Humans are more important than animals

Last week, the scientific journal NeuroImage published an article arguing that ‘by and large animal models offer very limited insights into the complex clinical picture of pain’ (1). The authors claimed that new procedures with humans, especially functional neuroimaging, should be more broadly adopted instead of animal-based studies into the nature and causes of pain.

BBC News, and several anti-vivisectionists who were invited to comment on the report on various radio stations, interpreted this as a call to end animal pain-research (2). The publication of the article came in a week (17 to 22 August) when the World Congress on Pain was taking place in Glasgow (3). I was there, along with several of the authors of the NeuroImage paper and hundreds of students, clinicians and academics who treat patients with pain or who research the causes and effects of pain.

‘Animal models’ try to recreate disease in an animal in order to study the progress and treatment of the disease in a highly controlled fashion. There are, without doubt, many problems with this approach to disease (4). Even the best animal models cannot hope to mimic all the facets of human disease. How, for example, can we model frustration at no longer being able to play football by using rats in a laboratory? We can’t, and the same is true for almost all psychological reactions to disease.

This is a particularly acute problem for pain researchers because some of the most troublesome chronic pain disorders – such as fibromyalgia, non-specific low back pain, irritable bowel syndrome and so on – do not have an obvious physical cause and psychological factors loom large. And animal models tell us little about these factors.

These problems are not, however, insurmountable. Anyone who has missed a night or two of sleep will likely be familiar with fatigue and feeling somewhat bruised with aches and pains in their joints and muscles. This feeling is not unlike what fibromyalgia patients report, and sleep-deprived rats can provide a model to explore the causes of at least some of the symptoms of fibromyalgia. There were 37 presentations at the World Congress on Pain that describe animal pain models, including models of complex regional pain syndrome, bone fracture pain, osteoarthritis, neuropathic pain and visceral pain. Almost 200 presentations included ‘animal’ in their title and almost all of the talks on neurobiology included a reference to animal research to establish the basic knowledge.

So why, then, has NeuroImage thrown in the towel and run an article calling on these researchers to consider doing something else? In part, this has come about because of several new pain drugs that have failed the transition from animal to human. A class of drugs known as the NK antagonists, for example, works well in animals but has been largely ineffective in human trials. This is disappointing, but perhaps not that surprising. The most successful drugs for pain are opioids (poppy juice) and aspirin (willow bark), which were both discovered hundreds of years ago. Treating pain is difficult and there is a long history of failure. It seems unlikely that any one approach – animal models, brain imaging, microdosing or whatever – will suddenly yield success.

At the Congress I was able to meet with some of the authors and ask them about their article in NeuroImage (5). Those I spoke to agreed that animal research has played an important role in developing our understanding of the basic physiology of pain and that the BBC News headline overstated the case against animal pain-research. There was general agreement that animal research will continue to play an important part in advancing our understanding of pain biology. Opinions differed about the future role of animal research in drug discovery.

I think this is a necessary and sensible argument for pain researchers to have, and there is a strong case to be made for de-emphasising the role of animal models in developing pain therapy. Personally I am not convinced that any technique is likely to take us closer to curing the most troublesome pain disorders and so I believe we should continue with a broad approach and see what we get. But I understand that others see a way to success by redirecting resources from animal models towards neuroimaging, clinical trials, human tissue banks and other techniques of human study. I welcome the debate and the effort to put our money where our collective mouth is.

However, a major problem with the NeuroImage article is that the debate was posed not just as a scientific issue but also as an ethical one. The article followed a meeting organised by Focus on Alternatives, a group which brings together representatives from British non-profit organisations that advocate methods to replace the use of laboratory animals in research, education and testing (6). Members of Focus on Alternatives include the Hadwen Trust, which funds exclusively non-animal techniques in an effort to eradicate animal research (7). The Hadwen Trust does not believe that animal experiments are ethically supportable.

Gill Langley works for the science department of the Hadwen Trust – and she and her husband Chris Langley were both authors on the NeuroImage paper. Chris Langley was the lead author and is probably responsible for the tone of the paper being negative about the prospects for animal research. There is a very big problem when ethical concerns latch on to scientific discussion in this manner.

The ethical case for moving away from animal models of disease is based on a principled objection to animal research. That objection is based on the belief that using animals instrumentally to benefit humans is morally wrong and so animal research, and all instrumental use of animals, should stop. I have documented my many objections to this stance elsewhere (8). If we were to accept that using animals for research is morally wrong, then such research should logically come to an end, with no ifs or buts. That would be a potential disaster for medical research and experimentation.

Realising that this is likely to be a tough sell, moderate anti-vivisectionist groups, like Focus on Alternatives and the Hadwen Trust, have tried to sneak an ethical argument into scientific discussion by suggesting that animal procedures are not desirable and in an ideal world we would do something else. These arguments are spurious and should fail. Without a thoroughgoing principled objection to animal research, the only grounds for proceeding, or doing something else, are the needs of human beings. If we consider chronic pain an important issue for human beings, and animal models provide a way towards a cure, then we should do more – lots more – animal research. Under these circumstances, the more animal research we do, the more moral we are being.

We can argue that we should not waste our time and resources on rubbish animal models, which is what at least some of the authors of the NeuroImage article were hoping to get at, but not that animal models are immoral, which is what the Langleys believe.

Focus on Alternatives has successfully played a trick. It called a meeting of some excellent scientists for a creative discussion on how to advance human models of pain and better address the problem of pain. Its members then wrote an article ostensibly addressing the scientific problem of using animals but with an ethical objection to animal research layered on top.

This is a trick that campaigners have pulled off successfully before with a workshop on sepsis to address the limited value of animal sepsis models (9). Previously, however, this trick has not led to publication in a major specialist science journal such as NeuroImage. The publication in NeuroImage represents a propaganda coup for those who oppose animal research in principle and is to be very much regretted.

Stuart Derbyshire is a senior lecturer in psychology at the University of Birmingham.

(1) ‘Volunteer studies in pain research – Opportunities and challenges to replace animal experiments: The report and recommendations of a Focus on Alternatives workshop’, C.K. Langley, Q. Aziz, C. Bountra, N. Gordon, P. Hawkins, A. Jones, G. Langley, T. Nurmikko, I. Tracey., NeuroImage, Volume 42, Issue 2, 15 August 2008, Pages 467-473

(2) Call to end animal pain-research, BBC News, 14 August 2008

(3) World Congress on Pain, International Association for the Study of Pain

(4) The trouble with animal models, The Scientist, 21(7), p. 44

(5) I spoke with Anthony Jones, who was my Ph.D. supervisor, Turo Nurmikko and Irene Tracey. I also spoke with several other colleagues and friends at the congress who work with animal models of pain. The general consensus was that we are suffering from some overblown expectations of what animal models can deliver, but that animal models remain an important component of research into pain. The opinions and comments expressed in this article reflect that consensus but the reflection is being done by the author and the opinions should be attributed to the author alone. I make no claim to be speaking on behalf of the World Congress on Pain or anyone else except myself.

(6) Focus on Alternatives

(7) Hadwen Trust

(8) Time to abandon the three Rs, by Stuart Derbyshire, The Scientist, February 2006

(9) ‘Opportunities to Replace the Use of Animals in Sepsis Research. The Report and Recommendations of a Focus on Alternatives Workshop’, Chris Langley, Chris Brock, Gerard Brouwer, Alun Brown, Lucie Clapp, Jon Cohen, Tom Evans, Carol Newman, Samantha Orr, Barry Phillips, Andy Rhodes, Nigel Webster & Karl Wooldridge, Alternatives to Laboratory Animals 33, 641–648, 2005