The origin of SARS-CoV-2, revisited-Quest special
Since early in the pandemic, scientists have overwhelmingly concluded that the evidence makes a natural origin for SARS-CoV-2, the coronavirus that causes COVID-19, a far more likely explanation for the pandemic than a laboratory origin. Over the last three weeks or so, however, there has been considerable chatter about the “lab leak” hypothesis, and President Biden even ordered US intelligence agencies to look into it. What, if anything, has changed? Is there new evidence?
David Gorski on May 31, 2021
If, as I have, you’ve been paying attention to these things for a number of years, you know that, whenever there is a major outbreak, epidemic, or pandemic of infectious disease, one conspiracy theory always—and I do mean always—arises. That conspiracy theory is that the causative microbe was developed in a laboratory and/or escaped a laboratory. HIV, H1N1, the original SARS, Ebola virus, every single one of them gave birth to such conspiracy theories. Unsurprisingly, given its global scope and death toll, so it was with SARS-CoV-2, the coronavirus that causes COVID-19.
Even as far back as February 2020, I noted that antivaxxer James Lyons-Weiler was falsely claiming that he had “broken the coronavirus code” and found nucleotide sequences in its genome indicating that it had come from a laboratory working on coronavirus vaccines, while Nobel Laureate turned crackpot Luc Montagnier also endorsed the “engineered virus” idea. For someone who is supposedly an expert in bioinformatics, his analysis was risibly bad. Then came the “plandemic” conspiracy theory, in which antivaxxer and disgraced scientist Judy Mikovits claimed that SARS-CoV-2 was not only engineered but intentionally released. As we discussed at the time, the nucleotide sequence of isolates of SARS-CoV-2 analyzed early in the pandemic showed no evidence of “engineering,” no telltale signs of having been synthesized or modified in a laboratory, and a more recent WHO report similarly concludes that the likelihood of a laboratory origin for the virus compared to the odds of a natural origin is very low.
The “lab leak” hypothesis is resurrected
The idea that SARS-CoV-2 originated in a laboratory has continued to bubble under the surface of discussions of the pandemic but wasn’t really a major discussion point for a number of months—that is, until recently. Last week, for example, President Biden instructed US intelligence agencies to “redouble” their efforts to “collect and analyze information that could bring us closer to a definitive conclusion” regarding the origin of SARS-CoV-2. Before that, journalist Nicholas Wade published an article in the Bulletin of the Atomic Scientists (who knows why it was published there instead of in a virology or molecular biology journal) arguing that the virus originated in so-called “gain-of-function” experiments and was accidentally released.
This followed a letter published in Science by a number of scientists advocating investigating the origins of the coronavirus and saying that we “must take hypotheses about both natural and laboratory spillovers seriously until we have sufficient data”. The authors were apparently unhappy with a joint Chinese and World Health Organization (WHO) investigation published in March that concluded that an animal origin for SARS-CoV-2 was far more likely than a lab leak, as Steve Novella discussed at the time. Personally, I was unhappy at how unconcerned at least one of the signatories was over how their letter had been used by conspiracy theorists as support for their ideas.
“No actually,” Fauci, director of the National Institute of Allergies and Infectious Diseases (NIAID) said, around 12 minutes into footage of the event, which was held earlier this month but overlooked by most media outlets. “I am not convinced about that, I think we should continue to investigate what went on in China until we continue to find out to the best of our ability what happened.”
“Certainly, the people who investigated it say it likely was the emergence from an animal reservoir that then infected individuals, but it could have been something else, and we need to find that out. So, you know, that’s the reason why I said I’m perfectly in favor of any investigation that looks into the origin of the virus,” he continued.
“Will you in front of this group categorically say that the COVID-19 virus could not have occurred by serial passage in a laboratory?” Sen. Rand Paul had asked Fauci during a Senate hearing last Tuesday.
Fauci did not explicitly rule out such a possibility: “I do not have any accounting of what the Chinese may have done, and I’m fully in favor of any further investigation of what went on in China,” he said. “However, I will repeat again, the NIH and NIAID categorically has not funded gain of function research to be conducted in the Wuhan Institute of Virology.”
Meanwhile, a week ago The Wall Street Journal published a story titled “Intelligence on Sick Staff at Wuhan Lab Fuels Debate on Covid-19 Origin” (there’s no evidence presented that they were sick with COVID-19), while the Washington Post published an analysis titled “Timeline: How the Wuhan lab-leak theory suddenly became credible“. To be honest, the latter story simply told me how the conspiracy theory that SARS-CoV-2 had a laboratory origin had arisen even earlier than I thought it had, all without providing any new data that would lead me to view the “lab leak” hypothesis for SARS-CoV-2 origin as more likely than a natural origin. Moreover, the first article basically doesn’t provide such evidence either, given that US intelligence officials are still not certain what the researchers actually had and Director of National Intelligence Avril Haines told Congress last month that “the intelligence community does not know exactly where, when, or how Covid-19 virus was transmitted initially”.
These developments led me to start to wonder if there was anything in the evidence base that had led most scientists to conclude that the most likely origin of SARS-CoV-2 was natural. Meanwhile, there seems to be a lot of Twitter activity of this sort: https://platform.twitter.com/embed/Tweet.html?creatorScreenName=sciencebasedmed&dnt=false&embedId=twitter-widget-0&features=eyJ0ZndfZXhwZXJpbWVudHNfY29va2llX2V4cGlyYXRpb24iOnsiYnVja2V0IjoxMjA5NjAwLCJ2ZXJzaW9uIjpudWxsfSwidGZ3X2hvcml6b25fdHdlZXRfZW1iZWRfOTU1NSI6eyJidWNrZXQiOiJodGUiLCJ2ZXJzaW9uIjpudWxsfSwidGZ3X3R3ZWV0X2VtYmVkX2NsaWNrYWJpbGl0eV8xMjEwMiI6eyJidWNrZXQiOiJjb250cm9sIiwidmVyc2lvbiI6bnVsbH19&frame=false&hideCard=false&hideThread=false&id=1397931594200059904&lang=en&origin=https%3A%2F%2Fsciencebasedmedicine.org%2Fthe-origin-of-sars-cov-2-revisited%2F&partner=tfwp&sessionId=840b58e73fd7fe2b4a8a58e59c8613c4684946fa&siteScreenName=sciencebasedmed&theme=light&widgetsVersion=82e1070%3A1619632193066&width=550px
We here at SBM are big fans of Bayes’ theorem, and as a big fan of Bayesian analysis, let me just say that Mr. Gordon demonstrates an epic misunderstanding of Bayes’ theorem. Personally, I like this response: https://platform.twitter.com/embed/Tweet.html?creatorScreenName=sciencebasedmed&dnt=false&embedId=twitter-widget-1&features=eyJ0ZndfZXhwZXJpbWVudHNfY29va2llX2V4cGlyYXRpb24iOnsiYnVja2V0IjoxMjA5NjAwLCJ2ZXJzaW9uIjpudWxsfSwidGZ3X2hvcml6b25fdHdlZXRfZW1iZWRfOTU1NSI6eyJidWNrZXQiOiJodGUiLCJ2ZXJzaW9uIjpudWxsfSwidGZ3X3R3ZWV0X2VtYmVkX2NsaWNrYWJpbGl0eV8xMjEwMiI6eyJidWNrZXQiOiJjb250cm9sIiwidmVyc2lvbiI6bnVsbH19&frame=false&hideCard=false&hideThread=false&id=1397882683133464578&lang=en&origin=https%3A%2F%2Fsciencebasedmedicine.org%2Fthe-origin-of-sars-cov-2-revisited%2F&partner=tfwp&sessionId=840b58e73fd7fe2b4a8a58e59c8613c4684946fa&siteScreenName=sciencebasedmed&theme=light&widgetsVersion=82e1070%3A1619632193066&width=550px
See? Bayes theorem can cut both ways with respect to estimating prior probabilities. As many have pointed out, when a virus makes the jump from animals to humans, it often takes years to figure out the origin. As Dan Samorodnitsky points out:
So, figuring out where this particular virus came from will be a challenge. It can take years, decades, or more to find the source of a virus. Ebola, for instance, was identified in 1976, has caused multiple epidemics, and we still don’t really know what animal it spilled over from. To confirm beyond a reasonable doubt the virus’s origins, we’d have to sample wild animals and sequence the viruses they carry to find a close genetic relative, an astronomical task, haystacks within haystacks. In the absence of a smoking gun, there’s still good research that points in one direction. Take the phylogenetic analysis in preprint this week that, once again, suggests bats as a reservoir for SARS-CoV-2, with pangolins or civets as possible intermediate steps.
In other words, it’s only been less than a year and a half since the virus was identified and sequenced. Just because scientists haven’t yet found “smoking gun” evidence for what specific animal coronavirus made the jump to humans as SARS-CoV-2 (and where) does not make a lab origin more likely. It just doesn’t. The argument is just plain silly, and the vacuous invocation of Bayes’ theorem makes my brain hurt.
Bad logic and math aside, I’ve noticed that the lab leak hypothesis has definitely—shall we say?—evolved during the last year. Given the utter lack of evidence in the nucleotide sequences of SARS-CoV-2 for an “engineered” origin, the “respectable” people now claiming that the coronavirus came from a lab hasten to deny that they think it was “engineered” or a “bioweapon.” Basically, there are now two main versions of the “lab leak” hypothesis:
- An engineered SARS coronavirus created at the Wuhan Institute of Virology through “gain of function” experiments somehow escaped and caused the pandemic.
- A natural SARS coronavirus stored and studied at the Wuhan Institute of Virology somehow escaped and caused the pandemic.
I can say with a high degree of confidence based on existing evidence that the first version is so implausible as to have drifted well into conspiracy theory territory. The second is the version that “reasonable” people consider plausible, but there is no good evidence for either version. In any event, given how much these hypotheses have been discussed in the news as though there were some new evidence that now makes the “lab leak” hypothesis more likely (spoiler alert: there isn’t) and assaulted me on social media, coming from conspiracy theorists and non-conspiracy theorists, I just had to look into this issue again. Let’s look at each version of the hypothesis. I’ll start with the much less plausible version and then examine the more plausible “variant” (if you’ll excuse the term).
Version 1: The virus was engineered and escaped.
An excellent entry point to the claim that SARS-CoV-2 was engineered and then somehow accidentally released into the wild, thus causing the COVID-19 pandemic, is a news story in The Daily Mail that I saw on Saturday, because it contains a couple of major themes that I’ve found used by many to argue for a lab origin for the virus, as well as the dubious scientific arguments. The story touts an as-yet unpublished paper by British Professor Angus Dalgleish and Norwegian scientist Dr. Birger Sørensen, described in the story as being “set to be published in the Quarterly Review of Biophysics Discovery.” In typical Daily Mail fashion, the headline is basically a conspiracy theory:
he rationale in the paper, judging from the excerpts and statements by Dalgleish and Sørensen, rests on an appeal to incredulity, specifically disbelief that SARS-CoV-2 could have arisen from a natural source. Such arguments are perhaps the most common arguments for a “lab leak” that I’ve seen, usually accompanied with incorrect reasons why such an origin is “impossible.” This article is no different in that general form.
When I first read the article, I had never heard of these scientists before and had no idea who they were; so I did a bit of Googling. Unfortunately, a lot of what came up first in the search results were links to the Daily Mail story and others reprinting the story, but I did learn that Dr. Dalgleish is an oncologist at St. George’s, University of London and ran for Parliament as a member of the UK Independence Party during the 2015 United Kingdom general election, finishing fourth. He is also a Fellow of the Academy of Medical Sciences, the Royal College of Physicians, the Royal College of Pathologists, and the Royal Australasian College of Physicians. He’s famous for having been the co-discoverer of the CD4 receptor as the major cellular receptor for HIV. Sørensen is the chair of a pharmaceutical company, Immunor, which developed a coronavirus vaccine candidate called Biovacc-19.
Normally I don’t blog about unpublished papers, preferring to wait for the whole paper to be published, but The Daily Mail not only published the abstract, but several tables and figures from the unpublished paper. That’s really, really unusual. Most journals would not be in the least bit pleased to see a newspaper do that. The story states that the article was “exclusively obtained by DailyMail.com and slated for publication in the coming days.” Given the apparently enthusiastic participation of Dalgleish and Sørensen in interviews for the news story, it’s very hard to imagine how The Daily Mail might have gotten a copy of the paper from any other source besides the authors, although one of the three authors of the manuscript, Andres Susrud, posted an earlier version of the paper, which was not accepted: https://platform.twitter.com/embed/Tweet.html?creatorScreenName=sciencebasedmed&dnt=false&embedId=twitter-widget-2&features=eyJ0ZndfZXhwZXJpbWVudHNfY29va2llX2V4cGlyYXRpb24iOnsiYnVja2V0IjoxMjA5NjAwLCJ2ZXJzaW9uIjpudWxsfSwidGZ3X2hvcml6b25fdHdlZXRfZW1iZWRfOTU1NSI6eyJidWNrZXQiOiJodGUiLCJ2ZXJzaW9uIjpudWxsfSwidGZ3X3R3ZWV0X2VtYmVkX2NsaWNrYWJpbGl0eV8xMjEwMiI6eyJidWNrZXQiOiJjb250cm9sIiwidmVyc2lvbiI6bnVsbH19&frame=false&hideCard=false&hideThread=false&id=1398537970903392257&lang=en&origin=https%3A%2F%2Fsciencebasedmedicine.org%2Fthe-origin-of-sars-cov-2-revisited%2F&partner=tfwp&sessionId=840b58e73fd7fe2b4a8a58e59c8613c4684946fa&siteScreenName=sciencebasedmed&theme=light&widgetsVersion=82e1070%3A1619632193066&width=550px https://platform.twitter.com/embed/Tweet.html?creatorScreenName=sciencebasedmed&dnt=false&embedId=twitter-widget-3&features=eyJ0ZndfZXhwZXJpbWVudHNfY29va2llX2V4cGlyYXRpb24iOnsiYnVja2V0IjoxMjA5NjAwLCJ2ZXJzaW9uIjpudWxsfSwidGZ3X2hvcml6b25fdHdlZXRfZW1iZWRfOTU1NSI6eyJidWNrZXQiOiJodGUiLCJ2ZXJzaW9uIjpudWxsfSwidGZ3X3R3ZWV0X2VtYmVkX2NsaWNrYWJpbGl0eV8xMjEwMiI6eyJidWNrZXQiOiJjb250cm9sIiwidmVyc2lvbiI6bnVsbH19&frame=false&hideCard=false&hideThread=false&id=1398538314630717443&lang=en&origin=https%3A%2F%2Fsciencebasedmedicine.org%2Fthe-origin-of-sars-cov-2-revisited%2F&partner=tfwp&sessionId=840b58e73fd7fe2b4a8a58e59c8613c4684946fa&siteScreenName=sciencebasedmed&theme=light&widgetsVersion=82e1070%3A1619632193066&width=550px
There’s another huge red flag about this study and that’s the journal in which it was published, which was not in a molecular biology, biochemistry, or virology journal, but rather a biophysics journal. That’s not the first place I’d choose to publish an article of this sort, although QRB Discovery does describe itself as publishing “physical observations of relevance to biological systems, both experimental and theoretical, that may point towards an exciting direction, rather than the presentation of a traditional comprehensive study”, which might explain why Dalgleish and Sørensen decided to publish there instead of a more appropriate journal. Then there’s this excerpt of the story:
They said they tried to publish their findings but were rejected by major scientific journals which were at the time resolute that the virus jumped naturally from bats or other animals to humans.
So basically the authors went shopping until they found a journal that would accept their manuscript. There’s nothing inherently wrong with that. (Pretty much every scientist, myself included, has submitted a manuscript to a different journal after rejection by another journal, and many of us have had the unpleasant experience of having to submit to three or more journals before we could get an article published.) However, it does raise eyebrows when an article like this ends up in a journal that doesn’t seem appropriate for the material. Just look at the sorts of articles in the latest issue. They’re all pretty heavily weighted towards fairly hard core biophysical studies, rather than sequence analysis. Moreover, contrary to how it’s being described, as a “study,” in reality it’s more of a review article, with no new research published, at least as far as I can tell.
Now, let’s look at the Abstract and Conclusion sections, helpfully provided by the Daily Mail. Here’s the abstract:
Here’s the conclusion:
I can’t help but note the rather strange wording of the abstract, namely the authors’ claim that their analysis is so compelling that it “reverses the burden of proof” for those who consider a laboratory origin of the virus highly unlikely and a natural origin much more so. Be that as it may, before I discuss the article and the figures, I have to point out yet another red flag that I discovered in the Daily Mail article. It was such a big one that it literally deserves a facepalm. Here’s the excerpt from the article:
One tell-tale sign of alleged manipulation the two men highlighted was a row o
four amino acids they found on the SARS-Cov-2 spike.
In an exclusive interview with DailyMail.com, Sørensen said the amino acids all have a positive charge, which cause the virus to tightly cling to the negatively charged parts of human cells like a magnet, and so become more infectious.
But because, like magnets, the positively charged amino acids repel each other, it is rare to find even three in a row in naturally occurring organisms, while four in a row is ‘extremely unlikely,’ the scientist said.
‘The laws of physics mean that you cannot have four positively charged amino acids in a row. The only way you can get this is if you artificially manufacture it,’ Dalgleish told DailyMail.com.
Their new paper says these features of SARS-Cov-2 are ‘unique fingerprints’ which are ‘indicative of purposive manipulation’, and that ‘the likelihood of it being the result of natural processes is very small.’
And here’s the facepalm, much deserved:here’s really only one word to describe this claim: Bullshit. I’m sorry if anyone is offended by mild profanity, but that really is the only word to describe the claim above, and scientists were quick to call it out as such on social media, with examples:
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