[conistonwater]

There was an episode the TWiV podcast a few months ago where they discussed the biology-based evidence for why SARS-COV-2 wasn't made in a lab. I think it was this one: https://www.microbe.tv/twiv/twiv-762/ One nice thing about the podcast is that because they're scientists by personality they tend to focus far more on the biology of it, which I really appreciate. I listened to it at the time, but I don't remember what they said, to be perfectly honest.

[inciampati]

As a biologist (sorry for the appeal to authority, but it matches the tone of this thread), the evidence against a natural origin appears absolutely staggering.

You have a viral clade that completely descends from a single introduction event inside a major city. The virus does not undergo a period of host adaptation, but instead infects many millions over nearly a year before phenotypic changes are observed. This is simply fantastic. I know of no case where a virus jumped species without a period of adaptation to the new host. The fact that the entire clade has a root in October 2019 (and we can see this even because the first viruses sequenced differed by only one or two mutations from their common ancestor) indicates that there was not slow community spread before the initiation of the pandemic period. There is no weaker progenitor virus.

Considering as well the focus of research labs within the exact city where the pandemic arose makes any argument against the laboratory origin of the virus seem extremely weak. How does a serious and non-conflicted scientist explain all of these ultra-improbable coincidences?

[bhickey]

> The fact that the entire clade has a root in October 2019... indicates that there was not slow community spread before the initiation of the pandemic period. There is no weaker progenitor virus.

SARS-CoV-2 has an error checking polymerase and a relatively slow molecular clock. Just because observed sequences have little divergence from our first observation does not imply that we actually observed the species jump.

The preadaptation argument doesn't hold much water. SARS and MERS were deadly and high transmissible.

That said, let's suppose we did observe cases shortly after it initially infected humans. Shi's lab regularly went caving in search of coronaviruses in bats. These expeditions have previously been described as reckless. The possibility that a lab worker became accidentally infected in a cave shouldn't be counted out by anyone advancing GoF origin claims.

[inciampati]

The slow mutation rate helps us date the "spillover". But it isn't relevant to my argument. If we saw one, two, and three mutations per strain in late December, it means their common ancestor couldn't have been more than a few months prior. If we saw tens, or different clades with specific geographic distribution patterns, then we might look at those to understand where the introduction to humans was. My point is that this introduction probably happened in Wuhan itself, or there would have had to be a complex and highly improbable series of transmissions from a host animal (presumably a bat 1000km away from Wuhan) which spawned no daughter strains. And thanks to the high fidelity replication process of the virus, these strains would be exactly the same in phenotype as the one that showed up in Wuhan. Why did we miss them?

SARS-CoV-1 underwent clear adaptation in humans that was observed through sequencing. In observation, the mutation pattern over time wasn't initially driven by a stable molecular clock. There were easily-discoverable mutations which yielded phenotypic gain. The virus is high fidelity, but there is enough of it that it's exploring a wide range of possible options at every infection. For a virus close to optimum, very few of these will yield a benefit, and so we see mutations that are mostly synonymous that occur at a clock like rate. Sound familiar?

[native_samples]

The distinction between "lab workers got infected whilst physically at a lab" and "lab workers got infected whilst doing remote work intended to benefit the lab" seems quite small.

[bhickey]

There's a huge gulf between getting sick attempting to make a virus more virulent and getting sick while gathering natural samples in the field.

[inciampati]

Both involve research that was specifically intended to reduce risk of pandemics. If either is true, our response here should be to conduct this research with extreme care or even stop doing it.

If the lab origin hypothesis is not true, we should actually do more of exactly this kind of work. That's why it's important to understand and come to consensus about it. It's not just a curiosity or a chance to point the finger at countries and politics we don't like. The prescription for how we should behave is completely different depending on what we think happened.

[orwin]

I agree with you for the begining, but this part:

> The fact that the entire clade has a root in October 2019 (and we can see this even because the first viruses sequenced differed by only one or two mutations from their common ancestor) indicates that there was not slow community spread before the initiation of the pandemic period. There is no weaker progenitor virus.

is hard for me to understand.

Rural China in not rural USA. At all. I've hiked for a month in the Appalachian, another one in the Sierras, and spent two month in rural China. Rural china is as i used to imagine rural Africa.

Rural china have two particularities: young, probably younger than you imagine. You have villages with a median age of 15, with no middle-aged inhabitants. And enclaved. You have villages where you have to use a jeep (that the village do not own) to get to.

Is it possible, in you opinion, to have an early SRAS-Cov2 infecting a village, festing on the people for weeks or even months, then a parent coming back for his yearly vacations, getting infected, then going back to work in Wuhan?

I'm not a biologist, so i don't understand how viruses works, but i _know_ rural China (and rural europe, and rural USA.)

[inciampati]

This process would leave traces that we would have detected by now. If this happened, we should see viruses that sit outside the Wuhan-rooted SARS-CoV-2 clade but are otherwise the same. The rate that this happens would be low, but it would have been observed. I would expect that the epidemic required to spread from rural to urban regions would be large enough to throw off daughter strains that would have been circulating after the main outbreak was discovered. These would have been detected by the mobilization to find the origins and scope of the pandemic. Of course we can make stories about a perfect chain of transmission leading from a bat cave in southwest China to a major population center, where each step never resulted in obvious illness or community spread. I also enjoy science fiction. Some things make for nice stories but involve staggeringly improbable series of coincidences. And if the same virus (remember: thanks to it's error correcting mechanisms it doesn't change very fast) were let loose in another community, why would it not take up residence there? We would have to explain why people in Wuhan and the rest of the world were so much more susceptible to a virus that was completely wiped out along it's entire chain of transmission from probable animal host to human.

[orwin]

>> Of course we can make stories about a perfect chain of transmission leading from a bat cave in southwest China to a major population center, where each step never resulted in obvious illness or community spread. I also enjoy science fiction.

Yes, the part "where each step never resulted in obvious illness or community spread" is where i don't understand. I think i insisted on it enough, but it bears repetition: rural china is _young_ and _enclaved_. I've seen villages with 70 children, 10 adults total. Granted, the adults are "old" (i understand they are between 40 and 60, the life expectancy is not that high). You also have phantom villages. If you ever read Lord of the Flies, you can imagine how a village get abandonned and trashed.

How it works: people get kids early, did not declare them, go to work in the city and let the kids for the remaining farmers (often village chiefs and to ones speaking Mandarin, all the other speak in local dialects) and sometime grandparent. Few of the young adults stay (women that were "shamed" into staying from what i understood, the guide was not very proud and did not expand on this). Most of them come back either once or twice a year, sometime more if they work closer, but not more than once a month. Couples sometime come back to drop a kid or two in the village before going to work again.

> And if the same virus (remember: thanks to it's error correcting mechanisms it doesn't change very fast) were let loose in another community, why would it not take up residence there?

And if he did take residence, how would we know? If a 100-person village was infected, they would be immune by now. If only one external (or even ten, most asymptomatics don't transmit the virus if i understand that well) was infected and transmitted the virus directly in Wuhan, would it be possible?

One more fact: some parts of rural china are way less connected than western Africa. I did not visit Africa yet (my next month-long hike was supposed to be in Ethiopia, stopped for obvious reasons), but the preparation are less stringent, and the path easy to plot. I guess western Africa, with less mountains/hills, would be even more connected.

You see, i agree that a chimera might have escaped, is a possibility that i find more likely (let's say 45 to 80%, depending on the day). But as long as proponents of this theory dismiss the other theories as "science fiction" _when they view rural China as rural Europe_, i will have a bad time getting onboard the theory.

I'm not skeptic of everything, but still, the 2000's outbreak of BDBV or all those novel-ebola where we never find the index case nor the origin village, why couldn't they have been lab outbreak too? There is research in the area, they have to keep Chimeras for some of the EV because else they can't keep those new versions alive long enough, i'm pretty sure there is less security (i imagine, i don't know Africa very well). Were those ebola viruses with no index case lab outbreaks too? Why didn't we talk about it ever?

[bhickey]

HIV is believed to have first infected humans in the 1920s where it traveled up the Congo before arriving in Kinshasa. From there it radiated across Africa carried by truckers. Like you say, I haven't seen evidence to rule out rural circulation before arriving in Wuhan. Granted, I don't think this is the most likely series of events, but the GoF lab leak hypothesis is lacking support.

[tim333]

The documents that the article is based on demonstrate the lab was doing GoF experiments to infect humanized mice with chimeras based on bat coronaviruses and got a grant to do further such research starting in 2019. And lo - we get a break out of something looking like a bat based chimera that infects human cells in 2019. Bit of a coincidence there.

[belter]

Luc Montagnierd joint recipient of the 2008 Nobel Prize in Medicine for his discovery of the human immunodeficiency virus HIV has argued the virus was created in a lab.

"French Nobel prize winner: ‘Covid-19 was made in lab’"

https://www.connexionfrance.com/French-news/Disputed-French-...

https://en.wikipedia.org/wiki/Luc_Montagnier

Again, just another appeal to authority, to be analyzed further. I find curious his personal Wikipedia page still characterizes the controversy has him being accused of spreading a conspiracy theory, while today, its looking as one of the most likely causes.

[bsaul]

luc montagnier has a long list of insane public claims for the past decades (things about "water memory" comes to my mind , but there are others).

He lost credit a long time ago, way before covid, so i would be really cautious about citing anything he has to say about the virus.

[belter]

After further research...I am inclined to agree with you. I just found he also claimed 5G was helping spread Covid.

[inciampati]

This phenomenon keep happening with old Nobel laureates. Linus Pauling for instance...

For any public binary question with weak information, you'll find crazy people arguing both sides.

[arbitrage]

> sorry for the appeal to authority

You don't need to apologize for your knowledge and experience. We are not engaged in a roman-style rhetoric class where the mandate is to build all arguments upon a set of rules we never agreed to.

The wikipedia list of common logical fallacies is not a guideline to rational discourse in the 21st century.

[ddxxdd]

As far as I'm concerned, apologizing for the appeal to authority signalled that he was open to being criticized and challenged by layman, rather than choosing to belittle those who disagree with him without having his knowledge and experience.

In short, he demonstrated that he wasn't an "elitist".

[ksaj]

Origin of Life is full of ultra-improbable coincidences. How do scientists in that field explain it?

"There is no weaker progenitor virus."

I've never heard a scientist dealing with any level of Complexity declare a negative fact before. Having not discovered a weaker progenitor doesn't preclude its existence. This type of statement ignores all comparisons made to the bat coronaviruses that have very much been part of the discussion.

I read some of your other replies and agree with some, and can at least see the point of a lot of them. But the grander wide-brush statements weaken those points.

[michaelmrose]

An appeal to authority is only inherently invalid insofar as the authority claimed is irrelevant authority or used to paper over weaknesses in the actual argument. Forums not entirely overrun with imaginary internet doctors and cranks can probably start with the polite presumption that you are actually a biologist and proceed with reasonable discussion from there without further ado.