Tag Archives: animal experiments

Open Trials

Open Trials is a project led by Bad Science author Ben Goldacre that aims to form a complete collection of every clinical trial conducted around the world. A clinical trial is when a new medicine is tested in humans for the first time. The results from these trials are used to decide how well the medicine works and how safe it is. Currently, not all clinical trial results are published, especially when the findings are negative. This can have dangerous consequences on patient safety as medicine regulators and doctors may not be fully aware of a medicine’s effects. Therefore Open Trials is an important project.

However, before medicines are tested in humans for the first time, they are required to undergo pre-clinical tests in various species of non-human animals. These tests are required to show that the medicines are safe and effective in animal models before they are allowed to be tested in humans. However, the usefulness of these animal studies has been questioned because of the inherent biological differences between species. The results from animal studies are often very different from the results in humans, meaning that ineffective or unsafe medicines are given to humans in clinical trials. Conversely, potentially good medicines are rejected before they get to be trialed in humans because of poor results in animals.

What if we had an Open Trials–like project for pre-clinical animal studies, so that every animal study was recorded and all the results were openly available for others to review?

Here are some of the potential advantages of such a project:
– Overcoming issues such as publication bias. This occurs because studies with positive findings are more likely to be published leading to an unrepresentative and often misleading view of research that has been conducted.
– All data is given to regulators, so they can make a fully informed decision about whether a new medicine is allowed to be tested in humans.
– Finding out how useful and predictive the animal models are for human diseases and treatments.
– Reducing animal use by preventing duplication of animal studies, particularly ones with negative findings. If a study finds that a drug doesn’t work in mice, the results are unlikely to be published. Therefore other researchers might test the same drug again, without realising that it has already been proven ineffective.
Overall, more open reporting of all data can only be a good thing for science. Open trials is fantastic step forward, but more can be done for other types of experiments. This openness would be particularly valuable with animal studies due to the considerable ethical costs of the research.

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?

Beyond the Three Rs

For a long while after the Three Rs were first proposed by Russell and Burch, anti-vivisectionists rejected the concept, on the grounds that experiments on living vertebrates which cause them pain, suffering, distress or lasting harm, were ethically unacceptable and scientifically unnecessary, so there was no point in reducing, refining or replacing them. In recent decades,
however, some organisations, such as the BUAV and PETA, have moved tentatively into the middle ground, and have made positive contributions toward the Three Rs, without comprising their fundamental beliefs.

The ultimate goal of Russell and Burch themselves was replacement, which they said, “is always a satisfactory answer”, with reduction and refinement merely being steps along the way. That was also the position of the founders of FRAME, the Fund for the Replacement of Animals in Medical Experiments, although the charity has made many contributions in support
of the other two Rs, since its foundation in 1969.

The latest issue of ATLA contains two important articles about the future of the Three Rs, as well as the latest in an important series of outstanding exposures of the insurmountable limits of laboratory animals as models of humans.

In this issue of PiLAS, Craig Redmond argues the case for replacing the Three Rs with One R (Replacement),1 but goes further in saying that only what Russell and Burch defined as absolute replacement (where “animals are not required at all at any stage”) should be considered acceptable, since relative replacement can still involve suffering, as in the use of invertebrates,
less-sentient vertebrates, or cells and tissues taken from protected animals and used in vitro or ex vivo.

Michael Balls goes further in his ATLA Comment,2 proposing that “the time has come to plan for a future where the Three Rs will have served their purpose, animal experimentation will have been consigned to history, and humane biomedical science in research, testing and education will have become the norm, for the benefit of humans and animals alike”.

Finally, the article by Jarrod Bailey in the latest ATLA issue, on monkey-based research,3 demonstrates that major molecular differences, revealed by comparative
genomics and molecular biology, underlie inter-species phenotypic disparities. The collective effects of these differences are striking, extensive and widespread, and show that the superficial similarity between human and monkey genetic sequences is of little benefit for biomedical research.
Therefore, the extrapolation of biomedical data from monkeys to humans is highly unreliable, and the use of monkeys must be considered of questionable value, particularly given the breadth and potential of alternative methods of enquiry that are currently available to scientists.

References
1 Redmond, C. (2014). ‘One R’ is the new ‘Three Rs’. ATLA 42, P50–P52.
2 Balls, M. (2014). Animal experimentation and alternatives: Time to say goodbye to the Three Rs and hello to humanity? ATLA 42, 327–333.
3 Bailey, J. (2014). Monkey-based research on human disease: The implications of genetic differences. ATLA 42, 287–317.

The 9th World Congress on Alternatives and Animal Use in the Life Sciences

The 9th in this series of congresses which began in 1993, was held at the Hilton Prague Hotel, Czech Republic, on 24–28 August 2014. Its organisation was co-chaired by Dagmar Jirová (Prague) and Horst Spielmann (Berlin), on behalf of the Alternatives Congress Trust, with the administrative support of Guarant International.

The Congress was attended by about 1,100 participants, and the programme consisted of seven plenary lectures, more than 450 oral presentations, and about 500 posters. In addition, there was an exhibition with 60 booths, plus a number of satellite meetings and workshops, and many private discussion sessions.

The overall focus of the Congress was Humane Science in the 21st Century, as represented by nine main themes: new technologies; predictive toxicology; the Three Rs in academia and education; communication, dissemination and data sharing; efficacy and safety testing of drugs and biologicals; human relevance; ethics; refinement and welfare; and global co-operation, regulatory acceptance and standardisation.

The congress facilities provided by the hotel were superb, which helped to make this a particularly friendly congress. Many of the participants in the 1993 Congress were present, but it was also good to see a great number of younger scientists, 41 of whom had been specifically invited due to generous sponsorship.

It would be impossible to say much in detail about the Congress, given the enormous variety of topics covered. However, it is worth noting that two of the plenary lecturers gave contrasting insights into the state of humane science and the Three Rs as it is today.

Uwe Marx (Berlin) described the breathtaking progress being made toward developing a “human-on-a-chip”, as means of providing information of direct relevance to humans, replacing the need to resort to laboratory animal models. Early organ-on-a-chip versions — comprising artificial lungs, liver, kidneys, heart and gut — are already in use.

By contrast, Roman Kolar (Neubiberg) warned that many apparent commitments to the Three Rs have proved to be no more than lip-service, and political initiatives to avoid or replace animal experimentation have either failed dramatically, or have been watered down in the political decision-making process.

Of the Three Rs, it appeared that Reduction was rarely mentioned in Prague, and Refinement, however welcome, pales into insignificance in the face of the huge ethical and logistical dilemmas involved in maintaining animals under laboratory conditions. Replacement took the centre stage in most of the sessions, but, given the year-on-year increase in the production and use of, in particular, genetically-modified animals, there is a lot more to be done before humane science becomes more than just a dream. The 10th Congress will be held in Seattle in 2017 — it is to be hoped that much more progress will have been made by then.

Responsibility for Animal Experiments: Where the Buck Stops

bunny and arm

Sadly, just after the Animals (Scientific Procedures) Act 1986 had been amended1 to bring into force in the UK the new European Directive 2010/63/EU on the protection of animals used for scientific purposes,2 allegations were made about the abuse of laboratory animals at one of the country’s leading academic research establishments.3 Nothing more must be said about that, pending the outcome of various investigations. However, it raises the question of who is responsible for ensuring that animals are used properly, and who is culpable, when things go wrong.

In the UK, we have long experience of the clearly-defined responsibilities of the Home Office ministers and officials, including the Animals in Science Regulation Unit (ASRU) Inspectorate, and various named persons in the breeding or user establishment, including the certificate holder, the day-today care person, the veterinary surgeon, the project licensees and the personal licensees. The former EU Directive, Directive 86/609/EEC, said relatively little about specific responsibilities, but the new Directive says far more in several of its articles, as follows:

Article 23 requires Member States to ensure the competence of all staff, by seeing that all staff are adequately educated and trained before they perform any of their functions.

Article 24 spells out the specific requirements for personnel to be responsible for overseeing the welfare and care of the animals in the establishment, ensuring that the staff dealing with animals have access to information specific to the species housed in the establishment, and ensuring that the staff are adequately educated, competent and continuously trained, and supervised until they have demonstrated the requisite competence, whilst also ensuring that projects are carried out in accordance with the project authorisation.

Article 25 requires Member States to ensure that each establishment has a designated veterinarian with expertise in laboratory animal medicine, charged with advisory duties in relation to the well-being and treatment of the animals.

Article 26 lays down the requirement for an animal welfare body, while Article 27 outlines its tasks in relation to the welfare of the animals, the application of the Three Rs, the internal establishment and review of operating procedures with regard to monitoring, reporting and follow-up, including the development and outcomes of projects and their further contributions to the Three Rs.
Article 30 requires the Member States to ensure that all establishments keep records of the number and species of animals involved, their origins, their use and their death or re-homing.

Article 34 specifies that the competent authorities of the Member States must carry out regular inspections, to verify compliance with the requirements of the Directive, taking into account the number and species of animals involved, the record of the establishment in complying with the requirements of this Directive, the number and types of projects carried out, and any information that might indicate noncompliance.

Article 35 states that, when there is due reason for concern, the Commission shall undertake controls of the infrastructure and operation of national inspections in Member States, and the competent authority of the Member State concerned shall undertake measures to take account of the results of the control.

There are, of course, other individuals and organisations with responsibilities. These include the research funding bodies and the peer reviewers who assess research grant proposals, as discussed in a useful booklet, Responsibility in the use of animals in bioscience research,4 published by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs). Also of importance are the editors and editorial boards of the journals which publish articles which involve the use of laboratory animals, as was considered in a thoughtful article by Helen Galley.5

Given the clarity of the legislation and the specified responsibilities of so many different kinds of people, how can things go so wrong, as happens, as far as we know, on relatively rare occasions? First of all, human beings are involved, and whether those involved are doctors, lawyers, airline pilots, other professionals or even parents, we are a fallible
species and sometimes do wrong things, accidentally or deliberately. We need rules within which to work, and people in place to try to ensure that we do so, but they can’t watch all of us all of the time. In the end, it all depends on personal integrity, and, in the case of performing potentially-harmful experimental procedures on living vertebrates, the ultimate and inescapable responsibility must rest with those who actually perform the procedures. That is where the buck stops.

References
1 Anon. (2012). The Animals (Scientific Procedures) Act 1986 Amendment Regulations 2012. Statutory Instrument No. 3039, 57pp. London, UK: The National Archive. Available at: http://www.legislation.gov.uk/uksi/2012/3039/contents/made (Accessed 23.05.13).
2 Anon. (2010). Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. Official Journal of the European Union L276, 20.10.2010, 33–79.
3 Woolf, M. & Jacobson, S. (2013). Inquiry into ‘abuse’ of lab rats at college. The Sunday Times, 14 April 2013, p. 8.
4 Anon. (2013). Responsibility in the use of animals in bioscience research, 24pp. London, UK: NC3Rs. Available at: http://www.nc3rs.org.uk/downloaddoc.asp? id =719 (Accessed 23.05.13).
5Galley, H.F. (2010). Mice, men and medicine. British Journal of Anaesthesia 105, 396–400.