Tag Archives: ethics

Likelihood Ratios in Assessing the Safety of New Medicines

Robert A. Coleman

Until we know the true predictive value of animal-based methods
for predicting clinical safety issues, it is impossible to assess
the advantage or otherwise of non-animal based approaches

The use of animals in the discovery and development of new medicines has generated debate for decades. For much of this time, contrasting views have been primarily polarised on the basis of practicality versus ethics, with proponents arguing that for the development of new medicines to treat human disease, the end justifies the means, while the opponents’
chief objection has been the associated animal suffering. Commercial and public health pressures over the years have ensured that those in the ‘practicality camp’ have held sway.

More recently, however, the issue has become increasingly complex, with growing concerns that, irrespective of ethical considerations, data generated in animal (i.e. non-human) models are not necessarily or sufficiently relevant to human patients.1–3 There is now general consensus that inter-species variability is a real issue, and that animal models are far from perfect for the purpose of ensuring either the efficacy or the safety of potential new medicines intended for human subjects. Supporters of the continued use of animals argue that, while they do not provide an absolute indication of either efficacy or safety, in the absence of any other approach, one that is somewhat unreliable is better than none at all.

Such an argument has some merit, if indeed it is valid. However, in this field, all may not be entirely as it seems. Firstly, human-based in vitro and in silico alternatives are becoming ever more sophisticated,4 thus overcoming many of the criticisms originally directed toward them. For example, it has long been held that it would be impossible to model the complexity of the intact patient through a study of isolated cells and tissues, and while this problem may never be wholly overcome, the gap gets ever smaller. Secondly, it is important to understand that we really don’t know how good existing animal-based methods are. In the field of efficacy, there is a wealth of evidence that results obtained by using experimental animals can be hugely misleading.5–11 Here, we have the advantage that drugs that promise efficacy in patients on the basis of animal data can advance into clinical testing, and their utility can be directly assessed. For the majority of these drugs, the clinical outcome has been disappointing. With safety, the issue is different, as drugs with identified safety issues in animals will seldom, if ever, advance to clinical testing, thus the relevance of the animal data to safety in humans may never be determined. However, what we do know is that many drugs identified as safe in pre-clinical profiling eventually prove to cause serious and use-limiting side effects in human subjects. 12 The key question is, “Could such failures have been avoided, had we relied on human-based test methods?” Until we know how frequently non-animal methods could have identified safety issues that were missed by animal tests, it is impossible to assess the advantage or otherwise of those methods. It is a fact that, despite the continued use of animals as human surrogates in pharmaceutical research, there has never been a solid, published, peer-reviewed study demonstrating fitness for purpose, whereas reviews identifying the shortcomings are abundant.

Assessing the value of animal studies

It is for this reason that any information that sheds light on the actual value of animal-based testing for its intended purpose is of inestimable worth. Until recently, much evidence, while valuable, has been indirect. For example, a recent telling study demonstrated that pre-clinical fast-tracking (i.e. abbreviated safety testing) of potential new medicines resulted in no increase in the proportion of candidates that subsequently proved toxic in human subjects.
13 In another study, the ability of animal studies to detect serious post-marketing adverse events was demonstrably poor.14 While such reports add to the volume of data providing witness to the shortcomings of animal-based approaches to ensuring clinical safety, they do not provide a robustly measurable metric of predictive efficiency. In view of the colossal amount of data generated over the years in pre-clinical safety studies on thousands of new potential medicines, many of which have progressed to clinical testing and even to market, it is amazing that, until recently, no comprehensive analysis of such data has been applied in order to explore the value of the current approach to safety testing.

Likelihood ratios

In the light of such a background, it is of considerable significance that serious attempts are now being made to extract intelligence from the wealth of information available in publicly accessible sources, in order to shed more light on the actual predictive power of animal-based safety testing. A particular example is the utilisation of the Safety Intelligence Programme (SIP),15 which overcomes semantic issues to extract valid information from all available data sources. SIP has been used, for example, to explore the predictive power of animal models for the detection of liver toxicity associated with a wide range of human medicines,16 highlighting the highly variable efficiency of different models in combination with different drug toxicities. More recently, SIP has been used to particular effect in two studies that have explored directly the value of dogs, mice, rats and rabbits in predicting safety issues in human subjects.17,18 While most previous studies have relied on determining ‘concordance’ between animal and human data, that tells only a part of the story, and is too simplistic a measure to be of much real value. Its
problem is that it only deals with positive correlation, i.e. the frequency that toxicity in experimental animals and in human subjects coincide, ignoring the issue of true prediction. What is needed is a determination of likelihood ratios (LRs),19 both positive (PLRs) and negative (NLRs), to gain a more complete picture. What emerged when LRs were determined was that, although there was indeed some measure of concordance between positive toxicity data between animals and humans, in terms of LRs, none of the species proved to offer any useful level of real predictive power. Although the studies and their conclusions did not escape criticism from some quarters,20 the suggested limitations, real or perceived, are arguably irrelevant to its overall validity.21

What did emerge from the application of this approach were absolute values for both PLRs and NLRs for a wide range of specific drugs. The importance of this is that, for the first time, such measures can provide a robust yardstick against which to evaluate the relative merits of alternative approaches to toxicity testing.

Conclusions

To summarise, the use of more-rigorous approaches to the evaluation of animal models as predictors of the likelihood that any chemical will be similarly toxic or non-toxic in human subjects provides not only a realistic measure of their actual fitness for purpose, but crucially, also a basis by which the efficiency of other, ideally human-based, approaches can be evaluated through their exposure to the same range of drugs. The use of the same drugs ensures that any criticisms related to potential bias, or other potentially confounding factors, are negated. Such a prospective study would be of inestimable value. Dare we hope that the government and pharmaceutical companies will take up the challenge and fund
such a study?

Dr Robert A. Coleman
Independent Consultant
UK
E-mail: robt.coleman@btinternet.co
m

References

1 Wall, R.J. & Shani, M. (2008). Are animal models as good as we think? Theriogenology 69, 2–9.
2 Hartung, T. (2013). Food for Thought… Look back in anger — What clinical studies tell us about preclinical work. ALTEX 30, 275–291.
3 Pippin, J.J. & Sullivan, K. (undated). Dangerous medicine:
Examples of animal-based “safety” tests gone wrong. Washington, DC, USA: The Physicians Committee for Responsible Medicine. Available at: http://www.pcrm.org/research/animaltestalt/animal testing/dangerous-medicine-examples-of-animalbased-tests (Accessed 03.11.14).
4 Ashton, R., De Wever, B., Fuchs, H.W., Gaça, M., Hill, E., Krul, C., Poth, A. & Roggen, E.L. (2014). State of the art on alternative methods to animal testing from an industrial point of view: Ready for regulation? ALTEX 31, 357–363.
5 Pound, P., Ebrahim, S., Sandercock, P., Bracken, M.B. & Roberts, I. (2004). Where is the evidence that animal research benefits humans? British Medical Journal 328, 514-517.
6 Kaste, M. (2005). Use of animal models has not contributed
to development of acute stroke therapies: Pro. Stroke 36, 2323–2324.
7 Pippin, J.J. (2005). The Need for Revision of Pre-Market Testing: The Failure of Animal Tests of COX-2 Inhibitors, 23pp. Washington, DC, USA: The Physicians Committee for Responsible Medicine. Available at: pcrm.org/pdfs/research/testing/exp/COX2Report.pdf
(Accessed 04.11.14).
8 Hackam, D.G. & Redelmeier, D.A. (2006). Translation of research evidence from animals to humans. Journal of the American Medical Association 296, 1731–1732.
9 Knight, A. (2008). Systematic reviews of animal experiments
demonstrate poor contributions towards human healthcare. Reviews on Recent Clinical Trials 3, 89–96.
10 Matthews, R.A.J. (2008). Medical progress depends on animal models — doesn’t it? Journal of the Royal Society of Medicine 101, 95–98.
11 Seok, J., Warren, H.S., Cuenca, A.G., Mindrinos, M.N., Baker, H.V., Xu, W., Richards, D.R., McDonald-Smith, G.P., Gao, H., Hennessy, L., Finnerty, C.C., López, C.M., Honari, S., Moore, E.E., Minei, J.P., Cuschieri, J., Bankey, P.E., Johnson, J.L., Sperry, J., Nathens, A.B., Billiar, T.R., West, M.A., Jeschke, M.G., Klein, M.B., Gamelli, R.L., Gibran, N.S., Brownstein, B.H., Miller-Graziano, C., Calvano, S.E., Mason, P.H., Cobb, J.P., Rahme, L.G., Lowry, S.F., Maier, R.V., Moldawer, L.L., Herndon, D.N., Davis, R.W., Xiao, W., Tompkins, R.G. & Inflammation and Host Response to Injury, Large Scale Collaborative Research Program (2013). Genomic responses in mouse models poorly mimic human inflammatory diseases. Proceedings of the National Academy of Sciences of the USA 110, 3507–3512.
12 Li, A.P. (2004). Accurate prediction of human drug toxicity: A major challenge in drug development. Chemico-biological Interactions 150, 3–7. 13 Arnardottir, A.H., Haaijer-Ruskamp, F.M., Straus, S.M., Eichler, H.G., de Graeff, P.A. & Mol, P.G. (2011). Additional safety risk to exceptionally approved drugs in Europe? British Journal of Clinical Pharmacology 72, 490–499.
14 van Meer, P.J., Kooijman, M., Gispen-de Wied, C.C., Moors, E.H. & Schellekens, H. (2012). The ability of animal studies to detect serious post marketing adverse events is limited. Regulatory Toxicology & Pharmacology 64, 345–349.
15 Berry, S. (2012). Safety Intelligence Program Provides Insight into Drug-Induced Cardiac Effects. Stone, UK: Instem plc. Available at: http://www.biowisdom.com/content/safety-intelligence-program (Accessed 04.11.14).
16 Fourches, D., Barnes, J.C., Day, N.C., Bradley, P., Reed, J.Z. & Tropsha, A. (2010). Cheminformatics analysis of assertions mined from literature that describe drug induced liver injury in different species. Chemical Research in Toxicology 23, 171–183.
17 Bailey, J., Thew, M. & Balls, M. (2013). An analysis of the use of dogs in predicting human toxicology and drug safety. ATLA 41, 335–350.
18 Bailey, J., Thew, M. & Balls, M. (2014). An analysis of
the use of animal models in predicting human toxicology and drug safety. ATLA 42, 181–199.
19 Altman, D.G. & Bland, J.M. (1994). Diagnostic tests 2: Predictive values. British Medical Journal 309, 102.
20 Brooker, P. (2014). The use of second species in toxicology
testing. ATLA 42, 147–149.
21 Bailey, J. (2014). A response to the ABPI’s Letter to
the Editor on the use of dogs in predicting drug toxicity
in humans. ATLA 42, 149–153.

Download a pdf of this article. Likelihood Ratios in Assessing the Safety of New Medicines

The Cost of Standing Strong for Replacement

Katy Brown

To what extent does maintaining a stand against
the use of animals in experiments harm the
career progression of a young researcher today?

The experience of young researchers choosing to avoid animal experiments varies greatly, depending on the situation in which they find themselves. A series of interviews with young researchers, that were carried out as part of a Lush Prize Background Paper, pointed to the importance of centres or research groups dedicated to animal alternatives. It is clear that those students lucky enough to find themselves at one of these institutions have a much easier time in pursuing this career route. That said, there are still obstacles and challenges, including funding issues and resistance from those working outside these institutions. Those who choose this often difficult path outside specialist institutions may face a very tough time — in fact, two of the young people interviewed had no option but to decide on a career change, in large part due to issues around animal use. Individuals from a number of organisations involved in promoting alternatives to animal experiments and/or animal rights were asked to give their opinions on the feasibility of this career path choice by young researchers. What clearly came out of these interviews is that young researchers who wish to go into a career without ever being expected to use animals need to be determined, resourceful and tenacious. This is illustrated by comments such as:
— “You’ve got to get used to the fact that it may not always be an easy route.”
— “Forging an entire career in toxicology where you’re never involved in animal testing, is much more challenging.”
— “Some budding scientists may well be put off entering science, particularly toxicology, because of the issue of animal welfare.”

Interviews with young researchers

The issues surrounding this area were investigated in more depth by talking to six young researchers, not just from the UK, but also from Portugal, Denmark, Italy and the USA. Four were the recipients of the 2012 Lush Prize, and the two other individuals entered the life sciences, but chose to change career path, at least in part due to issues concerning animal use. Their full stories can be found in the Young Researchers Lush Prize Background Paper on the dedicated website (see here).

Sofia — the early-exiter — Portugal

Sofia started to study for a Biology BSc, but dropped out in the first year. At the point she decided to leave, she had not been asked to dissect or vivisect, but knew that before the end of the year she would be asked to do so. Sofia was concerned that the lecturers weren’t discussing these matters with the students and that the students were, in fact, apparently indifferent to the subject and perceived themselves as powerless. She felt that the general opinion of the student body was that dissection and vivisection were scientifically mandatory, and, even if they didn’t want to do it, there was nothing they could do to prevent it — and indeed that conscientious objection was something the great majority of students would not consider. In the end, she felt excluded from the course.

Joe — the committed conscientious objector — UK

Joe studied for a life science degree, then a related PhD, and finally took up a post-doctoral position. He avoided the undergraduate degree modules that would have involved dissection. During his PhD studies, there was increasing pressure on him to become involved in rodent studies, but he resisted this pressure, having stated at the start of his PhD that he would not be willing to carry out animal experiments. Initially, he was able to guide his own research in a way that avoided animal testing, by using non-animal methods. This did, however, get harder and harder as the research progressed, and he was encouraged “from the inside more and more to use non-human models to look at some of the key areas that he was investigating. He said that the position he ended up in, “essentially had me boxed into a corner from which changing career or carrying out animal experimentation (either directly or indirectly) were the only options.” He added that “the alternatives were pushed to one side, or not seen as being able to give the whole picture, by the people leading my research group.” Joe has changed his career path, and now works in the field of conservation.

Chiara — the well-supported enthusiast — Italy

Chiara works for Anna Maria Bassi, at the Analysis and Research Laboratory in Pathophysiology (LARF), in the Department of Experimental Medicine of the University of Genova, Italy. This laboratory is involved in the development and validation of in vitro models for use as alternatives to animal testing. Despite being based in this institution, with its non-animal research stance, Chiara’s major difficulty has been fundraising and finding partners with whom to develop new and competitive projects. She explained that, in Italy: there are very few research groups that promote in vitro models as alternatives to animal testing; the Italian Parliament has only very recently banned certain animal tests and endorsed funds for research on in vitro models with particular attention to the policy of the Three Rs and the European legislation; there are very few academic courses on alternative methods; and not very many research groups are devoted exclusively to working on in vitro models.

Felix — the motivated human research-focused scientist — USA

Felix has, since being an undergraduate, found it more useful to focus his research on a human-based approach, rather than an animal-based approach. He strongly believes that a human-based approach can provide more-relevant information, adding that he feels that “there was, and still is, some type of resistance by those that argue that much more information can be gathered from animal-based research.” He thought that “the most difficult steps are in the very early stages, such as undergraduate and post-graduate studies, where our scientific freedom is limited. However, for me, the post-doctoral stage has been most challenging, because our non-animal system has unfortunately been viewed with some level of resistance by some of our colleagues.”

Line — the animal-free testing convert — Denmark

Line started with the intent of working with animals, because she thought that she could help the animals — i.e. so that the animals used would be as few as possible, and would be as well taken care of as possible.” She then changed her career path, because she felt that it was stressful to be around animal suffering every day. She now works entirely on human tissue, which she feels is “very interesting from a scientist’s point of view”, because “when researching human health, the use of animal models will always be far less accurate than using humans.” She thought that the undergraduate level can be the most challenging when it comes to avoiding animal use, because “often you are not able to choose, as the institutions are streamlined and every student has to do the same courses.”

Liz — the slow-burner — UK

Liz studied A-level Biology, which involved a rat dissection. She was concerned about animal welfare and didn’t want to do the dissection, but she wanted to pass the course and go to university. She added, “It was said that we could apply to dissect a plant, but that we wouldn’t get as good a mark!” When she went to university, she didn’t study Biology. This was, in part, due to advice at her college that it would involve a lot of dissection. Having completed a work placement in the chemical industry and enjoyed it, she decided to go down that career path, but during the course of her degree she was more and more drawn to the options that involved a biological element.
For her MSc course, she chose Toxicology, with the long-term aim of working in a hospital and thus with humans, not animals. Her friend, who had completed the course, ascertained that there was no practical animal work involved.

She obtained a graduate job in a hospital toxicology laboratory, and then in a cancer prevention unit. Here, she was involved in examining human samples (breast tissue, etc.) from biopsies and surgery, for biomarkers of cancer, and she was also required to test organs from experimental animals. Liz said, “I was still training and learning, but felt that the experiments were not always well planned and the animal data derived were not always very informative.” She then decided to take more proactive action, and since then has completed a PhD in neurotoxicology, based on developing an in vitro brain model from human cells. This was followed by a postdoctoral position funded by the Humane Research Trust. After this first post-doctoral position, despite the promising nature of the brain cell model, Liz was unable to secure further funding, despite that fact that she “really felt that I had to get back to my original work, not only for myself, but also for the sake of those who’d supported me thus far.” Thankfully, due to the Lush Prize and funding from the British Brain Research Fund, she has been able to get her research aims back on track, at least for the time being. Liz added, “Because I have now chosen a career that specifically deals with developing replacement models, with a supervisor specifically involved in this field, avoiding animal use will not be an issue until I find myself unemployed. But due to it still being an emerging field, employment opportunities and funding are an issue, as is convincing our traditionalist colleagues of the worthiness of our research.”

Summary

The testimonies of these individuals largely speak for themselves. The responses point to the importance of specific institutions or research groups that focus on the development and use of alternatives, and these should, of course, be better supported. Those who find themselves outside such institutions or teams, are more likely to feel stranded and isolated. Then again, Liz did have the support of a research group dedicated to replacement, but she has still had a significant struggle to find funding. The interviews with some of these particular young researchers indeed pointed toward a tangible ‘cost’ in terms of having to steer their career on the often difficult path toward the use of non-animal based methods.

Katy Brown
Ethical Consumer Research Association
Unit 21, 41 Old Birley Street
Manchester M15 5RF
UK
E-mail: craig@lushprize.org

Download a pdf of this article. The Cost of Standing Strong for Replacement

The Use of Animals in Experiments — Not Because of Lack of Empathy?

Jolanta Zwolinska

The choice of an individual to use animals in experiments
is influenced by a wide range of social, religious and sometimes
career-driven factors, rather than a lack of empathy

Representatives of various religions and philosophical ideologies frequently make reference to the well known belief that one’s attitude toward the disabled, the sick, old people and children, is a measure of the humanity or moral value of the person. Yet, disputes arise when animals are included into the group of living beings entitled to the same type of consideration. The fact that they are used in scientific experiments is a highly controversial matter, and conflicting views are held by people both within and without the scientific community. This article presents a number of factors which might influence the decision of an individual to stand for or against animal use in experiments, including arguments voiced by representatives of the various sciences, both in support of or against the  continuation of animal experimentation.

Some historical and religious background

The approach adopted by ancient ethicists, in assuming  the dichotomy of human body and soul, resulted in man’s alienation from nature. Aristotle proclaimed a hierarchical structure of the world and the existence of essential differences between humans and animals, the latter being considered as inferior to the former. The intellect, according to that philosopher, was the main determinant of moral values.1 Adopted by the Judeo–Christian and Islamic traditions, the dogma of the immortal soul inherent in humans but not in animals, served to create a vast chasm between mankind and the animal world. Accordingly, Man rules over the world in which animals play an ancillary function.2–4 The cultures of Hinduism and Buddhism are based on the principles of respect for life and the protection of every living creature from suffering. Considered as being similar in their essence to humans, it is dictated in these religions that animals deserve to be protected and treated with reverence.3,5,6

Shaped throughout the ages, our stereotypical opinion of animals has been encoded into our collective consciousness, and cannot be easily overcome by newly emerging social concepts and ideas. For centuries, our attitude toward animals has been based on domination and power.4  In contemporary Christian culture, the majority of ethologists, psychologists and lawyers sympathise with an anthropocentric model of the biosphere, and take a negative stand with regard to animal rights. According to Bialocerkiewicz,5 animal rights reflect our attitude toward life and suffering and our appreciation of the universal principle of humanitarianism. Humans are not entitled to treat nature barbarically — i.e. to kill or mutilate, inflict pain or suffering. Bialocerkiewicz does not find any reason to recognise a unique role of mankind in the grand scheme of things, and emphasises a lack of religious, ethical or economic justification for awarding humans the right to take arbitrary decisions concerning the lives of other species.

The Catholic Church also acknowledges problems related to animal suffering. It speaks for an absolute ban on the mass breeding of animals and for the abandonment of procedures of animal testing used for cosmetics and various types of stimulants.7 According to Kozuchowski,8 a priest, it is our respect for ourselves and our claim to be perceived as more evolved beings that forbid us to treat animals as ordinary objects. A negative attitude toward animals is inevitably linked with a negative attitude toward other human beings.

The concept of ‘animal rights’ and morality

Cohen believes that rights result from contracts which are binding between members of a given community, and that rights, unavoidably, have inherently associated duties. Animals cannot undertake such obligations, and therefore they are not entitled to any rights in this sense (as cited in Mukerjee6). Guzek9 also points to the relativity of the concept of ‘animal rights’. He emphasises that rights can only be awarded to members of communities which are able to comply with commonly recognised ethical norms, so animals are not eligible to have such rights. Guzek believes that extremist activists of ‘animal right movements’ expect that animal rights should be similar
to, or identical to, human rights. Yet, evidence derived from observations shows that, whenever there is a conflict between animal rights and human interests, the latter always win. In Guzek’s opinion, human and animal rights are not, and cannot be, equal.9 Mukerjee, however, points out that children and mentally ill individuals cannot assume any obligations, nor do they comply with any norms, and yet they are not deprived of rights.6
According to Kotowska,4 the protection awarded to animals by the legal system of a given community depends on the attitude generally adopted by its members toward animals. If animals are treated as objects by the majority, then they will also be treated as objects by the adopted customary law, because there would, of course, be no one in such community to protest in their defence.
Many contemporary philosophers are reluctant to admit that it is pointless to extend our system of morality to include animals, opposing the claim that animal research does not constitute a moral problem. They emphasise the fact that speciesism is the cause of cruelty committed by man toward laboratory animals. Other philosophers take a less radical approach, accepting only some methods of animal use, and expressing favourable opinions about the banning of the most abusive research methods.6 Frey, a philosopher, emphasised that he was not an antivivisectionist, but that he accepted only those experiments with animals which yielded significant benefits and could also be conducted with human subjects.10 Singer, author of Animal Liberation,11 recognised by publicists as “the bible of the animal liberation movement”, believes that animal experimentation is acceptable only in the case of trial tests for life-saving drugs.

A contradiction in definition

The contradiction in the fact that people use animals as experimental models to acquire information pertaining to humans, and yet they refuse to acknowledge that animals have qualities recognised as human, is noted by Pisula.12 According to Griffin,13 the belief that no animal is capable of suffering or worthy of sympathy cannot be supported by any contemporary scientific evidence, and Spaemann14 emphasises that animals are not able to give meaning to, or control, their suffering. They are, indeed, doomed to suffer, in that it is particularly hard to endure, if they cannot respond to it with aggression or by escape. As a result of scientific progress, it is more and more difficult to justify the claim about the uniqueness of our species. Birmelin and Arzt, in their book, entitled Haben Tiere ein Bewusstsein [Do Animals Have Consciousness?],15 wrote: “…in terms of their mentality and emotions animals are more similar to us than we used to believe…”. What differs between us and animals, however, is not these qualities per se, but their intensity. Animals use senses which have become blunted in human beings. After long-term observations of social behaviour in elephants, zoologists assume that certain forms of morality and selfawareness may occur in more-highly evolved animals.16 Today, we also know that primates are able to experience emotions such as anger, fear, boredom, longing and loneliness.6

Opinions at the laboratory bench

It was emphasised by Mukerjee that scientists often decide to use animals, only if they are convinced that this is the only way to help people, and that sympathy for animals frequently affects this deliberation. Researchers try to reconcile the dictates of science with a humane approach — in fact, many of them love animals and volunteer to work for their benefit.6 Szyszko believes, however, that the choice of research method does not depend on sympathy for animals, or the need to acquire knowledge necessary for saving human health and life. Instead, it is proposed that senior academic staff members might sometimes encourage younger researchers to conduct animal experimentation, in order to contribute to the scientific accomplishments of the given institution.
As a result, animal experimentation is conducted all too often, and its purpose is not always justified by the needs of science. According to Szyszko, many higher-order animals suffer and die needlessly, frequently only to fulfil the excessive ambitions of young academics.17 In addition, Bialocerkiewicz highlights the fact that, in order to advance their careers and scientific outputs, some researchers are ready to carry out even the cruellest experiments, and gives an example of Baltimore, a physiologist awarded the Nobel Prize, who does not believe that “animal testing poses any moral problems”.5 As a result of such explicit approval by high-profile individuals, animals used in research can become perceived to be merely instruments — i.e. objects which can be exposed to any manner of tests.18 We see this in the fact that animals are often referred to as “experimental models”, “bioreactors”, or “source of replacement parts”, and this inevitably reinforces that idea that they have no rights and that they can be readily exposed to suffering and extermination.19 Feinberg insists that animals should not be treated as objects, although undoubtedly, they cannot be perceived in the same category as humans.20

Conclusion

Mukerjee points out that we are all morally responsible for the appropriately humane treatment of animals.6 The choice of an individual to use animals in experiments is influenced by a wide range of social, religious and sometimes career-driven factors, rather than a lack of empathy on the part of the researcher. Indeed, it is commendable that sensitivity to human pain and suffering defines the course of action for people professionally involved in medicine. What must be emphasised is that this sensitivity should be manifested as empathy for beings which are weaker and subordinate to humans, and the right choices should be made accordingly.
We should not make people suffer for the sake of animal welfare, but we also should not sentence animals to terrible suffering which leads to questionable benefits for people, not least in terms of the scientific validity of the results obtained. Due to progress in science, it is more and more difficult to justify the claim about uniqueness of our species, and being human is not only a privilege, but also an obligation to the creatures with which we share the Earth.

Jolanta Zwolińska
Faculty of Medicine
University of Rzeszów
Rzeszów
Poland
E-mail: jolantazwolinska@op.pl

References

1 Serpell, J. (1996). In the Company of Animals: A Study of Human–Animal Relationships, 2nd revised edition, 316pp. Cambridge, UK: Cambridge University Press.
2 Tatarkiewicz, W. (2004). History of Philosophy, 21st edn, 376pp. Warsaw, Poland: PWN.
3 Lejman, J. (2006). Animal ethics in the light of the idea of sustainable development. Problemy Ekorozwoju 1, 99–105.
4 Kotowska, M. (2011). Selected aspects of animal protection
according to criminal law. National and international perspectives. In Criminology of Contemporary Ecological Threats (ed. M. Kotowska & W.Pływaczewski), pp. 94–105. Olsztyn, Poland: Katedra Kryminologii i Polityki Kryminalnej, Uniwersytet Warmińsko-Mazurski.
5 Białocerkiewicz, J. (2005). Legal status of animals. Animal rights or legal protection of animals, 319pp. Toruń, Poland: Dom Organizatora.
6 Mukerjee, M. (1997). Trends in animal research. Świat Nauki 4, 68–76.
7 Krenzer, F. (2004). Morgen wird man wieder glauber. [You will believe again tomorrow. A Catholic faith information book.], 41st edn, 380pp. Limburg, Germany: Lahn-Verlag.
8 Kożuchowski, J. (2011). Ethical responsibilities of man toward the world of animals. Robert Spaemann’s Vision. Studia Ecologiae et Bioethicae UKSW 9, 29–48.
9 Guzek, J.W. (2005). Outline of Human Pathophysiology, 699pp. Warsaw, Poland: PZWL.
10 Frey, R.G. (1983). Vivisection, morals and medicine. Journal of Medical Ethics 9, 95–104.
11 Singer, P. (1995). Animal Liberation, 368pp. London, UK: Pimlico.
12 Pisula, W. (2001). Introduction to the monograph. In
Animal Minds
(ed. D.R. Griffin), pp. 16–17. Chicago, IL, USA: University of Chicago Press.
13 Griffin, D.R. (2004). Animal Minds, 320pp. Chicago, IL, USA: University of Chicago Press.
14 Spaemann, R. (2001). Grenzen: Zur Ethischen Dimension des Handelns [Borders: On the Ethical Dimension of Actions], 427pp. Stuttgart, Germany: Klett-Cotta.
15 Arzt, V. & Birmelin, I. (2001). Haben Tiere ein Bewusstsein [Do Animals Have Consciousness?], 279pp. Warsaw, Poland: Bertelsmann Media.
16 Vetulani, J. (2014). Bright prospects for thinking. Interview conducted by Rafał Romanowski, Żyjmydłużej 2, 10–13.
17 Szyszko, S. (2005). Epitaph for a dog (a few comments on ‘vivisection’). Przegląd Medyczny Uniwersytetu
Rzeszowskiego
1, 95–98.
18 Kornas, S. (2005). Animal experimentation. In Encyclopedia of Bioethics. Christian Personalism. The voice of the Church (ed. A. Muszal), pp. 128–132. Radom, Poland: Polskie Wydawnictwo Encyklopedyczne.
19 Żukow-Karczewski, M. (2013). Medical experiments and research involving animals. Polska: Wolnemedia.net. Available at: http://wolnemedia.net/historia/eksperymenty-i-doswiadczenia-medyczne-nazwierzetach/ (Accessed 21.05.13).
20 Feinberg, J. (1978). Human duties and animal rights. In On the Fifth Day: Animal Rights and Human Ethics (ed. R. Knowles Morris, R. & M.W. Fox), pp. 11–38. Lancaster, UK: Gazelle Book Services Ltd.

Download a PDF of this article: The Use of Animals in Experiments — Not Because of Lack of Empathy?

Personal Reflections on Veterinary Science Training and the Three Rs

Rosemary Elliott

Students against the thoughtless use of animals
in veterinary education need  support
to be true to their values, to use
science to uphold them, and to never
give up on advocating for the
highest standards of animal welfare

This opinion piece is something I needed to write personally, and it shocks me to notice the ten years that have passed since I enrolled as a mature-age student in veterinary science. It was a privilege to have this opportunity, and I am grateful that I can now advocate for animals in a way I never could have done before, particularly through my work with Sentient. By the time I enrolled in veterinary science, the faculty where I studied had made huge advances in the ethical use of animals in teaching, most notably through the banning of ‘terminal surgeries’. Since my time as a student, things have improved even more, and the faculty is leading the way in developing a national curriculum for animal welfare and ethics in veterinary teaching. Yet, despite this, some attitudes and practices ‘die hard’, and many of my experiences could only be described as vicarious trauma — hence the passing of so much time before I felt ready to give life to them with words.

Although the animals I speak of were used primarily for educational purposes, I do hope that those of you working in the laboratory setting with research animals, will find that my reflections will stimulate your own thinking and resonate with some of your experiences. We have much in common in our struggle to do our work and to do the best we can by the animals in our care.

Anatomy classes

Admittedly, I grew up with an idealised view of veterinary practice, starting with Dr Doolittle as a very small child, then moving on to All Creatures Great and Small and the other James Herriot books. Although 60 years had passed since the setting of those stories, with the onset of intensive farming, I went on assuming it was primarily about supportive teamwork and above all, empathy for animals.

The first wake-up call came in the form of Anatomy 1A. The laboratory, a huge room with grimacing dead greyhounds lying on metal trays, became a hothouse of anxieties, sometimes played out by the larking about that involved the throwing of body parts. The smell of formalin was so powerful that I can still conjure it up. In groups of three or four, we learned anatomy the traditional way, which some of us described as “being thrown a dead dog and a textbook”. There was minimal instruction, so we were left to hack away in the pursuit of identifying a lengthy page of anatomical features, ‘all examinable’, with the pressure to clean up before our class ended.

I don’t remember being told why they were always greyhounds, or how they were sourced. There was certainly no time for debriefing, and we learned early on that it was unacceptable to appear emotional. I soon became desensitised to this horrible scene until the 4th year, when I was initiated into surgical training on freshly-killed pound dogs of various breeds — soft and floppy and somehow, not being greyhounds, they seemed more individual, more like pets. I remember struggling with sad moments of wondering about their lives and whether they had been loved, and feeling ashamed of my tacit acceptance of greyhounds as production animals.

Now, this raises for me the question of respect for life, even after a life is over. If we are serious about honouring the dignity of animals and safeguarding their welfare, veterinary training must provide as many opportunities as possible for effective learning that reduces the number of animals used, such as initial skills training through videos and silicone simulator anatomical models. At Sentient, we also call for the veterinary profession to supply cadavers from ethical sources, rather than colluding with the widespread disposal of racing greyhounds by ‘convenience euthanasia’.

Practical animal husbandry training

Chickens and eggs
The Animal Husbandry practical classes on production animals were another shock. I expected state-of-the-art facilities for the animals, but the picnic atmosphere was killed for me by the sight of housing systems more typical of factory farming. The laying hens were all kept in battery cages, rows of little prisons with no natural lighting. Questioning this was frowned upon — we were there to show our enthusiasm and tick the boxes for the mastery of required skills. I was told these were working farms, the message to first year students from some staff members being that animal welfare is, by default, secondary to industry profit.

One of my saddest memories was being tested on my ability to remove a hen from a battery cage, restrain and examine her, then to return her to the cage, head first. She flapped with gusto and resisted going back inside. I felt I had performed an act of cruelty, giving her a tiny taste of what her body could do, but perhaps never would again. Then there was the class where chicks were deliberately infected with coccidiosis, so that we could observe the characteristic droppings. And the class on egg production, where the tutor smilingly broke fertilised eggs — to prove what, I don’t understand anymore — but leaving me with the image of an embryonic bird with a throbbing heartbeat, destined for the sink.

Compassion for birds was a disadvantage in veterinary training, where speciesism was very much alive and well. Most student complaints about animal treatment focused on mammals. In the 4th year, we were taught to euthanase chickens humanely, but were given needles of the wrong gauge, which caused their wing veins to blow. I felt murderous at the sight of students who laughingly persisted, while the ‘spent’ hens blinked helplessly as they were repeatedly traumatised by needles that failed to bring an end to their joyless lives. The demonstrator did not intervene. I learned nothing useful from this class — because after observing the other students, I decided not to even try. When I complained, the response was that they had run out of the correct-sized needles and would replace them at the next class, as if the problem had been purely a practical one.

This class could have formed a foundation for trainee veterinarians in the careful preparation and respect for birds during euthanasia. Instead, it reinforced the view of chickens as somehow less sentient, due to their status as production animals. We must consider how invoking the Three Rs would have helped here. Perhaps by the initial replacement of live birds by video footage of how to correctly perform euthanasia? But when it came to the use of live birds, which was essential, what was needed was a commitment by staff to the humane treatment of animals, and an expectation that students would demonstrate this attitude through their own behaviour. Instead, the atmosphere was cavalier and callous, and not at all conducive to any form of refinement.

Tail-biting management classes
The university’s pig farm was another indictment, with sows in sow stalls, and non-breeding pigs in dark little pens where we practised catching them with snares. This was the scene of my own most shameful memory, where, despite my opposition to unnecessary invasive procedures, I performed teeth-cutting, tail-docking and ear-notching on a piglet. I remember feeling terrified at the thought of this practical class, because of the expectation to ‘do as farmers do’ — which was ostensibly to improve the welfare of the piglets by preventing tail biting. I was unaware of any conscientious objection policy at that stage of my training. So I stalled for time, trying to look useful without actually doing anything, until the tutor presented me with my own piglet and a pair of what looked like pliers. He was clearly annoyed by my questions and my need for reassurance about avoiding the ear vein or how to create the least degree of trauma — a ridiculous question, in view of the fact that there was no analgesia.

I will always remember holding this warm, pink little being with the racing heart, who I just wanted to protect, but instead, I brutalised him. I try to cope with this memory by knowing that I worked as quickly as I could, and then rubbed his body all over to distract him from the pain, as I carried him back to his mother and made sure he found a teat to suckle on. I also try to cope by using this as the basis for my commitment from that day onwards to never again perform such an atrocity. But I will never forget standing there, praying the pain would soon end. I will never forget being inconsolable for days. I still cry at the memory of what I did. I betrayed my own values out of fear of failure and not being confident enough to stand up to pressure, aided by false reassurances that I was doing the right thing.

That night, I researched teeth cutting, and found a recent article in a veterinary journal that documented how the procedure predisposes to injury and infection in the mouth and gums. I have since visited free-range pig farms, where the ‘cannibalism’ we were indoctrinated with was not an issue. All these pigs kept their tails, and their baby teeth. I had been fed a lie, pressured into performing unnecessary and inhumane procedures on a piglet that would never be allowed on a puppy. And I was an educated adult, who had already considered these welfare issues and was not relying on this to earn a living.

My pathetic attempt at reduction, by limiting my actions to one piglet, did nothing to safeguard the welfare of that individual. Like so much of what we were expected to do in veterinary training, it simply should not have been allowed, because the procedure itself was unethical. In such cases, I believe we can be guided by the Three Rs to give priority to replacement, by showing students a video of these procedures, not least so that they know what to expect on farm visits. This can go hand-in-hand with advice about how these practices can be avoided through less-intensive husbandry practices. When invasive procedures are required, the focus should then be on initial video or simulator learning, to reduce the number of animals used, followed by refinement — i.e. teaching students to always use anaesthesia and/or analgesia to minimise stress and suffering.

Other lessons
There were multiple instances, where students at the university farm were expected to perform unnecessary invasive procedures on production animals as part of their learning experience, with routine farming practices cited as the ‘gold standard’. My question was always this: Why are we following the ways of the farmers, rather than offering something more as potential veterinarians? But most students, particularly those from rural backgrounds, accepted the status quo, citing the need for ‘real-world’ practice. It was also regarded as essential preparation for extramural farm placements, which brought further horrors that I will not elaborate on here. Common sights during my training were cattle being dehorned without analgesia, in some instances leading to maggot-infested wounds; the repeated attempts to lasso a terrified cow on a hot summer’s day, which led to her jumping a fence and almost breaking her hip; exsanguination of a sheep to prove the procedure is humane; and tail-docking and castration of lambs, who were pinned down on their backs in a ‘cradle’, all without analgesia, while students delayed the procedure by joking about who would remove which testicle.

Promotion of the Three Rs and alternatives
My reason for writing this, apart from my own need to debrief and reflect, is to think about the context that must be created, if the Three Rs are to be of use in veterinary education. Adherence to the Three Rs will only come about within a culture of empathy and respect for animals, which should also be extended to students. Offering a transparent conscientious objection policy, and reinforcing in every unit of study that there are alternatives to ethically-contentious procedures, is a crucial part of this. The way I coped was to find like-minded students, involve myself in the student-run animal welfare association, use the conscientious objection policy and formal avenues within the faculty to lodge complaints, and seek the support of staff members. And I will always be grateful to several academics, who were wonderful role models on how to uphold ethics in teaching, who had witnessed and objected to far worse in their own veterinary education, and who encouraged me and my fellow students to be true to our values, to use science to uphold them, and to never give up on advocating for the highest standards of animal welfare.

E-mail: rosemary.elliott@sentient.org.au