Slack / Private Message Drop — page 71

Here's the paper from Baric - not the insertion, but showing that cleavage broadens host range (https://pubmed.ncbi.nlm.nih.gov/31801868/) - which is what furin does. This is also not a new paper - I have been aware of this all along as well, so not a smoking gun, but there are several concerns here related to tissue culture [2020-06-11 15:21:34] [Kristian Andersen] I don't think the Zhou et al. paper shows that this is multiple indels - to me it just looks like a region not aligning very well? [2020-06-11 15:22:17] [Kristian Andersen] Let me spend some time on a table with things that bothers me - because there are several. [2020-06-11 15:23:20] [Eddie Holmes] That would be useful. Thanks. [2020-06-11 15:26:20] [Kristian Andersen] Yeah, let me get it all down - including the silly stuff :wink: [2020-06-11 15:42:57] [Eddie Holmes] Make sure there is a column in your table that can be used for 'possible natural explanation'. For example, I don't see why adaptation in animals/culture would then produce a virus that would need not to adapt in humans themselves. [2020-06-11 16:18:10] [Eddie Holmes] I also think that focusing on these genetic details - which are not conclusive - is in danger of missing the bigger picture: that bats (and like other wildlife) carry a huge diversity of coronaviruses some of which are closely related to SARS-CoV-2; that coronaviruses link species boundaries all the time; that 4 other CoVs have emerged in humans in the last 20 years; that furin cleavage sites are common in viruses and come and go all the time; that people have been warning about emerging CoVs for years. This is not a blue sky event. It just seems to me that we are going over the same arguments we went through in Feb. [2020-06-11 16:42:42] [Kristian Andersen] I of course agree with all of this (and still believe this is a natural virus), but the issue is that some of the new evidence certainly is peculiar - plus some additional details that have come to light, e.g., acquisition of furin site in tissue culture in bovine CoV. Nothing has changed in terms of prior risk of lab accident, but the issue is that we're dealing with the fact that WIV has been doing culturing of bat CoVs for over a decade exactly to understand what it takes for these viruses to emerge in humans (in BSL-2). We describe this in the paper and say that this work is performed "all of the world", but that isn't true - it has exclusively been going on at WIV. The EgoHealth grant was also specifically funded for this type of work (and described the kind of experiments to be done in tissue culture). This research primarily involves collecting and culturing viruses from bats in Yunnan - which is where RaTG13 is from and it seems plausible that SARS2 is also from there (no roosting bats in Wuhan in winter). A lot of the GOF work on SARS-like CoVs is also from WIV, although there are also other labs that have been doing that (e.g., Baric). None of this tells us anything new - but it means that given no data, I find both scenarios to be equally probable. Given the data we had seen at the time of our writing, I was highly skewed towards 'natural'. But with some of this new data (plus stuff I didn't know previously), I'm moving much more towards the middle (again). Suffice to say, since writing the paper I have explained to a ton of scientists (and policy makers) over and over again why this is a natural virus, and I have been pretty surprised to learn that most scientists I talk to believe there is a likely connection to the lab - people that are themselves doing GOF and culture-type of experiments, they know the