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The origin of Covid: Did people or nature open Pandora’s box?

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Re: The origin of Covid: Did people or nature open Pandora’s box?

#551

Post by lamontcg »

tripletao wrote: post #472
lamontcg wrote: post #433

Earlier quoted context omitted.

> Every other theory requires involving many more unsupported hypotheses. No it doesn't. All it takes is bats around farmed animals like minks or raccoon dogs. That sets up a natural "gain of function" experiment with the bats passing viruses off to the farmed animals who pass it sequentially through the entire farm. The humans who work at those farms then bring in human coronaviruses which could have recombined with…

If SARS-CoV-2 evolved on a farm, then shouldn't it be particularly easy to find an intermediate host? No need for wilderness expeditions, just go to the barn and start swabbing. But more than a year later, we're still waiting. And how does that explain its affinity for human ACE2? At least initially (right after it makes the zoonotic jump), the virus would probably show highest affinity for its animal host, and lower…

Yes, the thing I'm most pissed off at China about are the destruction of samples and the lack of investigation towards finding intermediate animals.

And we know that we didn't detect the virus early, it didn't originate in the wet market event. That market event was just big enough right in the middle of Wuhan so it made it unmistakable.

The only way you get that high of an affinity is through serial passage through actual humans, not through the lab.

And this should not be that surprising since we know that it takes several months for the virus to spread before it starts to cause massive numbers of deaths, the IFR is actually low compared to SARS-1 and MERS, and it tends to spread asymptomatically and undetected.

We know pretty much for certain now that it was spreading cyrptically in the area around Wuhan in Nov, and I would bet that the zoonotic jump was Oct or earlier.

And that is also why I suspect an intermediate animal with a more similar ACE2 to humans like minks being involved. So serial passage through one of those animals to get it close, followed by serial passage through humans to refine it.

Re: The origin of Covid: Did people or nature open Pandora’s box?

#552

Post by lamontcg »

jollybean wrote: post #469
lamontcg wrote: post #433

Earlier quoted context omitted.

> Every other theory requires involving many more unsupported hypotheses. No it doesn't. All it takes is bats around farmed animals like minks or raccoon dogs. That sets up a natural "gain of function" experiment with the bats passing viruses off to the farmed animals who pass it sequentially through the entire farm. The humans who work at those farms then bring in human coronaviruses which could have recombined with…

Except that after 15 months of global catastrophy and investigation, no evidence has been found in support of that. Please correct me if I'm wrong, but it would seem that if 'minks' were the problem, there would be trail of evidence to pick up on. Hence the notion of speculation / Occam's Razor.

Has China bothered seriously looking for that, or are they happy to distract by pointing the finger at Italy and making the argument over lab escape? I keep reading reports that China conveniently threw away all their wastewater samples and respiratory samples. I don't see much of an effort towards studying their farm animals or tracking down the bat origins.

There just hasn't been that much of an investigation. China seems to have done enough to provide an air of cooperation with WHO, while not producing anything solid.

For their domestic consumption they've also accomplished their propaganda goals. The global scientific community (outside of fringe articles like here) has generally dismissed the idea that it came from a lab, which China can amplify in front of its population. Then they just muddy the waters with the idea that it came in frozen seafood from Italy and they can move on. There's no incentive to investigating the zoonotic orgins.

And its the same thing here in reverse. Politically we just get articles like this to get people very made at China over the lab release hypothesis, which deflects from our own pandemic response.

Politically there seems to be very little will on the planet towards finding a zoonotic source.

Re: The origin of Covid: Did people or nature open Pandora’s box?

#553

Post by lamontcg »

tripletao wrote: post #466
lamontcg wrote: post #427

Earlier quoted context omitted.

> "Furin cleavage sites naturally occur in coronaviruses" > https://www.sciencedirect.com/science/article/pii/S187350612... They exist in the human HCoV-HKU1, HCoV-OC43, MERS-CoV and appear to have evolved independently at least 6 times in betacoronaviruses. Furthermore while this article claims that the furin cleavage site has not found in any sarbecoviruses, that is now outdated information: > "Evidence for SARS-Co…

What's your estimate of the relative prevalence of an FCS among the likely space of lab-created SARS-like coronaviruses vs. among natural, SARS-like coronaviruses? My understanding is that adding an FCS is a very common method of lab gain of function, but rare among such viruses in nature. I don't think the FCS is determinative, and I agree Wade's article overstates its significance. In a Bayesian analysis, it still…

It evolved at least 5+ times completely independently in nature in coronaviruses (and in other viruses).

The significance is zero. Nature itself knows how to figure it out.

> but rare among such viruses in nature.

This assertion is false. It is common among betacoronaviruses in nature, not rare. That was the point of those two articles.

We have even found two sarbecoviruses now (directly related to SARS-CoV-1 and SARS-CoV-2) in bats in Thailand which have an FCS.

It points literally 0% towards lab origin.

Re: The origin of Covid: Did people or nature open Pandora’s box?

#554

Post by tripletao »

lamontcg wrote: post #550
tripletao wrote: post #547

Earlier quoted context omitted.

For what it's worth, you're disagreeing with Dr. Shi herself here: > We have done bat virus surveillance in Hubei Province for many years, but have not found that bats in Wuhan or even the wider Hubei Province carry any coronaviruses that are closely related to SARS-CoV-2. I don't think the spillover from bats to humans occurred in Wuhan or in Hubei Province. https://www.sciencemag.org/sites/default/files/Shi%20Zheng…

Wuhan is the capital of Hubei and is going to attract the surrounding area (if a virus jumped to humans in Sidney, NY it would probably be detected in NYC). Distance from Yunnan will also be a factor and the virus jumping to humans from Yunnan to cities anywhere in the north will be much less likely. A proper model would look the migration of people and animals between different cities and provinces in China. And aga…

For emphasis, I'm not claiming the emergence in Wuhan (or the presence of an FCS, or the higher affinity for human ACE2 than for any other known animal, or the CCP's apparent coverup of something, or any other single factor) is determinative in itself. But there are multiple factors and no clear mechanism for dependence between them. Those should all be considered together, in a Bayesian analysis or whatever other statistical framework you prefer.

As to specific numbers, 10% seems too low to me--Wuhan is 6% of the population of Chinese cities at least as big as Wuhan, disregarding smaller cities entirely, including Foshan where the original SARS emerged, and disregarding Dr. Shi's expectation that origin closer to Yunnan was more likely. But at least we're within an order of magnitude of each other.

Knowing nothing whatsoever except that a pandemic emerged, what's your prior for lab vs. natural origin? It depends how you count, but we've had perhaps a dozen pandemics in the last fifty years, and one (the 1977 flu) was near-certainly lab-origin. So even with extreme optimism as to lab safety improvements, I can't see how you'd estimate less than e.g. 1%. For SARS-CoV-2, you'd perhaps adjust down for the novelty of the pathogen (since most lab work is with known pathogens--though most of the WIV's seems not to have been). It doesn't take that many p = 10% coincidences up to get to even odds or better, though.

Re: The origin of Covid: Did people or nature open Pandora’s box?

#555

Post by tripletao »

lamontcg wrote: post #553
tripletao wrote: post #466

Earlier quoted context omitted.

What's your estimate of the relative prevalence of an FCS among the likely space of lab-created SARS-like coronaviruses vs. among natural, SARS-like coronaviruses? My understanding is that adding an FCS is a very common method of lab gain of function, but rare among such viruses in nature. I don't think the FCS is determinative, and I agree Wade's article overstates its significance. In a Bayesian analysis, it still…

It evolved at least 5+ times completely independently in nature in coronaviruses (and in other viruses). The significance is zero. Nature itself knows how to figure it out. > but rare among such viruses in nature. This assertion is false. It is common among betacoronaviruses in nature, not rare. That was the point of those two articles. We have even found two sarbecoviruses now (directly related to SARS-CoV-1 and SAR…

Could you at least make a guess at the relative frequencies? My understanding was that hundreds of animal sarbecovirus strains are known, and of those only the two that you note above had an FCS (and not the rare CGG). On the other hand, I understand that adding an FCS is a common technique for lab gain of function, so that perhaps 5% of genetically-engineered SARS-like viruses would have one. That's how I got my ~3x.

It would be nice if each individual piece of evidence were all or nothing, either perfect evidence of lab origin in itself or perfectly irrelevant. I don't think real evidence usually comes that way, so it seems valuable to me to try to quantify even weak evidence.

And not that Nobel laureates don't have an unfortunate history of incorrect beliefs later in life: but I assume you're aware David Baltimore considers the FCS significant? He doesn't seem to have said anything else obviously crazy (unlike Mullis, Pauling, etc.), at least.

Re: The origin of Covid: Did people or nature open Pandora’s box?

#556

Post by tripletao »

lamontcg wrote: post #551
tripletao wrote: post #472

Earlier quoted context omitted.

If SARS-CoV-2 evolved on a farm, then shouldn't it be particularly easy to find an intermediate host? No need for wilderness expeditions, just go to the barn and start swabbing. But more than a year later, we're still waiting. And how does that explain its affinity for human ACE2? At least initially (right after it makes the zoonotic jump), the virus would probably show highest affinity for its animal host, and lower…

Yes, the thing I'm most pissed off at China about are the destruction of samples and the lack of investigation towards finding intermediate animals. And we know that we didn't detect the virus early, it didn't originate in the wet market event. That market event was just big enough right in the middle of Wuhan so it made it unmistakable. The only way you get that high of an affinity is through serial passage through…

Surely passage in human cell culture or in mice genetically engineered to express human ACE2 would also create that selection pressure in the lab? If SARS-CoV-2 was manipulated in the lab, that's the usual explanation I've seen given for that affinity.

Mink seem very unlikely to me, since I've seen papers reporting evidence of host adaptation on mink farms:

https://academic.oup.com/ve/article/7/1/veaa094/6025194

So if the virus first evolved in mink, it would have to have evolved enough in humans not just to favor human ACE2 but also to lose its affinity for mink (to the point it has to regain it later), all during that couple months of cryptic spread.

And do you really think China is doing a bad job looking for the intermediate host? I don't think that's impossible--for example, the true origin could be some agricultural practice so horrible that they consider the present uncertainty better than disclosing that. Lab origin has become strongly associated with anti-China political sentiment, though. (That seems stupid to me, considering that the USA was funding the WIV; but here we are.) So I'd be surprised that the CCP would pass up a chance to disprove that.

Re: The origin of Covid: Did people or nature open Pandora’s box?

#557

Post by [deleted] »

dumb1224 wrote: post #203
zby wrote: post #146

Earlier quoted context omitted.

The natural origin hypothesis is also pushed for ideological reasons - at this level of meta analysis we are at a stalemate. The article was good at revealing that there is not just ideology - but also material interests involved and that the two prestigious letters that were so categorical in dismissing the lab escape hypothesis were quite a bit tainted by conflicts of interests.

My colleague, an evolutionary biologist's comment on this: the virus is unlikely to prevail if manually tweaked since evolution does such an amazing job that it's very unlikely it alone could dominate and infect large populations.

[deleted]

Re: The origin of Covid: Did people or nature open Pandora’s box?

#558

Post by Closi »

dumb1224 wrote: post #537
zpeti wrote: post #532

Earlier quoted context omitted.

How about a virus that's just allowed to evolve inside human tissue? Not "manually tweaked" just allowed to evolve faster.

I'm not an evolutionary biologist. I merely want to pass on his comment. He studied the viral genome segments inserted in human genome. I can pass that question to him if you want.

The Coronavirus Gain-Of-Function research the Wuhan lab was doing probably wasn't manually tweaking the virus, or inserting viral genome segements.

It was more likely putting evolutionary pressure on Coronaviruses in order to change it's properties and behaviour.

Re: The origin of Covid: Did people or nature open Pandora’s box?

#559

Post by dumb1224 »

Closi wrote: post #558
dumb1224 wrote: post #537

Earlier quoted context omitted.

I'm not an evolutionary biologist. I merely want to pass on his comment. He studied the viral genome segments inserted in human genome. I can pass that question to him if you want.

The Coronavirus Gain-Of-Function research the Wuhan lab was doing probably wasn't manually tweaking the virus, or inserting viral genome segements. It was more likely putting evolutionary pressure on Coronaviruses in order to change it's properties and behaviour.

'Manually tweak' is a bad word invented by me. He didn't mean it was viral segment insertion either.

Regarding selection pressure people do that all the time, in fact it is far from easy to artificially apply environmental pressure and obtain highly functional new variants. In cancer research, xenograft are extremely tricky to do with immunodeficient animal models, let alone human tissue in the lab. Sure you can have some success but it's difficult enough to reproduce. His point is that even if an artificially selected highly viable variant was obtained, it is very unlikely it can prevail in real world nature selection (large scale too). I'm no expert but happy to read about any paper if it's not the case.

Re: The origin of Covid: Did people or nature open Pandora’s box?

#560

Post by ScottBurson »

lamontcg wrote: post #553
tripletao wrote: post #466

Earlier quoted context omitted.

What's your estimate of the relative prevalence of an FCS among the likely space of lab-created SARS-like coronaviruses vs. among natural, SARS-like coronaviruses? My understanding is that adding an FCS is a very common method of lab gain of function, but rare among such viruses in nature. I don't think the FCS is determinative, and I agree Wade's article overstates its significance. In a Bayesian analysis, it still…

It evolved at least 5+ times completely independently in nature in coronaviruses (and in other viruses). The significance is zero. Nature itself knows how to figure it out. > but rare among such viruses in nature. This assertion is false. It is common among betacoronaviruses in nature, not rare. That was the point of those two articles. We have even found two sarbecoviruses now (directly related to SARS-CoV-1 and SAR…

> It points literally 0% towards lab origin.

Even given the CGG codon? Sorry, not buying it. You can argue that its evidentiary value is weaker than the article suggests, but it's not 0%.

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