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Rapid Responses: Rapid Responses published:
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A need to develop computer simulated model?
- V D Ramanathan (2 February 2001)
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Meat and experiments
- J R Johnstone (2 February 2001)
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Ethics Committees have had a refining influence on animal experiments in Sweden
- Jann Hau (2 February 2001)
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animal research is morally indefensible
- Joy Zakarian (3 February 2001)
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Added value for all in the middle ground
- Michael Meredith (4 February 2001)
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More imagination; political will, needed
- Miriam Reik (4 February 2001)
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Repeated falsehood & competing interests
- Neville W Goodman (5 February 2001)
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The theory behind animal models
- Ray Greek, Jean Greek (5 February 2001)
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Three Rs of animal research should be registration, randomisation and reviews (systematic)
- Ian Roberts (5 February 2001)
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More funding for alternatives please
- Samantha Gray (6 February 2001)
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Re: The theory behind animal models
- Neil Ferguson (6 February 2001)
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Primum non nocere
- Iona Collins (8 February 2001)
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Re: Re: The theory behind animal models
- Susan Green (8 February 2001)
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Re: Dr. Goodman's note
- Miriam M Reik (9 February 2001)
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Journal editors have a role to play
- Penny Hawkins (9 February 2001)
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Re: Dr. Goodman's note: have we benefited?
- Neville W Goodman (14 February 2001)
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Animal experimentation: the need for scientific investigation
- Beata Gajek (14 February 2001)
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Animals do have rights
- Peter Morrell (17 February 2001)
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Re: Animal research: the need for a middle ground
- Barbara Biel (17 February 2001)
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In defence of animal research
- Terence Partridge (21 February 2001)
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Richard Smith's pet rabbit
- Anthony W Fox (21 February 2001)
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The great forests of ancient Europe
- Peter Morrell (1 March 2001)
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Re: In defence of animal research
- C K Yoe (12 March 2001)
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A 4th "R": "Remembering" the Animals...
- Bill Slaughter (4 October 2001)
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V D Ramanathan, Deputy Director, Dept. of Pathology Tuberculosis Research Centre (ICMR), Chennai, India.
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The editorial on trying to tread the middle path in the use of animals for medical research by Richard Smith is timely. The two extremes that some of the protagonists take mask the fact that it is possible to take a middle path. 'A' middle path rather than 'the' middle path and I would like to suggest one of them. We can use computer modelling for many of the animal experiments. This may not eliminate totally the need to do such experiments but will definitely help to reduce the number of those experiments. This, of course, may not be possible by medical researchers with essentially a biomedical background alone. Additional inputs from mathematicians, physicists and of course statisticians will go a long way in addressing this vexed problem. As a pathologist trying to understand not only the pathogenic mechanisms in tuberculosis but also in testing newer vaccines against this major killer infectious disease, I would like to reduce the number of animal experiments that I need to do. Any volunteers? V.D.RAMANATHAN MB, PhD(London)
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J R Johnstone, Self-employed 7 Bruce St, Nedlands 6009, Western Australia
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It is commonly a requirement of ethics committees that researchers justify the number of experimental animals they propose to use. Yet at the end of a day's work, they are free to eat as many animals as they wish. This is not because edible animals are treated better and suffer less than experimental animals. On the contrary, conventional animal husbandry allows procedures on unanaesthetised animals which would today not be countenanced in the laboratory. Why should the pleasures of the table be spared this inquisition? |
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Jann Hau, Professor, Head of Department of Physiology University of Uppsala, Sweden
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Ethics Committees have had a refining influence on animal experiments in Sweden Sir - The debate in the UK on animal research in general1 and in particular ethics committees and the impending Home Office review of the system2 prompted us to scrutinise the influence that ethics committees have had on animal experimentation in Sweden. In Sweden, the review of animal experimentation by animal ethics committees was made compulsory in July 1979. Until 1998 the decisions of the seven regional committees were advisory, after which they became regulatory. The scientists may, if their application is rejected, appeal to a higher court. We analysed if and how the committees have made provisions to project license applications and made approval of application subject to minor changes. The main reasons for these conditions and how the frequency developed over time were explored through analysis of protocols from the meetings of three ethical committees (January 1989 to September 2000). In total, 10,432 applications were processed: 7895 were approved, 1907 were approved with modifications, 427 were postponed, 105 were rejected, and the applicants withdrew 98. Some applications required more than one modification before approval. The relative frequency of modifications required by the ethics committees fluctuated between individual years from 10-30%, with an overall average of 18%. The three-year moving average showed an increasing trend from 16% to 29% during 1999 and 2000. This may reflect a media debate during this period on the ethics committees' role, which was initiated by a public governmental investiation.3 The project application modifications required by the ethics committees prior to approval may be grouped as listed in Table 1. Table 1 Reasons for modification requested by ethics committee 1989- 2000. Improvement of project design 442 Improvement of euthanasia method 212 Limiting animal number 201 Improved anaesthesia 198 Improved animal housing/husbandry 188 Earlier endpoint, general 187 Earlier endpoint, specific 156 Lack of licences/informed consent 137 Ensure licensed supervisor present 102 Improved pain relief 86 Formal errors in application 70 Other 37 Consult veterinarian (NVS) 11 Total 2027 The areas that the ethics committees focused on showed some variation with time. In recent years pain relief and ensuring presence of licensed supervisor seem to have received increasing attention, whereas the interest in introducing earlier humane endpoints seems to be decreasing. About three out of four modifications may be categorised as refinement of the applications with respect to animal welfare, and the modifications requested have had a positive influence on project designs. It should be emphasised, however, that the systems in the UK and Sweden cannot be directly compared. The Home Office Inspectorate has played a very active and professional role in improving project applications through dialogue with individual applicants. The introduction of ethics committees in the UK may simply result in this important activity being moved from being a remit of the Home Office Inspectorate to a responsibility of an ethics committee. Joakim Hagelin, Hans-Erik Carlsson and Jann Hau Division of Comparative Medicine, Department of Physiology Uppsala University, BMC Box 572, SE-75123 Uppsala, Sweden 1. Smith R. Animal research: the need for a middle ground. BMJ 2001; 322: 248-9. 2. UK government reviews animal experiments policy. Nature 2000, 408: 129. 3. Djurförsök: Betänkande av 1997 års utredning om alternativa metoder till djurförsök och försöksdjursanvändningens omfattning i framtiden mm. SOU 1998:75. Stockholm: Fritzes offentliga publikationer, 1998. |
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Joy Zakarian, volunteer Last Chance for Animals, San Diego
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It's true that the "three Rs" in regard to animal research may provide a common ground for agreement. However, I do not think that it's a simplification of the issue to state that it is morally indefensible to subject non-human animals to pain and distress for any reason; including vivisection, dietary or clothing choices, or for use in entertainment. Yes, I can imagine a world where animals are not used for any of the above, and where every animal, human and not, is allowed to live in peace. It is a world that I strive to help create. I believe that Mahatma Gandhi said it very well, "The greatness of a nation and its moral progress can be judged by the way its animals are treated. Vivisection is the blackest of all black crimes that man is at present committing against God and his fair creation." And in the words of George Bernard Shaw, "… you do not settle whether an experiment is justified or not by merely showing that it is of some use. The distinction is not between useful and useless experiments, but between barbarous and civilized behaviour. Vivisection is a social evil because if it advances human knowledge, it does so at the expense of human character." I am sorry about the death of your rabbit Dr. Smith. Just as her death upset you much more than you ever expected, the deaths of all of the rabbits, mice, rats, dogs, cats, monkeys, and other animals at the hands of humans in laboratories, slaughterhouses, fur farms, and circuses upset me much more than you can ever imagine. |
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Michael Meredith, Veterinary Director The Pig Disease Information Centre
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Is there "Added value" for in a middle ground approach Forty years ago, before animal rights militancy had driven animal research behind a wall of secrecy, the University of Manchester bravely invited an "Anti-Vivisection" group to tour their animal research laboratories and meet the research scientists. A friend of mine, a militant animal rights activist (with a highly polarised viewpoint), went along determined to confront these "animal torturers" and point out the errors of their ways. To my amazement, when he returned, he was full of praise for the researchers! My friend quite correctly admired the University's courage in opening their laboratory doors and facing frank discussion with "the enemy". However, what really turned his view around was that the researchers, far from being the "crazed animal torturers" of his imagination, were quite reasonable and caring people. In fact they took on board proposals that the animal rights group put forward for improvements in the quality of life of the laboratory animals, and a follow-up visit confirmed progress. Horror fantasies and projected aggression onto this animal research laboratory were unsustainable once a co-operative relationship had been established. When I drew attention to this amazing turnaround in my friend's views, he rationalised by saying "No, I haven't changed my mind about animal research, this laboratory is different from the others - it genuinely cares about its animals!" Was this laboratory different from others? Perhaps it was - perhaps because it invested in communication and contact rather than condemnation and distance, or perhaps because it took a long and sensitive look at the what, why and how of its activities in relation to the prevailing sentiment in society. A common pitfall for animal experimentation is the old "familiarity breeds contempt" situation - I have encountered some very reasonable, sensitive, and caring, doctors, scientists and vets who became inured over a period of time to what they were doing to sentient creatures in the name of medical or veterinary research. Both of the extreme polarised sides of the animal research debate regale us with visions of how good life could be for humans or animals, if we would just give allow them a free hand. Their visions are so self-empowering that both sides are willing to torment, maim and kill, as required. How many of these visions are fantasies I wonder? How many are worth the price that society (human and animal) may have to pay? We certainly need visions to further our quality of life, including the vision of living harmoniously with other creatures. Should our society facilitate all the visions that people seek to promulgate? If not, how can we "weed out" the visions that are about ignorance, personal ambition, projected emotions, funding desperation or commercial greed? All sectors of our society, voters, tax payers, researchers, regulators, animal rights workers, media, politicians etc. have a part to play in "adding value" to the lives of man and beast. I have proposed a model for such co-operation in the farm animal welfare sphere that could easily be extended to medical research. Dr. Michael Meredith |
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Miriam Reik, Executive editor Medical communication company
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The three Rs of Dr. Smith's editorial are sane and will help; beyond that, what is needed is some imagination and some political will. Political will: everyone in medicine knows of dozens of studies of animals that are basically trivial. Shall I spare you the details? Ethics committees, laboratory directors, and funding committees need the political will to declare firmly that some experiments involving animals have no merit, or not sufficient merit to warrant using animals. The bar has to be lifted. We refer to euthanasia as "sacrificing" animals, recalling the high price they pay. Let experimental work be worthy of such a price. Imagination: Some studies surely require whole body systems, but the principle of "replacement" should include a more imaginative use in finding human volunteers to replace nonhuman sacrifice--it would also speed the development and improve the safety of drugs. For instance, prisoners with lengthy jail terms who are offered time off in return for becoming subjects in trials may find the risk/benefit ratio worthwhile and agree. This would not obviate the principles of justice since the prisoner would, in fact, be "paying" for his crime by providing a public service. |
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Neville W Goodman, Consultant Anaesthetist Southmead Hospital, Bristol
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If someone (for example, Joy Zakarian) believes all animals can be accorded the same rights as humans, most of us think the belief unrealistic, but it is an arguable point of view. If someone states that medicine has learnt nothing useful from animals, that is simply wrong. We can debate animal research as much as we like in the pages of medical journals, but sensible solutions will not be found as long as the media allow this falsehood to be repeated. In the interest of "balance", every time the subject surfaces the newspapers and broadcast media allow people to repeat this falsehood. They usually back it up by citing thalidomide or certain other specific drugs, and using these singular pieces of evidence to justify the false statement that species differences between animals and humans make extrapolation impossible. This is a dialogue with people who believe that two plus two makes five, and has no solution. On a different and more general point, the BMJ requires to know of competing interests from all authors. This is a good idea when an author may, for example, have received commercial payment, or have written a competing book. More recently, some authors seem to be using this requirement to make personal statements. Last week, Iain Chalmers told us he had no stocks and shares; this week Richard Smith tells us his rabbit was killed by a fox. The main effect of these statements is to give this reader an uncomfortable sense of 'holier than thou'. None of us is perfect, and rarely can we be truly objective. As this is true of all of us, we can make allowances for other people without their having to bare their souls. |
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Ray Greek, Ray - President Americans For Medical Advancement , Jean Greek
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Animal Research: The need for a middle ground assumes that the animal model paradigm is functional in light of current knowledge. Both sides can point to supposed success and failures of animal models but neither seems to discuss the theory behind the use of animal models. In light of genetics, molecular biology, the theory of evolution and modern-day technology, that discussion is long overdue. Evolutionary biology lies at the heart of our argument that animal- models of human disease are scientifically untenable. Speciation is both the reason why it appears that we can use animal-models as well as the reason why in reality we cannot. Despite the fact that animal models appear feasible when first viewed, upon examination of the details of the differences between animals and humans, the shortcomings of the concept that animals can be used to model for humans are noticed. Because all animals, including humans have evolved from a common ancestor, we would expect them to have things in common. However evolution also teaches us that there will be differences, especially at the molecular level since different species evolved to fill different niches. Based on molecular biology we know that the differences lie chiefly in the regulatory genes. One way of speaking about the results of evolution is to categorize life forms into groups known as species. A species say Homo sapiens will have characteristics that are unique to it. It will also have characteristics that it shares with other species, like Drosophila melanogaster or Pan troglodytes. With the advent of molecular biology, we have learned that what each member of the species in question will have in common with the others is a collection of genes and the way those genes are regulated. While other species may have some of the same genes, the way the genes are regulated will be different. Because of very small differences in regulatory genes important differences exist between species. This is why small difference between species lead to huge differences at the cellular level which is where we focus when treating disease. A more concise way of explaining this would be to say that biological organisms are examples of a nonlinear complex system and that explains why small differences between biological systems negate extrapolation. Animals are used in research as models of humans. There are generally considered to be four type: induced, spontaneous, negative, and orphan models. A model here is a device that enables us to conceptualize unfamiliar phenomena by analogy to qualitatively different but familiar phenomena. Researchers maintain that animals are causal analogical models (CAMs) and can be used to study human disease. Causal analogies are a subset of analogy arguments in which causal assumptions arise based on the model. LaFollette and Shanks explain that the first condition that must be met in order for a thing to be considered a CAM is this: “X (the model) is similar to Y (the object being modeled) in respects {a…e}. X has additional property f. While f has not been observed directly in Y, likely Y also has property f.” So if drug Z causes death in an animal model (e.g., penicillin kills guinea pigs), or is safe in an animal (phen-fen was safe in dogs) researchers reason by analogy that it will also cause the same reaction in humans. Animals are used as causal analogical models. And the reasoning process used is called causal analogical reasoning (CAR). LaFollette and Shanks state that CAMs must satisfy two further conditions: (1) the common properties {a,…,e} must be causal properties which (2) are causally connected with the property {f} we wish to project – specifically, {f} should stand as the cause(s) or effect(s) of the features {a,…,e} in the model. The pervasiveness and acceptance of lab animal CAMs suggest a rigor that the experiments simply do not have. Completely isomorphic systems have a one-to-one correspondence between all elements in each system. No species is 100% isomorphic with another and no one seriously claims that nonhuman animals are completely isomorphic to humans. With systems as complex as the anatomy, physiology, and biochemistry of human and nonhuman animals, we now know that even infinitesimal dissimilarities are not incidental. Dissimilarities not only negate isomorphism, but can also give rise to additional differences in a nonlinear fashion. However, the question remains: Are intact animals good CAMs so they can be used to predict what a drug or procedure will do when applied to a human? Given evolutionary biology, there are reasons to think not. The causal/functional asymmetry theory implies that causal mechanisms may differ between species. Causal disanalogies mandate caution in extrapolating data between species. However there is data supporting the use of animal models as CAMs (penicillin cures infections in mice) and data refuting the use of animal-models as CAMs (penicillin kills guinea pigs). So we will examine the issue more closely. We agree that nonhuman animals and humans have things in common. Both are in the Animal Kingdom. Both are composed of DNA and cells, utilize ATP, and propagate certain information via action potentials. Humans have up to 99 percent of the same DNA as nonhuman primates. However there are differences. It is difficult to induce lung cancer in animals from cigarette smoke. Drugs that cause birth defects in animals do not do so in humans. Humans who eat a typical Western diet suffer from heart disease while animal fed the same do not. Despite the similarities, the use of animal CAMs also suffers from the systemic disanalogy argument. Since systems (organs, tissues etc.) may differ in subtle and unknown ways, the same exposures often cause different reactions in different species. In other words, for a CAM to be predictive, “there should be no causally-relevant disanalogies between the model and the thing being modeled.” Considering our knowledge of evolutionary biology, this is impossible without total knowledge of both the model (animal) and thing being modeled (human). Additional problems thwart animal models effectiveness as CAMs. CAMs must resemble the subject being modeled in all of the important respects. In terms of disease, CAMs assume the same 1) symptoms, 2) postulated etiology, 3) neurobiological mechanism, and 4) treatment response. The truth is that very rarely, if ever will two species fulfill all four criteria for any given disease. We do not know in advance which animal will simulate the medical condition in humans. We can only know that after studies in humans. Very small differences between humans and animals can lead to lethal errors when applying animal-model-based data to humans. Which animal is like the human? Compare the results of giving humans, mice and rabbits the drugs penicillin and thalidomide. Thalidomide acts on some rabbits as it does humans – causing the birth defect known as phocomelia. However, many drugs that injured humans tested safely on rabbits. How do you know in advance which animal will simulate the human condition? The unknowns between species are ubiquitous. To repeat, CAMs must have: 1) common causal features, 2) causal connections between the features, and 3) no causally relevant disanalogies. None of these can be known until we know 100% about the phenomena in humans. Animals can only be proven to be “models” empirically. That is to say, we must know what happens in humans first, then study animals to see if a particular animal replicates the human condition. Only by comparing results from experiments on animals with the results from human-based data can we determine if nonhuman animals are sufficiently similar to human to allow the extrapolation of experimental results as regards that particular substance or treatment only. But this is a catch-22. We can only know which animal mimics humans after we know what happens in humans. But after we know how humans respond there is no need to use animals. This gives us no new knowledge, is obviously not predictive, and thus obviates the need for animals. Therefore, it is a logical fallacy – circular reasoning – to use animal models. Again, we cannot say that an animal is a good model until we know that it reacts to a stimulus the same way humans do. We can only do this retrospectively. Therefore, animal models cannot be predictive. Animal models cannot prove a causal relationship in humans for the previously mentioned reasons. Epidemiology, in vitro research, clinical research, autopsies, mathematical and computer modeling and other human- based and technology-based research methods offer results that are much more reliable and hence are far superior methods of doing research. Researchers will insist that animals, notwithstanding their lack of isomorphism and inability to be CAMs are still necessary because without animals researchers could not evaluate the drug or procedure in an intact system. We agree that life processes are interdependent, that the liver influences the heart, which in turn influences the brain, which in turn influences the kidneys etc. Thus, the response of an isolated heart cell to a medication does not confirm that the intact human heart will respond as predicted by the isolated heart cell. The liver may metabolize the drug to a new chemical that is toxic to the heart while the original was not. We also concede that cell cultures, computer modeling, in vitro research, etc. cannot replace the living intact system of a human being. But the question is, can the animal model do better than the nonanimal methods? Can animal models still be predictive or helpful despite not being perfect? Lets go back to previous example. Lets assume system S1 has causal mechanisms {a,b,c,d,e} and system S2 has causal mechanisms {a,b,c,x,y}. If we stimulate sub-system {a,b,c} of S1 with stimuli sf and get result rf, then we would expect to get rf from {a,b,c}of S2 as well if the animal model is viable. However, this outcome will be highly probable if and only if {a,b,c} are causally independent of {d,e} and {x,y}. In biological systems, as those who argue in favor of intact systems emphasize, almost all systems interact. We have no a priori reason to think otherwise. This discussion will not end on the web site of the BMJ and it should not. The biomedical community needs to re-evaluate the use of animals just as the physics community evaluated Newtonian physics in light of relativity and quantum mechanics. There is always much to be gained from solid, open, transparent dialogue. Ray Greek MD
References 1. Public Affairs Quarterly 1993;7:113-30 2. Lafollette and Shanks. Brute Science Routledge 1996 p 63 3. Ibid. p112 4. New Scientist May 15, 1999 p26-30 5. LaFollette and Shanks. Brute Science Routledge 1996 p113 6. from Lafollette and Shanks. Brute Science Routledge 1996 |
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Ian Roberts, Senior Lecturer in Epidemiology Institute of Child Health
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Editor - Having found no reliable evidence from human clinical research about how much fluid should be given in the resuscitation of bleeding trauma patients I am working with others on a systematic review of controlled trials of fluid replacement in animal models.1 To date we have identified about 70 controlled trials. Some trials are properly randomised but many are not, the potential for selective publication of trials showing more promising treatment effects is considerable, and few if any of the trials, set their results in the context of a systematic review of all previous trials. Reducing bias is as important in animal research as in clinical research and it would seem appropriate to apply the strategies used to improve the quality of clinical research to improve animal research. I therefore propose the following three Rs of animal research: Registration: prospective registration of all trials in animals to reduce the potential for publication bias Randomisation: proper randomisation to reduce the potential for selection bias Reviews: systematic reviews to reduce bias and increase precision. Reference 1. Roberts I, Evans P, Bunn F, Kwan I, Crowhurst. Is the normalisation of blood pressure in bleeding trauma patients harmful? Lancet 2001;357:385-87. |
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Samantha Gray, Scientific Officer FRAME
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Throughout the recent, highly emotive debate regarding animal experimentation and the fate of Huntingdon Life Sciences, one crucial factor had been completely ignored, namely, the importance of non-animal alternative methods. The Fund for the Replacement of Animals in Medical Experiments (FRAME) is a charity which funds research into the development of alternative methods that do not require the use of animals. We were pleased to see the BMJ editorial, which acknowledged the vital role that alternative methods can play in realising a reduction in the use of animals in research and testing. British and European law dictates that animals can only be used when no non-animal alternative is available. Therefore, FRAME believes that the development of reliable alternative methods is the best way to achieve our ultimate goal of eliminating the need for live animal experiments altogether. Current levels of funding for alternatives research are disappointing, to say the least. If the government wants the decline in the numbers of tests on animals to continue, then this funding must be dramatically increased. Of course, it is not only the Government that can support this research, but also the industries that currently rely on animal research to develop and market their products. FRAME would like to see industry putting significantly more of its substantial resources into the development of new alternative methods. The development and validation of non-animal methods is a long and expensive process. However, the rewards are potentially great, in terms of the real benefits to science and to animal welfare. Dr Samantha Gray
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Neil Ferguson, Medical student Manchester
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I'm sorry, but I really do have to ask: what planet did Ray and Jean Greek come from? Their overly verbose and jargonised response was ridiculous. However much rhetoric that they expound, the simple fact of the matter is that animal testing does, on the whole, work very well. I think the Greeks have got carried away in their pretentious analysis and explanations of species differences. No, we are not primarily concerned with goings-on at the cellular level. The most important consideration is what happens to the animal as a whole (be it rat or human), and, in this way animals are very useful analogies. The examples given of specific species differences is also narrow-minded. It is part of the reason why we need to test drugs on a variety of species. |
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Iona Collins, SpR Orthopaedics Perth Royal Infirmary
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After all, Hippocrates didn't limit this instruction to just humans, did he? |
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Susan Green, Science Communications EFMA Europeans For Medical Advancement
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Medical student Neil Ferguson has evidently not reached the stage in his medical training which teaches the 'animal model' in medical research. We would urge him to learn more about the subject and at least read the paper 'SELECTION OF ANIMAL MODELS: Research Animal Methods' by Michael S. Rand, DVM Chief, Biotechnology Support Service, University of Arizona - Tucson. Rand concludes in his analysis of the problem of selecting animal models that because of the weakness of inter-species extrapolation 'It is impossible to give reliable general rules for the validity of extrapolation from one species to another. This has to be assessed individually for each experiment and can often only be verified after first trials in the target species (humans).' and ' Extrapolation from animal models, like medical art itself, will always remain a matter of hindsight, devoid of guarantees, although we humans usually demand absolutism from the medical profession and the research community. Science is knowledge in flow. And as we drift away towards unknown waters, we discover what is today’s state of the art, but tomorrow’s fallacy or truth.' Of course human disease is studied at the molecular level and this is where species differ one from the other. Rand is trying to justify the animal model - but he cannot justify it as a scientific methodology. The Greek's have taken the time to examine the animal model in depth and have offered us the scientific reasons why the animal model is scientifically invalid. Susan Green |
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Miriam M Reik, Executive Editor Medical Communications Company
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Dr. Goodman discusses the kinds of argument used regarding the appropriateness of animal research--the frequency with which thalidamide is cited by opponents of such research, their use of interspecies differences, etc. His disdain for these argument is apparent, and he counters them by asserting the falsehood of any statement claiming that humans haven't benefitted from animal research. Well, of course we have benefitted, but granting that much doesn't make the ethical questions disappear. I may benefit from stealing the crown jewels, but that doesn't make it right., and benefit doesn't make animal experiments, on the face of it, either right or wrong. We need a nicer analysis of assumptions. Starying alive, for a rabbit, is a major interest. We may sacrifice it--and thousands like it-- for our minor interest of producing another hair dye. We may benefit from another hair dye--especially our vanity will benefit--but is the trade-off between the rabbit's major interest for our minor benefit rational? Ethical? What is it, please? |
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Penny Hawkins, Senior Scientific Officer Research Animals Department, RSPCA
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The RSPCA welcomed the principles set out in Richard Smith’s editorial. The use of animals in research and testing represents a serious ethical dilemma that affects us all. Laboratory animals are used for an increasingly broad range of purposes and it is just not possible – or indeed helpful - to make broad sweeping statements about scientific validity, justification or suffering*. Issues subject to such polarised debate inevitably become very difficult to progress. This is of particular concern in this case since sentient animals who are capable of suffering are involved. The human race has a moral imperative to reduce the pain, suffering and distress that it inflicts on other animals to an absolute minimum. In the case of animal experiments, the principle of the Three Rs is an excellent practical starting point and the RSPCA is committed to promoting and supporting this concept. It is true, as the article stated, that some of those involved in laboratory animal use are giving greater consideration to implementing the Three Rs, but the editorial was over- optimistic about how universally the concept is applied (or even understood) and there is still a great deal to be achieved. Everyone involved in research animal breeding, care and use should be motivated to critically question their own use of animals – they are often much more inclined to question other peoples’. They also need to be more open to the concept of alternative approaches and to ways of minimising animal use and suffering. One problem we have encountered lies in the interpretation of baseline and ‘good’ welfare standards. For example, establishments often claim that they are active in implementing the Three Rs, when in fact they are merely implementing the minimum legal requirements. A likely reason for this is that the Three Rs are often seen as a separate issue and not part of mainstream life sciences. One way to raise the profile of the Three Rs and push for the principle demonstrably to pervade the whole of the life sciences would be for journal editors to insist that published papers include relevant and comprehensive information about the whole life experience of the animals involved. This could include their source, transport, husbandry and care, group sizes and structure, enrichment, what was actually done to the animals, protocol refinements, welfare problems (and what was done about them) and the animals’ eventual fate (and why). Journal space is of course at a premium, but it is possible to convey this information in surprisingly few words [1, 2]. Such a level of detail would not only provide guidance for other researchers wishing to improve animal welfare and reduce suffering, but would also give other interested parties an insight into what laboratory animals actually experience and for what purpose. This would surely help to depolarise the debate and enable more people with an interest to contribute to it in an informed and constructive way. Although the BMJ does not often publish animal research, perhaps it would consider this kind of comprehensive editorial policy to help steer this lurching debate towards the middle ground so that it can go further, faster? 1. Morton DB (1992) A fair press for animals. New Scientist 1816, 28- 30 2. Smith JA, Birke L, Sadler D (1997) Reporting animal use in scientific papers. Laboratory Animals 31, 312-317 *The RSPCA is opposed to all experiments or procedures that cause animals pain, suffering or distress. The Society supports the development of techniques that will result in the replacement of animal experiments, reductions in animal use and suffering and improvements in welfare while animal research and testing continues. Current charity law imposes constraints on all animal welfare charities such that they cannot oppose uses of animals for which there are no alternatives and where there is an overriding benefit to humans. |
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Neville W Goodman, Consultant Anaesthetist Southmead Hospital, Bristol, UK
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I agree with Mirian Reik: admitting humans have benefited does not remove the need for ethical debate. But at least she admits that humans have benefited. There are some who deny this, and it is that falsehood that helps skew any sensible discussion. |
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Beata Gajek, Secretary HEALtrust
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Controversies have always been a part of science. At worst, scientific arguments can result in acrimony, with alegations of dishonourable behaviour among the participants. Despite the potential for ill-will, disputes can be conducted with mutual respect. Controversies can invigorate and enhance interest and result in important advances in the contested field. Along with the well-documented decline of public trust in the infallibility and neutrality of expertise has come a growing demand for greater public participation in scientific and technical decision-making and policy formulation. The recent 'Science and Society' report conveys the message of the need for greater transparency and accountability amongst scientists in order to increase the potential for public participation in scientific and technical decision making processes. The use of the animal model as a model of human disease is one such issue which requires examination in the public arena. This highly contentious and controversial subject is worthy of serious scientific debate and inquiry. The Human Health and Animal Experimentation Education Trust HEAL are a registered charity committed to conducting research into and educating the public about the much disputed use of the animal model in medical research. We welcome submissions from both sides of the argument for and against the animal model. Later this year we are initiating public debate on the issue, at which opposing sides, of what we clearly identify as a scientific controversy, can offer their contributions in strictly moderated forae. The discussion over whether or not the 3R's should be implemented in this or that environment, is secondary to the more important question of whether or not animal experimentation is a scientifically valid methodology. The 3R's represents a compromisory welfare strategy for the benefit of the laboratory population and whilst it's full and comprehensive implementation may well be of extreme importance to animal welfare groups, it is not a relevant issue in the context of the question of animal experimentation as scientific methodology. Human health and medical progress is at the forefront of most people's minds and HEAL have a commitment to seeing that the best possible scientific investigation into the long-standing issue of animal experimentation in medical research is made public. Beata Gajek (Secretary)
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Peter Morrell, Hon Research Associate, History of Medicine Staffordshire University, ST4 2DE
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Sir, "The arguments over animal research are so polarised because the two sides have completely different ways of thinking. Opponents of research are concerned primarily with the rights and suffering of animals, whereas supporters are interested in the capacity of animal research to speed developments in understanding biology and preventing and treating disease." [1] I think this statement is factually inaccurate. Although this debate is polarised, it is not true that both sides think differently; nor is it true that opponents of animal research are primarily concerned with the rights of the animal; or even MORE concerned with animal rights than human rights. Nor am I sure they are any less concerned about speeding developments in understanding biology than scientists. This verges on implying that animal rights people do not understand biology or medical research and are therefore foolishly ignorant as well as deeply prejudiced against the whole of science. That seems like a feeble and unconvincing argument. They are often well informed. This paragraph quite blatantly bends over backwards to marginalise animals rights people as deviants and to lend some credence to animal experiments - and yet, puzzlingly, Smith calls that 'finding a middle ground'. Of the arguments I have read, I think that the main thrust in the argument of animal rights activists is that killing animals for ANY reason is ethically unsupportable. It is wrong. It is difficult to destroy such an argument precisely because of what might be called 'Gandhi's trump card' - who has the right to kill anyone or anything? Answer - nobody. It is this point that sits like an immoveable stone at the heart of their arguments and NOT any alleged ignorance of biology or a presumed loathing of science. Based upon that Hindu idea of non-harming [ahimsa], it therefore becomes very difficult to justify any animal experiments at all, because the animal rights people do not accept that human beings run planet earth any more than believing that we should place human interests over those of animals who share this planet with us. A good example is the destruction of the Brazilian rainforests. On the one hand, those outraged armchair philosophers who wring their hands worthily over this issue, conveniently try to portray the poor old frontier farmer in the Amazon as some kind of planet-destroying madman, when in fact he is only doing what our ancestors in Europe did centuries ago - clearing a little a little land for crops and towns and roads - pretty unremarkable stuff - ironically, in another time, we would have applauded it as 'progress'. What is disheartening is that the sheer scale of the destruction is so extensive and its obvious environmental impacts so dire. But can we in truth put our hand on our heart and say that we should have learned this lesson already? Who has the right to stop them clearing a little forest to make a meagre life for themselves? On the other hand, people say we should preserve the Amazon as a rich source of bio-diversity to obtain future undiscovered drugs. Well, what an utterly unworthy and selfish attitude of human beings. Does that mean they will NOT be saving those plants that do not contain such drugs? I think the animals rights people are quite right to say that such matters should be approached more even-handedly for all life-forms and not for humans first and animals and plants second. It is a demonstrably selfish attitude on our part. It is whole habitats [world biomes] that need protection from human impact, not just certain species. The same attitude applies to animal research - why should we use them to research drugs mainly for use by us? What possible ethical argument can support such behaviour? If we were the ethical planet custodians we pretend to be, then we should more vigorously preserve all life-forms and not just those of use to us. Then there are the politics and financial interests lying behind the whole argument and it all becomes very complex and tiresome. If there is any 'moral high ground' in this issue, then I'm sorry, but it is occupied by the ALF people, and not by the vivisectionists. These arguments are based upon thinking this matter over in a detached sort of way - I freely admit that if a close relative of mine were involved or if my career depended upon animal experiments, then my views might be different. Then again, I would probably never get entangled in such experiments, as I hated those cruel neurophysiology experiments at university. One problem in a debate of this kind is that you cannot find anyone who is truly neutral on an issue such as this - a point Dr Smith does make in his article. [1] BMJ 2001;322:248-249 (3 February), Editorials, Animal research: the need for a middle ground, Richard Smith http://www.bmj.com/cgi/content/full/322/7281/248 |
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Barbara Biel
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Animal researchers refuse to admit that animal research rarely works because every species of animal is different biomechanically and biochemically. Non-human animals are different not only from humans, but also from each other anatomically, physiologically, immunologically, genetically and histologically. Animal research not only hurts and kills animals, it kills humans too. For example, the drugs thalidomide, Zomax, and DES were all tested on animals and judged safe but had devastating consequences for the humans who used them. A General Accounting Office report, released in May 1990, found that more than half of the prescription drugs tested on animals and approved by the Food and Drug Administration between 1976 and 1985 caused side effects that were serious enough to cause the drugs to be withdrawn from the market or relabeled. Many noted physicians have spoken against vivisection. Dr. Albert Sabin, who developed the oral polio vaccine, testified at a congressional hearing: "[p]aralytic polio could be dealt with only by preventing the irreversible destruction of the large number of motor nerve cells, and the work on prevention was delayed by an erroneous conception of the nature of the human disease based on misleading experimental models of the disease in monkeys" (Stoller, Kenneth, M.D., "Animal Testing: Why a Doctor Opposes It," The Orlando Sentinel, June 25, 1990.). Dr. Charles Mayo, founder of the Mayo Clinic, stated, "I abhor vivisection. It should at least be curbed. Better, it should be abolished. I know of no achievement through vivisection, no scientific discovery, that could not have been obtained without such barbarism and cruelty. The whole thing is evil"(Quoted by William H. Hendrix, New York Daily News, Mar. 13, 1961.). There are sophisticated non-animal research methods that are accurate, more cost-effective, and less time-consuming than animal research. Such non-animal research methods include: epidemiologic studies (or comparative studies of human populations), clinical research, in vitro research, computer modeling, safety tests using human cells, and medical applications, to name just a few. These methods have contributed to many advancements in medicine by providing important information about smoking and cancer, cholesterol and heart disease, high-fat diets and common cancers, chemical exposures and birth defects, the mechanism of transmission of AIDS, abnormalities in the brains of victims of Alzheimer's disease, schizophrenia, epilepsy, and autism. The AIDS virus was isolated in human serum, and in vitro methods are providing new insights into the virus' effect on human cells. Animal researchers are stuck in their old ways. They are not open- minded to new methods or too lazy to learn new techniques. Animal researchers don’t want to bother engaging in real medicine based on prevention and clinical research. As a result, we are losing ground in the fight against cancer, cardiovascular diseases, AIDS, diabetes, muscular dystrophy, Alzheuimer’s disease, birth defects, and many others. We don’t even have a cure for the common cold! Vivisection is also immoral. Non-human animals are not research tools. They are individuals capable of experiencing not only crude emotions like fear, but far more subtle and complex emotions such as love, grief, pride, shame, joy, and loneliness. The cognitive psychologist, Bernard Baars stated, "The basic facts have come home at last. We are not the only conscious creatures on earth." Charles Darwin's theory of natural selection proved that human beings are in fact animals and, as such, they evolve according to the same evolutionary dynamics as non-human animals. Therefore, we humans have moral obligation to treat animals with respect and dignity. Sincerely,
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Terence Partridge, Head of Muscle Cell Biology MRC Clinical Sciences Centre
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Dear Sir,
It would seem from the rapid responses to Richard Smith’s article that the three Rs do not represent the hoped-for middle ground for discussion by all interested parties. Those who are fundamentally opposed to the exploitation of animals, irrespective of any value that might be derived, logically, see no value in debating methods of merely reducing the amount of animal suffering involved. In this absolute form, the anti-vivisectionist view cannot make any constructive contribution to the 3Rs discussion since the stance itself is not responsive to argument, being simply a statement of deeply ingrained individual ethical taste. A straightforward proclamation of the righteousness of this stance, perhaps bolstered by quotations from others who agree, does not constitute debate. We can all declare our deeply held convictions and cite authority in their support — how do we evaluate their relative merits? Some anti-vivisectionists invoke religious principle but we are not all Jains and there is no obvious embargo on the exploitation of animals in the Judeo-Christian and Muslim religions, indeed ‘The Gadarene Swine Incident’ appears to issue Christians with a Carte Blanche for animal experimentation for medical purposes. All that remains for debate is the circumstances under which one group of people assume the right to impose their personal ethical tastes, on another group of people with different, equally strongly held, ethical views: an impasse. Useful and constructive discussion of Dr Smith’s suggestion is possible only for those who accept the notion that a factor in the debate is the cost:benefit ratio of animal suffering to gain in human health. Logically, this would encompass the great majority of the population, who eat products generated by exploitation of animals, much of it by methods and practices that would not be permitted in medical research laboratories. There is a second marginally more covert absolutist line of opposition to animal research, arguing that it has no benefit in practice or in principle to human health. The Greek’s, in their letter, propound an interestingly formulaic variant of this theme that merits response. They make a detailed critique of animal experimentation as a means of gaining information applicable to human health, reasoning that there is a logical inconsistency in such practice on the basis that one cannot use animals as Causal Analogical Models (CAMs) because they differ in unknown ways from the human target system. It is an intriguing irony that their theoretical model of scientific data acquisition is itself an analogical model and one must ask how well this corresponds to the actual conduct of biomedical research or defines the place of animal models in the scheme of things. They examine the simple idea of using an animal as if it were a direct surrogate for man in a model system for testing the efficacy and safety of a drug or procedure. This model portrays a unidirectional flow of information from experiment to conclusions. If true I too would deplore it, but in my experience it bears no resemblance to animal research as it is actually performed. Drugs or procedures are never applied to animals in such an informational and intellectual vacuum. Rather, there is a to-and-fro of information and hypothesis between a variety of sources of data, drawn from experiments spanning a range of disciplines and techniques, that are used as a screen to select for drugs/procedures that look sufficiently effective to be worth following up in human trials. In practice, the focus of much animal research lies towards elucidating fundamental principles and testing candidate treatments, selected on the basis of prior knowledge as likely to influence the mechanisms that maintain us alive and in good health. In such work animal experiments provide only part of the spectrum of data on which hypotheses and conclusions are founded and are used where they are thought likely to provide more reliable data than other experimental methods. Quite apart form any moral imperative, animal experiments are too costly, arduous and time consuming to be taken-on lightly. The formality of the Greek’s analysis gives an impression of objectivity that is belied by their conclusions. Because, in their paradigm, no animal model could be relied on to replicate all of the potential benefits and dangers of a drug when used in man, they conclude that animal experiments should not be performed. But the same analysis could equally well justify the contrary conclusion, namely we should extend the study to the widest possible range of species, so as to increase the chances of identifying useful or dangerous effects and using this knowledge as guidance as to what we should look out for in subsequent human trials. Astonishingly, having dismissed animal models on the basis that they are not isomorphic CAMs, they go on to commend tissue culture and computer models which are less isomorphic and even poorer analogues of in vivo processes. Interpreted strictly, their argument would even invalidate tests on humans: drug trials commonly illustrate the unreliability of human patients as perfect CAMs of other human patients. Reports abound of huge variations in responsiveness to drugs and of intolerance of their side effects - even the humble peanut, a nutritious and useful food additive for the majority spells disaster for those with peanut allergy. Anyone who works in biological science knows that there are defects in all model systems, yet scientific advance in biological and medical knowledge has demonstrably occurred by making the best of what is available. Happily, what is available is getting better. Non-invasive methods for following what goes on inside the living body, such as Magnetic Resonance Imaging and Positron Emission Tomography, provide new ways of following the efficacy of treatments. These can be applied to man and non-human animal models with little or no traumatic effect. Such methods have the dual benefit of making it possible to define more precisely what goes on in human patients and in animal models and to gather far more information. |
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Anthony W Fox, President. EBD group Carlsbad, California
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Sir- The editorial (BMJ 2001; 322:248-249) about animal research makes some useful points. However, its "Conflicts of interests" at the end makes reference to the recent demise of Richard Smith's pet rabbit, evidently at the hands of a fox. Three issues come to mind: 1. Have we reached the stage where the editorial material in the BMJ is dependent on the health, or otherwise, of its editors' pets ? 2. If Richard Smith's pet rabbit is a conflict of interest, then how incomplete must be all the other such statements by other authors ? 3. In the spirit of true evidence-based investigation, is it certain that a fox was the culprit ? Was there an eye witness ? There are many animals that have learned to eat rabbits since they were introduced into the British Isles in the 11th century. Tony Fox
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Peter Morrell, Hon Research Associate, History of Medicine Staffordshire University, ST4 2DE
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Sir, In a previous email I said: "outraged armchair philosophers who wring their hands worthily over this issue, conveniently try to portray the poor old frontier farmer in the Amazon as some kind of planet-destroying madman, when in fact he is only doing what our ancestors in Europe did centuries ago ..." [1]. I now beg your indulgence to bring to your attention the following superb quotation on this very subject: "For at the dawn of history Europe was covered with immense primaeval forests, in which the scattered clearings must have appeared like islets in an ocean of green. Down to the first century before our era the Hercynian forest stretched eastward from the Rhine for a distance at once vast and unknown; Germans whom Caesar [102-44 BC] questioned had travelled for two months through it without reaching the end. Four centuries later it was visited by the Emperor Julian [331-363 AD], and the solitude, the gloom, the silence of the forest appear to have made a deep impression on his sensitive nature. He declared that he knew nothing like it in the Roman empire. In our own country the wealds of Kent, Surrey, and Sussex are remnants of the great forest of Anderida, which once clothed the whole of the south-eastern portion of the island. Westward it seems to have stretched till it joined another forest that extended from Hampshire to Devon. In the reign of King Henry II [1133-1189]. the citizens of London still hunted the wild bull and the boar in the woods of Hampstead. Even under the later Plantagenets the royal forests were sixty-eight in number. In the forest of Arden it was said that down to modern times a squirrel might leap from tree to tree for nearly the whole length of Warwickshire. The excavation of ancient pile-villages in the valley of the Po has shown that long before the rise and probably the foundation of Rome the north of Italy was covered with dense woods of elms, chestnuts, and especially of oaks. Archaeology is here confirmed by history; for classical writers contain many references to Italian forests which have now disappeared. As late as the fourth century before our era Rome was divided from central Etruria by the dreaded Ciminian forest, which Livy [59 BC to 17 AD] compares to the woods of Germany. No merchant, if we may trust the Roman historian, had ever penetrated its pathless solitudes; and it was deemed a most daring feat when a Roman general, after sending two scouts to explore its intricacies, led his army into the forest and, making his way to a ridge of the wooded mountains, looked down on the rich Etrurian fields spread out below. In Greece beautiful woods of pine, oak, and other trees still linger on the slopes of the high Arcadian mountains, still adorn with their verdure the deep gorge through which the Ladon hurries to join the sacred Alpheus, and were still, down to a few years ago, mirrored in the dark blue waters of the lonely lake of Pheneus; but they are mere fragments of the forests which clothed great tracts in antiquity, and which at a more remote epoch may have spanned the Greek peninsula from sea to sea." [2] Sources [1] BMJ Letter, Animals do have rights, 17 February 2001, P Morrell [2] Sir James Frazer, The Golden Bough, Ch 9, The Worship of Trees, MacMillan, London, 1922 Golden Bough online http://www.bartleby.com/196/ Other Links: Julius Caesar
Emperor Julian
King Henry II
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C K Yoe, Semi-retired chemical engineer
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Somewhere near the bottom of Terence Partridge’s response to the Greeks’ critique of animal-based medical research, one sentence sticks out like a sore thumb: “drug trials commonly illustrate the unreliability of human patients as perfect CAMs of other human patients.” If human patients are so unreliable as models of other human patients, how much LESS reliable must animal models be? He depicts animal research, not as “unidirectional flow of information from experiment to conclusions”, but as the “to and fro of information and hypothesis” and as “elucidating fundamental principles and testing candidate treatments, selected on the basis of prior knowledge”. There is a term that encapsulates his methodology precisely: “trial- and-error.” It is a well-known technique used in mathematics whenever an analytical solution is not available, and involves an iterative procedure with successively closer approximations to the true solution until either you feel you are close enough or (more commonly) you get fed up. He concludes: “Anyone who works in biological science knows that there are defects in all model systems, yet scientific advance in biological and medical knowledge has demonstrably occurred by making the best of what is available.” In essence, therefore, such advance has derived from the lottery of trial-and-error that is animal research. C.K. Yoe |
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Bill Slaughter, medical student none
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Hello all--I see the last post was some months ago and so suppose I've lost out on the main body of comments, but thought I'd throw this in to the discussion anyway: A few years ago when I started medical school, I learned our university had 2 annual gatherings to acknowledge and honor the humans whose cadavers we use in training, but nothing for the (hundreds of thousands) of animals (invertebrate to non-human primates) used in biomed research. Not feeling qualified to be totally for or against the use of such animals in each instance they are used (and hearing quite compelling stories on the one hand from lab techs about animal lives trivially and needlessly used, and on the other from principal investigators in lectures about their opinions about absolute need to continue using other species), I decided to start an annual gathering simply acknowledging the animals used. We've done this now at the University of Washington in Seattle USA for 3 yrs now. I've found that there are several such gatherings annually in Buddhist NE Asia (Korea, Japan) and a handful of others in N America, the oldest being since 1995 at the Univ. of Guelph, Ont, CA. 10/22/01 at the annual conference in Baltimore of the American Assn for Lab. Animal Science (AALAS--research vet. convention), three of us who founded 'animal acknowledgement' gatherings in our organizations are leading a panel discussion on this issue, in hopes of supporting others in other organizations who might have an interest in starting similar gatherings (Mon 10/22/01 12n-2pm). We've striven to keep our annual event focused on simply thinking about the animals and our thoughts and feelings about them, with no strong pro- or anti-animals-in-biomed stance. This is because this is a very large (2nd-3rd in $ in USA) with a huge community of researchers, but also a university with an active animal rights community, and a public institution paid for by the general public, with their range of beliefs about the morality of such use of other species. Seemed like some sort of middle ground everyone can agree on--simply reflecting on the animals used. I realized when starting this event that this is a very charged topic on our campus, and that it is even more so in the UK (we started it at a time when rumor had it that a website targeted for murder animal- using researchers in the UK or mainland Europe) but hope it can be part of some sense of reflection on all sides on this matter. We call it "Remembering the Animals", partly specifically to "add a fourth 'R'" to Russell and Burch's other three. Pls consider posting this msg; if anyone is interested in info about what we do (and which we've gathered about such events elsewhere), pls consider getting in touch with me. A classmate and I wrote one article on this (Western Jrnl of Medicine 8/01, including tips on starting such an event at one's own organization in the electronic version of the article). |
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