12 / 10 / 2021
Guest blog: what can be done to help journal editors when confronted with a common ethical dilemma?
Clare Stanford is Professor Emerita of Translational Neuropharmacology at University College London. In this guest blog, Clare outlines the ethical dilemmas faced by journal editors when receiving manuscript submissions describing research that uses animals, and argues that editorial boards should establish formal journal policies that encourage and promote refinement of any contentious procedures involving animals.
An important role for members of many journal editorial boards is to check that any manuscript describing research that used animals includes a statement to confirm that the work complied with the authors’ institutional and national regulations and was approved by their local ethical review body. Yet, even with this assurance, journal editors can still be left with a challenging dilemma about whether or not to recommend publication of the article. This problem arises because some research reports describe procedures that are permitted in some jurisdictions but would not be in others. These disparities can cause a conflict for some editors: i.e., the desire to attract and publish high-quality research reports that will enhance their journal’s international profile versus the problem that some reports describe research that is controversial and might even be prohibited in the editor’s own laboratory.
For instance, in the UK and European Union, there is an absolute ban on research that involves the use of cosmetics, tobacco products and great apes but this is not the case, worldwide. Other examples that raise ethical concerns which I have encountered recently, include the use of chloral hydrate, 75% alcohol, ether or even carbon dioxide (!) as surgical anaesthetics and decapitation of unanaesthetised adult rats. None of these procedures is banned, worldwide, but probably should be.
Another common problem is where the parameters of a procedure, which is widely regarded as ethically acceptable, have been modified without obvious justification, in ways that raise ethical concerns. For instance, the Chronic Mild Stress procedure, which is used to induce ‘anhedonia’, typically involves applying a series of stressors to animals, none of which causes overt physical discomfort and all of which would be regarded as mild or moderate. Yet, many manuscripts describe studies in which the types and intensities of the individual stressors have been changed to those that would be regarded by most readers as imposing moderate / severe harm, even before considering their cumulative severity. Some of the individual stressors (e.g., 24 h food and water deprivation, swimming in ice-cold water) are so severe that they would never be permitted in some jurisdictions and yet the procedure is still described as Chronic Mild Stress.
These examples provide evidence that merely requiring authors to include a statement to confirm that their work had regulatory and ethical approval does not ensure that the research procedure was either justified or paid due regard to the 3Rs and animals’ welfare. Judging from the number of publications that fall into these grey areas, many editorial boards have not even acknowledged this problem, let alone grasped the nettle and made a decision on how best to deal with it.
At the moment, editors seem to grapple with these difficult decisions on an ad hoc basis. One option is to reject the work, simply because it would not have been authorised by their own regulators or ethics boards, but that drags editors into a further dilemma. Given that the animals have already been used in these procedures, and presumably something has been learned from their experience, there is little to be gained from blocking publication of the findings. The animals will not benefit from that decision and they will have suffered for no purpose at all. Worse still, other groups will be unaware of the findings and might repeat the study. The alternative option is to turn a blind eye to the problem and to approve publication, on the basis that the work was regarded as scientifically and ethically justified in the author’s jurisdiction. After all, the journal is an international resource and so its editors should not enforce parochial welfare and ethical standards on the wider scientific community.
This dilemma could be resolved if journals were to commit to a policy that requires authors to confirm that they explored scope for refinement (and minimizing harms) of any procedure that is potentially contentious (e.g., any that involve stress, or food / water deprivation) and that they can provide assurance that the severity of the procedure was the minimum necessary, commensurate with achieving the research objective(s). A(SP)A and Directive 2010/63/EU require that already and so do some journals. One that has taken this problem on board (The Journal of Psychopharmacology) now incorporates the following text in its Instructions to Authors:
Experiments in which animals experience a moderate or severe noxious stimulus, or stress (e.g. electric shocks, immobilization, prolonged bouts of swimming), will require special justification, particularly in respect of the type, duration and intensity of the stimulus. Authors should include a statement to confirm (and, ideally, provide evidence) that the use of a less severe procedure would compromise the objectives of the experiment. In this context, authors must consider the cumulative harm to animals that have experienced more than one form of noxious stimulus and/or stress.
Another, the British Journal of Pharmacology, has recently included similar advice:
Editors may ask authors to describe in their manuscript how discomfort, distress, and pain were avoided and minimized, and to confirm that animals did not suffer unnecessarily at any stage of an experiment.
Obviously, compliance with these rubrics is the key to the solution. There remains the worry that some authors merely pay lip-service to the intended requirement by inserting a token sentence along the lines of: “Every effort was taken to minimize harm to / suffering of the animals”. To help resolve that problem, journals could go a step further and ask authors to provide the evidence that supports the statement: i.e., that less harmful procedures were tried, but abandoned, because they did not produce the necessary change in the animals. This could be provided as supplementary information alongside each published article or by citing an earlier publication from the author’s laboratory. Such a policy would help to reassure readers that the severity of the procedure and the harm to the animals was necessary and scientifically justified.
At the very least, journal Editorial Boards should be encouraged to address this dilemma and to decide what to do about it. To be able to rely on a formal journal policy which requests confirmation that the use of controversial procedures was justified would certainly help editors who are trying to decide on whether or not to reject manuscripts for publication on ethical grounds.