| 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... |
"Letter
A Letter reports an important novel research result, but is less substantial than an Article. Letters typically occupy four printed journal pages. This format begins with an introductory paragraph (not abstract) of 150 words maximum, summarizing the background, rationale, main results and implications. This paragraph should be referenced, as in Nature style, and should be considered part of the main text, so that any subsequent introductory material avoids too much repetition of the introductory paragraph. The text is limited to 2000 words, excluding the introductory paragraph, Methods, references and figure legends. As a guideline, Letters allow up to 30 references. Letters should have no more than 3–5 display items (figures and/or tables). A Methods section is published online-only, immediately following the main text and figures. It should be written in such detail that experiments can be reproduced by others.
Letters include received/accepted dates and may be accompanied by supplementary information. Letters are peer reviewed."
https://www.nature.com/nmat/about/content
It doesn't take long to discover the above - so why did Wade fail to do the work to check what it was he was attacking?
2) "Since the SARS2 spike protein is not of this calculated best design, the Andersen paper says, therefore it can’t have been manipulated." What I read was that the SARS2 protein doesn't work in theory, because the theory is wrong (a bad approximation that is subject to intensive research world wide - protein dynamics are a big step beyond the art of protein structure prediction as I understand it.) It would be irrational for a team to attempt to build a SARS2 binding protein - essentially they would be shooting into the dark. The space of random search for this kind of structure isn't just huge - it's incomprehensible, consequently the chance of coming upon the SARS2 protein by chance is vanishingly small. If Chinese scientists did have the capability to do dynamic bindings calculations that would have found the SARS2 spike I would think that they would be employing them for a number of decisive military innovations - as well as staggering commercial gain. We know that the Russians capabilities to do hypersonic flow calculations because we see this in their torpedoes and ICBM's.... we would see similar evidence in China for this. We don't.
3) "With serial passage, each time the virus’s progeny are transferred to new cell cultures or animals" but this is addressed Anderson et-al; in an entire section of their article : "The acquisition of both the polybasic cleavage site and predicted O-linked glycans also argues against culture-based scenarios. New polybasic cleavage sites have been observed only after prolonged passage of low-pathogenicity avian influenza virus in vitro or in vivo17. Furthermore, a hypothetical generation of SARS-CoV-2 by cell culture or animal passage would have required prior isolation of a progenitor virus with very high genetic similarity, which has not been described. Subsequent generation of a polybasic cleavage site would have then required repeated passage in cell culture or animals with ACE2 receptors similar to those of humans, but such work has also not previously been described. Finally, the generation of the predicted O-linked glycans is also unlikely to have occurred due to cell-culture passage, as such features suggest the involvement of an immune system18."
Now - I count three arguments in that section of the article alone. Two of them are flatly ignored by Wade. It's almost as if he hasn't actually read Andersen's work.