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Letters

Animal research

BMJ 2001; 322 doi: https://doi.org/10.1136/bmj.322.7302.1603 (Published 30 June 2001) Cite this as: BMJ 2001;322:1603

Journal editors could help raise profile of three Rs of animal research

  1. Penny Hawkins, senior scientific officer (Research_Animals{at}rspca.org.uk)
  1. Research Animals Department, RSPCA, Horsham, West Sussex HH13 7WN
  2. Institute of Child Health, London WC1N 1EH
  3. Pig Disease Information Centre, Lolworth, Cambridgeshire CB3 8DS
  4. FRAME (Fund for the Replacement of Animals in Medical Experiments), Nottingham NG1 4EE
  5. 51 Woodbourne Avenue, London SW16 1UX

    EDITOR—The RSPCA (Royal Society for the Protection of Cruelty to Animals) believes that the use of laboratory animals presents an ethical dilemma that affects everyone. Animals are used for a broad range of purposes, and thus it is not possible or constructive to make sweeping statements about scientific validity, justification, or suffering. Issues subject to such polarised debate are inevitably difficult to resolve. In this case, sentient animals 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—replacement, reduction, refinement1—is an excellent practical starting point, and the RSPCA is committed to promoting and supporting it. Greater consideration is now given to implementing this concept, but it is not universally applied (or understood), and much is still to be achieved. One 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 them to pervade the whole of the life sciences, would be for journal editors to insist that published papers include comprehensive information about the lifetime experiences 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 at a premium, but it is possible to convey this information in surprisingly few words. 2 3 Such detail would provide guidance for other researchers wishing to improve animal welfare and reduce suffering, as well as giving other interested parties an insight into what laboratory animals actually experience and why. This would help to depolarise the debate and enable people with an interest to contribute to it in an informed and constructive way.

    Although the BMJ rarely publishes animal research, perhaps it would consider this kind of comprehensive editorial policy to help steer the debate towards the middle ground so that it can go further, faster.

    References

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    Ethics committees have influenced animal experiments in Sweden

    1. Jann Hau, professor (Jann.Hau{at}bmc.uu.se)
    1. Research Animals Department, RSPCA, Horsham, West Sussex HH13 7WN
    2. Institute of Child Health, London WC1N 1EH
    3. Pig Disease Information Centre, Lolworth, Cambridgeshire CB3 8DS
    4. FRAME (Fund for the Replacement of Animals in Medical Experiments), Nottingham NG1 4EE
    5. 51 Woodbourne Avenue, London SW16 1UX

      EDITOR—The debate in the United Kingdom on animal research1 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 that date they became regulatory. Scientists may, if their application is rejected, appeal to a higher court.

      Reasons for modification requested by ethics committee 1989-2000

      View this table:

      We analysed whether and how the committees have approved the applications subject to minor changes. We explored the main reasons for these conditions and how their frequency varied over time by analysing protocols from the meetings of three ethics committees (Jan 1989-Sept 2000). Altogether 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 table shows how the modifications to project applications that were required by the ethics committees before approval may be grouped.

      The frequency of modifications required by the ethics committees varied over the years from 10% to 30% (overall average 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 government investigation.3

      The areas that the ethics committees focused on has varied with time. In recent years pain relief and ensuring the presence of a licensed supervisor seem to have received increasing attention, whereas the interest in introducing earlier humane end points seems to be decreasing.

      About three quarters of the modifications may be categorised as refinement with respect to animal welfare, and the modifications requested have had a positive influence on project designs. The systems in the United Kingdom and Sweden cannot, however, be directly compared. The Home Office Inspectorate has played an active and professional part in the United Kingdom in improving project applications through dialogue with individual applicants. The introduction of ethics committees in the United Kingdom might simply result in this important activity being moved from the inspectorate to being a responsibility of an ethics committee.

      References

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      Three Rs should be registration, randomisation, and reviews (systematic)

      1. Ian Roberts, senior lecturer in epidemiology (ian.roberts{at}ich.ucl.ac.uk)
      1. Research Animals Department, RSPCA, Horsham, West Sussex HH13 7WN
      2. Institute of Child Health, London WC1N 1EH
      3. Pig Disease Information Centre, Lolworth, Cambridgeshire CB3 8DS
      4. FRAME (Fund for the Replacement of Animals in Medical Experiments), Nottingham NG1 4EE
      5. 51 Woodbourne Avenue, London SW16 1UX

        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.

        References

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        Would middle ground approach give “added value”?

        1. Michael Meredith, director (pdic{at}btinternet.com)
        1. Research Animals Department, RSPCA, Horsham, West Sussex HH13 7WN
        2. Institute of Child Health, London WC1N 1EH
        3. Pig Disease Information Centre, Lolworth, Cambridgeshire CB3 8DS
        4. FRAME (Fund for the Replacement of Animals in Medical Experiments), Nottingham NG1 4EE
        5. 51 Woodbourne Avenue, London SW16 1UX

          EDITOR—Forty years ago, before animal rights militancy had driven animal research behind a wall of secrecy, the University of Manchester invited an antivivisection group to tour its animal research laboratories and meet the research scientists. My friend, an animal rights activist with a highly polarised viewpoint, was determined to confront these “animal torturers.” When he returned he was, surprisingly, full of praise for the researchers.

          He admired the university's courage in opening its laboratory doors and facing frank discussion with “the enemy.” He found that the researchers, far from being the crazed animal torturers of his imagination, were reasonable and caring. They accepted 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.

          Aggression projected on to this animal research laboratory was unsustainable once a cooperative relationship had been established. When I drew attention to the turnaround in my friend's views he rationalised it by saying, “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, because it invested in communication and contact rather than condemnation and distance, or perhaps because it took a long and sensitive look at its activities in relation to the prevailing sentiment in society. A common pitfall for animal experimentation is that familiarity breeds contempt. I have encountered very caring doctors, scientists, and vets who became inured over time to what they were doing to sentient creatures in the name of medical or veterinary research.

          Both 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 them a free hand. 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 may have to pay?

          We 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 those that are about ignorance, personal ambition, projected emotions, or commercial greed?

          All sectors of society have a part to play. I have proposed a model for such cooperation in the welfare of farm animals that could easily be extended to medical research (http://www.pighealth.com/).

          More funding must go towards finding alternative non-animal methods

          1. Samantha Gray, scientific officer (sam{at}frame-uk.demon.co.uk)
          1. Research Animals Department, RSPCA, Horsham, West Sussex HH13 7WN
          2. Institute of Child Health, London WC1N 1EH
          3. Pig Disease Information Centre, Lolworth, Cambridgeshire CB3 8DS
          4. FRAME (Fund for the Replacement of Animals in Medical Experiments), Nottingham NG1 4EE
          5. 51 Woodbourne Avenue, London SW16 1UX

            EDITOR—Throughout the recent, highly emotive debate regarding animal experimentation and the fate of the medical research firm Huntingdon Life Sciences1 one crucial factor has been ignored—namely, the importance of non-animal alternative methods. The Fund for the Replacement of Animals in Medical Experiments (FRAME) is a charity that funds research into the development of alternative methods that do not require the use of animals. We were pleased to see Smith's editorial, which acknowledged the crucial role that alternative methods can have in bringing about a reduction in the use of animals in research and testing.2

            British and European law dictates that animals can be used only when no non-animal alternative is available. The development of reliable alternative methods is the best way of achieving the fund's ultimate goal of eliminating the need for live animal experiments.

            Current levels of funding for research into alternative methods are disappointing. If the government wants the decline in the number of tests on animals to continue then this funding must be dramatically increased. As well as the government, the industries that currently rely on animal research to develop and market their products could support this research into non-animal methods. The Fund for the Replacement of Animals in Medical Experiments would like to see the industries putting considerably more of their resources into developing alternative methods.

            The development and validation of non-animal methods is long and expensive. The rewards, though, are potentially great in terms of the benefits to science and to animal welfare.

            References

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            Various fallacies persist in vivisection debate

            1. J H Botting, retired (r.botting{at}qmw.ac.uk)
            1. Research Animals Department, RSPCA, Horsham, West Sussex HH13 7WN
            2. Institute of Child Health, London WC1N 1EH
            3. Pig Disease Information Centre, Lolworth, Cambridgeshire CB3 8DS
            4. FRAME (Fund for the Replacement of Animals in Medical Experiments), Nottingham NG1 4EE
            5. 51 Woodbourne Avenue, London SW16 1UX

              EDITOR—MacDonald might not have produced such a favourable review of Croce's book on the ethics of experimenting on animals had she had the time and inclination to research his claims that animal research is scientifically flawed.1

              Thalidomide was never tested in pregnant animals before its use in patients. After the first publication describing fetal abnormalities in babies whose mothers had taken thalidomide during pregnancy the drug was shown to be teratogenic in rats, mice, hamsters, rabbits, and three species of monkeys. The mandatory teratogenic tests on potential medicines instituted by the regulatory authorities as a result of the thalidomide disaster prevented a similar tragedy with the oral acne treatment retinoin. This medicine, because of its efficacy, was marketed despite its known teratogenicity in laboratory animals. Since it was labelled as having a confirmed teratogenic risk, only a few cases of fetal abnormality occurred as a result of inadvertent exposure.

              The claim that isoprenaline is well tolerated in cats at doses 175 times greater than those considered safe for humans is also incorrect. The human data were gathered from patients taking isoprenaline during the hypoxic conditions of an asthma attack; if cats are rendered similarly hypoxic they also become sensitive to the cardiotoxic actions of isoprenaline.

              The antivivisection literature is replete with emotive propaganda and exaggerated claims of “bad science.” A definitive examination of the literature, however, generally exposes criticisms as spurious. Their perpetuation in books such as Vivisection or Science does nothing for the ethical debate.

              References

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