Chat message

Slack / Private Message Drop, pp.489-490 [SLACK_000703] · slack_pm:msg:05106

Date: 2021-02-06 07:25
Type: chat message · slack
recipient: Kristian G. Andersen, Robert F. Garry, Edward C. Holmes
speaker: Andrew Rambaut
Topics: Natural origin / zoonotic spillover Furin cleavage site and molecular features Lab-leak / accidental release hypothesis

Recipients on this medium are inferred from channel membership, not per-message addressing.

The question is how much we want to directly enter the fray? I was quite happy with just talking about the natural origins based on the available bat and pangolin sequences but obviously that doesn't address these arguments. Ifwe want to go full on to attack these ideas I think we have:1. You can't go from RaTG13 to SARS-CoV-2 by passaging. Require the induction of 1200 mutations, about half ofwhich are reversions back to the common ancestor. Even if you did it, that would be a shit load of passages sowould be unfeasible in animals. And passaging SC2 in cells causes all sorts of stuff to happen like loss of FCS (although perhaps that is just some cells).2. You can't use modern molecular techniques to create this virus 'de novo' because you have no idea what mutations you would put in. You still need a starting virus that is almost identical to SC2 and just introduce a few things (i.e. FSC and the odd ACE2 contact residues). And you would introduce the perfect cleavage site and theoptimum RBD. So this means something almost the same as SC2 exists or existed in a lab without any publication.3. The only plausible lab origin theory (and possibly the only one that isn't a conspiracy in the event itself) is that someone collected SC2 as part of a collection of samples, was working in through them perhaps to isolate orsequence them and infected themselves (without knowing) and then transmitted (without knowing). But this is simply specific subsection of the zoonotic hypothesis - no different from bat->farmer->market worker. Given it isspecific and this would afford a single unique opportunity for the virus to jump, it is vanishingly less likely than the other types of contact humans have with animals.

Extracted statements

Rule-extracted, not adjudicated. The grade says what may be done with each one; read the document above before relying on any of them.

Statement	Grade	Attribution	Stance
I was quite happy with just talking about the natural origins based on the available bat and pangolin sequences but obviously that doesn't address these arguments.	own voice, substantive	speaker_own	asserts
And you would introduce the perfect cleavage site and theoptimum RBD.	own voice, substantive	speaker_own	asserts

Statement

Grade

Attribution

Stance

I was quite happy with just talking about the natural origins based on the available bat and pangolin sequences but obviously that doesn't address these arguments.

own voice, substantive

speaker_own

asserts

And you would introduce the perfect cleavage site and theoptimum RBD.

own voice, substantive

speaker_own

asserts

In context

A single line often inverts meaning once you see what it answers, so neighbouring messages are always shown.

2021-02-06 07:25 Andrew Rambaut

The question is how much we want to directly enter the fray? I was quite happy with just talking about the natural origins based on the available bat and pangolin sequences but obviously that doesn't address these arguments. Ifwe want to go full on to attack these ideas I think we have:1. You can't go from RaTG13 to SARS-CoV-2 by passaging. Require the induction of 1200 mutations, about half ofwhich are reversions back to the common ancestor. Even if you did it, that would be a shit load of passages sowould be unfeasible in animals. And passaging SC2 in cells causes all sorts of stuff to happen like loss of FCS (although perhaps that is just some cells).2. You can't use modern molecular techniques to create this virus 'de novo' because you have no idea what mutations you would put in. You still need a starting virus that is almost identical to SC2 and just introduce a few things (i.e. FSC and the odd ACE2 contact residues). And you would introduce the perfect cleavage site and theoptimum RBD. So this means something almost the same as SC2 exists or existed in a lab without any publication.3. The only plausible lab origin theory (and possibly the only one that isn't a conspiracy in the event itself) is that someone collected SC2 as part of a collection of samples, was working in through them perhaps to isolate orsequence them and infected themselves (without knowing) and then transmitted (without knowing). But this is simply specific subsection of the zoonotic hypothesis - no different from bat->farmer->market worker. Given it isspecific and this would afford a single unique opportunity for the virus to jump, it is vanishingly less likely than the other types of contact humans have with animals.
2021-02-06 07:28 Robert F. Garry open

Damn you are good - so well stated Andrew!
2021-02-06 07:33 Robert F. Garry open

:beer:
2021-02-06 07:40 Robert F. Garry open

For #3 I would add that Alina, Baker et al have recommended stopping all these activities, which of course is 180degrees opposite to what needs to be done. If you want to leave the world completely vulnerable to SARS3, SARS4 etc, sure stop studying sarbecovirus diversity.
2021-02-06 07:55 Andrew Rambaut open

The way to do it may be to leave them with a couple of very specific things that they need to prove if they are to turn out to be right - the major one is that a live virus, collected from the wild, that was SARS-CoV-2 or near-identical to itwas in a lab in Wuhan in November 2019. Then just let them obsess about that whilst everyone else moves on. The problem at the moment is that they say all these vague notions about passaging and engineering that seem plausible to people who don't know what is required.

Full conversation →