zlacker

[parent] [thread] 11 comments
1. jedueh+(OP)[view] [source] 2021-04-09 23:27:19
Hi, I actually wrote a direct response to this idea in my original post.

https://drive.google.com/file/d/1vRbACWf90iBC35xNOwlI5bWcUq0... (Footnote 1)

Also, you can literally look around on this exact post and find people who believe that this virus was cooked up in a lab. There were also a lot of people on my original post who believed that.

As is often the case: never underestimate the intellectual overconfidence of people with little knowledge of the subject matter.

To draw a very clear distinction in the sand, I never said we can be 100% certain that this virus didn't originate in a lab. It's just really really unlikely. And there isn't any real evidence to support it. /Maybe/ some circumstantial evidence in the geographic proximity. But even that is probably irrelevant if the current epidemiological evidence is to be believed, which shows that the virus likely jumped into humans outside of Wuhan entirely. See here: https://www.reddit.com/r/science/comments/gk6y95/covid19_did...

In order of likelihood, based on all available evidence and expert consensus:

zoonotic release >>> accidental lab release of a wildly collected virus >>>>>>> accidental lab release of a "cooked up" virus > intentional lab release of a "cooked up virus"

replies(2): >>trevel+bh >>ricksu+LE3
2. trevel+bh[view] [source] 2021-04-10 02:41:47
>>jedueh+(OP)
James,

I read your post on Reddit back in the day. It was evasive and frankly condescending because you basically argue against something no-one familiar with the science is claiming: that COV is a chimeric virus that is the product of copy-and-paste genetic manipulation rather than directed evolution or gain-of-function research that has resulted in phylogenetic drift against something that was found in the wild -- most likely RaTG13.

And why should anyone take your writing seriously when you don't even talk about "gain of function" research or the various other techniques that have been used in the past decade to aerosolize viruses like H5N1? If you know about them and are deliberately omitting all mention and analysis you are just being dishonest. If you don't then you clearly aren't an expert.

There are also lots of on-topic scientific claims you could address that would let people evaluate your competence and also provide illumination -- what do statistical models say about how long it would take for RaTG13 to evolve into COV19 in the wild? What about in a lab? How likely or unlikely it is to find virii so far away from known ancestors? What are the chances of finding them once we start looking in the wild -- should we have expected to find a closer ancestor by now? And what about the claims made by the State Department about WIV, its closure in September (related: who in the West should be able to confirm/deny if this is the case)? I'd also personally be interested to hear how long it takes to develop research mice with ACE2 receptors since their existence by mid-2020 surely suggests a targeted research agenda that preceded the outbreak? Could scientists in Beijing really have done that in 2 months or whatever?

If you want to be taken seriously, you need to frame the top two or three most credible lab-escape scenarios that work with what is actually public knowledge. Then address the evidence for and against. Setting up strawmen argument, knocking them down and then virtue-signalling on racism isn't useful or on-topic.

replies(1): >>jedueh+en
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3. jedueh+en[view] [source] [discussion] 2021-04-10 04:14:09
>>trevel+bh
Hi I actually discussed the GOF several times in my post and subsequent comments. You can find them here:

-http://www.reddit.com/r/science/comments/gk6y95/covid-19_did...

-http://www.reddit.com/r/science/comments/gk6y95/covid-19_did...

I also address the statistical models you describe, here:

-https://www.reddit.com/r/science/comments/gk6y95/covid19_did...

I go into detail about petri dish vs lab animals vs accelerated evolution and how implausible it is.

Re: sampling viruses in the wild this isn't necessarily my area of expertise, I'm a lab guy. But I do know a lil bit about it, re: ebola in bats mostly. Only that it actually takes much longer than you think, and it has to do with our sampling methods. RNA is really really really short lived outside the host, and our sampling methods aren't that good at finding it inside animal secretions, they're optimized for humans and humans want to be sampled. you don't need to squeeze a human to get them to pee in a cup, or spit in one, or hold still to swab them like you do bats. So sampling is much more difficult. And since it's out in the field, the RNA decays more quickly too. Some advances have been made in this but it still is quite difficult.

To give you an idea, here is a paper all about the vastly MASSIVE amount of estimated undiscovered viruses out there (figure 3 in particular): https://www.nature.com/articles/nature22975

I address the state department stuff also: https://www.reddit.com/r/science/comments/gk6y95/covid19_did...

Re: research mice, the mouse germination time from IVF to F1 (the first useful generation of mice) is about 12-16 weeks. Not that long on the global timescale, but really long in science. You can see a source for this here: http://ko.cwru.edu/info/breeding_strategies_manual.pdf

And that's from Case Western in Ohio, not a Chinese source. It really is that fast.

I'm sorry I'm not framing my arguments in precisely the way you want them, I framed them how I received the arguments out there having discussions in the real world with real skeptics. I then constructed the post to respond to those arguments I had been asked about.

I'm sorry, but that's just the way it is. Take it or leave it.

replies(1): >>trevel+oN
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4. trevel+oN[view] [source] [discussion] 2021-04-10 10:43:18
>>jedueh+en
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+iS >>jedueh+CS >>jedueh+pU
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5. jedueh+iS[view] [source] [discussion] 2021-04-10 11:49:49
>>trevel+oN
>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+i01 >>trevel+fG3
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6. jedueh+CS[view] [source] [discussion] 2021-04-10 11:53:42
>>trevel+oN
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.
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7. jedueh+pU[view] [source] [discussion] 2021-04-10 12:13:29
>>trevel+oN
>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+OB3
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8. jedueh+i01[view] [source] [discussion] 2021-04-10 13:20:47
>>jedueh+iS
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+nK3
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9. trevel+OB3[view] [source] [discussion] 2021-04-11 16:06:32
>>jedueh+pU
> 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.

10. ricksu+LE3[view] [source] 2021-04-11 16:26:32
>>jedueh+(OP)
(reposting sans downmodded comment)

Here is fresh evidence (< 1 wk ago) that labs in Wuhan have worked on unpublished coronaviruses:

https://arxiv.org/abs/2104.01533

The above findings are replicable by any bioinformatician operating on published sources. This preprint was reviewed by one of the authors of the Human Genome Project’s landmark 2001 paper having served as an HGP sequencing team leader at the Whitehead Institute:

https://twitter.com/kevin_mckernan/status/137939900576396083...

The findings critically undermine Western zoonotic scientists’ (Daszak of the WHO-convened study particularly) claim that they knew what viruses WIV researchers were working on.

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11. trevel+fG3[view] [source] [discussion] 2021-04-11 16:36:14
>>jedueh+iS
> 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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12. trevel+nK3[view] [source] [discussion] 2021-04-11 17:12:37
>>jedueh+i01
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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