- Email: [email protected]
Animal tests after the genome
CORRESPONDENCE
in the UK, due, in large part, to the use of animals to predict toxic effects in human beings. Yet the results of a 10year multicentre assessment of in-vitro cytotoxicology have shown that use of human tissues to predict human hazard is more accurate than any protocol involving animals or their tissues.3 As an example, TRAIL was a promising new cancer drug that seemed safe and effective in mice and monkeys. Tests on human liver cells in culture showed, however, that the drug was highly toxic and would cause liver damage or failure. On the other hand, Hoffman LaRoche asked Physiome Sciences to test a cardiac drug on their virtual heart, after animal tests proved inconclusive, and the US Food and Drug Administration approved the drug based on Physiome’s computer tests. You cite public support for essential animal work, but many surveys show most people abhor animal experimentation.4,5 This issue is clearly of concern to around 30 million people in the UK. I do not believe your predicted increase in the use of primates in genomic research will be acceptable to them. Persuading regulatory authorities to accept validated alternatives, and helping to speed the validation process, are useful contributions that could be made by scientific organisations, and the government should give financial incentives to reward such efforts. As the prime function of such authorities is, indeed, to ensure the safety of the public, they should act with urgency to accept and mandate the use of tests and techniques that are, beyond any doubt, more safe and reliable for human health. Kathy Archibald Animal Aid, The Old Chapel, Bradford Street, Tonbridge, Kent TN9 1AW, UK 1 2 3
4
5
Editorial. Animal research in the postgenome era. Lancet 2001; 357: 817. Dove A. CD18 trials disappoint again. Nat Biotech 2000; 18: 817–18. Clemedson C, Ekwall B. Overview of the Final MEIC Results: I. The In Vitro—In Vitro Evaluation. Toxicol In Vitro 1999; 13: 657–63. Aldhous P, Coghlan A, Copley J. Animal experiments: let the people speak. New Scientist 1999; 2187: 26–31. Travis A, Treanor J. Guardian Jan 23, 2001.
Sir—The Fund for the Replacement of Animals in Medical Experiments (FRAME) is a scientific charity that funds and conducts research into the development of methods that do not require the use of animals, as you discuss.1 FRAME promotes a moderate, but nonetheless determined, approach by encouraging consideration of the ethical and scientific issues involved in the use
1806
of laboratory animals. We advocate the adoption of the three Rs—reduction, refinement, and replacement. As you point out, the three Rs message is not reaching the general public. The media prefer to highlight the two extremes of the animal experimentation debate to provoke a heated, and generally unproductive, argument, which causes organisations such as FRAME difficulty in getting their voice heard. You go on to discuss the potential implications of the human genome project on the numbers of animals that are used in research. The unravelling of the human genome tells us only what genes are present, but not their function or role in human disease. Therefore, further animal work will probably be done to investigate gene function. Research is already underway in a largescale mutagenesis screen that aims to produce more than 40 000 mutant mice. In these screens, genes are altered by a chemical to try to produce mice that show features of human diseases, and to understand the function of particular genes. FRAME is concerned about the scientific merit of the work and the numbers of animals involved, and thinks their welfare is being severely compromised.2 In the UK, the Home Office must decide that the benefits of research outweigh the costs to the animals used before it allows research to proceed. Of the 26 000 mice screened so far, 98% of animals (>25 000 mice) have shown no effect, and presumably were destroyed. Furthermore, a substantial proportion of the remaining 2% of animals will have shown signs that were not relevant to any human disease. These animals would be of little, if any, scientific value, but would probably experience harmful effects of the mutation. We are alarmed at the scale of this wastage, since the so-called costs to the animals seem to be large, and the actual benefits of the research small. This issue of weighing up costs and benefits, which is fundamental to the operation of the Animals (Scientific Procedures) Act 1986, also applies to work on transgenic animals. It is not possible to predict accurately the costs before genetically modified animals are generated. The continuing, and increasing, interest in the use of genetically modified animals suggests that we must review the legislation to protect the welfare of these animals, and to ensure that all the research done on them is scientifically valid and truly worthwhile.
1
Samantha Gray
Department of Dermatology, Tel-Aviv Sourasky Medical Center, and the Sackler Faculty of Medicine, Tel-Aviv University, 6 Weizman Street, Tel-Aviv 64239, Israel (e-mail [email protected])
FRAME, 96–98 North Sherwood Street, Nottingham NG1 4EE, UK (e-mail:[email protected])
2
Editorial. Animal research in the postgenome era. Lancet 2001; 357: 817. Jenkins ES, Gray S, Combes RD. Mutagenesis screens: can they be justified? ATLA 2001; 29: 63–68.
Street crime as a treatment for migraine Sir—My wife’s singular flaw is that she has migraine headaches, frequently precipitated by stress, sometimes for no apparent reason. Unless the attack is so severe that she has no choice but to surrender and wait it out by lying motionless in a dark room, she insists on business and pleasure as normal. No medication provides relief from what is generally 2–3 days of torment. We went on a short holiday to Europe without our two adolescent children (who are a highly suspect cause for stress). My wife was silently suffering an attack that had begun on the eve of our arrival. On the first morning of our tour, while we were descending the escalator to the subway, we were attacked from behind by four young muggers while a fifth blocked our way in front. My wife held on to her bag for dear life, but one mugger succeeded in wrestling my wallet out of my grasp. I shouted as loudly as I could and tackled the perpetrator, but he managed to throw his spoils to his partner in crime, whereupon I set off on a mad chase after my cash, credit cards, and dignity. I lost all of them in the crowd. When I rejoined my wife, crestfallen and much poorer, she was visibly shaken and trembling. Then she looked up amazedly and exclaimed “Hey, my headache is gone”. The hammer banging on her skull, the throbbing in her eye socket, the photophobia and phonophobia had been wiped out in seconds. I won’t go so far as to advocate reproducing this kind of scenario. Yet, even in this era of evidence-based medicine, I believe that this anecdotal observation is worth a mention in the medical literature with the hope that it might lead to a better understanding of migraine, its cause and pathogenesis. More importantly, I hope that it will ignite the imagination and provide the seed from which new alternative treatments will emerge in the future. Ronni Wolf
THE LANCET • Vol 357 • June 2, 2001
in the UK, due, in large part, to the use of animals to predict toxic effects in human beings. Yet the results of a 10year multicentre assessment of in-vitro cytotoxicology have shown that use of human tissues to predict human hazard is more accurate than any protocol involving animals or their tissues.3 As an example, TRAIL was a promising new cancer drug that seemed safe and effective in mice and monkeys. Tests on human liver cells in culture showed, however, that the drug was highly toxic and would cause liver damage or failure. On the other hand, Hoffman LaRoche asked Physiome Sciences to test a cardiac drug on their virtual heart, after animal tests proved inconclusive, and the US Food and Drug Administration approved the drug based on Physiome’s computer tests. You cite public support for essential animal work, but many surveys show most people abhor animal experimentation.4,5 This issue is clearly of concern to around 30 million people in the UK. I do not believe your predicted increase in the use of primates in genomic research will be acceptable to them. Persuading regulatory authorities to accept validated alternatives, and helping to speed the validation process, are useful contributions that could be made by scientific organisations, and the government should give financial incentives to reward such efforts. As the prime function of such authorities is, indeed, to ensure the safety of the public, they should act with urgency to accept and mandate the use of tests and techniques that are, beyond any doubt, more safe and reliable for human health. Kathy Archibald Animal Aid, The Old Chapel, Bradford Street, Tonbridge, Kent TN9 1AW, UK 1 2 3
4
5
Editorial. Animal research in the postgenome era. Lancet 2001; 357: 817. Dove A. CD18 trials disappoint again. Nat Biotech 2000; 18: 817–18. Clemedson C, Ekwall B. Overview of the Final MEIC Results: I. The In Vitro—In Vitro Evaluation. Toxicol In Vitro 1999; 13: 657–63. Aldhous P, Coghlan A, Copley J. Animal experiments: let the people speak. New Scientist 1999; 2187: 26–31. Travis A, Treanor J. Guardian Jan 23, 2001.
Sir—The Fund for the Replacement of Animals in Medical Experiments (FRAME) is a scientific charity that funds and conducts research into the development of methods that do not require the use of animals, as you discuss.1 FRAME promotes a moderate, but nonetheless determined, approach by encouraging consideration of the ethical and scientific issues involved in the use
1806
of laboratory animals. We advocate the adoption of the three Rs—reduction, refinement, and replacement. As you point out, the three Rs message is not reaching the general public. The media prefer to highlight the two extremes of the animal experimentation debate to provoke a heated, and generally unproductive, argument, which causes organisations such as FRAME difficulty in getting their voice heard. You go on to discuss the potential implications of the human genome project on the numbers of animals that are used in research. The unravelling of the human genome tells us only what genes are present, but not their function or role in human disease. Therefore, further animal work will probably be done to investigate gene function. Research is already underway in a largescale mutagenesis screen that aims to produce more than 40 000 mutant mice. In these screens, genes are altered by a chemical to try to produce mice that show features of human diseases, and to understand the function of particular genes. FRAME is concerned about the scientific merit of the work and the numbers of animals involved, and thinks their welfare is being severely compromised.2 In the UK, the Home Office must decide that the benefits of research outweigh the costs to the animals used before it allows research to proceed. Of the 26 000 mice screened so far, 98% of animals (>25 000 mice) have shown no effect, and presumably were destroyed. Furthermore, a substantial proportion of the remaining 2% of animals will have shown signs that were not relevant to any human disease. These animals would be of little, if any, scientific value, but would probably experience harmful effects of the mutation. We are alarmed at the scale of this wastage, since the so-called costs to the animals seem to be large, and the actual benefits of the research small. This issue of weighing up costs and benefits, which is fundamental to the operation of the Animals (Scientific Procedures) Act 1986, also applies to work on transgenic animals. It is not possible to predict accurately the costs before genetically modified animals are generated. The continuing, and increasing, interest in the use of genetically modified animals suggests that we must review the legislation to protect the welfare of these animals, and to ensure that all the research done on them is scientifically valid and truly worthwhile.
1
Samantha Gray
Department of Dermatology, Tel-Aviv Sourasky Medical Center, and the Sackler Faculty of Medicine, Tel-Aviv University, 6 Weizman Street, Tel-Aviv 64239, Israel (e-mail [email protected])
FRAME, 96–98 North Sherwood Street, Nottingham NG1 4EE, UK (e-mail:[email protected])
2
Editorial. Animal research in the postgenome era. Lancet 2001; 357: 817. Jenkins ES, Gray S, Combes RD. Mutagenesis screens: can they be justified? ATLA 2001; 29: 63–68.
Street crime as a treatment for migraine Sir—My wife’s singular flaw is that she has migraine headaches, frequently precipitated by stress, sometimes for no apparent reason. Unless the attack is so severe that she has no choice but to surrender and wait it out by lying motionless in a dark room, she insists on business and pleasure as normal. No medication provides relief from what is generally 2–3 days of torment. We went on a short holiday to Europe without our two adolescent children (who are a highly suspect cause for stress). My wife was silently suffering an attack that had begun on the eve of our arrival. On the first morning of our tour, while we were descending the escalator to the subway, we were attacked from behind by four young muggers while a fifth blocked our way in front. My wife held on to her bag for dear life, but one mugger succeeded in wrestling my wallet out of my grasp. I shouted as loudly as I could and tackled the perpetrator, but he managed to throw his spoils to his partner in crime, whereupon I set off on a mad chase after my cash, credit cards, and dignity. I lost all of them in the crowd. When I rejoined my wife, crestfallen and much poorer, she was visibly shaken and trembling. Then she looked up amazedly and exclaimed “Hey, my headache is gone”. The hammer banging on her skull, the throbbing in her eye socket, the photophobia and phonophobia had been wiped out in seconds. I won’t go so far as to advocate reproducing this kind of scenario. Yet, even in this era of evidence-based medicine, I believe that this anecdotal observation is worth a mention in the medical literature with the hope that it might lead to a better understanding of migraine, its cause and pathogenesis. More importantly, I hope that it will ignite the imagination and provide the seed from which new alternative treatments will emerge in the future. Ronni Wolf
THE LANCET • Vol 357 • June 2, 2001