A single line often inverts meaning once you see what it
answers, so neighbouring messages are always shown.
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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 toSARS-CoV-2; that coronaviruses link species boundaries all the time; that 4 other CoVs have emerged in humans inthe 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.
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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 intissue 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 toemerge 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 involvescollecting 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 alikely connection to the lab - people that are themselves doing GOF and culture-type of experiments, they know the risks and don't seem to think that a natural explanation is more likely than lab culture.
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Fair points. But that work isn't exclusively done at the WIV because as you say yourself the Baric lab are doing it. Istill don't quite see what the new data is. The bovine stuff? What else is there? To me, there is more evidence against lab escape than when we wrote the paper. I think the bats not roosting in winter argument is nothing because I reckon it went through an intermediate host anyway. Do you have a copy of the EgoHealth grant?
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Aim3: https://projectreporter.nih.gov/project_info_description.cfm?aid=9819304&icde=50404048&ddpara m=&ddvalue=&ddsub=&cr=1&csb=FY&cs=DESC&pball=
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2020-06-11 17:11
Kristian G. Andersen
> But that work isn't exclusively done at the WIV because as you say yourself the Baric lab are doing it No, that work _is_ exclusively at WIV AFAIK. Baric's lab is doing (did) gain of function research where they created reverse genetics systems to study the viruses. All of this is done in BSL-3, so much (much!) less risk of exposure. The work in Shi's lab is different - here they are taking bat CoVs and culturing them under BSL-2 in cell lines from different animals - to e.g., understand which ones can infect human cells and what type of mutations that occur inT/C may make them permissive. They probably have more than 10 papers where they describe that type of work onall kinds of SARS-like CoVs.
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Got it, thanks. That helps.
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Have the Shi lab published all the viruses they use in these culture experiments? Do they find the same mutations that appear in SARS-CoV-2?
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In our paper we argue against (a) manipulation and (b) tissue culture. Our main arguments were that manipulation ishard, but the German's came out and created a reverse genetics system of SARS2 in less than two weeks, soclearly it's not that hard. Our arguments against tissue culture mostly came down to the O-linked glycans and a'mucin-like' domain. But by now it seems clear that these don't actually form a mucin-like domain, but rather those glycans modulate the function of the furin site. All our arguments about natural viruses emerging, the RBD identicalin pangolin CoVs, etc., all still stand. The main new things that bothers me the most:1. Lack of selection (a lot of the selection is for replication in a particular host species, so yes, I would assume culture would lover selection during subsequent transmission in humans - however, immune selection will still occur).2. Gain of furin cleavage of bovine CoV in tissue culture.3. Loss of furin site in tissue culture meaning it's active.4. The little details about the furin site - e.g., that it's exactly in the spot where experiments had previously inserted it,the fact that the exact sequence exist in a cat CoV, Shi herself being sketchy with details and considering lab accident, etc. But all of this can go both ways
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Unclear to me if they published sequences of all these viruses - it's a lot and names are changing over time (e.g.,RaTG13 had a different name previously).