[tripletao]

We already know that the EcoHealth Alliance sought funding for DEFUSE, which involved making chimeras of "random isolates" (novel coronaviruses collected by the WIV from nature) and certain known backbones. They proposed to do that work in North Carolina, not Wuhan, and the proposal was rejected for safety concerns; but it gives general insight to the kind of work they wanted to do, and might have continued with other funders.

https://www.documentcloud.org/documents/21066966-defuse-prop...

So is it really that crazy to think they made a chimera of two "random isolates"? David Relman didn't think so:

> This argument fails to acknowledge the possibility that two or more as yet undisclosed ancestors (i.e., more proximal ancestors than RaTG13 and RmYN02) had already been discovered and were being studied in a laboratory—for example, one with the SARS-CoV-2 backbone and spike protein receptor-binding domain, and the other with the SARS-CoV-2 polybasic furin cleavage site. It would have been a logical next step to wonder about the properties of a recombinant virus and then create it in the laboratory.

https://www.pnas.org/content/117/47/29246

Of course the opportunities for a lab accident aren't limited to genetic engineering. SARS-CoV-2 could be a naturally-evolved virus, but one that was sitting harmlessly in a remote cave until WIV researchers collected it. SARS-CoV-2 could also be naturally-evolved, and spread to some hapless villager who then made a day trip to Wuhan; but the point is that we don't know, and all options require investigation until we do.

[alevskaya]

Yeah, I used to engineer viruses and immune cells, etc. I've read that grant a few times. Again, a rejected _American_ grant for work to be done in Baric's lab in North Carolina. Most of the work outlined in it involved chimeric genomes that would be obvious. There's a few sentences about verifying properties of full-length quasispecies isolates, but the QS experiments aren't well outlined - a lot of chimeric experiments and re-syntheses, all which would likely leave pretty tell-tale signs.

Of course it's possible to describe a physically possible route to sampling, lab accident, and infection. Anyone can come up with these just-so stories. Professors too! Making a chimera of random isolates is crazy story. It's incredibly annoying to mess with 30kb RNA viruses. You have no idea. That's just not how a skilled practitioner would go about asking these questions. There's a reason most work on these things are in characterized strains.

These stories remain ludicrous when compared with the unambiguous epidemiological evidence for zoonosis that we have in hand. You're simultaneously alleging this tight collaboration between western scientists and WIV, but positing that somehow all these western scientists were in the dark about a conspiracy to do this massive amount of work without our knowledge, or an active conspiracy on the part of a significant percentage of western virology to hide it. All in a field that before the pandemic was a completely undramatic backwater of science!

The power of "lab-leak" isn't its strength as an evidence-backed scientific hypothesis, it's its power as a compelling work of fiction, and I doubt any amount of hard evidence will kill it.

The damage it does is distracting us from the unregulated wild-meat and fur industries that were the overwhelmingly likely cauldron for evolving these strains (as in SARS-1!). If we yet again fail to shut down those sources, we risk another pandemic just like this happening again in a few decades. That's where international attention and pressure should be applied, not this cockamamie distraction.

[tripletao]

> These stories remain ludicrous when compared with the unambiguous epidemiological evidence for zoonosis that we have in hand.

What would you consider the strongest evidence for zoonosis? All previous pandemics of novel[1] viruses have been of natural origin. But the technology to enable such an accident has only existed for a few decades, so that seems far from decisive. No one had died in a plane crash before the Wright brothers, but that doesn't mean the risk wasn't there.

We've found lots of viruses related to SARS-CoV-2 in bats; but no one questions that the virus is ancestral in bats, just whether it passed through some postdoc's hands on its way to humans. We've found new bat viruses in Laos, and perhaps SARS-CoV-2 emerged naturally from that; but the WIV was also sampling in Laos, so perhaps it emerged that way too. I don't think natural zoonotic origin is impossible, but I certainly don't see unambiguous evidence for it.

> The damage it does is distracting us from the unregulated wild-meat and fur industries that were the overwhelmingly likely cauldron for evolving these strains (as in SARS-1!).

I'd certainly argue for restricting those industries, even if this pandemic turns out to be lab-origin, just as I'd argue for restricting certain virological research of concern even if this pandemic turns out to be natural-origin. Per above, neither risk seems small enough to me to ignore for the sake of the other.

1. I say "novel" to exclude the 1977 flu pandemic, which somehow nobody gets upset about even though ~700k people died.