In that April slack conversation, the lead author expressed strong, persistent concern about a lab cultured virus that had adapted and become pandemic-ready through that process. Lab culturing = lab manipulation.
Authors have taken their names off papers for much less.
Also, in the accompanying press release from Scripps, Kristian Andersen says:
“These two features of the virus, the mutations in the RBD portion of the spike protein and its distinct backbone, rules out laboratory manipulation as a potential origin for SARS-CoV-2.”
The lead author of Proximal Origin wrote this in slack on April 17, a month after the letter had been published in Nature Medicine:
"Okay, so about the current news. Is there any reason to believe that they might be onto something, or is it all smoke and mirrors? Eddie Holmes - any insights on the China side? The main things from my perspective:
1. Bioweapon and engineered totally off the table
2. If there is no engineering and no culturing, then it means that somebody magically found a pre-formed pandemic virus, put it in the lab, and then infected themselves. The prior on that vs somebody coming into contact with an animal source infected with the virus is as close to zero as you can get. Humans come into contact all the time with SARS-like CoVs, but the likelihood of somebody finding exactly that pandemic virus and infecting themselves is very very low (make no mistake - if they did find that pandemic virus. then they would get infected if they grew it in the lab - but the likelihood of them finding it in the first place is exceedingly small (or so one would hope - otherwise, good luck World avoiding future pandemic).
3. But here's the issue - I'm still not fully convinced that no culture was involved. If culture was involved, then the prior completely changes - because this could have happened with any random SARS-llke CoV of which there are very many. So are we absolutely certain that no culture could have been involved? What concerns me here are some of the comments by Shi in the SciAm article ("I had to check the lab" etc) and the fact that the furin site 1s being messed with in vitro. Yes, it loses it but that could be context dependent. Finally, the paper that was shared with us showing a very similar phenomenon (exactly 12bp insertion) in other CoVs has me concerned...
I really really want to go out there guns swinging saying "don't be such an idiot believing these dumb theories - the president is deflecting from the real problems" but I'm warned that we can't fully disprove culture {our argument was mostly based on the presence of the O-linked glycans - but they could likely play a different role... We also can't fully rule out engineering (for basic research) - yes, no obvious signs of engineering anywhere, but that furin site could still have been inserted via gibson assembly (and clearly creating the reverse genetic system isn't hard - the Germans managed to do exactly that for SARS-CoV-2 in less than a month)."
And:
"Shi didn't do any GOF work that I'm aware of - but GOF work isn't the concern here. She did A LOT of work that involved isolating and culturing SARS-like viruses from bats (in BSL-2) and that's my main concerning scenario (we cite several of those in the paper - if you have a look at those original publications, it's definitely concerning work, no question about it - and is the main reason I have been so concerned about the 'culture' scenario)."
I don't think much more needs to be said. The above messages are self-explanatory.
Re: weakening of their claim, not only did Worobey et al. have to remove these instances of unscientific language, but they also had to insert a new study limitations section and this clarification in their article:
“However, the observation that the preponderance of early cases were linked to the Huanan market does not establish that the pandemic originated there.”
By the time the case definition requirement for a link to the market was removed (Jan 18, 2020), nearly 200 cases had been confirmed. This is not including the number of cases that were suspected/clinically diagnosed.
The 174 cases with onset in Dec 2019 considered by Worobey et al. include both confirmed cases and clinically diagnosed cases. Therefore, most, if not all, of these cases had been identified using the criteria that the patients had to either be linked to the market or, if unlinked to the market, have been identified at hospitals near the market or in the neighborhood of the market.
"In the first days of the epidemic in Wuhan, cases were identified on the basis of clinical features, including fever and acute respiratory symptoms, radiology and epidemiological features. An association with the Huanan market was identified among some of the earliest recognized cases and, for a short period until mid-January 2020, exposure to the Huanan market was included in the case definition. It rapidly became clear, however, that there were cases without a link to the Huanan market, and this element of the definition was dropped a few days after being introduced (Annex E3)."
Yes, there is much more evidence. My medium blog also cites the Chinese CDC in early 2020 and the China-WHO joint report, both of which corroborate the fact that case definitions used in Dec 2019 to mid-Jan 2020 required a link to the market or at least that the patient had to be admitted to a hospital near the market or live in the neighborhood of the market.
On the unlinked cases - if you read my medium post, it explains that even the cases with no connections to the market had been identified with ascertainment bias. Local investigators had searched hospitals and the neighborhood near the market for cases even if they had no link to the market.
On your 2nd point, I've clarified that it was not a rewording but a removal of both claims of dispositive and incontrovertible evidence from the preprint. This means that peer review flagged both of these strong assertions in the manuscript and the authors had to remove both of them.
Here is my evaluation of a recent Science Magazine publication, "The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic".
Authors have taken their names off papers for much less.