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1. The ethics of animal experimentation |
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This section introduces ethical aspects of animal experimentation including the “3Rs”. Animals are unable to give informed consent, and in any case th European legislation protects all vertebrates and cephalopods from two thirds of the way through gestation or as soon as they can live independently. Guidance on UK legislation is given here. In 1959 two British scientists, Bill Russell and Rex Burch (above) wrote “The Principles of Humane Experimental Technique” (see here) in which they introduced the “3Rs”. These should be used to assess every experiment. Replacement: Wherever possible live animals should be replaced by non-sentient or less sentient alternatives such as cell cultures, invertebrates or mathematical models. There are many examples where this has been successful.
Refinement: Pain, distress or lasting harm should be minimised.
Reduction (the main subject of this web site) Use the minimum number of animals consistent with achieving the objectives of the study This involves:
Harm-benefit analysis Some sort of harm/benefit analysis should also be used to ensure that trivial work is not done. Of course, the harm is to the animals and the benefit is to humans so this has to be somewhat subjective. In most cases special justification is required for work involving cats, dogs, horses and non-human primates.
There are several organisations concerned specifically with the welfare of laboratory animals. These include: Center for Alternatives to Animal Testing FRAME (Fund for the Replacement of Animal in Medical Experiments): The National Centre for Replacement Refinement and Reduction UFAW (The Universities Federation for Animal Welfare) The RSPCA (Royal Society for the Protection of Animals)
Organisations promoting research methodology and evidence-based medicine SYRCLE: A centre focussing on systematic reviews of publications involving laboratory animals SABRE Research UK. (Promoting the use of systematic reviews for better health care)
Laboratory animals as models Laboratory animals are used as models of humans or other species. In about the year 2000 a number of anti-vivisectionists suggested that the use of animals as models was scientifically invalid because animals are different from humans. Were they right? Little has been written about the theory of models. This pdf looks at the way in which models have been used historically, and shows that they have been of critical importance in the develop of modern medicine. Click arrow.
The “Understanding Animal Research web site explains in detail why animal research is necessary, giving modern examples.
There are problems as shown in these Surveys of statistical quality of published papers 1. This survey of 133 papers (McCance, 1995 Aust. Vet. Journal. 72:322) commissioned by the editors of the Australian Veterinary Journal found that In the opinion of the statistician:
2. If humans or animals lose a large proportion of their blood they go into a state of shock. These studies use animal models to find ways of reducing mortality. But a meta-analysis of 44 such studies (Roberts et al 2002, BMJ 324:474) found that:
3. In this study (Perel et al 2007, BMJ 334:197-200) the authors studied six interventions where the results were known in humans and then did a meta-analysis of all the animal studies they could find to see whether they predicted the human outcome. The results were: In only three cases did the animal studies predict the human outcome. There was clear evidence of publication bias; most academic investigators only publish positive studies so a meta-analysis tends to over estimate the benefits. The authors noted that many papers seemed to be poorly designed.
A survey of a random sample of 271 papers involving live mice, rats or on-human primates (Kilkenny C, Parsons N, Kadyszewski E et al. Survey of the quality of experimental design, statistical analysis and reporting of research using animals. PLoS One 2009;4:e7824.) found that of the papers studied:
(Click arrow for a pdf) Over-all conclusion More examples (including some quite recent ones) of papers reporting the need for better experimental design are given in the Notes and Comments page.
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