The background to the establishment of the European Centre for the Validation of Alternative Meth... more The background to the establishment of the European Centre for the Validation of Alternative Methods (ECVAM) is reviewed, and the main events at the opening of the Centre and an ECVAM symposium on practical aspects of validation are summarized. Finally, recommendations made to ECVAM for consideration in developing the Centre's strategy are listed.
During the last century, public concern has increased over the actual or potential adverse effect... more During the last century, public concern has increased over the actual or potential adverse effects experienced by animals as a consequence of scientific activities. There has been a corresponding increase in special provisions for controlling the use of laboratory animals, since general provisions for animal protection are unlikely to cope with complex scientific activities involving the deliberate use of procedures likely to be painful. Such controls on the use of animals for scientific purposes attempt to balance the legitimate needs of society, science and industry (to have information and products derived from the use of experimental animals) against the equally legitimate ethical concerns of society that animals should not be used except when necessary and for worthy ends, and that animal use and suffering should be minimized as far as possible, through optimal deployment of the Three Rs (replacement, reduction and refinement), a concept pioneered by Russell and Burch (1959).
Isoprenaline,db-CAMP and ionophore Br-X537A induced glycogenolysis and glucose release from A. me... more Isoprenaline,db-CAMP and ionophore Br-X537A induced glycogenolysis and glucose release from A. means liver organ cultures in the presence or absence of medium Ca2+. loGhoreA23187 had similar effects, but only in the presence of external Ca 8
Thanks are also due to Mrs Margaret Pearson and the writer's parents for their support and encour... more Thanks are also due to Mrs Margaret Pearson and the writer's parents for their support and encouragement and to Miss Lisa Probyn for typing the manuscript.
ABSTRACT Before in vitro tests can be regarded as acceptable for use in regulatory toxicology, th... more ABSTRACT Before in vitro tests can be regarded as acceptable for use in regulatory toxicology, their relevance and reproducibility must be formally validated in interlaboratory studies incorporating both a blind trial and independent assessment of their outcome. The purpose of a validation study must be clearly defined in terms of level of toxicity testing (e.g. potency, hazard, risk), type of testing (e.g. screening, adjunct, replacement), type of toxicity (e.g. ocular irritancy, neurotoxicity) and chemical spectrum of interest (e.g. all chemicals, certain classes of chemicals). Current developments in in vitro methodology are also likely to have a major impact on in vitro toxicology, including advances in the maintenance of differentiated cells and tissues, the manipulation of cells for specific purposes (e.g. by cell immortalisation and gene transfer), the measurement of cellular functions and responses, understanding of mechanisms of toxicity (including metabolic activation and the identification of cellular targets), and human cell and tissue culture. Strategies for the integrated use of cell culture methods and other non-animal alternatives are discussed, with particular reference to animal/human and in vitro/in vivo extrapolation.
FRAME'S role in drawing attention to the special scientific and ethical concerns raised by th... more FRAME'S role in drawing attention to the special scientific and ethical concerns raised by the use of non-human primates as laboratory animals is reviewed, with special emphasis on the FRAME/CRAE proposals to the British Government (1987) and the RSPCA/FRAME survey of research on non-human primates conducted in Great Britain between 1984 and 1988. Attention is then focused on the moral case and the scientific case against using chimpanzees as laboratory animals, with particular emphasis on research on AIDS. Finally, a call is made for universal agreement that no more laboratory experiments should ever be performed on chimpanzees.
Experience has shown that the outcome of large and expensive validation studies on alternative me... more Experience has shown that the outcome of large and expensive validation studies on alternative methods can be compromised if their managers do not insist that optimised test protocols and proof of their performance are submitted before the start of the formal validation study. One way for the sponsors of validation studies to confirm both the likely relevance of a method for its stated purpose and its readiness for validation would be to require a prevalidation study before formal validation was contemplated. This process would involve the developers (or other proponents of the method) and selected independent laboratories in protocol refinement (Phase I) and protocol transfer (Phase II). The optimised protocol would then be assessed in a protocol performance phase (Phase III), which would involve the testing of a relevant set of coded test materials and an evaluation of a proposed prediction model. In certain circumstances, a successful outcome of Phase III might be sufficient for ...
Make no mistake, the debate over animal experimentation has become deadly serious. In Britain, we... more Make no mistake, the debate over animal experimentation has become deadly serious. In Britain, we've seen bombings, hunger strikes and death threats. The scientists involved, labelled 'torturers', live in fear of becoming the next target. Peaceful campaigners for animal rights find themselves branded as 'terrorist sympathisers'. Yet amidst the violence and rhetoric, one thing is missing: no one really knows what the public think because they haven't been asked where they would draw the line on animal research. "Until now, that is. To let the people's voice be heard, [we] commissioned Market & Opinion Research International (MORI) to ask a representative sample of British adults whether they supported or opposed each of a series of hypothetical experiments. "The results provide the most complete picture so far of the public's views on animal research-from die-hard activists who even oppose experiments that don't harm animals to the 1 in 20 people prepared to let monkeys die to test cosmetics. Yet despite these divergent opinions, our poll reveals that most people seem to carefully weigh the pros and cons of each experiment before deciding whether or not to give their support. "Researchers, antivivisectionists and regulators alike will find some grains of comfort and some disturbing messages in our poll. We hope these results will provide a new starting point for a rational debate on the future of animal experimentation in Britain and elsewhere.
, 110 scientists, including five winners of the Nobel prize and 38 Fellows of the Royal Society, ... more , 110 scientists, including five winners of the Nobel prize and 38 Fellows of the Royal Society, wrote to the Minister for Science, Lord Sainsbury of Turville, to ask him to "liaise urgently with the Home Office to draw up a plan to safeguard the future of biomedical research in the UK". Their complaint was about "bureaucracy and delays" which "are impeding the use of animals in research", and they implied that the Home Office was no longer applying the principle that the needs of science and industry should be balanced against the welfare of the animals used. As a result, they claimed, British researchers are placed at a disadvantage in comparison with their overseas competitors, who can get permission for a project requiring the use of animals "in weeks or even days", whereas it can take "six months or longer" with the Home Office system. The headlines in the next day's Times suggested that "Excessive bureaucracy could drive medical research abroad" and gave a rather damning interpretation of the aims of the 110 signatories: "Scientists seek more animal test freedom". Under another stark heading, "Of mice and men: researchers in revolt", The Times gave their names in full. The list of signatories includes many scientists who are long retired and/or have been against the aims of the Animals (Scientific Procedures) Act 1986 ever since it was first discussed in Parliament in 1985. Many of the others are physiologists of one kind or another, who are striving, it is to be hoped in vain, to regain their dominance over British biomedical research, which characterised the last century. Production of the letter sent to Lord Sainsbury was coordinated by Professor Nancy Rothwell, a physiologist at the University of Manchester, who is also a member of the UK Life Sciences Committee (UKLSC), which promotes the interests of a number of scientific societies. The letter reflects complaints which have been made repeatedly in the literature of the Research Defence Society, which has long complained about the slowness of the licensing system, and, more recently, about the impact of the Ethical Review Process, which was introduced in April 1999. It is true that successive Governments have failed to appoint sufficient Home Office inspectors to advise the Home Secretary effectively on the application of the 1986 Act, but problems also arise from the low quality of applications submitted by some scientists, and the slowness of others in responding to questions put to them by the Home Office Inspectorate. According to a subsequent report in The Guardian (4 July 2000), entitled "Scientists predict big rise in animal tests", Professor Rothwell said that, "Writing a project licence application is one of the hardest things scientists do". 1 This certainly does not encourage confidence in the quality of their applications for funding to support the research itself! The report in The Guardian was based on the claim that the Government "is braced for a massive increase in scientific experiments over the next few years, as the completion of the human genome project causes applications for research licences to flood in". Professor Colin Blakemore, a prominent advocate of freedom to conduct animal experiments, and one of the 110 signatories of the Sainsbury letter, had said that he would not be surprised "if there is a 10% increase year-on-year in the total number of animals applied for over the next five years". However, the Government is also apparently aware that "a rise in the number of
The background to the establishment of the European Centre for the Validation of Alternative Meth... more The background to the establishment of the European Centre for the Validation of Alternative Methods (ECVAM) is reviewed, and the main events at the opening of the Centre and an ECVAM symposium on practical aspects of validation are summarized. Finally, recommendations made to ECVAM for consideration in developing the Centre's strategy are listed.
During the last century, public concern has increased over the actual or potential adverse effect... more During the last century, public concern has increased over the actual or potential adverse effects experienced by animals as a consequence of scientific activities. There has been a corresponding increase in special provisions for controlling the use of laboratory animals, since general provisions for animal protection are unlikely to cope with complex scientific activities involving the deliberate use of procedures likely to be painful. Such controls on the use of animals for scientific purposes attempt to balance the legitimate needs of society, science and industry (to have information and products derived from the use of experimental animals) against the equally legitimate ethical concerns of society that animals should not be used except when necessary and for worthy ends, and that animal use and suffering should be minimized as far as possible, through optimal deployment of the Three Rs (replacement, reduction and refinement), a concept pioneered by Russell and Burch (1959).
Isoprenaline,db-CAMP and ionophore Br-X537A induced glycogenolysis and glucose release from A. me... more Isoprenaline,db-CAMP and ionophore Br-X537A induced glycogenolysis and glucose release from A. means liver organ cultures in the presence or absence of medium Ca2+. loGhoreA23187 had similar effects, but only in the presence of external Ca 8
Thanks are also due to Mrs Margaret Pearson and the writer's parents for their support and encour... more Thanks are also due to Mrs Margaret Pearson and the writer's parents for their support and encouragement and to Miss Lisa Probyn for typing the manuscript.
ABSTRACT Before in vitro tests can be regarded as acceptable for use in regulatory toxicology, th... more ABSTRACT Before in vitro tests can be regarded as acceptable for use in regulatory toxicology, their relevance and reproducibility must be formally validated in interlaboratory studies incorporating both a blind trial and independent assessment of their outcome. The purpose of a validation study must be clearly defined in terms of level of toxicity testing (e.g. potency, hazard, risk), type of testing (e.g. screening, adjunct, replacement), type of toxicity (e.g. ocular irritancy, neurotoxicity) and chemical spectrum of interest (e.g. all chemicals, certain classes of chemicals). Current developments in in vitro methodology are also likely to have a major impact on in vitro toxicology, including advances in the maintenance of differentiated cells and tissues, the manipulation of cells for specific purposes (e.g. by cell immortalisation and gene transfer), the measurement of cellular functions and responses, understanding of mechanisms of toxicity (including metabolic activation and the identification of cellular targets), and human cell and tissue culture. Strategies for the integrated use of cell culture methods and other non-animal alternatives are discussed, with particular reference to animal/human and in vitro/in vivo extrapolation.
FRAME'S role in drawing attention to the special scientific and ethical concerns raised by th... more FRAME'S role in drawing attention to the special scientific and ethical concerns raised by the use of non-human primates as laboratory animals is reviewed, with special emphasis on the FRAME/CRAE proposals to the British Government (1987) and the RSPCA/FRAME survey of research on non-human primates conducted in Great Britain between 1984 and 1988. Attention is then focused on the moral case and the scientific case against using chimpanzees as laboratory animals, with particular emphasis on research on AIDS. Finally, a call is made for universal agreement that no more laboratory experiments should ever be performed on chimpanzees.
Experience has shown that the outcome of large and expensive validation studies on alternative me... more Experience has shown that the outcome of large and expensive validation studies on alternative methods can be compromised if their managers do not insist that optimised test protocols and proof of their performance are submitted before the start of the formal validation study. One way for the sponsors of validation studies to confirm both the likely relevance of a method for its stated purpose and its readiness for validation would be to require a prevalidation study before formal validation was contemplated. This process would involve the developers (or other proponents of the method) and selected independent laboratories in protocol refinement (Phase I) and protocol transfer (Phase II). The optimised protocol would then be assessed in a protocol performance phase (Phase III), which would involve the testing of a relevant set of coded test materials and an evaluation of a proposed prediction model. In certain circumstances, a successful outcome of Phase III might be sufficient for ...
Make no mistake, the debate over animal experimentation has become deadly serious. In Britain, we... more Make no mistake, the debate over animal experimentation has become deadly serious. In Britain, we've seen bombings, hunger strikes and death threats. The scientists involved, labelled 'torturers', live in fear of becoming the next target. Peaceful campaigners for animal rights find themselves branded as 'terrorist sympathisers'. Yet amidst the violence and rhetoric, one thing is missing: no one really knows what the public think because they haven't been asked where they would draw the line on animal research. "Until now, that is. To let the people's voice be heard, [we] commissioned Market & Opinion Research International (MORI) to ask a representative sample of British adults whether they supported or opposed each of a series of hypothetical experiments. "The results provide the most complete picture so far of the public's views on animal research-from die-hard activists who even oppose experiments that don't harm animals to the 1 in 20 people prepared to let monkeys die to test cosmetics. Yet despite these divergent opinions, our poll reveals that most people seem to carefully weigh the pros and cons of each experiment before deciding whether or not to give their support. "Researchers, antivivisectionists and regulators alike will find some grains of comfort and some disturbing messages in our poll. We hope these results will provide a new starting point for a rational debate on the future of animal experimentation in Britain and elsewhere.
, 110 scientists, including five winners of the Nobel prize and 38 Fellows of the Royal Society, ... more , 110 scientists, including five winners of the Nobel prize and 38 Fellows of the Royal Society, wrote to the Minister for Science, Lord Sainsbury of Turville, to ask him to "liaise urgently with the Home Office to draw up a plan to safeguard the future of biomedical research in the UK". Their complaint was about "bureaucracy and delays" which "are impeding the use of animals in research", and they implied that the Home Office was no longer applying the principle that the needs of science and industry should be balanced against the welfare of the animals used. As a result, they claimed, British researchers are placed at a disadvantage in comparison with their overseas competitors, who can get permission for a project requiring the use of animals "in weeks or even days", whereas it can take "six months or longer" with the Home Office system. The headlines in the next day's Times suggested that "Excessive bureaucracy could drive medical research abroad" and gave a rather damning interpretation of the aims of the 110 signatories: "Scientists seek more animal test freedom". Under another stark heading, "Of mice and men: researchers in revolt", The Times gave their names in full. The list of signatories includes many scientists who are long retired and/or have been against the aims of the Animals (Scientific Procedures) Act 1986 ever since it was first discussed in Parliament in 1985. Many of the others are physiologists of one kind or another, who are striving, it is to be hoped in vain, to regain their dominance over British biomedical research, which characterised the last century. Production of the letter sent to Lord Sainsbury was coordinated by Professor Nancy Rothwell, a physiologist at the University of Manchester, who is also a member of the UK Life Sciences Committee (UKLSC), which promotes the interests of a number of scientific societies. The letter reflects complaints which have been made repeatedly in the literature of the Research Defence Society, which has long complained about the slowness of the licensing system, and, more recently, about the impact of the Ethical Review Process, which was introduced in April 1999. It is true that successive Governments have failed to appoint sufficient Home Office inspectors to advise the Home Secretary effectively on the application of the 1986 Act, but problems also arise from the low quality of applications submitted by some scientists, and the slowness of others in responding to questions put to them by the Home Office Inspectorate. According to a subsequent report in The Guardian (4 July 2000), entitled "Scientists predict big rise in animal tests", Professor Rothwell said that, "Writing a project licence application is one of the hardest things scientists do". 1 This certainly does not encourage confidence in the quality of their applications for funding to support the research itself! The report in The Guardian was based on the claim that the Government "is braced for a massive increase in scientific experiments over the next few years, as the completion of the human genome project causes applications for research licences to flood in". Professor Colin Blakemore, a prominent advocate of freedom to conduct animal experiments, and one of the 110 signatories of the Sainsbury letter, had said that he would not be surprised "if there is a 10% increase year-on-year in the total number of animals applied for over the next five years". However, the Government is also apparently aware that "a rise in the number of
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