Research ethics and non-human subjects

Translational Psychiatry published a controversial study ahead of the recent update of Springer Nature's research ethics guidelines. But it is not too late to withdraw the article. If the handbook's references to the rights to nonhuman life and the avoidance of unnecessary suffering really have value, this is exactly what Translational Psychiatry must do now

Princeton – In August, Springer Nature, publisher of 3000 academic journals, including the Nature portfolio of the world's most influential scientific journals, released new ethical guidelines for its editors, addressing the balance between academic freedom and the risk that publishing some research harm specific groups of people. The handbook also mentions, albeit very briefly, research using animals.

There are long-established guidelines that prohibit the publication of articles based on experiments or evidence that fail to protect the rights of human research subjects. The new guidance goes beyond this, meaning editors must reject research that contributes to knowledge and properly protects its research subjects if, for example, it indirectly contributes to the stigmatization of a vulnerable human group.

The updated ethics guidance therefore adds a number of new and complex considerations to the already difficult decisions that editors of scientific journals must undertake. The handbook leaves enough room for different interpretations, either more favorable to academic freedom, or more protective measures for the rights and dignity of members of particular groups of people. It remains to be seen whether the guidance will narrow the range of topics - and if so, to what extent - in which scientists can hope to be published in a mainstream scientific journal.

The Journal of Controversial Ideas, of which I am co-founding editor, has already published papers that other journals have rejected, not because of flaws in the research, but because they espouse views contrary to widely held and strongly held political beliefs or ethical. I wouldn't be surprised if Springer Nature's new ethics handbook brings us more such papers.

One aspect of the guidance that I unreservedly welcome, in this regard, is the statement that "research must also respect the rights of non-human life". This would be more useful if it were accompanied by a short list of rights that non-human life possesses. I can understand why that task was not attempted. But the guidance includes, among a list of harms to be avoided, "unnecessary suffering of non-human animals as a result of experiments".

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Against this background, consider the article titled "Mild Chronic Unpredictable Stress Produces Depressive Behavior, Hypercortisolemia, and Metabolic Dysfunction in Adolescent Cynomolgus Monkeys," published in 2021 in the journal Springer Nature Translational Psychiatry. The article describes how the researchers – mainly from Chongqing Medical University, China, but with two co-authors at American universities – raised monkeys in large social groups for the first year of their lives, and then caged them, alone, for 70 days.

For adolescent social animals, removal from a social group and isolation is already extremely stressful. Additional stress was inflicted on the monkeys in five cycles of seven days each. On each of these 35 days, the monkeys were subjected to: 12 hours of loud noise, 12 hours without water, 24 hours without food, four hours in a more confined space, 12 hours of stroboscope, a temperature of 10 degrees Celsius for ten minutes, and inevitable electric shocks to their legs 3-4 times for 10-15 seconds.

Although the paper's title suggests only "mild" stress, by the researchers' own account, the experimental protocol was severe enough to force the monkeys to spend significantly more time than a control group in what the researchers called "the huddle posture " - hanging heads down at shoulder level or below. The researchers conclude that the stresses they caused "may induce depressive and anxiety-like behaviors."

The Springer Nature Research Ethics Handbook reiterates a longstanding and widely used requirement that authors of manuscripts reporting research on living vertebrates or higher invertebrates confirm that all experiments were conducted in accordance with relevant guidelines. The article reporting the research just described includes this statement:

"Animals were maintained under an experiment protocol approved by the Ethics Committee of Chongqing Medical University (approval no.: 20180705) in accordance with the recommendations of the "Use of Nonhuman Primates in Research" and the "Guide for the Care and Use of Animals laboratory'"

Requiring researchers to confirm that they have followed relevant guidelines may protect editors from criticism, but often fails to protect animal research subjects.

People for the Ethical Treatment of Animals (PETA), an American animal rights organization, asked Emily Trunnell, who has a PhD in neuroscience from the University of Georgia, to review this and two similar experiments with monkeys. In a letter to the editor of Translational Psychiatry, she wrote: "In essence, the monkeys were tortured for these experiments." She also points out that because the stresses inflicted on the monkeys were quite different from those that commonly cause depression or other forms of mental illness in humans, a nonhuman primate animal model is unlikely to be useful for studies of human depression.

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Translational Psychiatry published this study before the latest update of Springer Nature's research ethics guidelines. But it is not too late to withdraw the article. If the references in the guide to the rights to non-human life and the avoidance of unnecessary suffering really mean anything, this is what Translational Psychiatry should be doing now.

(The author, a professor of bioethics at Princeton University, is the founder of The Life You Can Save. He is currently working on an updated edition of his book, Animal Liberation, first published in 1975. Comment it was written for the global journalism network, "Project Syndicate", of which "Koha Ditore" is also a part.