| 1) A letter in Nature is not an opinion piece - it's a peer reviewed short article. "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. |
> The Correspondence section provides a forum for comment on issues relevant to the journal’s community. This format may not be used for presentation of research data or analysis. A Correspondence should not exceed more than two printed pages and can range from 300-800 words; it is limited to one display item and up to 10 references. Article titles are omitted from the reference list. Correspondence may be peer-reviewed at the editors’ discretion.
Given that, I don’t think Wade’s characterization is dishonest.
It’s funny that you’re accusing Wade of not reading Andersen et al’s work, because it reads like you didn’t read his work - or even the excerpt that I posted!
For instance, take this notion that SARS-CoV-2’s spike protein doesn’t “make sense” or that “the theory is wrong” and can’t explain it. First of all, that’s not what Andersen et al actually says at any point. It really does just say:
> [while] SARS-CoV-2 may bind human ACE2 with high affinity, computational analyses predict that the interaction is not ideal and that the RBD sequence is different from those shown in SARS-CoV to be optimal for receptor binding. Thus, 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
That is to say, accusing Wade of not reading the work he’s criticizing because he doesn’t address an argument made elsewhere (where?) is unfair at best.
That said, even if Andersen et al were saying what you’re saying they did, Wade clearly accounts for this in the very excerpt I posted: he claims that GoF researchers simply don’t design proteins like this. Serial passage as a mechanism in particular doesn’t seem to require some fantasy of Chinese scientists expertly constructing some bizarro inexplicably dangerous spike protein by hand.
I can’t defend Wade’s failure to connect these dots himself, but all of the other claims in the letter are similarly addressed explicitly or implicitly. Humanized mice, discussed in the article, have immune systems; if serial passage were conducted in them it wouldn’t be surprising if it looks like an immune system were indeed involved. And on the flip side, the polybasic furin cleavage site, which Andersen et al claim as evidence that the virus must be natural is actually one of the most damning pieces of evidence for manual manipulation: it’s well understood that this could make a virus more easily infect humans, that scientists know how to artificially add them, and its particular construction in SARS-CoV-2 (as discussed by Wade in great detail) looks very artificial.
Putting that together: WIV scientists deliberately adding the furin cleavage site to some bat coronavirus, possibly (though not necessarily!) RaTG13, to help it jump species and then conducting serial passage in humanized mice is a straightforward and plausible origin story for SARS-CoV-2, in line with the sort of work we know WIV was doing, that accounts for Andersen et al’s concerns completely.