Coronavirus is not man - made
We analyze the hypothesis of the laboratory origin of SARS-CoV-2
In early February of this year, WHO specialists who visited Wuhan said at a press conference that they exclude [1] the version about the artificial origin of the SARS-CoV-2 coronavirus. The virus probably got to us from bats through an unknown intermediate host. And yet, according to a Levada Center survey published in March, 64% of Russians said that "the coronavirus was created artificially and is a new form of biological weapons" [2] (Fig. 1).
Indeed, during the epidemic, a lot of versions about the artificial origin of the coronavirus appeared in the media. Most of them suspected the Wuhan laboratory, but there were also accusations against the United States and even the Russian "Vector". It was claimed that SARS-CoV-2 was made using HIV genome sequences, human genes, that it was a coronavirus from a scientific publication in the journal Nature – all this was discussed in detail on the pages of my blog [3-4].
But one conspiracy theory did not appear in the yellow media or in a private blog, but migrated from Habr'a [5] to the pages of the quite respectable scientific journal BioEssays [6]. In an article by Rossana Segreto and Yuri Deigin, it was said that the SARS-CoV-2 coronavirus "could be synthesized by combining a genome similar to the RaTG13 coronavirus with a receptor-binding domain of a coronavirus similar to that found in pangolins." It is curious that Yuri (the author of this hypothesis, originally posted on Habr'e) has this first scientific article.
On March 9th, the BioEssays journal published a detailed analysis of the numerous errors found in this article and an analysis of evidence in favor of the natural origin of the SARS-CoV-2 coronavirus. We did this work with Alexander Tyshkovsky, a senior researcher at the Laboratory of Systemic Biology of Aging at Lomonosov Moscow State University and Harvard Medical School.
Let's analyze the problems of the article by Segreto and Deigin point by point.
1. The RaTG13 coronavirus from bats is the closest known relative of the SARS-CoV-2 coronavirus. However, there is only 96.2% similarity at the genome level between these two viruses. From these differences, an approximate estimate of the time of divergence of these coronaviruses follows – 1948-1982 (40-70 years ago). Even cultivation in the laboratory will not help to significantly speed up this process: for example, cultivation of a related SARS-CoV virus for 30 days resulted in only 0.02% of differences at the genome level. Consequently, it would take more than 15 years to create SARS-CoV-2 from RaTG13 in such an experiment.
One could argue that there are methods to accelerate the accumulation of mutations during the evolution of viruses in the laboratory. However, such methods leave "traces": some mutations occur more often with this approach than in natural conditions. We don't see such traces on the evolutionary path leading to SARS-CoV-2. On the contrary, nucleotide substitutions occurred with the same relative frequencies as on the evolutionary path of another natural coronavirus – SARS-CoV (Fig. 2).
2. The receptor-binding domain of the coronavirus found in pangolins is also not suitable for the creation of the SARS-CoV-2 coronavirus. Segreto and Deigin write about the identity of this domain with that of SARS-CoV-2, but this is true only at the level of amino acid sequences. At the genetic level, the similarity between the RNA regions encoding these domains is only 86.6% (Fig. 3). Which means that the accumulation of these differences would also take many years. Despite the fact that the coronavirus from pangolins was discovered only in 2019.
3. Insisting that the SARS-CoV-2 coronavirus is a product of combining a coronavirus from a bat and a coronavirus from pangolins, Segreto and Deigin talk about a low probability of natural recombination, "given the low population density of pangolins and the low incidence of coronaviruses in them." For such a scenario, two coronaviruses had to get into one pangolin at the same time, which may seem unlikely. But almost all the coronavirus strains we see in pangolins are descended from bat viruses. And the current pangolin coronavirus is no exception. Therefore, even if we were talking about the recombination of two coronaviruses, it could well occur in bats, where viruses do it all the time. And after that, the resulting virus could get into the pangolin, and such a scenario no longer seems unlikely.
Finally, Segreto and Deigin do not even mention an article in the journal Nature Microbiology, in which they studied the evolution of coronaviruses and concluded that SARS-CoV-2 is probably not a product of recombination at all. Judging by the spike protein gene, the RaTG13 bat virus emerged during recombination. So if we are to talk about some kind of artificial origin of the coronavirus, then rather this. However, it was opened a few years before SARS-CoV-2, so even here conspiracy theorists will fail.
4. Another argument of Segreto and Deigin is that they discovered a section of SARS-CoV-2 RNA that can be cut by the FauI enzyme. Such enzymes are used by gene engineers, and the place for cutting is located inside the 12 nucleotide insert in the furin site, which plays an important role in the penetration of the virus into cells. It would seem that here it is – a clue hinting at an artificial origin. However, the fact is that genetic engineers know about thousands of such enzymes, and each of them learns its own nucleotide sequence. To show how easy it is to find the site of cutting of some enzyme in any interested part of the gene, we used a simple program NEBCutter. We looked at how many potential "cutting sites" can be found in the 500-nucleotide neighborhood of the site that is being cut by FauI. There were 287 such sites, 180 of them unique (examples can be seen in Fig. 4).
In other words, on average, every third nucleotide is cut by some kind of enzyme. The authors make a typical mistake of the "Texas Shooter" when they first "shoot" and then finish drawing the target. There were no a priori reasons to single out exactly the FauI site, and inside the 12-nucleotide fragment under discussion, the site of cutting some enzyme would almost certainly be found (I will omit the calculations, but the probability of this is about 99.5%).
These are not all the errors and incorrect assumptions in the article that we found, but some may be too complicated for popular presentation. It is worth noting only the objections to related conspiracy theories hinted at by Segreto and Deigin in the same article. The idea that SARS-CoV-2 is not made from the mentioned known bat or pangolin viruses, but from some unknown viruses carefully hidden in the Wuhan laboratory is not falsifiable (does not meet the Popper criterion, cannot be verified). Moreover, it loses in probability to the hypothesis of recombination of two unknown viruses in nature due to fewer additional assumptions (Occam's razor principle).
In their article, Deigin and Segreto also write that using the methods of modern synthetic biology, it would be possible to print absolutely any genome, including the SARS-CoV-2 genome, "without leaving traces." This, of course, is true, but it is not an argument, since modern methods of synthetic biology could recreate any virus, and SARS-CoV-2 does not stand out here. You might as well write an article about the laboratory origin of any of the causative agents of the common cold.
Psychologist Rob Brozerton has a wonderful book: "Distrustful Minds. What attracts us to conspiracy theories" [8], which I never tire of recommending. It contains several interesting features of human thinking, pushing to believe in unsubstantiated conspiracies.
Firstly, people tend to have a "proportionality error" – this is the expectation that big events should have big reasons. It's hard for people to believe that the president of a powerful country was killed by an ordinary person or that the closure of airports around the world happened because of some pathetic random mutation. It is curious that conspiracy theories arise around the most dangerous viruses, but I have not met, say, a theory that a secret laboratory is behind the creation of the herpes virus.
Secondly, people tend to teleological thinking – the idea that everything happens for some purpose. Previously, people animated nature, saw the wrath of spirits or gods in earthquakes, thunder or squall. Now these phenomena are clear to people, but the causes of epidemics are baffling many. And they are similarly looking for a reasonable beginning. In this, conspiracy thinking is close to creationism [9].
Thirdly, people are prone to projections – attempts to understand the thinking of other people, putting themselves in their place. In 2011, an article was published in the British Journal of Social Psychology that people who believe in conspiracy theories would be more willing to participate in a conspiracy themselves [10].
All this together gives us an information epidemic about how terrible scientists poison people with viruses, and then poison them again with vaccines in order to introduce chips to everyone and control humanity through 5G. And if effective coronavirus vaccines have already been created, the victory over conspiracy theories is still only a dream for us. But, at least, you need to strive for it, especially on the pages of scientific journals.
References:
[1] https://www.rbc.ru/society/09/02/2021/602269ca9a79476961c9fcfb
[2] https://www.levada.ru/2021/03/01/koronavirus-vaktsina-i-proishozhdenie-virusa/
[3] https://scinquisitor.livejournal.com/173753.html
[4] https://scinquisitor.livejournal.com/174949.html
[5] https://habr.com/ru/post/497956/
[6] Segreto, R., & Deigin, Y. (2021). The genetic structure of SARS‐CoV‐2 does not rule out a laboratory origin. BioEssays, 43, e2000240. https://doi.org/10.1002/bies.202000240.
[7] Tyshkovskiy, A., Panchin, AY. (2021). There is no evidence of SARS‐CoV‐2 laboratory origin: Response to Segreto and Deigin. BioEssays, https://doi.org/10.1002/bies.202000325
[8] https://evolutionfund.ru/project/1/book/3/nedoverchivye-umy-chem-nas-privlekayut-teorii-zagovorov
[9] Pascal et al. 2018. Creationism and conspiracism share a common teleological bias. Current Biology. 28. 847-870.
[10] Douglas et al. 2011. Does it take one to know one? Endorsement of conspiracy theories is influenced by personal willingness to conspire. British Journal of Social Psychology. 10 (3): 544–552
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