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More on animal research's three Rs It is indeed time to abandon the "three Rs,"-- reduction, refinement, and replacement -- but not for the reasons Stuart Derbyshire outlines. The three Rs assume that animals can be used as causal analogical models, but this assumption is flawed. A systematic review of the use of calcium channel blockers for stroke and the role animal-based research played revealed that said research made no contribution to the decision to proceed with clinical use of the drugs. Similar reviews on fluid resuscitation, treatments for stroke and other diseases have concluded essentially the same; that animal studies were either misleading or provided little data of ultimate interest for proceeding to clinical trials. Ray Greek President, Americans for Medical Advancement Los Angeles DrRayGreek@aol.comStuart Derbyshire asserts that we are going to need more animals in the future, not less. The data does not support this claim. The use of animals in laboratories from 1970 to 1995 halved in most of the countries where these trends have been followed. Since 1995, the downward trend has slowed or reversed due to the use of genetically modified animals, mostly mice. I suspect that this is a temporary hiatus. Sir Peter Medawar, the Nobel Prize-winning immunologist and the man who actually launched the "alternatives" concept -- despite the fact that Derbyshire believes the concept came from animal advocates - stated in 1969 that the use of animals on the current scale was a temporary episode in biological research and that, paradoxically, research on animals would provide society with the knowledge that will make it possible for us, one day, to dispense with the use of them altogether. Andrew N. Rowan The Humane Society of the United States Washington, DC arowan@erols.com Animal research doesn't benefit only humans. Ecotoxicologic studies frequently use live animals and have been responsible for saving lives, reducing suffering and protecting the well-being and fertility of incalculable numbers of animals, in addition to protecting the environment. In some cases, the studies have taken products off of the market or restricted their use. In others, they have prevented products from reaching the market and the environment in the first place. There are many ways to investigate toxicity, including modeling, comparison with similar chemicals and tests on receptors expressed in tissue culture. However, none of these are as definitive as tests on live animals and live animal exposure was inevitable for products that made it through all the stages of development and into field testing or the market. Chuck Kristensen Spider Pharm Yarnell, Ariz. chuck@spiderpharm.com Because Stuart Derbyshire emphasizes the tremendous loss to human knowledge that constraints on animal research would bring, it appears that he believes that research using whole animals is the only way to increase our knowledge of biological processes. In fact, in vitro models, especially those using human cells and tissues, now provide a tremendous tool to decipher biological complexity in ways that would be essentially impossible in whole animals. These advances especially influence the study of human health. In today's pharmaceutical companies, drug development and safety assessments rely heavily on human in vitro systems as opposed to classical animal models. Rodger D. Curren President, Institute for In Vitro Sciences Gaithersburg, Md. rcurren@iivs.org Stuart Derbyshire writes that submitting to the three Rs "risks the future of animal research. Successful promotion of animal research can only begin when we withdraw support for the three Rs." It is curious that the focus is on "the future of animal research" and the "promotion of animal research," not the future or promotion of biomedical research. This makes it sound as though the point is to do research on animals, when in fact the point is to do the best possible research, whether it requires animals or not. The three Rs are key elements in the toolbox that scientists need to conduct the best possible research, which, it has now been shown, is humane research. Alan M. Goldberg Director of the Center for Alternatives to Animal Testing The Johns Hopkins University, Bloomberg School of Public Health choward@jhsph.edu (communications coordinator email) It is difficult to fathom quite whom Stuart Derbyshire thinks he's defending in his ill-informed and misleading article on the three Rs. And, equally, what he thinks he's defending them from. In my experience of working with the UK's scientific community, both in academia and industry, there is widespread support for implementing the three Rs and little concern that it will somehow impede the progress of research. In fact, an increasing number are recognizing that innovations in the three Rs are actually innovations for all of science and that results can be applied more broadly: for example, to benefit human health. He may be right that scientists carrying out research are expressing a belief that animals are sufficiently different to humans to make such activities justifiable. But am I the only one who sees no reason why this means that they cannot consider the welfare of those animals, or how their use might be replaced? The recent establishment of the NC3Rs (National Center for 3Rs) by the UK Government, illustrates the point. Vicky Robinson National Center for 3Rs vicky.robinson@nc3rs.org.uk In a recent report on the ethics of research involving animals, the Nuffield Council on Bioethics identified a wide range of different ethical positions on animal research that exists in society. The Council's 18-strong working party on the ethics of research involving animals, which I chaired, included campaigners who were fundamentally opposed to research, those who defended it, academic and industry scientists, and philosophers. Despite the diversity of views on the committee, our report identifies agreement on several important issues and highlights the crucial importance of the three Rs. Stuart Derbyshire's point of view is misconceived on both scientific and moral grounds.Better animal welfare, through refinements, often means better science. In addition, whereas further discussion of the moral issues alone will not solve the conflicts about animal research, scientific efforts to implement the three Rs can help to lessen disagreement. There is a moral imperative to use currently available alternatives and to develop new alternative methods where gaps exist. Our report, available at www.nuffieldbioethics.org, recognizes this and makes a number of recommendations to further promote the three Rs in research. Baroness Perry of Southwark The Nuffield Council on Bioethics London bioethics@nuffieldbioethics.org Stuart Derbyshire responds: Greek suggests there is no clinical value to animal research. I believe he is wrong but welcome the debate. Even if animal research does lack clinical value, however, it will retain scientific value. Rowan believes the overall trend for animal research is down despite recent increases. Nevertheless, we use a lot of animals and, if animal research has value, then more animal research should provide more value. Goldberg argues that the best research is humane research. If Goldberg means research that protects animal welfare is best then he is in a fix. Giving animals deadly viruses, bacteria, cancers and untested drugs, or slicing them open for experimental surgeries and procedures, does not protect animal welfare. In my opinion, development of the NC3Rs by the UK government illustrates a deep ambivalence regarding animal research that can only impact negatively on efforts to increase animal research. Baroness Perry believes there is a moral imperative to use available alternatives. Human vivisection is rejected regardless of any alternatives; a moral imperative that can be swayed by availability is not very imperative. As the radical animal rights philosopher Tom Regan has argued, there is an alternative to animal research, which is not to do it (Defending Animal Rights, University of Illinois Press, 2001). The authors of these letters appear to agree with Regan in principle but not in practice. Such 'defense' of animal research is morally bankrupt and destined to fail. Links within this articleS. Derbyshire, "Time to abandon the three Rs," The Scientist, February 2006. http://www.the-scientist.com/2006/2/1/23/1/J. Horn et al., "Nimodipine in animal model experiments of focal cerebral ischemia: a systematic review," Stroke, October, 2001. PM_ID: 11588338P. Pound et al., "Where is the evidence that animal research benefits humans?" British Medical Journal, February 28, 2004. PM_ID: 14988196A.N. Rowan, F.M. Loew, "Animal research: a review of developments, 1950-2000," in The State of the Animals 2001, D.J. Salem, A.N. Rowan, eds., Washington, DC: Humane Society Press, 2001. http://files.hsus.org/web-files/PDF/MARK_State_of_Animals_Ch_07.pdf

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