[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.