Animal testing: Why we should cease and desist

Science is nothing without debate - so we\'d like you to get your teeth into our new section. To kick-off we take a look at animal testing in scientific research. This month the BUAV put forward the case for the abolition of animal testing.

There are, increasingly, question-marks over whether many animal experiments actually work, and whether using and developing a panoply of the available non-animal methods would produce better results. We will return to the important question of efficacy, but animal experimentation is first and foremost a matter of ethics: is it justified to cause pain and distress to innocent animals when it is not for their benefit and, self-evidently, they do not consent?

The debate about animal experiments tends to be polarised but in fact, from an ethical perspective, there are two crucial tenets which the protagonists share. First, everyone accepts the overriding importance of finding cures for diseases, and of products being safe. We believe that research (humane research) and health spending should be given the highest priority, and ring-fenced even in these times of austerity.

Second, however, no one believes that any means whatsoever are justified to attain those objectives. Let me explain what I mean. Nearly everyone agrees that it is unethical to experiment on people without their consent for the benefit of other people (we are not talking about clinical trials where healthy volunteers and patients consent to participation). Sadly, history is littered with examples of such experiments. The ethical stance is taken despite the fact that, without question, experimenting on people would be much more efficacious for human diseases. Not even the staunchest animal research advocate would dispute that animals are, at best, a blunt instrument for investigating human diseases. Far and away the best way, scientifically, to find the cure for AIDS, or cancer, would be to experiment on people, not animals. But as a society we say, quite rightly, that that would be unethical – it would be desperately unfair for the human victims, even though far more people might thereby avoid suffering and losing their lives.

Similarly, some believe that it is wrong to experiment on immature human embryos, even though they freely acknowledge that failing to do so may well retard finding cures for horrible diseases.

So, in other words; a desirable end does not necessarily justify the means employed. Often as a society we impose a self-denying ordnance. All those opposed to animal research do is to apply that principle to animal experiments. As with non-consensual human experiments, animals neither consent to nor benefit from being experimented on – it is against their vital interests. Like humans, they are liable to suffer, physically and mentally, from the experience and they neither desire nor deserve the suffering.

Those opposed to animal experiments are consistent in their approach to the two situations. In the nomenclature of ethical philosophy, their position is one of deontology – if something is wrong, one should not do it, irrespective of undesired consequences or opportunities foregone. Those supporting animal research, on the other hand, are inconsistent – they apply a deontological approach to experiments on people but a utilitarian one to experiments on animals. They argue that causing suffering to animals in laboratories is justified if there is a sufficient benefit to someone else (usually humans, occasionally other animals).

That inconsistency can only be justified if experiments on people and experiments on animals are qualitatively different. But in fact they share all the ethically crucial factors – capacity to suffer, absence of benefit for the individual and absence of consent. Why should (non-human) animals be left out of the ethical equation – the circle of compassion, as Albert Schweitzer called it – when their vital interests can be just as adversely affected?

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Certainly, there are differences between human and nonhuman animals, but they do not justify a different ethical approach. For example, although it is true that most (though not all) people are more intelligent than most animals; intelligence is not an ethically relevant criterion, not least because no ethical choice is exercised in acquiring it. We do not differentiate between the rights of more and less endowed human beings.

Many say that people are more important than animals. That is, of course, a subjective, self-interested view – it rather depends on whom you ask; the person or the dog. The more important point is that greater value, if it exists, does not justify causing pain to those of perceived lesser value. Those engaged in animal research no doubt see themselves as dedicated, compassionate people of principle, but it is inescapable that their root belief is that it is acceptable to cause suffering – sometimes very great suffering – to animals simply because their suffering is thought to matter less than that of people and that in turn is because they matter less.

We suggest, by contrast, that the true mark of an enlightened society is the protection it accords to the weak and ‘unimportant’, whether human or animal, and that relative value is a very poor guide to ethics. In matters of ethics, the identity of the victim should be irrelevant. What matters is the victim’s capacity to suffer.

In fact, a great many animal experiments fail any sensible utilitarian test as well as a deontological one. Every year experiments take place in their millions to test inessential products; as part of fundamental research where any ultimate hoped-for benefit to humankind is at best remote or minor; where the quality of the science is poor, the research is duplicating previous research; where a variety of non-animal approaches (including human volunteer and epidemiological studies) could produce results at least as reliably; or where suffering of animals in laboratories is not minimised (as successive investigations of laboratories show is routine). But we do not shrink from opposing the remaining small minority of animal experiments that we are told are for genuinely important reasons, done as a true last resort and with suffering minimised – just as we would human experiments meeting those criteria.

Suffering really is the key to the ethical debate. The very reason we have ethical rules is because our behaviour may adversely affect others. The greater the suffering, the greater the injustice. Astonishingly, some animal researchers still seek to deny that any real suffering is involved. Not only is this an affront to common sense and science, it misunderstands the legal position. Under UK law, a licence is only required if an experiment may cause ‘pain, suffering, distress or lasting harm’¹. The approaching four million experiments started in the UK in 2009 were therefore liable to cause suffering (in its broad sense).

“Not one of the 60 or more candidate vaccine for AIDS tested successfully on primates has worked in patients. Similarly, over 1,000 potential neuroprotective stroke treatments have been tested in animal models but none of the 100 which have progressed to human trials has proved successful”

In any case, look at the facts. According to Home Office statistics from 2009, 18,583 procedures involved interference with the brain, 3,124 saw the induction of psychological stress, 90,260 involved acute lethal toxicity and 8,096 physical trauma, 433,205 were for cancer research (including deliberately inducing tumours in animals) and 10,566 involved carcinogenicity toxicity tests. This is a huge catalogue of suffering. Many experiments last for months or even years, so that even if there is anaesthesia (as usually there is not) and/or analgesia, the animal will suffer once this has worn off. Death is sometimes an endpoint in animal experiments – the researchers need animals actually to die or be near death as a result of a toxic substance to generate the required data. Botox, largely used as a cosmetic, is batch-tested in precisely this way on tens of thousands of animals each year in the UK.

At Cambridge University, the subject of a BUAV undercover investigation a few years ago, marmosets had their skulls sawn open in craniotomies before strokes and Parkinsonian symptoms were artificially induced. They were forced over a period of months to undergo stressful tests under a severe water restriction regime. The project licences contained a long list of serious anticipated adverse effects, including repeated seizures and inability to self-care, and Cambridge’s own documents acknowledged the stress the marmosets were under. Yet, the marmosets were left unattended for up to 15 hours post-brain surgery – quite legally, the Home Office said. A number died as a result of their injuries or had to be euthanised on welfare grounds. An independent expert (who has himself been an animal researcher) thought that they would have suffered significantly simply as a result of their housing conditions.

The pharmaceutical industry has successfully lobbied to be allowed, under the revised European animal experiments directive, to be able in some circumstances to cause suffering which is both severe and prolonged – surely an obscenity in a civilized society –and to be able repeatedly to re-use the same animal in experiments each causing ‘moderate’ suffering (bearing in mind that even a ‘single’ use can comprise several surgical procedures if the same animal needs to be used). They want to continue to plunder primates from the wild for breeding, despite the great distress everyone acknowledges this causes.

So much for the ethics. Let us return to the scientific question. How reliable are animal experiments? Those supporting animal experiments often claim that almost every medical advance is due to animal experiments. It is undoubtedly true that the development of treatments and testing of products almost always involves animals – the notorious poisoning LD50 test has even been carried out with water. But the key question is whether, scientifically, the use of animals is necessary or beneficial. The reasons animals are used are many, including the conservatism of regulators, habit and fear of product liability litigation if new methods are embraced, not necessarily because scientific rationale compels their use.

Indeed, the opposite is very often the case. It is a sobering fact that, as the US Food and Drug Administration said: “Nine out of ten experimental drugs fail in clinical studies because we cannot accurately predict how they will behave in people based on laboratory and animal studies”². In the case of the Northwick Park monoclonal antibody clinical trial catastrophe, the drugs had been tested on primates at 500 times the dose given to the volunteers and considered to be safe. Subsequent laboratory tests showed that the effects could have been predicted using in vitro methods³.

Not one of the 60 or more candidate vaccine for AIDS tested successfully on primates has worked in patients. Similarly, over 1,000 potential neuroprotective stroke treatments have been tested in animal models but none of the 100 which have progressed to human trials has proved successful. A former director of the US National Cancer Institute has remarked: “The history of cancer research has been the history of curing cancer in the mouse. We have cured mice of cancer for decades and it simply didn’t work in human beings”⁴.

None of this is a great advert for animal research. Where systematic retrospective analyses of the ability of animal models to predict effects in humans have been carried out, they are predictive less than half the time for reproductive toxicity, acute toxicity and drug efficacy5-8. Animal research has undoubtedly generated an enormous amount of data. Some effects in some animal species will coincide with effects in some people for some drugs – the law of averages dictates that is so. But the point is that no one can have any real idea when they will. And, in the process, it is inevitable that potentially valuable treatments will be missed – had penicillin been tested in guinea-pigs, in whom it precipitates death, it might never have seen the light of day.

Quite apart from the suffering involved, it cannot be right to use scarce resources in such important fields with scientifically questionable methodology. More humane science benefits humans, as well as animals. In August, David Jacobson-Kram, the FDA’s executive director for pharmacology and toxicology, said that they “want to migrate away from animal testing” (for health and resources reasons)9. Slowly, the penny is dropping.

Fortunately, there are better ways, ethically and scientifically. We will leave it to the Dr Hadwen Trust to explain their role in a future article in this series. In the meantime, we do encourage animal researchers to be more open about their work, so that debate can be informed. Information can be given on an anonymous basis to allay any safety fears – thankfully diminishing to vanishing point according to the ABPI, save with one or two laboratories – and shorn of genuinely commercially sensitive information. Animal experiments are not simply a private matter between researchers and their funders, regulators and consciences.

The public, not just in Britain, is profoundly uneasy about animal experiments. A recent YouGov poll in the UK, Germany, France, Sweden, Italy and the Czech Republic found very large majorities opposed to causing suffering to primates, cats and dogs, experiments on any species causing severe suffering and any experiments not for life-threatening or serious human conditions (and for much greater transparency). Very many people oppose all animal experiments, of course, but if the law just prohibited what these particular respondents objected to, the number of animal experiments would be significantly reduced. Certainly, other opinion surveys paint a less clear-cut picture, but that just underlines the need for meaningful information and the informed debate which can then follow.

The BUAV always welcomes the opportunity of engaging in debate about animal experiments, in a calm and reasoned manner. Laboratory News is to be commended for facilitating the debate.

 

Author   Michelle Thew is chief executive of BUAV References: 1.    Section 2(1) of the Animals (Scientific Procedures) Act 1986 2.    Mike Leavitt, Food and Drug Administration, Press Release. Jan 12th 2006 3.    Duff, G.W. (2006) Expert Group on Phase One Clinical Trials: Independent report to the Secretary of State for Health. 7 December 2006. The Stationery Office; London UK 4.    Dr. Richard Klausner, former director of the US National Cancer Institute, quoted in Cimons, M. Cancer drugs face long road from mice to men. Los Angeles Times, 6 May 1998, pA1 5.    Bailey, J., Knight, A., Balcombe, J 2005. The future of teratology research is in vitro. Biogenic Amines 19, 97-145. 6.    Olson H, Betton G, Robinson D, Thomas K, Monro A, Kolaja G, et al. 2000. Concordance of the toxicity of pharmaceuticals in humans and in animals. Regulatory Toxicology and Pharmacology 32: 56-67 7.    Pound P, Ebrahim S, Sandercock P, Bracken MB, Roberts I, Pound, P, et al. 2004. Where is the evidence that animal research benefits humans? British Medical Journal 328, 514-7. 8.    Perel P, Roberts I, Sena E, Wheble P, Briscoe C, Sandercock P, et al. 2007. Comparison of treatment effects between animal experiments and clinical trials: systematic review British Medical Journal, 334; 197-200 9.    Pfizer May Gain as U.S. Devises Speedy Alternative to Animal Safety Tests , Bloomberg 5 August 2010