Animal use for scientific purposes raises ethical issues, whatever the level and nature of any suffering involved. Procedures that can cause severe suffering are of particular concern and the justification for using these deserves special scrutiny.
Harms and benefits in law
Many regulatory systems use a harm-benefit analysis to examine the justification for research projects, where the likely harms to animals are considered against the potential benefits of the research. Where suffering may be high, the expected benefit must be proportionately high, but the aim should be to avoid severe suffering wherever possible.
The UK Home Office recognises that severe suffering is of particular ethical concern, and requires special justification for project licence applications involving severe suffering. Projects including severe procedures on 'special' species (dogs, cats, primates and horses) must be referred to the national committee (the Animals in Science Committee); and all projects involving severe protocols must undergo a retrospective assessment. UK and EU legislation also includes an absolute upper limit to harm - long-lasting, severe pain, suffering or distress that cannot be ameliorated is not permitted.
A key factor in the harm-benefit analysis and ethical evaluation of research using severe procedures is its translational, or predictive, value. If a severe procedure is proposed because it is believed to be necessary for an animal 'model' of a serious human disease to reproduce the severe suffering seen in humans, from an ethical perspective the results must be translatable. There are examples in the literature where potentially severe models (e.g. rodent middle cerebral artery occlusion in stroke research) have poor predictive validity, i.e. medicines that work in preclinical trials fail to provide benefit in clinical trials. There are many potential reasons for translational failure, including poor pre-clinical experimental design, inappropriate animal 'models', inherent species differences and heterogeneity of patients in clinical trials. Whatever the reason, the justification for severe suffering is compromised if translation is poor. Similarly, if such models generate a long series of papers, but these do not lead to new therapies in the clinic, at some point it will no longer be ethical to continue that line of research.
Many other questions relate directly to benefit and have a bearing on the justification for severe procedures. For instance, could a particular clinical issue be resolved more rapidly and effectively via human behaviour change protocols, 'social prescribing', or policy changes, than with a new medicine? Is there a good level of dialogue with relevant clinicians, to ensure that the proposed benefits are realistic and actually wanted and needed in the field? For 'basic' research in which suffering may be severe, how much weighting should be given to human knowledge and interest, without an immediate applied medical benefit?
Addressing differing perspectives
There is wide agreement on the need to reduce severe suffering using the Three Rs. However, there may be differing perspectives on the more challenging questions around benefit and 'need' as set out above, and about the ethics of going ahead with the research, and it is important to accept and address these. (See 'Doing ethics', appendix 2 of the RSPCA Lay Members' Resource Book).
In the UK, an ideal forum for discussing such issues is the local (institutional) Animal Welfare and Ethical Review Body (AWERB). One of its functions is the provision of a forum for discussion and development of ethical advice; an ideal place to discuss how severe models and procedures will be reviewed and refined within an establishment and decisions made. By opening the issue up to wider consultation, additional in-house expertise may be brought to bear, enabling severe suffering to be limited or avoided. When all perspectives are taken into account, it might be decided to define the types of benefit and purpose for which severe protocols may, or may not, be permitted within the establishment, or to mandate that all potentially severe procedures are managed as moderate via the use of humane endpoints.
Other issues that could be considered as part of an ongoing ethical discussion are: whether it is more, or less, ethically acceptable to use animals of certain species in severe protocols; and how people within the establishment actually interpret the concept of 'severe'; for example, views about 'harms that ought not to be done' and 'naturalness' may be important to staff.
More information about ethical review can be found on the RSPCA website.