Kristian G. Andersen, Andrew Rambaut, W. Ian Lipkin, Edward C. Holmes, Robert F. Garry
2020 · Nature Medicine
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Sorry I should have been more clear. From a US federal government perspective, the fault for the sloppy science in the 2020 paper lies with the NIH and not the CDC. Will edit my comment above. https://doi.org/10.1038/s41591-020-0820-9
Fauci was relatively quick to dismiss the idea of the virus being human-modified, in a press briefing on April 17, 2020 [0]: > Q Mr. President, I wanted to ask Dr. Fauci: Could you address these suggestions or concerns that this virus was somehow manmade, possibly came out of a laboratory in China? > THE PRESIDENT: Want to go? > Q You studied this virus. What are the prospects of that? > DR. FAUCI: There was a study recently that we can make available to you, where a group of highly qualified evolutionary virologists looked at the sequences there and the sequences in bats as they evolve. And the mutations that it took to get to the point where it is now is totally…
consistent with a jump of a species from an animal to a human. (The study he refers to is "The Proximal Origin of SARS-CoV-2" [1], published March 17.) It seems that much was made of this particular remark. It doesn't rule out the idea of an unmodified virus leaked from the lab, but the widespread theories have always been aimed at the gain-of-function research occuring there. [0] https://trumpwhitehouse.archives.gov/briefings-statements/re... [1] https://doi.org/10.1038/s41591-020-0820-9
You provided no references, and you've made your claims in generally nonstandard terms. Given that, I don't think it's reasonable to criticize other users for guessing incorrectly what you meant to say. > There are studies pre SARS-CoV-2 about coronavirus in natural environments (like bat caves), and they found motifs that we found also in SARS-CoV-2. You're doing it again here, but I think you're probably referring to Andersen's Proximal Origin: https://www.nature.com/articles/s41591-020-0820-9 But nobody disputes that SARS-CoV-2 evolved mostly in bats; the question is whether its path from bats to humans included a trip through the lab. No genomic evidence can…
distinguish between a novel natural virus and a chimera of two novel natural viruses. As Davis Relman wrote: > Some [that's Andersen] have argued that a deliberate engineering scenario is unlikely because one would not have had the insight a priori to design the current pandemic virus. This argument fails to acknowledge the possibility that two or more as yet undisclosed ancestors i.e., more proximal ancestors than RaTG13 and RmYN02) had already been discovered and were being studied in a laboratory—for example, one with the SARS-CoV-2 backbone and spike protein receptor binding domain, and the other with the SARS-CoV-2 polybasic furin cleavage site. It would have been a logical next step to wonder about the properties of a recombinant virus and then create it in the laboratory https://www.pnas.org/doi/pdf/10.1073/pnas.2021133117 The WIV had the biggest collection of novel sarbecoviruses in the world.
Likely precursors have been known in both bats and pangolins since virtually the start of the pandemic (see below) and are widely found in those populations to this day; the entire catalogue of possible precursor genomes in both wild bats and pangolins is (and likely will remain) extremely undersampled (to the degree we barely see any of the current picture of the wild viral load of these animals), so your apparent expectation of them being found in anything like the population of almost entirely domesticated populations of Arabian dromedaries (MERS) and entirely domesticated commercial cattle (current H5N1 spillover risk) is quite simply ludicrous. As it’s entirely…
possible the spillover mutation was either within a single, long-eaten, animal sample or occurred in a single human post-infection there’s no reason to assume the original lineage of SARS-CoV-2 itself would ever be captured in any wild animal population. I don’t even know how to speak to the bizarre (but possibly simply badly communicated on your part) assertion that human -> animal re-transmission events either should (or even could) result in a magic cessation of circulation in humans, as that’s just nonsensical. Post human SARS-CoV-2 lineage infections still persist in animal populations (mink, for example) and likely will continue to do so essentially forever… there’s literally nothing immaculate about this entire situation. https://www.nature.com/articles/s41591-020-0820-9
I would strongly suggest not blindly trusting "peer reviewed" and "top journals", especially on topics that are not easily provable. "We conclude that despite widespread use of narcotic drugs in hospitals, the development of addiction is rare in medical patients with no history of addiction. "https://www.nejm.org/doi/10.1056/NEJM198001103020221 "Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus." https://www.nature.com/articles/s41591-020-0820-9
>Any politicised science should be treated with extreme. skepticism Proximal Origin[1] and the deliberate manufactured narrative of conflating criticism of it's blatant flaws to a conspiracy theory[2,3,4] was diabolical, I personally hope Nature's reputation is destroyed because of it. [1] https://www.nature.com/articles/s41591-020-0820-9 [2] https://theintercept.com/2023/07/12/covid-documents-house-re... [3] https://theintercept.com/2023/01/19/covid-origin-nih-emails/ [4] https://rogerpielkejr.substack.com/p/why-proximal-origins-mu...
You can read the paper in question here [1]. In cases like this where there's little to nothing in the way of experimentation or generalizations, all they're doing is assessing the evidence and offering their opinion on whatever they believe is most likely. The catch being in this case, what they said they believe is probably not what they did. [1] - https://www.nature.com/articles/s41591-020-0820-9
There is one sentence in the paper this is about (https://www.nature.com/articles/s41591-020-0820-9) that I think overstates the conclusion: > we do not believe that any type of laboratory-based scenario is plausible But the paper itself really isn't about any type of lab-based scenario, the actual content only applies to an engineered virus as in the hypotheses that this is either a bioweapon or an experiment that accidentally escaped. The hypothesis that this could be a virus collected for the lab and then accidentally released can't be addressed at all by the paper. To me this is more like clumsy writing, but I can understand if you read this as a paper overstating its…
conclusion. But it's really not something that would mislead anyone even quickly skimming the paper. The parts Nate Silver complains about look to me more like the kind of difference you'd expect between internal, informal chat and what you write in actual publications. I'd expect scientists to speculate wildly at first, then collect data and evaluate what that data actually means.
For all those criticizing the debate format as unsuitable for truth discovery, I would remind them that no form of information is immune from manipulation. Recall the highly cited The proximal origin of SARS-CoV-2. https://www.nature.com/articles/s41591-020-0820-9
> those weren't conspiracy theories but alternative explanations of the known facts supported by at least as much evidence (not much, not conclusive, but neither had the alternative) as their explanation. This just isn't true. There wasn't anywhere near as much evidence for the lab leak theory as their was for a natural origin which is why the lab leak theory was determined to be unlikely compared to other theories. Even the people who were pushing the conspiracy theory admitted to the lack of evidence. Tom Cotton, one of the first in politics to push the theory, said himself: "Now, we don’t have evidence that this disease originated there, but because of China’s…
duplicity and dishonesty from the beginning, we need to at least ask the question to see what the evidence says" (https://www.cnn.com/2020/02/18/politics/coronavirus-cotton-f...) For example there is an early article from a 'low credibility' right biased news website (https://mediabiasfactcheck.com/daily-mail/) The Daily Mail, and even they had a microbiologist explain: "at this point there's no reason to harbour suspicions' that the facility had anything to do with the outbreak, besides being responsible for the crucial genome sequencing that lets doctors diagnose it" (https://www.dailymail.co.uk/health/article-7922379/Chinas-la...) Same story with this article which was pushing the bio-weapon theory. (https://www.washingtontimes.com/news/2020/jan/26/coronavirus...). It also stated that evidence was incredibly weak without dismissing it entirely: "In principle, outward virus infiltration might take place either as leakage or as an indoor unnoticed infection of a person that normally went out of the concerned facility. This could have been the case with the Wuhan Institute of Virology, but so far there isn’t evidence or indication for such incident." Meanwhile, other theories being talked about at the time were supported by actual science such as genome analysis (https://www.nature.com/articles/s41591-020-0820-9) and note that here too they weren't totally dismissing any other theories either, only presenting the best evidence we had saying: "Although the evidence shows that SARS-CoV-2 is not a purposefully manipulated virus, it is currently impossible to prove or disprove the other theories of its origin described here...More scientific data could swing the balance of evidence to favor one hypothesis over another." > The most prominent event was probably in September 2021, when Lancet published a rebuttal to their February 2020 article flatly declaring any non-nautural-origin theories to be "conspiracy theories". The opinion piece February did not flatly declare every non-natural origin theory to be a conspiracy. What it said was "We stand together to strongly condemn conspiracy theories suggesting that COVID-19 does not have a natural origin." which is very different from saying that all theories of a non-natural origin are by definition conspiracy theories. Those same authors made that explicit in a followup article (July 21) saying: "Careful and transparent collection of scientific information is essential to understand how the virus has spread and to develop strategies to mitigate the ongoing impact of COVID-19, whether it occurred wholly within nature or might somehow have reached the community via an alternative route, and prevent future pandemics." They did not dismiss that other options were possible. They were just saying "We want evidence, not conjecture" > Can you show me an article in NYT or WaPo in the period between February 2020 and September 2021 that describes natural origin and lab leak theories as equal possibilities, each of them could yet be proven true and each of them being legitimate alternatives and areas of scientific enquiry? They weren't equally supported by the evidence, but there are certainly cases where articles on those (left-biased) sites made it clear that a lab leak was possible and that the origin of the virus was not certain. https://www.nytimes.com/2021/05/27/health/wuhan-coronavirus-... https://www.nytimes.com/2021/06/14/science/covid-lab-leak-fa... https://www.washingtonpost.com/opinions/2021/05/27/medias-de... https://www.washingtonpost.com/politics/2021/05/30/scientist...
Asserting that understanding the origins of a virus helps control its adverse impacts is completely bog-standard fare in the literature. Finding it suspicious in this case smacks of an isolated demand for rigor and unfamiliarity with the field. Even a cursory look at papers making a case for a zoonotic origin is likely to reveal statements to the same effect, here's just two for example: https://www.sciencedirect.com/science/article/pii/S009286742... >Failure to comprehensively investigate the zoonotic origin through collaborative and carefully coordinated studies would leave the world vulnerable to future pandemics arising from the same human activities that have…
repeatedly put us on a collision course with novel viruses. https://www.nature.com/articles/s41591-020-0820-9 > Detailed understanding of how an animal virus jumped species boundaries to infect humans so productively will help in the prevention of future zoonotic events. For example, if SARS-CoV-2 pre-adapted in another animal species, then there is the risk of future re-emergence events.
I think one. I can't vouch for any of the detail. (Just like almost everyone else) https://www.nature.com/articles/s41591-020-0820-9 "Furthermore, if genetic manipulation had been performed, one of the several reverse-genetic systems available for betacoronaviruses would probably have been used19. However, the genetic data irrefutably show that SARS-CoV-2 is not derived from any previously used virus backbone"
That article is reporting on the letter by Andersen et al [1] that Nicolas Wade addresses in his article in the Bulletin of the Atomic Scientists [2] that was published a few weeks back, right around the time the lab hypothesis started gaining steam; it's still probably the strongest case that's been made for it. I think it dispatches the Andersen letter quite handily, but YMMV: > A second statement that had enormous influence in shaping public attitudes was a letter (in other words an opinion piece, not a scientific article) published on 17 March 2020 in the journal Nature Medicine. Its authors were a group of virologists led by Kristian G. Andersen of the Scripps…
Research Institute. “Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus,” the five virologists declared in the second paragraph of their letter. > [...] True, some older methods of cutting and pasting viral genomes retain tell-tale signs of manipulation. But newer methods, called “no-see-um” or “seamless” approaches, leave no defining marks. Nor do other methods for manipulating viruses such as serial passage, the repeated transfer of viruses from one culture of cells to another. If a virus has been manipulated, whether with a seamless method or by serial passage, there is no way of knowing that this is the case. Andersen and his colleagues were assuring their readers of something they could not know. > [...] The two reasons the authors give for supposing manipulation to be improbable are decidedly inconclusive. > First, they say that the spike protein of SARS2 binds very well to its target, the human ACE2 receptor, but does so in a different way from that which physical calculations suggest would be the best fit. Therefore the virus must have arisen by natural selection, not manipulation. > If this argument seems hard to grasp, it’s because it’s so strained. The authors’ basic assumption, not spelt out, is that anyone trying to make a bat virus bind to human cells could do so in only one way. First they would calculate the strongest possible fit between the human ACE2 receptor and the spike protein with which the virus latches onto it. They would then design the spike protein accordingly (by selecting the right string of amino acid units that compose it). Since the SARS2 spike protein is not of this calculated best design, the Andersen paper says, therefore it can’t have been manipulated. > But this ignores the way that virologists do in fact get spike proteins to bind to chosen targets, which is not by calculation but by splicing in spike protein genes from other viruses or by serial passage. With serial passage, each time the virus’s progeny are transferred to new cell cultures or animals, the more successful are selected until one emerges that makes a really tight bind to human cells. Natural selection has done all the heavy lifting. The Andersen paper’s speculation about designing a viral spike protein through calculation has no bearing on whether or not the virus was manipulated by one of the other two methods. > The authors’ second argument against manipulation is even more contrived. Although most living things use DNA as their hereditary material, a number of viruses use RNA, DNA’s close chemical cousin. But RNA is difficult to manipulate, so researchers working on coronaviruses, which are RNA-based, will first convert the RNA genome to DNA. They manipulate the DNA version, whether by adding or altering genes, and then arrange for the manipulated DNA genome to be converted back into infectious RNA. > Only a certain number of these DNA backbones have been described in the scientific literature. Anyone manipulating the SARS2 virus “would probably” have used one of these known backbones, the Andersen group writes, and since SARS2 is not derived from any of them, therefore it was not manipulated. But the argument is conspicuously inconclusive. DNA backbones are quite easy to make, so it’s obviously possible that SARS2 was manipulated using an unpublished DNA backbone. > And that’s it. These are the two arguments made by the Andersen group in support of their declaration that the SARS2 virus was clearly not manipulated. And this conclusion, grounded in nothing but two inconclusive speculations, convinced the world’s press that SARS2 could not have escaped from a lab. [1] https://www.nature.com/articles/s41591-020-0820-9 [2] https://thebulletin.org/2021/05/the-origin-of-covid-did-peop...
https://www.nature.com/articles/s41591-020-0820-9 To the Editor — Since the first reports of novel pneumonia (COVID-19) in Wuhan, Hubei province, China, there has been considerable discussion on the origin of the causative virus, SARS-CoV-2 (also referred to as HCoV-19). Infections with SARS-CoV-2 are now widespread, and as of 11 March 2020, 121,564 cases have been confirmed in more than 110 countries, with 4,373 deaths. SARS-CoV-2 is the seventh coronavirus known to infect humans; SARS-CoV, MERS-CoV and SARS-CoV-2 can cause severe disease, whereas HKU1, NL63, OC43 and 229E are associated with mild symptoms. Here we review what can be deduced about the origin of…
SARS-CoV-2 from comparative analysis of genomic data. We offer a perspective on the notable features of the SARS-CoV-2 genome and discuss scenarios by which they could have arisen. Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus.
The third tweet demonstrates nothing. The linked Nature paper in the third tweet [0] may demonstrate why a reservoir animal is more likely than the virus being artificially engineered, but damned if I can understand the reasoning in it. Maybe someone with a biology background or just plain smarter than me can explain it better. In any case, my original point still stands, without exculpatory evidence for the Wuhan lab or the discovery of a reservoir animal, the lab leak theory should not be dismissed and any attempt to do so is just politics. [0]https://www.nature.com/articles/s41591-020-0820-9
I understand that this type of discourse is par for the course on Twitter and Facebook, but please don't track it in here. Because you asked, the expert consensus at the time was that it was highly improbable that the virus was of lab origin: https://www.nature.com/articles/s41591-020-0820-9 While you're right that laypeople in media and on twitter indulge in absolutes and sensationalism, the science seemed to be carried out appropriately. So if knocking over straw men is your thing, twitter is the more appropriate venue.
> Nobody ever dismissed it There was at least one paper calling it "natural selection", and some folks who read it agreed that it ruled out laboratory accidents: "The high-affinity binding of the SARS-CoV-2 spike protein to human ACE2 is most likely the result of natural selection on a human or human-like ACE2 that permits another optimal binding solution to arise. This is strong evidence that SARS-CoV-2 is not the product of purposeful manipulation." https://www.nature.com/articles/s41591-020-0820-9 https://twitter.com/ehundman/status/1246597925288816640 https://www.newsweek.com/claim-that-coronavirus-came-lab-chi...
This article is written by a journalist who is clearly knowledgeable about safety practices and mistakes in US labs, but does not consider the extensive knowledge we have about the sequence of SARS-COV2. The preponderance of evidence supports a natural origin of the virus. This is no way exonerates the Wuhan government from possible culpability—indeed government officials did deliberately suppress information—but this investigative opinion doesn’t pass scientific muster. Misinformation. https://www.nature.com/articles/s41591-020-0820-9
If it was lab created independent scientists would be able to figure it out and there would be evidence that it was. But it looks like there is not: https://www.nature.com/articles/s41591-020-0820-9 Now maybe the virus mutated from those initial 174 cases but that's unlikely. China does have a narrative that covid19 reinfections are coming from imported frozen foods though so I'm not sure why they are pushing that angle. It's probably an economic one and to save face. But maybe it's real.. if it is we are screwed.
I am keeping an open mind, which is why I refer to a consensus and not a fact. We have reasonable evidence that this is likely not a synthetic virus: https://www.nature.com/articles/s41591-020-0820-9 Given that, we have to think about prior probabilities: what is more likely, and requires fewer assumptions? i.e. that the virus emerged via the bountiful natural mechanisms that evolution has bestowed upon the world (and that have wrought pestilence upon humans many times), or via those channels plus a mistake in a lab in Wuhan? It seems like a key part of the theories around the Wuhan Institute of Virology is that the virus emerged in Wuhan; in fact, we do not know where…
the virus emerged in humans. There's evidence that the virus was in Italy in December 2019: https://wwwnc.cdc.gov/eid/article/27/2/20-4632_article Obviously it would be a bit of a leap to link that to the Lazzaro Spallanzani National Institute for Infectious Diseases, a BSL4 facility. It is an entirely possible theory, but it cannot and will not become the consensus view of scientists without some real evidence. The consensus view among virologists is that the virus originated in bats, where it either spread to humans directly or through an intermediate host. A painstaking effort to identify the source is underway: https://www.nature.com/articles/d41586-020-03165-9
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