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A critically important issue

Posted by elliotrspca on 06 Jul 2012 at 08:33 GMT

This paper raises some critically important issues relating to the difficulties that can arise when balancing requirements to conduct pathogenesis research on the one hand, against the need to minimise animal suffering and improve welfare on the other. The use of animals in research that can cause severe suffering, yet aims to tackle diseases that cause significant suffering in humans and other animals, represents a pressing ethical dilemma and it is very encouraging to see PLoS Pathogens drawing attention to this and calling for more discussion.

Consideration of these issues is timely given the imminent transposition of EU Directive 2010/63 into domestic legislation by EU member states. EU2010/63 requires retrospective severity assessment of the actual degree of suffering that animals experience during scientific procedures. This shift (in terms of UK legislation) from prospective assessment of the upper limit of suffering into one of four severity levels (mild, moderate, substantial or unclassified) to the retrospective assessment of the actual suffering experienced by the animal will, most likely, result in a renewed focus on humane endpoints.

Retrospective severity assessment also offers an opportunity to assess sources of suffering and to avoid substantial or severe suffering. Currently a protocol may be classified prospectively as being substantial because there is a risk that animals may experience significant pain, distress or lasting harm. Retrospective review offers the opportunity to clearly define what proportion of animals actually experience severe suffering and may also indicate opportunities, through protocol modifications and the use of humane endpoints, to prevent animals from experiencing this most severe level of suffering.

We agree with the authors that there is a need for field-specific guidance on acceptable humane endpoints, based on systematic studies into biomarkers and validated predictors of death or survival. Humane endpoints require an appreciation of welfare indicators specific to the species being used and some form of metric or biomarker related to the pathology being studied. These two factors, in combination, allow a clear decision point to be defined where the animal will be euthanased to prevent further suffering.

There is a critical need for humane endpoints to be clearly and widely reported to ensure that as many animals benefit as possible. For example, the threshold weight losses cited in the opinion paper range from 15 to 30 %, with no scientific justification provided, which raises serious questions about harmonisation of endpoints (or at least the reporting of animal use). While further research into appropriate endpoints may well be needed, from ethical and animal welfare aspects it would be preferable to conduct systematic analyses of data that have already been gathered in pathogenesis studies in a particular field, so as to avoid conducting new studies that would cause animal suffering. Alternatively, validation studies could be conducted on the back of research that would have been carried out in its own right, without increasing suffering or creating demands for further animal use.

We also agree that a better definition of the term ‘humane endpoint’ is required, and share the authors’ view that euthanasing an animal who is already moribund will probably not prevent much suffering at all. Guidance on humane endpoints should thus include a definition that includes the concepts of reducing suffering to a minimum and implementing endpoints as early as possible. Surrogate biomarkers (e.g. core body temperature, body weight, blood chemistry, cytokine levels) in conjunction with behavioural monitoring should permit an early indication of “the point of no return” for the animal, i.e. a combination of clinical signs following which the animal will not recover.

The authors’ call for collaborative research should certainly be supported, with the provisos relating to avoiding animal use mentioned above, and with the presumption that the Three Rs of replacement, reduction and refinement would be fully implemented in the case of ongoing research that would also be used to provide data to support guidance. We hope very much that the editor’s request for discussion and the author’s call for action provoke reflection and new initiatives to reduce animal suffering in pathogenesis research.

However, it is not possible to gauge how much support there is for this approach within the pathogenesis community, as nobody has responded to the editor’s call for opinions! We believe that open discussion can only benefit both animal welfare and science, and hope that further contributions will follow.

Elliot Lilley, Penny Hawkins, Maggy Jennings
Research Animals Department, RSPCA, UK

No competing interests declared.

RE: A critically important issue

PLoS_Pathogens replied to elliotrspca on 13 Jul 2012 at 11:45 GMT

Thanks for your contribution. I fully agree that this is a critical issue that would benefit from broad input from the pathogenesis community; I do hope that more readers will respond with their views and suggestions. Of note, I am hoping that this conversation will be continued in future Opinions solicitations, so suggestions for sub-topics would also be appreciated.

Glenn Rall
Opinions Editor
PLoS Pathogens

No competing interests declared.