further issue related to social and scientific value arises due to the lack of obligatory registries for past and ongoing animal studies, as it is required and implemented for research with humans in many countries. Often, negative results from animal research are not published. This may lead some research groups to undertake research that was already conducted by other colleagues, but not published. This, in turn, results in a waste of researchers’ time and other resources and disrespects the requirement of social and scientific value, as no new knowledge is generated. To overcome this issue, researchers and scientific journals should be encouraged to publish negative results, and obligatory research registries should be established. Admittedly, some administrative and practical difficulties need to be surmounted to establish such registries (Baker et al. 2014). For example, steps have to be taken to ensure that researchers cannot use such registries as a source of inspiration for their own research, and procedures have been suggested to this end (Bert et al. 2019). Nonetheless, registries may be useful for preventing the multiplication of already conducted studies which did not result in any new knowledge. That is, such publicly accessible registries could reduce publication bias and thus respect the requirement of social and scientific value (ter Riet et al. 2012; Kimmelman and Anderson 2012; Muhlhausler et al. 2013; Jansen of Lorkeers et al. 2014).

A second requirement for animal research is, as discussed earlier, scientific validity. To respect this requirement means that enough animals must be enrolled in studies to yield reliable, statistically sound results. To avoid confirmation bias, the studies should be blinded and randomized. Furthermore, experiments need to be reported in a comprehensible manner, enabling other researchers to replicate the study. This presupposes a detailed description of the experiments—including the sex, age, and health status of the animals involved, along with the method and details of the statistical analysis.

As outlined above, the requirement of scientific validity is not always perfectly respected in research—whether with humans or with animals—which is why some researchers talk about a “crisis of reproducibility” (Begley and Ellis 2012; Begley and Ioannidis 2015; Jarvis and Williams 2016). If research with animals is conducted, it should be ensured by the researchers, Animal Ethics Committee, and journal editors that the methods and statistical analysis are well described and sound. This can be done by offering researchers better training about methods and potential biases, as well as by making it obligatory for all articles involving animal research to follow the various guidelines in place for planning and reporting animal research before being accepted for publication. One option to enforce compliance with such reporting would be for journal editors and reviewers to reject articles that do not fulfill these requirements. This may provide an incentive for researchers to improve their manuscripts accordingly. In turn, research laboratories ought to train their researchers to plan and report their studies so that they can more easily fulfill this requirement.

A further requirement for research with humans is independent review by an Institutional Review Board IRB. As discussed earlier, independent review is also required for animal research in most countries; however, the current evaluation practices of Animal Ethics Committees AECs have several issues. AECs are not yet obligatory in all countries, nor do they necessarily comprise totally independent evaluators—that is, evaluators who are not potentially biased. Furthermore, different AECs may come to opposite verdicts for many studies when evaluating the very same protocols, revealing a lack of clear-cut standards for ethical animal research (Plous and Herzog 2001). A further issue is related to the fact that AECs often do not follow international guidelines, but rather national ones; hence, approval by an AEC in one country may imply a very different protection standard than in another country. Finally, a study conducted in Switzerland produced evidence that the reporting of methods in research protocols is often insufficient yet nonetheless approved by Swiss Animal Ethics Committees due to implicit confidence rather than evidence of scientific rigor (Vogt et al. 2016). While the focus of the study was on Switzerland, similar situations may occur in other countries.

However, this does not mean that AECs are problematic per se and should be eliminated. Rather, they should be reformed. AECs—similar to IRBs—fulfill the important functions of assessing studies’ aims and methods as well as approving the research populations. In order to adequately fulfill this role without undue influences, it should be ensured that AEC members are factually independent from the specific research institution and researchers whose protocols are under evaluation. Another option would be for potentially biased committee members to have to leave the room during the discussion of research protocols which could give rise to conflicts of interest. In addition, all committee members should be appropriately trained. Furthermore, at least one trained ethicist ought to be involved in the evaluation process (Nobis 2019), to provide ethical expertise and to ensure that the committee actually focuses on ethical issues and not predominantly on scientific validity. Moreover, clearer criteria for ethical animal research have to be put in place to reduce variation among the AECs’ verdicts. For example, this can be achieved by establishing binding international guidelines for ethically acceptable research with animals—as is already in place for research with humans. An example is the Declaration of Helsinki, which presents universal ethical principles for research with humans (World Medical Association 2013). It was established in 1964 by the World Medical Association, and while it is not legally binding, it has nonetheless positively influenced and inspired many national legislations and regulations which govern research with humans. Similar international guidelines or declarations for research with animals would make the evaluation process less arbitrary, as similar standards for animal research would be in place worldwide. After all, animals of the very same species should benefit from similar protection standards, regardless of where exactly the research is undertaken around the world. This would also, in turn, reduce the risk of researchers leaving one country to conduct animal research in another country with less stringent reviews and laws.

A further requirement in place for research with humans is fair subject selection. That is, researchers should justify why they enroll specific groups in their study. In current animal research practices, animals are frequently exposed to more risks than humans, while receiving no benefits for themselves, or only a few. As Chong Choe Smith writes: “nonhuman animals bear a disproportionate share of the burdens of research without a showing of sufficient justification—for example, a showing that there are morally relevant and significant differences to justify the ethical use of nonhuman animals in research” (Choe Smith 2014: 181). In principle, researchers should always choose the best model for their research. But in practice, some species, such as rodents, may be more frequently used in animal studies because they are easily available and do not demand a huge investment of space and money, even though they are not themselves afflicted by the condition under investigation. However, if they are an inappropriate model for the condition being studied, then the study should not be conducted with them in the first place. That is, fairness ought to prevail when enrolling animal research subjects: animals should only be used in studies if they are afflicted with the condition under investigation, if they stand to benefit directly or indirectly from the study’s results, or if the risk and harm level is so low that benefits to other species than their own can be justified. This means that Animal Ethics Committees should scrutinize the animal population chosen for study purposes, and demand a justification for why a specific species was singled out. Animal Ethics Committees should treat animals in research similarly to human research subjects who cannot express themselves for or against their participation in research, such as persons in a coma, infants, and severely cognitively disabled individuals. In such cases, Institutional Review Boards should check whether enrolling these groups is necessary for achieving the study’s aims, or whether these particular groups were, for instance, selected for mere convenience. The same reasoning can be extended to research animals, as their situation is similar—that is, dependency and inability to speak up for themselves.

Let me now turn to the requirement of a favorable risk-benefit ratio. We refrain from conducting studies with human research populations if the harm and risk involved is too high for them, even if the results obtained would be highly beneficial to society at large. And certainly we would (and should) not accept the death of human research subjects as a normal consequence of a study. That is, studies with humans must have a favorable risk-benefit or harm-benefit ratio. However, animals seldom benefit from the research undertaken on them: the results obtained predominantly serve the human species—a morally problematic distribution of burdens and benefits. Note, though, that research with humans may be permissible even if the research subjects themselves do not benefit from it—if the research participants can consent to the study and are informed of the concomitant risks, or if the harm and risk threshold is so low that participation is permissible without direct consent (when the participants are unable to give informed consent themselves). In the latter cases, consent by proxy in the best interests of these individuals and approval by an IRB is needed. The acceptable risk threshold in the case of humans unable to give informed consent remains disputed in the literature (Kopelman 2004; Binik 2014). I cannot define a harm- and risk threshold for animals here, as this would be a task for a separate project. However, it can be noted that there should be some upper harm and risk threshold for animal research, as is the case of research with humans (Beauchamp and Morton 2015). Likely, such risk threshold in the case of animal research should be similar to risk thresholds in research with humans who cannot speak up for themselves.

This brings me to the requirement of informed consent. Readers may be surprised to learn that the extension of informed consent to research animals is actually quite frequently discussed in the literature. Hope Ferdowsian and Chong Choe, for example, state: “although many animals exhibit intelligence, rationality, and maturity, language barriers prohibit informed consent” (Ferdowsian and Choe 2013: 236). Holly Kantin and David Wendler speak of “the lack of a common language” (Kantin and Wendler 2015: 466), and Jane Johnson and Neal Barnard mention “communication barriers” (Johnson and Barnard 2014: 133). However, these characterizations are misleading. The concept of language and communication barriers suggests that if animals could talk, then the ethical challenge provided by informed consent would be resolved. But much more than merely language and communication skills are needed for providing informed consent. Informed consent presupposes cognitive capacities such as rationality, the ability to know how to act intentionally in one’s best interest, understanding complex circumstances, and the like. According to Richard Healey and Angie Pepper, animals are incapable of giving informed consent because they “cannot understand, form, and communicate complex intentions about normative concepts like rights and duties” (Healey and Pepper 2021: 1225). That is, animals are incapable of giving waivers for their bodily integrity and thus authorizing others to undertake an otherwise impermissible action, such as administering a drug.

Nonetheless, there is another understanding of informed consent that can be fruitfully applied to the case of research animals: assent and dissent (Kantin and Wendler 2015; Fenton 2020). Many animals, such as dogs, can show us what they want with their actions—for example, their food preferences, or which walking route they wish to take with their human guardian. Animals’ embodied actions can serve as indicators of their wishes and preferences; their agency helps us to understand their will and their intentions. Applied to animal research, this means that some form of consent can be obtained by observing animals’ behavior: many animals are physically capable of showing whether they wish to partake in research or not. Hence, researchers should observe if animals show any signs of dissent (expressions of discomfort or pain, escape actions, etc.). Although it may be difficult to determine the exact source of unease in research animals (since it may also be due to fear, hunger, and the like), paying close attention to dissenting behavioral cues can help to determine whether the animal is at ease during a study. In practice, this may mean that different methods or analgesia should perhaps be explored to maintain animals’ welfare. In the case of strongly dissenting animals, their exclusion from research must be considered.¹²

In some cases, it is also possible to obtain assent from research animals, by which I mean their approval of what is happening to them. Assent can manifest itself as animals’ not showing disapproval or resistance, their showing approval of what is happening to them, or their affirmative behavior, such as when they join a study setting deliberately, of their own will.¹³ An example are chimpanzees in reserves who participate in studies involving video games which test their cognitive capacities: they often engage in such research of their own will, since it presents them with a welcome distraction from their daily life.

This means that in practice, close attention should be paid to animals’ behavior and preferences during studies. Researchers should look out for potential behavioral cues that are signs of assent, and steps should be taken if dissent is perceived. If one is skeptical about embodied assent or dissent, or in cases in which it may be hard to perceive—for example, in fish—consent by proxy in the animals’ best interests can be considered, provided by human guardians of animals (e.g., in the case of companion animals), or by one or several persons who were officially assigned with this task.

A final requirement for ethical research with humans, according to Emanuel, Wendler, and Grady, is respect for research subjects. In practice, this means that research participants should be allowed to withdraw at any time from a study (an aspect I already touched upon when discussing respect for animals’ dissent). Further considerations related to respect for human study participants include: ensuring privacy protection, immediately informing research participants of newly discovered risks or benefits, and communicating the clinical study’s results to the participants. To be sure, these requirements may not seem relevant or applicable to the case of animals. However, there is a further understanding of respect for research participants which is relevant, namely, that researchers maintain the welfare of their research subjects. This can be described as beneficence. Yet current research practices involving animals often fall short of this requirement. For example, it is common practice to induce harmful conditions and diseases in animals, such as cancer or lameness, for the purpose of research—a practice we would deem inacceptable if humans were involved. In my view, non-speciesist research with animals requires that we respect animals’ claims to bodily integrity and to the absence of disease, just as we do in research with humans. In practice, this means that it should no longer be allowed to induce diseases and other harmful conditions (such as cancer) in animals.

This brings me to another important point: bringing animals into existence merely to serve as research subjects. Many animals are bred for research purposes, and they will normally spend their whole lives in research settings (such as small cages), with limited possibilities to pursue individual and species-typical behavior. These animals are not brought into existence for their own sake; rather, they are exclusively bred as mere means to the end of research, and usually they will experience a rather low quality of life. If we want to respect animals’ basic claims, then we must regard such pure instrumentalization in the form of selective breeding as problematic from a moral perspective.¹⁴ Indeed, we usually think that it is morally reprehensible to bring children into existence solely as mere means to an end, such as serving their parents; the same should hold for research animals. To be sure, humans can bring domesticated animals into existence, but these animals must always be valued for themselves: they cannot exclusively be bred for the purpose of animal research alone, being deliberately infected with diseases or having other harmful conditions inflicted upon them. This means that non-harmful or minimally invasive research with already existing sick or healthy animals remains ethically permissible, as long as it is in the interest of these animals to participate in a given study, or the (additional) harm and risk level is low. That said, breeding animals solely for the purpose of research is morally problematic if we want to respect animals’ basic claims.

Lastly, respect for animals also means that their claim to continued existence must be respected: research animals should not automatically be put to death once a study ends, unless unavoidable suffering or pain makes euthanasia necessary.¹⁵ If we were no longer allowed to breed animals for research purposes, studies would then have to be conducted with already existing animals, such as companion animals or domesticated animals who may themselves benefit from the research results. That is, we would have “animals-as-patients” in research (Johnson and Degeling 2012). These animals would likely have a home where they are taken care of; if not, rehoming or placing animals in sanctuaries should be envisaged.

6.4 Research Animals as a Particularly Vulnerable Group

What follows from the arguments presented here with regard to research animals’ vulnerability? I argued, in a first step, that animals can be considered particularly vulnerable under current principles governing animal research, as the requirements in most current guidelines—the 3Rs, social and scientific value, scientific validity and independent review—are often not fully respected. Therefore, many research animals can currently be qualified as a particularly vulnerable group: they are at increased risk of not being given what they are due. In a second step, I argued that current research standards for animal research are insufficient from a moral point of view, as they do not duly protect animals’ most basic claims. I further showed that, in order to respect animals’ fundamental claims, we do not need to abolish animal research entirely, as this would deprive animals of research findings which could be beneficial to individual animals, to their species, or to other species. Instead, I argued that we can model animal research on research with humans. After all, research with humans who cannot speak up for themselves and consent to their participation in studies is permissible as long as some basic requirements are met and the risk level is low. The same can—and should—apply to animals’ involvement in research. That is, the ethical principles and requirements in place for research with humans should be extended to animals used in research. In particular, I showed how the requirements of social and scientific value, scientific validity, independent review, fair subject selection, favorable harm-benefit ratio, informed consent, and respect can be extended and applied to research with animals. It follows that it should no longer be allowed for humans to breed animals for the sole purpose of research, to induce diseases and other harmful conditions in them, and to prematurely kill them.

If one takes the arguments proposed here seriously, it appears that only non-invasive animal research is ethically permissible. Examples include behavioral studies, harmless or minimally invasive practices such as drawing blood samples, and the use of the animals after their natural death. Further cases of admissible research are those in which “the disease or condition being investigated is one that naturally occurs in the study animal; the animal enrolled in the experiment is already afflicted with that disease or condition; and participation in the research offers the chance of benefit (or no more than minimal risk) to the individual participant” (Johnson and Barnard 2014: 139).

If we take respect for animals’ basic claims as the starting point for ethical animal research, we must acknowledge that most animals currently used in research are particularly vulnerable: many, if not most, current research practices are deeply speciesist and disregard animals’ most basic claims merely because they belong to animals. Importantly, though, not all research animals face a higher risk of having their claims unjustly considered in all circumstances. Rather, vulnerability among research animals is a matter of degree. The situation for particularly vulnerable animals therefore presents itself similarly to the case of research with human beings: not all human research subjects are particularly vulnerable; rather, whether an individual or population can be described as particularly vulnerable depends on the specific context of the study, the specific population involved, and the study protocol. Moreover, to regard all animals as particularly vulnerable research subjects would mask the fact that there are different types of studies (behavioral research, non-harmful studies, and invasive studies), different review boards with more or fewer (speciesist) biases, different animal species with different needs, varying risk thresholds, diverging guidelines in various countries, and so on.

How, then, do we reduce animals’ vulnerability in research to an acceptable level? In the short term, AECs have a role to play: when reviewing research protocols, they can and should identify potential unjustified harms in a given research protocol, and take active steps to lower the risks.¹⁶ That is, the specific protection depends on the particular study protocol, the species in question, and the type of claim that is more likely to be ignored. Research animals’ situations can be improved by giving their claims more attention, by introducing consent by proxy in their best interest, by adapting research protocols, by lowering the level of harm and risk, or, in many cases, by not undertaking the research at all because it is problematic from a moral point of view. In the long term, we are morally required to take active steps to alter animal research to render it more similar to research with humans. For example, in the case of research with humans, it is not allowed to induce disease in a research subject to investigate its natural progression, nor is it allowed to kill research subjects once a study ends. The same restrictions should hold for research with animals. Ultimately, we should establish international guidelines for research with animals which strongly prescribe and regulate what can be done to and with these creatures, or which can at least inform national guidelines to render research with animals more comparable to research with humans—and thus more ethical.