zlacker

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1. trevel+(OP)[view] [source] 2021-04-10 10:43:18
Everyone knows that mutations that increase transmissability generally hurt morbidity. Is there some reason you think this supports zoonotic hypothesis? It is public knowledge RaTG13 was collected from a mine shaft where a similar virus killed 50% of infected workers and where WIV was doing significant sampling work.

https://www.frontiersin.org/articles/10.3389/fpubh.2020.5815...

Your comments on mutation rates confirm that RaTG13 is not closely related to COV (we knew that) and imply we should expect to find a closer relative. Yet we haven't. And the paper you share argues (again) against your conclusions by pointing out that neither Yunnan nor Wuhan are expected hotspots for missing zoonoses to emerge. We've also now spent more than a year hunting there and elsewhere in SEAsia and haven't discovered anything remotely related. But China won't let anyone look at or sample Tongguan mineshaft.

Your comments on the State Department factsheet don't say anything except express a vague chummy solidarity that would lead a reasonable person to believe that SOMEONE in your group of international scientists should be able to confirm or deny allegations the WIV was in fact shutdown for a week in September. If no-one cannot confirm or deny this direct and very specific allegation how can anyone take seriously your claim that international civilian researchers would have any clue who was doing what kind of research in the facility or with its materials elsewhere? And if your mouse answer is correct surely it should take significantly longer than 4 months to bootstrap a program that can do practical experiments on mice with human ACE2 receptors, if only because IVF is hardly the start of the process.

None of these things support your argument. They just raise further questions that you seem to have zero interest in flagging or asking, despite having a very keen interest in the conclusions that you want people to draw. Science does not work that way.

replies(3): >>jedueh+U4 >>jedueh+e5 >>jedueh+17
2. jedueh+U4[view] [source] 2021-04-10 11:49:49
>>trevel+(OP)
>Your comments on mutation rates confirm that RaTG13 is not closely related to COV (we knew that) and imply we should expect to find a closer relative. Yet we haven't. And the paper you share argues (again) against your conclusions by pointing out that neither Yunnan nor Wuhan are expected hotspots for missing zoonoses to emerge

It's really funny you mention that because when I presented this paper in my departmental journal club, that was the #1 criticism levied. This model over-enriches for South America and under-enriches for East Asia.

Mostly it has to do with (in my opinion) their under-reliance on host-specificity and over-reliance on overall biological diversity. The Pacific Northwest is a hotbed of ecological and biological diversity in rodents among other things, but we haven't had any major outbreaks out of that area yet (knock on wood).

Papers can be wrong or whatever. Or underappreciate things. Lots of other scientists think there's a massive underappreciated reservoir of bat-related viruses in Asia. Peter Daszak is the obvious one, but also Heinz Feldmann, Christian Drosten, Peter Daniels, basically anyone who has ever studied bat viruses or influenza viruses believes there's a lot left undiscovered in Asia. That's also why several of the most recent hemorrhagic fever virus meetings from Keystone was in Hong Kong. SARS-1 is a big memory there, and not a very long ago one.

>SOMEONE in your group of international scientists should be able to confirm or deny allegations the WIV was in fact shutdown for a week in September. If no-one cannot confirm or deny this direct and very specific allegation how can anyone take seriously your claim that international civilian researchers would have any clue who was doing what kind of research in the facility or with its materials elsewhere?

My BSL3/4 was shut down all the time. For maintenance or whatever. They're facilities that go down for maintenance often because of how important it is to make them safe. Anytime an autoclave broke, or a fan broke, you had to take it down because it no longer met the biosafety standards set forth in the protocols.

I personally have no idea if it was shut down for a week in September, that's a very specific thing. Do you know exactly when a company in your line of work started doing work from home? Or when it was shut down for an internet outage? etc. etc. That's a very specific thing.

Sure I could ask around and probably figure that out. But I also don't want to, because I'm not interested in fueling your conspiracy theory when I have no idea what relevance that would have to the likelihood of a lab leak. Given how often these facilities shut down. They do it yearly as a rule, and often 4-5 times per year due to other maintenance reasons. And yes that includes brand new facilities. I cannot tell you how many times people at the BSL4 in Montana here in the US told me about facility shutdowns as reasons they couldn't conduct my experiments! It delayed my PhD a bit!

IVF is actually ALMOST the start of the process since we already had the ACE2 gene sequence. I suppose you would have to clone it and that might take a month. So altogether probably 3-4 months. Especially since it was TOP priority, like drop everything else and do this.

I'll give you an example. In my work, we had to clone Stat1 and Stat2 knockout mice, these are a model for Zika and for testing ebola vaccines and creating anti-Ebola antibodies, I published a paper all about it you can look it up in my gscholar linked elsewhere here.

Anyway, to go from idea to first generation of mouse (I didn't actually do the work, just watched someone else do it this was really early in my PhD)... it took about 6 months. And that's with a zillion other things on our plates. If it was the ONLY thing we were doing? Yeah it probably could have been done in 4 months. Probably 3 if you gave us unlimited funding and perfect facilities.

Science doesn't work the way you want it to work either, btw. It's not about wild hypotheses and conspiracies about people hiding stuff from the public. It's not about supposition and theoretical thought experiments. We rely on concrete data to make very small conclusions based on probability, and then test them.

Unfortunately, this really isn't a testable hypothesis either way. That's why the occam's razor factor matters so much here. It really is a probabilistic argument.

I never said it was impossible that this was a lab leak, only really unlikely.

replies(2): >>jedueh+Uc >>trevel+RS2
3. jedueh+e5[view] [source] 2021-04-10 11:53:42
>>trevel+(OP)
Also, btw, month at the LONGEST for that ACE2 cloning. An experienced cloner using In-Fusion could probably do it in like a week. Or two weeks.
4. jedueh+17[view] [source] 2021-04-10 12:13:29
>>trevel+(OP)
>Everyone knows that mutations that increase transmissability generally hurt morbidity. Is there some reason you think this supports zoonotic hypothesis? It is public knowledge RaTG13 was collected from a mine shaft where a similar virus killed 50% of infected workers and where WIV was doing significant sampling work.

Why would this support either hypothesis? The cleavage site clearly has nothing to do with RATG-13 and it is probably one of the main drivers of SARS-CoV-2 pathogenesis. See here:

-https://www.nature.com/articles/s41586-021-03237-4

-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457603/

But before you say "See! Gotcha! That means that the cleavage site is the smoking gun!"

It also looks, from a molecular perspective, like a natural recombination event. See here:

-https://www.frontiersin.org/articles/10.3389/fgene.2020.0078...

replies(1): >>trevel+qO2
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5. jedueh+Uc[view] [source] [discussion] 2021-04-10 13:20:47
>>jedueh+U4
And you also don't have to take my word for it re: China's problem with zoonotic transmission. Here are scientific review articles that demonstrate that consensus:

https://pubmed.ncbi.nlm.nih.gov/26654122/

https://pubmed.ncbi.nlm.nih.gov/30806904/

https://pubmed.ncbi.nlm.nih.gov/16940861/ (this one says wet markets, which probably are an issue, but not as big as initially thought, and probably not the origin of CoV-2)

https://pubmed.ncbi.nlm.nih.gov/27726088/

https://pubmed.ncbi.nlm.nih.gov/27426214/

https://pubmed.ncbi.nlm.nih.gov/30832341/

https://pubmed.ncbi.nlm.nih.gov/19906932/

replies(1): >>trevel+ZW2
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6. trevel+qO2[view] [source] [discussion] 2021-04-11 16:06:32
>>jedueh+17
> Why would this support either hypothesis?

So why did you bring it up? The observation doesn't support zoonotic hypothesis at all, although it could support lab leak if we assume GOF was done on a natural or modified virus with a higher IFR rate, such as the ones known to be present in Tongguan where WIV sampled RaTG13.

Similarly -- it isn't clear why you are talking about the cleavage site. You appear to think it argues against some sort of hypothesis. But you haven't stated what you think the most credible lab-leak scenario is and why. It isn't even clear that COV came from RaTG13.

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7. trevel+RS2[view] [source] [discussion] 2021-04-11 16:36:14
>>jedueh+U4
> I personally have no idea if it was shut down for a week in September, that's a very specific thing. Do you know exactly when a company in your line of work started doing work from home?

I'm quite familiar with my own industry and could easily fact-check claims of this specificity or follow-up with people who would know. If I could not do this, I would not be making appeals to authority in public.

> Sure I could ask around and probably figure that out. But I also don't want to, because I'm not interested in fueling your conspiracy theory when I have no idea what relevance that would have to the likelihood of a lab leak.

Conspiracy theory? This is a claim by the US Government. And you're clearly interested in "debunking" it given the amount you have written on the topic and your holding proactive AMAs. So - yeah - this leaves anyone reading your comments wondering (1) why you are rebutting strawmen arguments, (2) why you don't appear familiar with the facts [i.e. pushed the wet market hypothesis long after we knew it wasn't the origin], and (3) why you still aren't addressing basic, specific and addressable claims from sources with assumed credibility who take a different position.

> Science doesn't work the way you want it to work

The sad thing is that it does. You figure out what the most viable hypotheses are and then evaluate the evidence. Update your priors based on what you find and repeat the process. That's how you end up being able to make statements about Occam's Razor. Quite different from building strawmen, knocking them down and calling anyone who asks questions you a conspiracy theorist.

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8. trevel+ZW2[view] [source] [discussion] 2021-04-11 17:12:37
>>jedueh+Uc
I don't see the point. We know that zoonotic transmission and natural origin is possible. The question is about how likely it is to be the origin of COV. No-one who has been to Wuhan would expect zoonotic transfer. And certainly not of aersolized bat coronaviruses.

afaict the strongest evidence against lab-origin is the claim that COV was circulating in Italy in early autumn 2019, although I've read lately that the tests claiming this are now apparently suspect. go figure.

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