It is the most influential scientific article of 2020, and the 4the most influential in history according to the Altmetric data. With over 6 million hits in five years and over 32,000 online citations in social and news media, " The proximal origins of SARS-CoV-2", often referred to simply as "Proximal Origins," has shaped the scientific debate around the origins of Covid-19 since the start of the pandemic, when it was published in the prestigious journal Nature Medicine March 17, 2020. Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a deliberately manipulated virus." he concluded categorically. The article was immediately cited on X (Twitter) by the editor-in-chief of Nature Medicine, Joao Monteiro, with this comment: “ Let's put an end to conspiracy theories about the origin of #SARSCoV2 and help stop the spread of misinformation“.
Let's put conspiracy theories about the origin of #SARSCoV2 to rest and help to stop spread of misinformation – great work from @K_G_Andersen #covid19 https://t.co/ekJNDl9Brx
— Joao Monteiro (@JMinImmunoland) March 17, 2020
A context that mixes scientific theories and conspiracy theories
At the time, it must be remembered that the lack of data and fear led to the emergence online of dangerous false information such as the deliberate use of Covid-19 as a biological weapon by the "deep state", then supported by the dissemination of the documentary "Hold Up" in November 2020, the effectiveness of hydroxychloroquine against Covid-19 or the creation of the Covid-19 virus from the HIV virus. Some even suggest that a old one of Science and Future titled "The world's most dangerous virus has been created" is evidence that the Covid-19 virus was created in a laboratory. In reality, this 2012 issue dealt with genetic modification experiments on H5N1 avian flu, which had caused controversy. However, the lab exit theory takes several forms, from the creation of a biological weapon to a handling accident during coronavirus experiments. Only the latter is considered possible, or even, according to researchers, probable, by experts in the field.
But in 2020, in this context where any theory other than natural emergence was drowned in fanciful theories, the position taken by the five experts who signed "Proximal Origins" discourages any mention of the hypothesis of the emergence of the Covid-19 virus following an accidental release from the laboratory, then equated with conspiracy theories - a confusion maintained by the National Institute of Health and Medical Research (Inserm) himself.
“ CIt was the first time in my career that I read an opinion piece sold as a science article.", reports virologist Etienne Decroly, research director at the CNRS. This article has " closed the door to debate", considers with hindsight Alexandre Hassanin, phylogeneticist (the study of kinship links between species), specialist in mammals at the Sorbonne University. Perhaps for fear of losing credibility, major journals like Nature, Science Or Cell have since published almost exclusively works mentioning only the hypothesis of the emergence of the virus by zoonosis. “ It's not easy to publish on the subject. I've always been careful in my manuscripts not to even mention the lab leak; it's frowned upon in the scientific community." regrets Alexandre Hassanin. I participated in sending a few articles that simply aimed to say that this question must be explored with the tools of modern science, but it must be recognized that their publication was quite difficult.", testifies Etienne Decroly.
The main arguments of “Proximal origins”
The text of "Proximal origins" is based mainly on three important scientific arguments regarding the analysis of the virus. First, its so-called "RBM" domain, which binds to ACE2, the gateway to the host cell, had a novel sequence and was notably very different from the SARS-CoV-1 coronavirus responsible for the 2003 epidemic. Although very effective in reality, this sequence was until then considered theoretically suboptimal, the authors point out, and would therefore not have been chosen to make a virus artificially more infectious. In addition, this sequence is found almost identically in a pangolin coronavirus, demonstrating that this sequence can emerge naturally, they argue. But for other researchers, this close proximity to this existing virus could also indicate a use in the laboratory: one of its precursors infecting bats and whose empirical effectiveness had been observed was taken as a basic model for genetic modifications, leaving the RBM sequence as is.
Second, no known virus is close enough to Covid-19 to have served as the basis for a supposed laboratory modification. However, the pace of science and the productivity of the WIV make it likely that they possess a much larger viral database than what has already been published, as we explained. in episode 2 of this series on the origins of Covid-19.
The final argument of "Proximal origins", the furin cleavage site, decrypted in a previous episode. This portion of sequence, which is new to the SARS-CoV-2 family of viruses (sarbecoviruses), has made Covid-19 highly infectious and generated much debate. Again, researchers believe this feature is compatible with natural emergence both because other sites of this type exist in other coronavirus families, but also because its detailed sequence includes an additional letter (an amino acid) never before used by researchers who have integrated a furin cleavage site: instead of RRAR, we find PRRAR. There is no reason why anyone would choose to introduce this site", concludes with Science and Future researcher Alex Crits-Christophe, who did not co-author "Proximal Origins" but other publications arguing in favor of the emergence of Covid-19 through zoonosis.
A similar sequence, PRRVR, has, however, been observed in a laboratory-modified MERS-type coronavirus. in 2017 after 30 passages (viral transmissions in the laboratory) in humanized mouse cells, according to additional data mentioned in a corner of a publication of 2024. The modified virus was particularly lethal to mice. Proline (the letter P, editor's note) did not emerge as a result of these experiments, it already existed in the MERS virus around the cleavage site", Alex Crits-Christophe corrects, however. If this sequence had been taken as a model in the laboratory, it also remains to be clarified why PRRVR would have transformed into PRRAR in SARS-CoV-2. On the other hand, random mutations during natural infections in host species – as yet unknown – do not require logic to emerge. A process that is, however, very difficult to differentiate from one obtained by successive passages in the laboratory, making this type of manipulation always compatible with the data. " It is now impossible to refute the hypothesis that someone took a virus that already had pandemic potential and then manipulated it in stages.", admits Alex Crits-Christophe. " But this is an unverifiable hypothesis for which there is no evidence.. »
Accusations of scientific misconduct
In view of the ongoing debates five years after its publication, the good faith of the signatories of "Proximal Origins" could be questioned, and even described as scientific misconduct calling for the retraction of the article by the collective of scientists and activists. Biosafety Now, very committed to opposing risky virological experiments – and in particular those that involve adding to the infectious power of the virus through genetic modifications, what is called "gain of function". The cause is the revelation of private messages between scientists, including the authors of "Proximal origins", suggesting that they still thought it plausible that the Covid-19 virus had emerged from the WIV at the time of publication of their article.
According to the history of exchanges between the authors and the journal Nature Medicine, the sentence " we do not believe that selection during passage, or any other type of laboratory scenario, is necessary (to obtain the SARS-CoV-2 sequence) » of the version of March 3, 2020 became, on March 4, “ We do not believe that any laboratory scenario is plausible. » – its final version. However, on April 17, Kristian Andersen (one of the authors) wrote about their Slack messaging channel : " The problem is, I'm still not completely convinced that any culture (in the laboratory, editor's note) is not involved". If in the rest of the conversation the scientist lets himself be convinced that the hypothesis of laboratory experiments is not the most probable, this shows that the debate was not as closed as the text published in Nature Medicine suggested. The reasons that would have pushed these researchers to harden their conclusions are not known, some private messages reporting pressure coming from "up"Whether social, political or academic, this pressure would have contributed to the publication of a text that was undoubtedly too radical in light of the available elements - although none of its signatories has since retracted their statements.
“ As is often the case with epidemics, this affair cannot be removed from its geopolitical context.", reacts Renaud Piarroux, whose field investigations narrated in "Cholera - History of a Disaster" (Editions CNRS) revealed the responsibility of the Blue Helmets in the cholera epidemic in Haiti in 2010. " A potential laboratory accident in Wuhan, contamination of a river in Haiti by UN peacekeepers, or the arrival of a ship loaded with tissues containing fleas and the plague in Marseille in 1720 are not just accidents; they are also events involving political interests.. »
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