Chat message
Slack / Private Message Drop, pp.31-33 [SLACK_000245] · slack_pm:msg:00320
Page text: p.31, p.32, p.33 · original PDF
- Date
- 2020-05-22 07:26
- Type
- chat message · slack
- recipient
- Kristian G. Andersen, Robert F. Garry, Edward C. Holmes
- speaker
- Andrew Rambaut
Recipients on this medium are inferred from channel membership, not per-message addressing.
Should I reply? I am so tired of this shit.
```John Sudworth
>
Re: hello from the BBC
I received your automated reply... and of course totally understand how busy you are. But I wonder if you'd have time at least to cast your eye over this very brief set of notes (responding to a number of points in the Nature Medicine paper) that I have received from a molecular biologist contact of mine, who has long experience in vaccine development and gain of function research (his comments are in blue): (NATURE MEDICINE ARTICLE IN BLACK TYPE)In theory, it is possible that SARS-CoV-2 acquired RBD mutations (Fig. 1a) during adaptation to passage in cell culture, as has been observed in studies of SARS-CoV11. The finding of SARS-CoV-like coronaviruses from pangolins with nearly identical RBDs, however, provides a much stronger and more parsimonious explanation ofhow SARS-CoV-2 acquired these via recombination or mutation19. (COMMENTS FROM MOLECULAR BIOLOGIST IN BLUE TYPE) This has two problems in respect of the second half assumption 1. doesnt prove it didn't happen in a petri dish - themixing could have happened naturally in a co-infected pangolin that had two related coronavirus infections at the same time, or in a petri dish where two viruses were infecting the same human cells. Both equally possible, latter probably more plausible - how many co-infected pangolins are out there? But third scenario they don't touch onmight be the most plausible of all - rather than postulating random recombination between the two viruses - the third possibility is that a researcher deliberately inserted the pangolin spike mutation into bat virus to see what this did. This can be done in a matter of weeks and does not rely on chance. 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 oflow-pathogenicity avian influenza virus in vitro or in vivo17.Yes if you postulated the virus found these 4 amino substitutions one by one - I agree this is highly implausible.Pluasible scenario is that it got all 4 substitutions all at the same time - ie by recombination event between twoco-cultured viruses which can happen in days OR by researcher deliberately introducing these 4 substitutions all atthe same time which is a very simple process. It is the acquisition en masse of these 4 key new residues and nothing in flanking sequences that raises the distinct impression that someone deliberately inserted these 4 residuesin one step - with recombination would expect some variability on either side of these 4 substitutions between bat and pangolin spike sequences - there is absolutely none - all the residues on each side are identical - this is whatis so concerning. 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. The Wuhan institute is the only place in the world that has the most highly similar virus to SARS-CoV-2 which is the bat virus - so this or a related virus from bats could have been the starting point , although I agree the similarity at96% is still lower than what you might expect - something closer to 99% would be more like the smoking gun but ofcourse we don't know what other bat viruses they have in the institute that they have not have sequenced or may have chosen not to reveal (I am not suggesting this is the case). If they did indeed find a bat virus in their stocks with99% identity apart from the polybasic cleavage site then would they be comfortable to disclose this as then the only conclusion was that COVID19 was artificially created in their lab. The institute has published widely that they were doing GOF research on coronaviruses and were supported by NIHto do so. As to this specific work, if it was being done (we don't know that either way) presumably it was too preliminary to publish. Also the virus could still have been created inadvertently without their knowing in scenario 1above. 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 This is just pure speculation as we don't yet know what the immune system recognises in COVID-19 spike and what role if any the glycans play in this and how this might be different to precursor viruses (for which we have noinformation!). So where this is coming from I just don't know.My questions are these: Are any of the points he raises valid?If so, should the claims that a lab leak can be categorically ruled out be re-examined?And further, given that no lab is 100% safe, given that the Wuhan Institute has carried out GOF research on bat coronaviruses, given that it stores many others, and given that it is situated very close to the first known outbreak, ought there at least to be a proper, independent investigation of its records and procedures? If finding out where itcame from is of vital global importance, shouldn't all possibilities be considered?I should add that I have no hidden agenda. I am in Wuhan at the moment and have been covering the outbreak herein China from the beginning. My intention is simply to examine the evidence and to try to help our audiencesunderstand the scientific debate. I would welcome any thoughts and views you can provide me over email... and, iftime ever becomes available, the chance to talk on the phone would be brilliant.I appreciate your time considering this request as well as all the work you and your team are doing on this public health emergency.```