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The perils of preprints

BMJ 2020; 370 doi: https://doi.org/10.1136/bmj.m3111 (Published 17 August 2020) Cite this as: BMJ 2020;370:m3111

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BMJ RAPID RESPONSE to BMJ editorial by van Schalkwyk et al The perils of preprints BMJ 2020 370:m3111

Dear Editor

The editorial by van Schalkwyk et al The perils of preprints BMJ 2020 370:m3111 recently came to my attention. It raised several issues that may in particular interfere with current investigations on nicotinic receptors. Although published months ago, it urgently needs to be examined in detail to set the record straight.

First, van Schalkwyk et al. mention “two preprint publications examining the association between smoking and covid-19 which were widely disseminated before formal peer review”. The second, of which I am first author, was in fact reviewed by the editor of Comptes Rendus de l’Académie des Sciences-Biologies, accepted 18th April 2020 a few days after Queios dissemination and immediately published in Comptes Rendus-Biologies with, according to Google Scholar, 191 citations compared to 3 for the Qeios preprint. Furthermore, van Schalkwyk et al. state “while ignoring the broader evidence base on tobacco related harms”. This statement simply overlooks the last sentence of our Comptes Rendus paper: - “One should not forget that nicotine is a drug of abuse (55) responsible for smoking addiction. Smoking has severe pathological consequences and remains a serious danger for health”. Both statements thus need to be modified.

Second, and more importantly, the BMJ editorial indicates that our cited paper is “coauthored by a researcher (evidently myself) with historical links to the tobacco industry” (ref 8). “Historical links with tobacco industry” may mean for the unprepared reader that I (and my lab) worked for – in other words “for the benefit of” – the tobacco industry. The aim of the tobacco industry has always been to promote the sale of cigarettes and to favor tobacco smoking. All those who are familiar with my scientific work, and my personal life, can state that this has never been the case. Quite the opposite. This is an important ethical concern for my reputation as a scientist. The interview published in La lettre du Collège de France: Entretien avec Jean-Pierre Changeux and Marc Kirsch, Hors série 2010 p. 18-27 https://doi.org/10.4000/lettre-cdf.282 illustrates my lifetime concern and dedication to fight tobacco smoking and its dramatic consequences for health.

I acknowledge that between 1995 and 1998, the Council of Tobacco Research (CTR) financed a project from my laboratory (ref 8) entitled “Targeted Disruption of the beta 2 and alpha 4 Neuronal Nicotinic Acetylcholine Receptor Subunit Genes in the Mouse”, with the aim to support an American postdoctoral fellow in my laboratory. The grant was, of course, approved by the direction of the Pasteur Institute and its CTR origin publicly mentioned in the acknowledgments. Most importantly, the main scientific outcome of the project was the paper by Picciotto et al “Acetylcholine receptors containing the 2-subunit are involved in the reinforcing properties of nicotine” published in Nature 1998 391:173-7. This most quoted paper (1003 citations, web of science) was not only an unambiguous scientific demonstration of the addictive effect of nicotine on an animal model (that the tobacco companies have always denied) but also the first identification of the 2-containing nicotinic receptor as the target of nicotine addictive action. In other words, the outcome of the research to which CTR contributed is sharply opposed to the interests of the tobacco companies and specifically to any benefit for the sale of cigarettes. Moreover, my opinion is that this paper offered an argument for the condemnation of the Tobacco companies resulting in the $209 billion Tobacco Master Settlement Agreement of 1998.

Furthermore, van Schalkwyk et al mention in ref 8 a document which indicates that I was a “collaborator” of Targacept, a subsidiary of R.J. Reynolds Tobacco Company. In fact, I never received any financing from Targacept, neither for myself nor for my laboratory and never signed any contract of collaboration with Targacept (which would have been against the rules of the Pasteur Institute). On the other hand, several compounds synthesized by Targacept appeared to be potentially of great interest to me as orthosteric or allosteric modulators of the nicotinic receptor with potential use as antidepressant (TC5214) or cognitive enhancers (Bradanicline TC- 5619) for patients with Alzheimer Disease. This “dual use” of nicotine is presently a theme of considerable interest for the pharmacology of neurodegenerative diseases and of Covid 19 (EMBO Mol Med 2021 13(8):e14122).

Lastly, the same reference 8 mentions papers “to which Philip Morris contributed financially: https://www.pnas.org/content/104/51/20570,https://www.pnas.org/content/1.... ”

These two papers were produced in collaboration with other laboratories that shared the financial expenses of the research. They were headed by distinguished colleagues which research deals with important features of the structural organization and molecular dynamics of the nicotinic receptor that are entirely unrelated to the promotion of tobacco smoking. Moreover, in both cases, the financial help was to support fellowships for dedicated young scientists who were, and are still, suffering from the dramatic difficulties encountered in many countries to finance scientific research.

I agree with the view of van Schalkwyk et al that the fight against tabaco addiction remains a priority at the world scale. But this should not be a pretext to harm the reputation of colleagues and, most of all, to interfere with research carried out in related fields of considerable importance for medicine.

Competing interests: No competing interests

24 November 2021
Jean-Pierre G CHANGEUX
Emeritus professor
none
College de France and Institut Pasteur Paris France
Paris, France