Philosophical Concepts

The foundation for the philosophy of animal rights may be said to have been laid down by the Greek philosopher and mathematician Pythagoras of Samos circa mid-fifth century BC. Quotes attributed to him include

• “Animals share with us the privilege of having a soul. Alas, what wickedness to swallow flesh into our own flesh, to fatten our greedy bodies by cramming in other bodies, to have one living creature fed by the death of another?”
• “As long as man continues to be the ruthless destroyer of lower living beings he will never know health or peace.”
• “For as long as men massacre animals, they will kill each other” (Pythagoras of Samos 2015).

A somewhat contrasting view regarding animals having souls was expressed by the thirteenth-century Saint Thomas Aquinas, as he was reported to believe that animals did not have souls and thus were not worthy of moral concern, but that cruelty to animals was unacceptable because cruel behavior toward animals would progress to cruelty to other humans (Aquinas 1956).

From Pythagoras’s time until about the time of the Industrial Revolution (ca. late eighteenth century through the mid-nineteenth century), public interest in animal welfare, let alone animal rights, was largely nonexistent, as the average person throughout the world was more interested in personal survival. Two examples of the emerging interest in animal welfare were

1. The establishment of the first regulations pertaining to the welfare of farm animals in America found in the Massachusetts Body of Liberties issued in 1641, which contained the following regarding animal care:
   1. “Article 92. No man shall exercise any Tirranny or Crueltie towards any bruite Creature which are usuallie kept for man’s use.”
   2. “Article 93. If any man shall have occasion to leade or drive Cattel from place to place that is far of, so that they be weary, or hungry, or fall sick, or lambe, It shall be lawful to rest or refresh them, for competant time, in any open place that is not Corne, meadow, or inclosed for some peculiar use” (Massachusetts Body of Liberties 1641).
2. During the mid-nineteenth century, the emerging animal rights and welfare movement in England caught the attention of Queen Victoria and led to her recognizing the efforts of the Society for the Prevention of Cruelty to Animals (SPCA) (organized in 1824) to foster animal welfare and bestowing upon them the authority to add “Royal” to their name, indicating her support for their efforts (RSPCA) (Royal Society for the Prevention of Cruelty to Animals 2015).

Returning to the subject of whether animals have souls, the seventeenth-century French philosopher and mathematician Rene Descartes postulated that animals did not have souls; therefore, animals were not subjects of moral concern. In simplistic terms, Cartesian philosophy would allow humans to do whatever they wish with and to animals, without concern for any possibility of the animals suffering therefrom. Without souls, Descartes believed that animals could be viewed as being nothing more than equivalent to machines, and any vocalizations that an observer could possibly interpret as the animals being in pain should be of no more moral concern than a squeaky wheel on a wagon (Rene Descartes 2015). While the Cartesian philosophy might have been the philosophy of choice by biomedical scientists conducting surgical research with animals before 1846, when the first successful use of ether as an anesthetic was demonstrated (Robinson and Toledo 2012), it is unlikely that contemporary biomedical scientists would consider themselves as accepting of this philosophy.

Another ethical position, utilitarianism, was emphasized by eighteenth- and nineteenth-century English philosopher Jeremy Bentham, who published the following:

The day may come when the rest of the animal creation may acquire those rights which never could have been withholden from them by the hand of tyranny. The French have already discovered that the blackness of the skin is no reason why a human being should be abandoned without redress to the caprice of a tormentor. It may one day come to be recognized that the number of legs, the villosity of the skin, or the termination of the os sacrum are reasons equally insufficient for abandoning a sensitive being to the same fate. What else is it that should trace the insuperable line? Is it the faculty of reason, or perhaps the faculty of discourse? But a full-grown horse or dog is beyond comparison a more rational, as well as a more conversable animal, than an infant of a day or week or even a month, old. But suppose they were otherwise, what would it avail? The question is not, Can they reason? nor Can they talk? but, Can they suffer? (emphasis added)

This quote is given in its entirety to provide context. The last three phrases in the paragraph are frequently quoted by animal rights advocates and are generally considered to be the modern foundation for the philosophy of animal rights, as it effectively introduces suffering or, more accurately, sentience, that is, having the capacity to feel pain and suffer, into the moral and ethical equation. Simply, sentient animals should have the right not to suffer (Bentham 2007).

Even though Bentham’s quote would seem to imply that he anticipated the contemporary animal rights movement, and certainly opposed gratuitous mistreatment of animals, he did not oppose the use of animals by humans, including the use of animals in biomedical activities. In a letter to the editor of the Morning Chronicle (March 4, 1825), he stated, “I never have seen, nor ever can see, any objection to the putting of dogs and other inferior animals to pain, in the way of medical experiment, when that experiment has a determinate object, beneficial to mankind, accompanied with a fair prospect of the accomplishment of it. But I have a decided and insuperable objection to the putting of them to pain without any such view.” This stresses the foundation of the utilitarian view that weighs benefits and costs and focuses on the overall good an activity provides. Also, even though Bentham’s quote in the preceding paragraph is often quoted by vegetarianism advocates, there does not seem to be any reference to him being a vegetarian himself.

Philosopher Peter Singer, another utilitarian often quoted by animal rights activists, defines speciesism as “a prejudice or attitude of bias in favor of the interests of members of one’s own species against those of members of other species” (Singer 1975). In “A Philosophical Self-Portrait,” he elaborates that speciesism is an “essential philosophical view ” [that] is simple but revolutionary. Species is, in itself, as irrelevant to moral status as race or sex. Hence all beings with interests are entitled to equal consideration: that is, we should not give their interests any less consideration than we give to the similar interests of members of our own species. Taken seriously, this conclusion requires radical changes in almost every interaction we have with animals, including our diet, our economy, and our relations with the natural environment.” He goes on to indicate that his “ethical position is a form of preference-utilitarianism” (Singer 1997).

Since the philosophy of utilitarianism and the “ethical position of preference-utilitarianism” have been introduced at this point, it is worthwhile to provide an abbreviated explanation of these terms here. Utilitarianism is a form of philosophical thought that the “consideration of right conduct should be the usefulness of its consequences; specifically: a theory that the aim of action should be the largest possible balance of pleasure over pain or the greatest happiness of the greatest number” or “the belief that a morally good action is one that helps the greatest number of people” (Merriam-Webster Online Dictionary 2015). Preference utilitarianism may be defined as the equal consideration of the preferences of all individuals (both humans and animals) involved (my condensation of various definitions found). A more detailed discussion of the philosophy of utilitarianism is included in a separate section below.

Representing the animal rights view, philosopher Bernard Rollin makes the case that there are no “morally relevant” reasons for excluding animals as “objects of moral concern”; thus, by extension, they are deserving of “rights.” In his book titled Animal Rights and Human Morality, he states, “From a strictly philosophical point of view, I think that we must draw a startling conclusion: If a certain sort of research on human beings is considered to be immoral, a prima facie case exists for saying that such research is immoral when conducted on animals.” It seems to me that if one were to accept this point of view, all research on animals would be immoral, and thus unethical, since the research subjects could not give informed consent (although, possibly, a court appointed “guardian” for the animal subjects could give consent and owners of animals could give consent for their animals to participate in clinical therapeutic trials). Further in the same paragraph, he states that this “criterion would effectively curtail the vast majority of research” in basic biological and applied basic biomedical research, the development of drugs and therapeutic chemicals and biologics, the testing of consumer goods, the use of animals in education (demonstration, dissection, surgery practice, high school science projects, etc.), and the extraction of products from animals (e.g., serum, musk, and blood). He does appear to accept the premise that animals can be used in biomedical activities under the same conditions that permit the use of human subjects; for example, the specific animals used will potentially benefit from the specific study (Rollin 1981). In a more recent report, Professor Rollin seems to make the case that there are no moral grounds to support the use of sentient animals in most, if not all, biomedical activities (Rollin 2012).

Philosopher David DeGrazia argues in his book titled Taking Animals Seriously: Mental Life and Moral Status that “equal consideration for animals is more reasonable than its denial, given the failure of opponents of equal consideration to meet their burden of proof ” those who doubt that animals should be extended equal consideration should note that a commitment to giving animals serious consideration would be enough to support most of the foregoing conclusions” (referring to the cases made in the previous content of the book). Dr. DeGrazia sums up his position by providing the reader with 15 ethical conclusions regarding our treatment of animals, which include (the verbiage in parentheses is my suggested examples) “Don’t cause unnecessary harm” (e.g., meat eating is unnecessary for individuals who have viable alternative food options), “Make every reasonable effort not to provide financial support for institutions that cause or support unnecessary harm” (e.g., don’t support circuses or movies that include animal acts), “Don’t kill sentient animals unnecessarily” (e.g., for food or for most research), and “There is a presumption against disabling sentient animals (that is, damaging their ability to function in ways that significantly interfere with their ability to live a good life) and, if they are non-dangerous, the presumption is virtually absolute” (e.g., research involving any animal impairment would be unacceptable) (DeGrazia 1996).

From a more moral–legal perspective, attorney and professor of law Gary L. Francione makes the case that only by incrementally destroying the legal concept of animals as property can true animal rights ever be achieved. Late in his book titled Rain without Thunder: The Ideology of the Animal Rights Movement, he states, “In a sense, we are really only talking about one right”“the right not to be treated as property”. As long as animals are regarded as property, we cannot really talk about their rights. That property cannot have rights follows from what it is to be property”. We can be responsible for property, but not to property” (Francione 1996). The content of this 1996 book explains in detail what was meant by the statements in the “Point/Counterpoint” article cowritten by Professor Francione and Dr. Regan, discussed below.

As this chapter is being written, there are at least two current efforts attempting to reclassify animals from merely “property” to “sentient beings,” one in New Zealand (Library of Congress 2015) and another in the National Assembly in Quebec City, Canada (Anonymous 2015c), as well as continuing efforts in the United States to obtain “personhood” status for chimpanzees (Slate Website 2015). Interestingly, in a blog post copyrighted in 2006, Professor Francione made the case that the campaign to gain personhood for chimpanzees is “problematic because [it] suggest[s] that a certain species of non-human is ”special’ based on similarity to humans. That does not challenge the speciesist hierarchy”“it reinforces it”“in at least two ways” (Francione 2006). This position is completely consistent with his contention in his book.

Melding together the ethical and legal points, Dr. Regan and Professor Francione published an article in which they state, “Many animal advocates hold that there really is no difference between animal welfare and animal rights. Others claim that while there is a difference, advancing animal welfare is a necessary prerequisite to advancing animal rights. Given either assumption, many conscientious activists conclude that we must support welfarist means in our march toward animal rights ends. ” We believe these views are mistaken. Not only are the philosophies of animal rights and animal welfare separated by irreconcilable differences, and not only are the practical reforms grounded in animal welfare morally at odds with those sanctioned by the philosophy of animal rights, but also the enactment of animal welfare measures actually impedes the achievement of animal rights. ” The goal of the animal rights movement is nothing less than the total liberation of nonhuman animals from human tyranny” (Regan and Francione 1992, emphasis added). By the use of the phrase “irreconcilable differences,” it would seem to me these authors are clearly saying that there is no philosophical way to justify the use of animals in any way that benefits humans and, presumably, other animals. It also seems that they are saying that the enactment of animal welfare laws will impede the ultimate goal of no animal use, presumably because if the general public is convinced that animal “welfare” is achieved, they will not support the more radical implementation of animal rights as envisioned by strident animal rights advocates.

Philosopher Tom Regan also makes the case that animals are “moral patients” deserving of rights. It appears that he bases his argument on an expansion of Jeremy Bentham’s “Can they suffer?” test. Moral “agents” have the capacity to speak for themselves, for example, a fully mentally competent adult human. Moral patients are members of a moral community that cannot speak for themselves and must have someone speak for them, for example, an adult human in a coma or a newborn infant. Regan advances the proposition that sentient animals are deserving of moral “concern” and, by virtue of this fact alone, are deserving of being considered moral patients, leading to the necessity for someone to speak for them and, presumably, protect them from use in biomedical activities (Regan 1983).

Providing a slight contrast to the modern animal rights viewpoint, philosopher Michael Allen Fox states, “The conclusion [that] ” so far as it pertains to animals ” [their lack of the] various degrees the possession of capacities on which moral autonomy or agency depends, animals fail to meet the conditions specified for full membership in the moral community and likewise fail to qualify for having rights” (Fox 1986). Interestingly, approximately a year after his book was published, Fox published a retraction and indicated that he had changed his mind and no longer supported the case that he made in the book (Fox 1987). Regardless of Fox’s recanting his arguments for supporting the use of animals in biomedical activities, what he presented in the book in support of the quote cited above would seem to be valid and would support the necessary and ethical use of animals in biomedical activities, at least in activities with a high benefit-to-risk ranking.

In making the case for animals having moral rights, Professor Jerry Tannenbaum has postulated a number of “myths of the animal rights movement” that are germane to our discussion (Tannenbaum 1995):

• Myth 1: “One must choose between animal rights and animal welfare.” He discusses the reasons that aspects of concern for animal welfare might support the conclusion that animals have moral rights to certain levels of care and to limitations on how they may be used or treated; thus, there is nothing to support the position that animals do not have rights. He goes on to make the case that animals have moral rights that devolve from the fact that they are sentient and have interests. Since the intended audience for his book, titled Veterinary Ethics: Animal Welfare, Client Relations, Competition and Collegiality, is veterinarians, Professor Tannenbaum goes on to make the case that veterinarians (and by extension, those of us involved in biomedical studies with animals?) should accept his premise that animals have moral rights so that they are not marginalized in the public arena of debate over animal rights. That said, one could make the case that these terms are not synonymous; that is, animal welfare is ensuring responsible care and use of animals however they are being used (in biomedical activities, as pets or service animals, in agriculture, in zoos and aquatic parks, etc.), while animal rights, as defined by the strident animal rights movement, would require “nothing less than the total liberation of nonhuman animals from human tyranny” (Regan and Francione 1992).
• Myth 2: “Animals do not yet have legal rights.” He makes the case that the various statutes that exist to protect animals from cruel treatment can be considered sufficient to conclude that animals should be considered as having legal rights. In this regard, he also states, “If one believes, as many people surely do, that animals should have some legal rights, one is not thereby committed to the demand of the animal rights movement that animals should be given legal standing to sue their owners, their veterinarians, or other people for money or other kinds of relief. The concept of legal rights for animals, like the concept of moral rights for animals, does not entail the platform of the animal rights movement.” While Professor Tannenbaum makes a compelling case here, another possible case could be made that animal welfare statutes do not convey to animals any rights; rather, they simply codify human obligations to animals similarly to many of the statutes that govern the protection of endangered species of flora (certainly such protected plants would not be considered as having rights).

Presenting yet another viewpoint on the use of animals in biomedical activities, Sir William Paton, an eminent British pharmacologist, makes the case that the use of animals in biomedical activities to advance knowledge in medicine [both human and veterinary], biology, and the basic sciences is the most ethical use of animals of all the ways humans use animals (emphasis added). His reasoning is that any knowledge gained from such studies would live on in perpetuity, while, the benefits, whatever there are of using animals for other purposes, are time limited (Paton 1984).

Utilitarianism

As noted previously, utilitarianism is a form of philosophical thought that “the determining consideration of right conduct should be the usefulness of its consequences; specifically: a theory that the aim of any action should be the largest possible balance of pleasure over pain or the greatest happiness of the greatest number” or “the belief that a morally good action is one that helps the greatest number of people [or animals?]” (Merriam-Webster Online Dictionary 2015).

While it appears that animal rights has emerged as a recognized system of philosophical thought regarding the status of animals, utilitarianism is most likely a philosophy that would be a better fit for most people’s views. In the “Summary and Conclusion” of the 1986 Office of Technology assessment report about the use of animals in biomedical activities, it is stated, “Because it extends the scope of moral concern to animals without committing itself to a vulnerable theory of animal rights, Utilitarianism has become the theory of choice among those who would press for more constraints on humans’ treatment of animals” (U.S. Congress 1986).

This report from a government committee composed of representatives from many stakeholder perspectives is one of the few attempts to present an unbiased assessment of the pros and cons, or need and value, of the use of animals in biomedical activities”“thus the conclusion that the most appropriate philosophical approach to such use is utilitarianism, simplistically, the greatest good for the most individuals. That said, even this approach is fraught with problems since it is unclear who or what should be considered within the term individuals, and animals cannot speak for themselves and cannot articulate an “informed decision” to participate as a subject in biomedical activities. Besides, when considering the “utility” of any specific proposed biomedical activity, further questions are evoked, including, what criteria will be used to balance the “good” versus “bad” of the activity? Unfortunately, there are no universally accepted guidelines for how to calculate the utility of any particular use of animals (see also the “Risk (Harm) versus Benefit Assessment” section that follows later).

Another source, philosopher Carl Cohen, says that “utilitarianism appeals to many people”“it is practical and concrete and seems to make sense in daily life. Utilitarianism does not say using animals for research is wrong; what it does say is that to decide on the moral rightness of an action you need to look at whether that research might promote an aggregate good for a greater number of people than not doing the research. Some would include animals in this equation since animals do benefit from research. For the Abolitionist, animal research would be wrong since it is morally wrong to use an animal merely as a means, even ” to a good end” (Cohen 1986).

Morally Relevant Difference between Humans and Animals

One can make the claim that in order for a living entity to claim rights, it must be a member of a moral community (North Carolina State University 2015), that is, a community in which individual members can make moral decisions and recognize right from wrong. Also, with rights come obligations that members of the community must be willing to accept, that is, obligations to recognize the rights of others. It is unlikely that animals can either recognize obligations to other animals or knowingly accept them. If animals had rights, they would have them even if the human species did not exist, and any prey animal would be able to exercise its right not to be eaten by a predator (an obviously absurd situation). However, to the best of our knowledge, only humans possess the intellectual capacity to make moral decisions and accept reciprocal obligations; therefore, the logical conclusion is that only humans have rights. An objection to this point of view is that there are individual humans who are not able or competent to make moral decisions (e.g., infants, persons in a coma, and persons with dementia); however, an argument can be made that such persons either have the potential to make claims for their rights (e.g., the infant who grows up to be a mentally competent adult) or previously had such capabilities but no longer do (e.g., the person in an irreversible coma). Thus, all persons should be considered members of the moral community.

That said, and even if this conclusion is correct, the fact that only humans have rights does not give us the unhindered right to do whatever we want to, or with, animals. Since all humans are members of a moral community, mostly capable of recognizing right from wrong and accepting the obligations that come with rights, and it is generally recognized that it is wrong to mistreat animals, we are thus obligated to treat animals humanely. However, this obligation is to us, to our own humanity, and not to the animals per se, although one could say that this obligation also imposes on humans a moral duty to not mistreat animals.

While animals may not have rights, nations and states can and do confer on them legal protections and impose legal restrictions on how they may be used and treated, for example, animal abuse and control laws and international wildlife protection treaties. These legal protections may severely restrict how we may use animals and what we can do to animals. Furthermore, enforcement of these protections may even result in severe penalties for violating the laws. The laws do not convey rights to animals; rather, they simply codify our moral obligations to animals as defined by our various societies and cultures. While there are a number of highly respected philosophers who have made the case that animals have moral rights based on their sentience, one can still contend that in order to have rights, individuals need to be members of a moral community, and no animals currently share this status with humans.

Our body of laws pertaining to animal protection form the foundation for animal welfare within our society. Most importantly in this regard is the generally high degree of public concern for animal welfare that is found throughout most contemporary societies and cultures, including the vast majority of individuals working in various biomedical activities. We should keep in mind that animal welfare as a concept is not synonymous with the philosophy of animal rights, especially as this latter term is defined by the most radical animal rightists. An animal welfarist believes in responsible pet ownership, responsible animal agriculture, humane animal care, and so forth. A true animal rightist demands no human use of animals, including but not limited to pet ownership and agriculture, and no animal care (since animals should not be property requiring care). In the utopian world of the true animal rightist, no animal will be subjugated to human welfare, need, or desire.

One argument made by proponents of rights for animals is that there are no morally relevant differences between a mature animal (see discussion on Regan above), with its full mental faculties, and a severely mentally deficient human, for example, a brain-dead person. However, a case can be made that there is, in fact, at least one significant, morally relevant difference between humans and animals, and that is morality itself. So far as we know and can determine at present, the human species is the only species that attempts to interact with its environment (e.g., protect the rain forest) and other species in some moral way (e.g., save endangered species). Obviously, there may be some variability from culture to culture with regard to the definition of what actions are and are not moral. That said, we are the only species that has ever worried about the fate of other species. It would seem to me that this characteristic of humans in general should certainly be considered a morally relevant difference, thus supporting the conclusion that only humans have rights.

The 3Rs

Replacement, reduction, and refinement (the 3Rs), proposed by Russell and Burch in their 1959 book titled The Principles of Humane Experimental Technique, have become foundational planks for many laws, regulations, guidelines, and local policies governing oversight of biomedical activities involving the use of animals throughout the world, and should continue to be such into the future. While the widespread implementation of these principles most certainly has resulted in more humane animal use, and in some reduction in the numbers of animals used (especially “higher” vertebrate mammals), it is unlikely that the total numbers of individual animals have decreased significantly when all species are counted. The growing importance of zebrafish and genetically modified rodents in biomedical activities may actually lead to an increase in the absolute number of animals being used in biomedical activities in the future.

• Replacement: In the original 1959 book, this term was meant to mean actual replacement of animals with “insentient material” (i.e., absolute replacement). Over time, the meaning has evolved to include the substitution of an animal with another animal species “lower” on the phylogenic scale (i.e., relative replacement).
• Reduction: Originally defined to mean “reduction in the numbers of animals used to obtain information of a given amount and precision.” Some of the ways to implement the reduction of animals are to ensure that proposed activities are well designed and statistically valid, that one is using the best animal model available, that the animals are in the best health possible (including free of confounding microorganisms), and that the animals receive the best care possible to minimize induced variables that can negatively affect the animals, resulting in the need for more animals to obtain statistically valid study results. Interestingly, this may actually require the use of more animals in a given activity if it were needed to ensure statistical validity of the activity, thus negating the need for repetitive studies, which would ultimately reduce the numbers needed to obtain valid results.
• Refinement: Originally defined to mean “any decrease in the incidence or severity of inhumane procedures applied to those animals which still need to be used.” Today, this R includes using procedures that will minimize pain, discomfort, and distress. One concept for implementing refinement is especially promising: whenever possible, make the animals willing members of the research team. For example, nonhuman primates can be taught to present an arm for a blood draw in return for receiving a desired food treat.
  Another example of refinement is to select or train dogs through positive reinforcement to voluntarily run on a treadmill if required in a project studying cardiovascular function. Unfortunately, this approach is generally reserved for use in long-term studies, as it requires time and enhanced human interaction. Positive human interaction can also improve animal welfare but will likely increase human attachment to the animals. This should be encouraged, as it will benefit the animal; however, for many studies the animals must be euthanatized at the end. In respect for human caretakers, procedures should be in place to minimize the emotional impact on the people who have become attached to the animals, perhaps by having other individuals not so attached conduct the euthanasia and collection procedures. Other, short-term examples of refinement include the use of multimodal analgesia for procedures that historically use no or only one analgesic, or use of nonpharmaceutical therapies (e.g., environmental enrichment, heating pad, and soft bedding) if painful procedures are being performed and analgesics must be withheld for scientific purposes.
  Tannenbaum and Bennett (2015a) have recently published in the Journal of the American Association for Laboratory Animal Science an excellent and exhaustive discussion about the 3Rs, including their original meaning and how the meanings and intent have evolved since first proposed. In addition, a letter to the editor, authored by Carbone (2015), along with a rebuttal by Tannenbaum and Bennett (2015b), further illuminates some of the contemporary aspects of the 3Rs. These three publications are well worth reading for a more thorough understanding of the importance of the 3Rs with regard to contemporary efforts to establish ethical programs of animal care and use in biomedical activities.

In Europe, “Directive 2010/63/EU revising Directive 86/609/EEC on the protection of animals used for scientific purposes ” is firmly based on the principle of the Three Rs, to replace, reduce and refine the use of animals used for scientific purposes” (European Directive 2010/63/EU).

U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training

Although intended to be applicable to biomedical activities accomplished with funds provided by the U.S. government, these principles would likely be just as applicable to all biomedical activities involving animals conducted anywhere in the world.

The development of knowledge necessary for the improvement of the health and well-being of humans as well as other animals requires in vivo experimentation with a wide variety of animal species. Whenever U.S. Government agencies develop requirements for testing, research, or training procedures involving the use of vertebrate animals, the following principles shall be considered; and whenever these agencies actually perform or sponsor such procedures, the responsible Institutional Official shall ensure that these principles are adhered to:

1. The transportation, care, and use of animals should be in accordance with the Animal Welfare Act (7 U.S.C. 2131 et. seq.) and other applicable Federal laws, guidelines, and policies.
2. Procedures involving animals should be designed and performed with due consideration of their relevance to human or animal health, the advancement of knowledge, or the good of society.
3. The animals selected for a procedure should be of an appropriate species and quality and the minimum number required to obtain valid results. Methods such as mathematical models, computer simulation, and in vitro biological systems should be considered.
   Proper use of animals, including the avoidance or minimization of discomfort, distress, and pain when consistent with sound scientific practices, is imperative. Unless the contrary is established, investigators should consider that procedures that cause pain or distress in human beings may cause pain or distress in other animals.
4. Procedures with animals that may cause more than momentary or slight pain or distress should be performed with appropriate sedation, analgesia, or anesthesia. Surgical or other painful procedures should not be performed on unanesthetized animals paralyzed by chemical agents.
5. Animals that would otherwise suffer severe or chronic pain or distress that cannot be relieved should be painlessly killed at the end of the procedure or, if appropriate, during the procedure.
6. The living conditions of animals should be appropriate for their species and contribute to their health and comfort. Normally, the housing, feeding, and care of all animals used for biomedical purposes must be directed by a veterinarian or other scientist trained and experienced in the proper care, handling, and use of the species being maintained or studied. In any case, veterinary care shall be provided as indicated.
7. Investigators and other personnel shall be appropriately qualified and experienced for conducting procedures on living animals. Adequate arrangements shall be made for their in-service training, including the proper and humane care and use of laboratory animals.
8. Where exceptions are required in relation to the provisions of these Principles, the decisions should not rest with the investigators directly concerned but should be made, with due regard to Principle II, by an appropriate review group such as an institutional animal care and use committee. Such exceptions should not be made solely for the purposes of teaching or demonstration.

NASA Sundowner Principles

In October 1996, the National Aeronautics and Space Administration (NASA) convened a meeting of a group of diverse individuals to “implement bioethics policies for animal experimentation” sponsored by or involving NASA. The group consisted of a public policy expert, three bioethicists, and representatives from the animal welfare community, AAALAC International, NASA, and other federal agencies involved in animal research. This diverse group concluded that (Rowan 2000)

Among the basic moral principles generally accepted in our culture, three are particularly relevant to the ethics of research using animals: respect for life, societal benefit, and non-maleficence.

• Respect for Life”“Killing entails moral costs:
  • Living creatures deserve respect. This principle requires that animals used in research should be of an appropriate species and health status and should involve the minimum number required to obtain valid scientific results [reduction]. It also recognizes that the use of different species may raise different ethical concerns. Selection of appropriate species should consider cognitive capacity and other morally relevant factors. Additionally, methods such as mathematical models, computer simulation, and in vitro systems should be considered and used whenever possible [replacement].
• Societal Benefit”“Advancing knowledge and health is a strong justification for research:
  • The advancement of biological knowledge and improvements in the protection of the health and well-being of both humans and other animals provide strong justification for biomedical and behavioral research. This principle entails that where animals are used, the assessment of the overall ethical value of such use should include consideration of the full range of potential societal goods, the population affected, and the burdens that are expected to be borne by the subjects of the research.
• Non-Maleficence”“Minimization of distress, pain, and suffering is a moral imperative:
  • Vertebrate animals are sentient. This principle entails that the minimization of distress, pain, and suffering is a moral imperative [refinement]. Unless the contrary is established, investigators should consider that procedures that cause pain or distress in humans may cause pain and distress in other sentient animals.

Because of the diversity of this group, representing a broad range of philosophical thought and beliefs, these three principles resulting from the group’s deliberations should be considered foundational components of any institution’s program for the ethical use of animals in biomedical activities.

Religion

Most of the religions of the world include tenants that encourage concern for animals and their welfare, and some even revere certain species of animals and give them special status within their culture. A few religions so revere all animal life that they will go to great extremes to live lives without harming even the most humble of creatures, such as insects (e.g., Jainism [Anonymous 2015a]). The Reverend Professor Andrew Linzey has also made a case that animals have rights from a theistic perspective, that is, animal “rights [can be] based on the inherent worth of creatures possessing the property of being elected by God in love” (Cahill 2016). Therefore, on a global basis there may be situations where a proposed biomedical activity using animals may be morally acceptable within some segment of a local culture, but the range of animals acceptable for use might be limited by consideration for regional or local religious concerns; for example, dogs are generally considered to be “dirty” in Islam but can be kept as pets with some reservations (Banderker 2015). Persons involved in biomedical activities should be aware of any such concerns and design proposed activities and staffing plans accordingly.

Biomedical Activities Are Not Monolithic

As illustrated in Figure 4.1, the term biomedical activities (or more generally referred to as “biomedical research”) encompasses a very broad range of activities involving the use of animal subjects, and this diversity presents another very large layer of complexity to ethical issues involved therein.

Figure 4.1

Illustration of the interrelationships between the types of biomedical activities on the left and the different biomedical disciplines involving the use of animal subjects on the right; that is, all four types of biomedical activities are found in each (more...)

Often, the public discourse regarding the use of animals in biomedical activities focuses on the benefits that “might” be derived only for humans. However, a significant proportion of such activities are undertaken with the direct or tangential intent of benefitting animals (e.g., development of a vaccine for an emerging disease, such as parvovirus in dogs). Also, in many cases the goal of an activity involving animal subjects is simply the advancement of knowledge without definitive knowledge of its benefit for either humans or animals, that is, basic research activities.

If it is decided that it is “unethical” to use animals in biomedical activities intended to benefit humans, the ethical principle of justice, which would include equal consideration of the interests of all (sentient?) animal subjects, would dictate that it is also unethical to use animals in biomedical activities intended to benefit other animals (e.g., endangered species captive propagation research or research to develop a vaccine for a newly discovered disease of dogs or horses), that is, “what’s good for the goose is good for the gander.” In contrast, one might even be able to make the case that the principle of beneficence, that is, the obligation to do good and avoid harm, would dictate that efforts to save an endangered species should be performed, even if it meant that some animals of the same species or another similar species might die during this effort. Another example of this conundrum is the use of some members of an animal species, deliberately infected with a newly identified pathogen resulting in overt disease in the recipients, to develop a vaccine for the newly discovered fatal disease in order prevent the disease in future populations of the species (e.g., Potomac horse fever in horses).

As an example of how this conundrum might apply to, and impact on, public opinion on a global scale, consider the widely accepted concern for endangered species. There are 181 parties currently signed on to the provisions of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES 2015), and in the United States, there is strong public and political support for the Endangered Species Act (1973). If there were laws prohibiting the use of sentient animals in biomedical activities, then the critical research needed to protect endangered species, including field studies and captive breeding for reintroduction efforts, would have to cease since such activities would likely involve using animal subjects.

A recent report noted the possibility that research for a vaccine against the Ebola virus using chimpanzees will result in a vaccine that likely can be used to protect the remaining and endangered wild chimpanzees from this fatal disease (Choi 2014). If this were to be the result of current vaccine development efforts, it would be another example of a discovery involving the use of animals that turns out to be critically important to animals. As an aside, Dr. Francis Collins, director of the National Institutes of Health (NIH), announced on November 19, 2015, that the NIH will permanently stop using chimpanzees for biomedical testing and is retiring its remaining chimpanzee population, thus potentially decreasing the probability of development of a successful vaccine (St. Fleur 2015).

Basic research often can seem like we are looking for keys to locks unknown. Because of this level of general ambiguity, basic research is often poorly understood by the general public; thus, what may be perceived as “unnecessary” or “trivial” may lead to public outcry about the cruelty of any use of animals in such pursuits. Senator William Proxmire (Democrat, Wisconsin, 1957–1981) would periodically issue “golden fleece awards.” These awards were targeted at federally funded scientific research that he considered wasteful. However, the creation of this award reflected the fundamental misunderstanding of how science works, and how such research can turn out to be extremely important regardless of whether it makes sense to nonscientists. Indeed, such research can have a major impact on society. The nature of scientific research is that its impact is hard to predict (Anonymous 2015b).

However, without the foundation of basic research, followed by applied research, biological and medical advances would be impossible. When speaking to public or lay audiences and describing this point, I have frequently been asked, “How much basic research ultimately turns out not to have been of any particular significance?” My response, “Probably a significant percentage!” often surprises the questioner. I then go on to say, “However, the problem is that no one can, a priori, tell which basic research endeavors will fall into this status.” Two examples that illustrate this point involve discoveries in the then emerging discipline of genetics in the 1930s and 1940s:

• During the 1930s and 1940s, there were two investigators conducting basic genetic research. One was Dr. George Snell, who was studying the genetics of mice at the Jackson Laboratory in Bar Harbor, Maine. The other was Dr. Barbara McClintock, who was studying the genes in corn at Cornell University’s College of Agriculture and the Department of Botany at the University of Missouri–Columbia. It is highly unlikely that either Dr. Snell or Dr. McClintock, in the 1930s and 1940s, could have predicted that their basic research would lead to genetic discoveries that proved to be critically important in what is now known as “medical genetics” and would lead to their receipt of Nobel Prizes in Physiology or Medicine in 1980 (shared with two others) and 1983, respectively. Yet, their discoveries proved to be significant foundational blocks in the development of today’s medical genetics.
• Another example unrelated to direct human interests that seems to be enlightening for laypersons is the captive breeding programs that have successfully allowed for the reintroduction of the endangered whooping cranes, California condors, and black-footed ferrets into their historic habitat ranges. All these species were on the brink of extinction when the captive programs began. Without captive breeding research efforts involving similar species (sand hill cranes, Andean condors, and nonthreatened ferret species, respectively), these three recovery efforts likely would not have succeeded.

Finally, it is critical to be realistic regarding the speed with which research goes from the benchtop to the bedside. This fact is poorly understood by the general public, which, in turn, can lead to opposition to some basic research studies involving animals when the ultimate value of the activities may not be known for decades. Finding disease cures can take up to a century”“from some initial basic science discovery, a single brick in an allegorical huge pyramid, to the final “useful” product at the pyramid’s apex is very hard for lay individuals to comprehend. The authors of one analysis, titled “From Scientific Discovery to Cures: Bright Stars within a Galaxy,” state, “new treatments depend upon a broad base of scientific knowledge plus special contributions from a few exceptional scientists.” Working backwards through the published medical literature, the analysis team looked at the step-by-step advances that were necessary to lead to the development of two drugs. According to this analysis, more than 7000 researchers from 5700 different institutions, working in succession over 100 years, were needed to develop a cancer drug. In support of this concept, the development of a cystic fibrosis drug was also daunting: 2900 scientists with ties to 2500 different institutions, laboring for 60 years. The bottom line, according to study coauthor Alexander Pico, is that “it takes contributions from a surprisingly large and complex network of individual scientists working in many locales to reach a cure” (Williams et al. 2015). Misunderstanding of this aspect of discovery can lead laypersons to oppose, what seems to them, to be excessive or frivolous use of animals in biomedical activities.

Changing the Legal Status of Animals

Recently, some animal rights groups have mounted campaigns to change references to animal “owners” in laws, statutes, and regulations to read animal “guardians.” At least three U.S. cities have adopted amendments to their animal welfare statutes to replace the term animal owner with the term animal guardian: Boulder, Colorado; West Hollywood, California; and Berkeley, California. While the sponsors of this movement allege that their motive is simply to raise the public’s awareness of their responsibilities to their animals, it is likely that their real agenda is to give legal “standing” to animals as things other than property (since the word guardian has very specific legal meaning and is defined as “a person lawfully invested with the power, and charged with the duty, of taking care of the person” (Garner 2009). It would not be much of a stretch to have this definition revised to substitute the word animal for the word person.

Such a change could theoretically lead to someone seeking legal guardianship of an animal that is not theirs based on a perception that the existing guardian (e.g., an animal in a research institution) is unfit. Should such a court case be filed, and even if the original guardian prevails in court, the potential legal fees could be significant. Further, if an animal needed expensive veterinary care that the guardian (in this example a private individual) could not afford, he or she might be liable for charges of animal endangerment for not providing the care and could be brought into court by someone suing on the animal’s behalf.

While it is highly unlikely that these efforts to change the legal status of animals will lead to such draconian results, it is highly likely that there will be a good deal of turmoil created by this seemingly insignificant change in verbiage among the general public, animal owners, legislators, and most significantly, lawyers and veterinarians.

One development over the last several years that might indicate that these concerns about the possibility of legal turmoil over this issue, as well as other animal-related issues, such as personhood for chimpanzees, are valid is the burgeoning number of law schools that offer or have offered credit for animal law courses or seminars (at least 119 schools) (NABR 2015a) and that have received millions of dollars to support such courses (NABR 2015b).

Perhaps if the efforts to use a term other than owner for persons who “own” animals were to advocate for use of the term caretaker, or some similar term not fraught with potential legal implications, the goal of recognizing that animals are not just things may advance more rapidly. In regard to concerns that “unfit” owners, that is, those that abuse or treat animals cruelly, ought to be sanctioned, it is worthwhile to remember the many laws, regulations, and international treaties that exist to protect animals include serious sanctions for both individuals and institutions for violations thereof.

Other Contemporary Issues

When attempting to justify the value of the use of animals in biomedical activities, it may be necessary to include consideration of a subset of contemporary cultural and ethical issues:

• Is it morally acceptable to use animals for any human purpose? Could the use of any captive or domestic animal for any purpose whatsoever be equivalent to forced human slavery? It is unlikely that this represents the majority ethical viewpoint for most cultures. However, it is possible to say that some individuals might take this ethical position. If one should conclude that the answer to this question is no, further discussion about the value or necessity of using animal subjects in biomedical activities would be purely academic.
• There are different cultural perceptions regarding the moral acceptance of animal use, which can encompass the way the animal is used, the purpose of the use, or even the species being used. It is likely that most cultures and societies accept the use of some species of animals as pets. There are species of animals that are revered in one culture that may be eaten in another (e.g., cows and dogs). There are species that have a significant place in the cultural heritage of various native peoples, and may still be hunted even though they are nationally recognized as endangered (e.g., whales and eagles). These varied perceptions further complicate efforts to resolve the moral and ethical aspects of animal use in biomedical activities.
• What is the “necessity” of any particular use of animals? As will be discussed in more detail in the “Risk (Harm) versus Benefit Assessment” section that follows, what is necessary with regard to biomedical activities is a prominent consideration in numerous laws, regulations, policies, and guidelines that pertain to animal use in biomedical activities. Is it necessary to use an animal for a specific research proposal, and is it necessary to use a specific species? Is it necessary to genetically modify an animal model to do the research, even if it means that the animal may develop a disease that might be painful? Unfortunately, there is no universally accepted definition of what necessary means when used in this context. For example, in a study designed to develop a new treatment for some major emerging human disease, would it be necessary that the potential treatment be such as to save a minimum of 1000 human lives, or would the saving of 10 lives be an acceptable “cost” in terms of animals used? Even the eminent medical missionary who fostered a “reverence for [all] life” philosophy, Albert Schweitzer, has been quoted as saying that “it is necessary for the advancement of medical understanding” (emphasis added) when asked about his views on the use of laboratory animals for biomedical research (Pittman 1990).
• Problematic words. Many of the terms that we use in discussing the ethical use of animals lack precise or universally accepted definitions. With regard to the use of the term obscenity, there is an old adage; it can be hard to define, but “we know it when we see it.” Well, this colloquial expression can apply equally well to the terms well-being, distress, and suffering; we cannot exactly define them, but we know them when we see them.
  General well-being: To assess an animal’s general well-being, one may use physiological criteria, behavioral criteria, or functional criteria, or a combination of all three, in an effort to arrive at an approximation of well-being.
  • Physiological criteria: Animals must be able to maintain internal homeostasis in order to survive. Most physiological parameters can be measured, many by non- or minimally invasive procedures (e.g., body temperature or blood cortisol levels). “Normal” ranges for the parameters can be established, and animals with values within those parameters may be said to have an appropriate level of physiological well-being.
  • Functional criteria: Functional means can the animal function normally within the circumstances of its life; for example, can it obtain and utilize adequate nutrients to maintain itself, can it engage in adequate reproductive behavior to propagate its species at a relatively normal rate, and/or can it engage in sufficient grooming behavior to prevent injury to itself?
  • Behavioral criteria: Many persons involved in trying to assess animal well-being advocate that behavioral criteria are more reliable than are either physiological or functional criteria. They base their position on the proposition that psychological and subclinical physiological stress or distress will manifest in abnormal behavior. The problem with this approach is that there is no uniform agreement on what is the normal behavioral baseline against which to judge whether a particular behavior is abnormal. For example, should we use the normal behavior of tigers living in the wild as the baseline for assessing the behavior of a captive-bred tiger living in a zoo when the cat has never known what life in the wild is like and appears to be physiologically and functionally doing well even though it repeatedly paces in its enclosure (mimicking a tiger’s travels over its range?) without injury?
  Psychological well-being: The U.S. Federal Animal Welfare Act implementation regulations (Part 3, “Standards,” Subpart D, §3.81) require that institutions provide “environment enhancement to promote [the] psychological well-being” of nonhuman primates (Federal Animal Welfare Act and Animal Welfare Regulations 2013, emphasis added). While one may be able to assess the general well-being of an animal by using the three criteria above, assessing its psychological well-being may not be so simple. “To assess an animal’s ”psychological’ state (”well-being’ or otherwise), requires [lingual] communication of feelings”; thus, “when evaluating an animal’s well-being, the most parsimonious [simplistic] approach is to use behavioral indices. To say that ”abnormal’ behaviors indicate abnormal ”psychology’ is to make a great leap and say that you are able to get inside the mind of animals” (Rasmussen 2000). Therefore, we can truly assess psychological well-being only in conscious, lingual humans. Even with a nonverbal human patient, psychological well-being cannot be assessed. For example, persons in comas do not receive antidepressant drugs since it cannot be determined that they are depressed. There can be no psychological intervention with a person in a coma since their psychological state cannot be determined.
  In truth, there is probably no universally accepted way to assess the psychological well-being of any nonhuman animal, even though it is required in the U.S. regulations for nonhuman primates. To meet this requirement, behavioral criteria appear to be acceptable to ensure compliance with the law.
  Distress: Distress may be defined as physical or mental anguish or suffering; however, as has been stated many times, much of the difficulty in achieving a broadly accepted approach to categorizing, and then addressing, pain and distress is due to the absence of a concise definition. From a behavioral perspective, this inability to arrive at a Webster’s Dictionary type of definition is due in part to the fact that (1) pain and distress are not discrete states, but are a continuum of experience; (2) signs differ between species, and most animals hide signs of pain because such a sign of weakness may provoke an attack from predators or subordinate members of the group; (3) there is a lack of specific behavioral indicators of pain and distress; (4) in the course of identifying distress, interobserver variability can be large; and (5) there is a tendency to anthropomorphize, which is encouraged by U.S. government principle IV. That principle states that “unless the contrary is established, investigators should consider that procedures that cause pain or distress in human beings may cause pain or distress in other animals” (Institute for Laboratory Animal Research 2011). Note that this principle seems to associate distress with pain, which is commonly, but not universally, the case. Distress may be caused by factors other than pain, for example, noise, crowded enclosures, pheromones from other species, and environmental temperatures. As with psychological well-being discussed above, distress is often assessed by the animal’s behavior. Physiological and functional criteria can also be used, with behavior, to identify distress.
  Suffering: One could define suffering as an unpleasant emotional state associated with pain or distress. However, this definition would not seem to provide practical guidance when attempting to determine whether an animal is suffering when obvious gross indications are absent. Trying to define suffering in a manner that would be acceptable to all, which covers all the possible situations that may be associated with animal use in biomedical activities, is very difficult and, possibly, impossible. The previous discussion regarding well-being would seem to be applicable here, as if well-being is adequately addressed in an institution’s animal care and use program, animal suffering would be minimized or eliminated to the maximum extent possible.
  Alternatives: The term alternatives is most frequently interpreted as meaning the replacement of animals in biomedical activities with nonanimal technology. Tissue cultures (both human and animal), computer modeling and simulation, in vitro techniques, and retrospective statistical analyses are only a few examples of techniques that can replace the use of animals in some cases. Several organizations have been established to promote and develop nonanimal alternatives (e.g., the U.S. Department of Agriculture Animal Welfare Information Center [2015], the Interagency Coordinating Committee on the Validation of Alternative Methods [2015], the Center for Alternatives to Animal Testing [2015], FRAME [2015], and the National Centre for the Replacement, Refinement & Reduction of Animals in Research [2015]).
  Is there an acceptable alternative methodology that does not require the use of animals? There are a few circumstances where a nonanimal alternative can replace the use of an animal. For example, for some compounds the Corrositex test method for dermal corrosivity can be used as a stand-alone assay for evaluating corrosivity and replace the use of animals (Corrositex 2015). It is likely that as more is learned about cellular biology and function, as well as molecular biology, the development of more nonanimal methodologies will be validated and replace animals used in some research activities. However, the “horns of our dilemma” are that the primary reason animals are used in biomedical research activities is the exquisite complexity of intact living organisms. It is highly unlikely that alternative methodologies will replace most animal use any time soon. However, what is certainly safe to say is that validated, nonanimal methodologies will be welcomed by most individuals responsible for biomedical activities currently involving the use of live animal subjects, if for no other reasons than a simple aversion to the use of sentient animals for biomedical activities and, from a purely pragmatic calculation, the alternative may be less expensive and faster than using animals. Few researchers would prefer the complexity and burden of animal experimentation if there were accurate alternatives.
  As is true of general science advancements today, potential alternative technologies are emerging rapidly. For example, recent reports have been published describing the development of a “brain” in a dish (cell culture) that may replace animals in studies of brain cell function in some cases (Erickson 2015). At the 2015 annual meeting of the American Association for Laboratory Animal Science, the keynote speaker, Dr. Uwe Marx, presented an exciting summary of current efforts to develop human “multiorgan chips” or micro test cells. Other presentations elaborated on some of the organ test systems in existence that can simulate one or two organs that can be used in toxicological testing in lieu of live animals. While these systems are largely in the validation stage, Dr. Marx believes that within 20 years, there will be validated systems that will consist of up to 10 different “organoids” on a single chip that will actually be capable of interacting with each other, thus providing a cell culture–based alternative to a living animal for screening tests of candidate pharmaceutical agents or toxicological studies.
  Another relatively new nonanimal alternative to live animals has been developed for teaching veterinary students rectal palpation of cattle and horses using haptic (sense of touch) virtual reality simulators. Using these simulators, veterinary students gain the ability to conduct such exams before they conduct them on live animals, significantly reducing the need for live animals in the students’ early efforts to learn how to accomplish these diagnostic examinations (Farminguk Web Page 2015). Along with high-fidelity mechanical manikins, these simulators are reducing the use of live animals in many medical and veterinary school training programs.
  As an aside, most individuals proposing to use animal subjects in biomedical activities are usually well informed about the latest validated alternative (to animals) technology that would be appropriate for use in the proposed activities and invariably will have already incorporated them into their activities. After all, as already noted, it is in their own self-interest to use the best, and least expensive, technology to obtain the highest-quality data. Besides, most scientists and research technicians will likely be emotionally delighted to use a nonanimal alternative, rather than live animals, so long as the alternative methodology provides equivalent results.
• Where to draw the line?
  If society were to decide that at least sentient animals have moral or legal rights, where along the taxonomic scale should the line be drawn? Today, most laws and regulations governing how we treat animals apply only to vertebrate animals and, in some cases, only certain vertebrate species. The theory for selecting these taxonomic criteria is that only vertebrates have the anatomical and physiological capacity to be considered sentient and thus experience pain. However, it has been well demonstrated that at least some invertebrate species, for example, octopuses, have a level of intelligence that would infer sentience (Borell 2015). Even earthworms produce endorphins, which are hormones that are known to function to reduce pain in humans (DeGrazia 1996), perhaps indicating that earthworms can feel pain and thus might be sentient. It might be concluded that trying to define a firm line dividing animals into those that are deserving of rights and those that are not, based on sentience, would be extremely difficult, if not impossible. Thus, the best ethical approach would be to provide the best, least aversive care for all animals used in biomedical activities.

Media Portrayal of Animal Use in Biomedical Activities

The cover art of the December 26, 1988 Newsweek magazine issue depicted an illustration of a black and white striped cat sitting in a completely bare, wire cage just slightly larger than the animal. The expression on the cat’s face staring at the observer could be anthropomorphically interpreted as “apprehensive.” The cover presents multiple subliminal messages that could sway a layperson’s perception about biomedical activities involving the use of animals. To begin with, the animal shown is a “warm and fuzzy” cat, not a “creepy crawly” rat or mouse. In addition, the photo implies that the cat lives in a sterile cage that is obviously way too small for it and lacks food, water, a litter box, or a resting shelf. Then, finally, what might be the most powerful subliminal message is in the title and, most importantly, the subtitle, i.e., “The Battle over Animal Rights: A Question of Suffering and Science” [emphasis added]”“that is, animal suffering is the norm in research using animals (with the “truth” of this statement being “proven” by the obvious “cruelty” of how the cat is being housed)!

Much of the media material about the use of animals in biomedical activities over the last five or so decades appears to be biased toward the animal rights point of view, frequently equating animal rights and animal welfare as synonyms. These apparent biases are frequently a result of the reporters or commentators not being well versed about the material they are presenting. Another significant reason for this misreporting is the research community’s apparent reluctance to present the facts about our biomedical activities. For example, an institution gets a multi-million-dollar, multiyear grant for a project involving the use of animal subjects, but the announcement of the grant emphasizes the dollar amount and alludes to the importance of the project in terms of human health or scientific discovery, but rarely mentions the animals to be used. Announcements of some new, allegedly significant discovery usually laud the institutional support and the scientist making the discovery but almost never includes any acknowledgment of the critical role the use of animals played in making the discovery. One can make the case that emphasizing the use of animals in our biomedical activities carries the risk that those opposed to such animal use may target institutions that are forthcoming. However, by having highly ethical caring and legally compliant animal care and use programs that can withstand public scrutiny, along with being proactive and forthcoming with our public stakeholders, including the media, we should be able to ultimately persuade the general public of the validity of our activities.

Some Specific Examples of the Value of Animal-Based Medical Research

In the 1960s, thalidomide (generic name rofecoxib, trade name Vioxx), a drug used in sleeping pills and sedatives, was discovered to help alleviate morning sickness in pregnant women and was widely used in Europe and other countries. However, due to one Food and Drug Administration (FDA) inspector who believed that there were insufficient animal data to support its use in pregnant women, and in spite of much pressure to approve the drug for use in the United States, thalidomide was not approved for sale in the United States for use by pregnant women. Within several years of thalidomide being first prescribed for pregnant women, it became obvious that the drug was causing limb malformations in newborn infants and its sale was halted worldwide. The FDA inspector who held up approval of the drug in the United States was Dr. Frances Kelsey, a Canadian working at the FDA. In 1962, Dr. Kelsey was awarded the President’s Award for Distinguished Federal Civilian Service by President John F. Kennedy, largely in recognition of her efforts to keep thalidomide out of the U.S. market (Wikipedia Web Page 2015). In June 2015, she was named to the Order of Canada, again largely in recognition of her efforts to keep thalidomide off the market, but also for being “an instrumental figure in shaping and enforcing drug licensing protocols.”

Dr. Albert Sabin, recognized as the developer of the oral polio vaccine, in a personal letter to this author, dated September 28, 1991, noted thusly, “My own experience of over 60 years in biomedical research amply demonstrated that without the use of animals and of human beings, it would have been impossible to acquire the important knowledge needed to prevent much suffering and premature death not only among humans but also among animals.” Also, in a paper published in the Journal of the American Medical Association, Dr. Sabin noted that “during the preceding four years approximately 9,000 monkeys, 150 chimpanzees, and 133 human volunteers have been used thus far in the quantitative studies of the various characteristics of different strains of polioviruses” (Sabin 1956). Even though use of the oral polio vaccine has been discontinued in many of the world’s developed countries (due to the reported incidence of 1 in 2.4 million cases of induced polio in recipients of the vaccine and the increased safety of the injectable vaccine), it is still used in many developing countries due to the ease of administration and some cultural resistance to the injectable vaccine.

Dr. Helen Taussig was the codeveloper (with Drs. Alfred Blalock and Vivien Thomas) of the Blalock–Taussig–Thomas shunt for correcting the malposition of cardiac vessels with or without ventricle perforations in newborn infants (commonly called the blue baby syndrome, which, uncorrected, invariably led to the death of the affected infants). In a personal conversation with this author (ca. mid-1960s), she indicated that the use of dogs was absolutely critical in the development of the shunt, and because of the results of the dog studies, early surgeries on human infants were largely successful. On September 28, 1962, in testimony before the congressional house hearing of the Subcommittee of the Committee on Interstate and Foreign Commerce, Dr. Taussig affirmed that the use of dogs had been critical for the development of the Blalock–Taussig–Thomas shunt and noted that the procedure had “saved thousands of lives throughout the world. It opened up the field of pediatric cardiac surgery” (Taussig 1962).

Dr. Emanuel Grunberg, while not as well known by the public as Drs. Sabin and Taussig, was a member of the team that discovered the antituberculosis drug isoniazid. In the early 1950s, Dr. Grunberg was working at Roche Pharmaceuticals, where there was a major program to find an antibiotic that would be effective against Mycobacterium tuberculosis, the causative agent of human tuberculosis. Prior to the discovery of isoniazid, the only antibiotic that was available to treat tuberculous was streptomycin, but it was more bacteriostatic than bactericidal and treatment could take years and long-term use of the drug could lead to some serious potential side effects, such as vertigo and allergic reactions. Over dinner at his son’s house one evening (ca. mid-1980s), Dr. Grunberg told this author that testing of isoniazid in mice was a critical factor in discovery of the drug, as in vitro testing with it indicated only marginal effectiveness against M. tuberculosis. However, when tested in mice it proved to be highly effective against the bacterium, an effect ultimately determined to be a result of a metabolic product produced by the animals that was the active agent. Isoniazid is still considered to be a first-line medication in the prevention and treatment of tuberculosis.

Is History Prologue?

In a 2011 Hastings Center Report, Dr. Larry Carbone wrote, “History is informative, but not conclusive. To say that dogs were vital to the discovery of the role of the pancreas in diabetes in the 1920s is not to conclude that other approaches could not have worked then, or that the dog studies would be necessary in the twenty-first century” (Carbone 2011). Dr. Carbone’s implied caution about using the criticality of some past use of animals as justification for continued use of animals can be problematic when viewed through the lens of contemporary technological knowledge.

However, conscientious application of the 3Rs should maximize the probability that future use of animals in biomedical activities will prove to have been valid in the context of our knowledge today. Contemporary knowledge may still require an animal model for studies of diabetes, but it may be a genetically altered mouse hosting human pancreas cells rather than dogs. More importantly, critical well-designed research, based on well-documented rationale and that can best be completed using animals today, should not be delayed on the hope that a better alternative might be discovered sometime in the future.

Selected Examples of the Laws and Regulations That May Apply to Biomedical Activities Conducted in the United States and Canada

• Federal Animal Welfare Act and Regulations (http://www.aphis.usda.gov/).
• Public Health Service Policy (http://grants.nih.gov/grants/olaw/olaw.htm) and the associated Guide for the Care and Use of Laboratory Animals (the Guide), published by the National Research Council, and most recently revised in 2011 (https://grants.nih.gov/grants/olaw/Guide-for-the-Care-and-use-of-laboratory-animals.pdf).
• Good Laboratory Practice Act. This act and its implementing regulations are enforced by the federal FDA, and the provisions of the act may impact how the care and use of animals is documented when animals are used in biomedical activities resulting in data submitted in support of applications for approval of a new pharmaceutical agent or medical device (http://www.21cfrpart11.com/files/library/pred_rules/mcdowall_glp_annotate.pdf).
• Good Manufacturing Act. As with the Good Laboratory Practice Act, this act and its implementing regulations are enforced by the federal FDA and the provisions of the act may impact how the care and use of animals is documented when animals are used in activities involving the manufacturing of pharmaceutical products (e.g., to test efficacy) (http://www.fda.gov/Drugs/DevelopmentApprovalProcess/Manufacturing/ucm169105.htm).
• Lacey Act. Under the Lacey Act, it is unlawful to import, export, sell, acquire, or purchase fish, wildlife, or plants that are taken, possessed, transported, or sold (1) in violation of U.S. or Indian law or (2) in interstate or foreign commerce involving any fish, wildlife, or plants taken possessed, or sold in violation of state or foreign law. The law covers all fish and wildlife and their parts or products, plants protected by the CITES, and those protected by state law. Commercial guiding and outfitting are considered to be a sale under the provisions of the act (http://www.fws.gov/international/laws-treaties-agreements/us-conservation-laws/lacey-act.html).
• Convention on International Trade in Endangered Species of Wild Fauna and Flora (https://www.cites.org/). Depending on the species of animals being sought for biomedical activities, CITES provisions may preclude using them and/or may require special permits and waivers to obtain them.

Other Import and Export of Animals

• Animal and Plant Health Inspection Service (APHIS) (https://www.aphis.usda.gov/wps/portal/aphis/ourfocus/importexport)
• Centers for Disease Control and Prevention (CDC) (http://www.cdc.gov/importation/bringing-an-animal-into-the-united-states/)
• U.S. Fish and Wildlife Service (http://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/books/NBK19632/).
• Interstate transport”“APHIS

State and Local Regulations

Institutions using animals in research, teaching, or testing may be subject to additional state and local laws. State and local legislatures should be consulted for more details. For example, in the state of Nevada, the Nevada Department of Wildlife requires permits for trapping wild native animals for research and for having and maintaining certain prohibited species, such as African clawed frogs.

Guidelines

Many professional societies publish “best-practice” guidelines for use of animals in biomedical activities. While such guidelines may not be legally binding, they may affect public perceptions about an institution’s animal care and use program, as well as a program’s ability to obtain AAALAC International accreditation. Some examples of such guidelines are

• Guide for the Care and Use of Agricultural Animals in Research and Teaching (Ag Guide). The Ag Guide is published by the Federation of Animal Science Societies (FASS) and was most recently updated in 2010 (http://aaalac.org/about/Ag_Guide_3rd_ed.pdf).
• Guidelines of the American Society of Mammalogists for the Use of Wild Mammals in Research (http://www.mammalsociety.org/uploads/Sikes%20et%20al%202011.pdf).
• The Ornithological Council’s Guidelines to the Use of Wild Birds in Research (http://www.nmnh.si.edu/BIRDNET/guide/).
• The American Society of Ichthyologists and Herpetologists’ Guidelines for the Use of Fishes in Research (2013) (http://www.asih.org/sites/default/files/documents/publications/asf-guidelines-use-of-fishes-in-research-2013.pdf) and Guidelines for Use of Live Amphibians and Reptiles in Field and Laboratory Research (http://www.asih.org/sites/default/files/documents/resources/guidelinesherpsresearch2004.pdf).