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Comment by lamontcg | Hacker News Reader

Serial passage isn't magic, it is just what nature does.

In the lab you'll get a handful of mutations not thousands.

After serial passage through some large fraction of a billion humans, with large evolutionary pressures due to the recent species jump, the delta variant is still well over 99% homologous to the reference Wu-1 strain.

A 96.1% different would require serial passage through billions of organisms, but they measure this difference in terms of years of evolution in nature which is on the order of 30-40 years.

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In the lab we can vastly exceed natural mutation rates, rendering this appeal to nature baseless.

The rate of evolution is a function of the mutation rate and the effective population size. There is no reason to believe that a lab setting, with highly parallel evolution on a very large, diverse population, will be as slow as passage through hosts in nature. The application of mutagens, and also the lack of selection by a host immune system can support much higher rates of change. And in coronaviruses, recombination is also very frequent, and this could easily give rise to multiple % levels of divergence in a single step. Finally, it's trivial to synthesize a genome of this size, and also to synthesize pools of related viruses based on common backgrounds.

Disclaimer: not a microbiologist.

The 30-40 year figure assumes the related virus is a direct ancestor and it stayed within the same species, which is quite a big if. It's useful as a metric within a single population, but not exactly evidence hard enough to play genetic detective.

If they just share ancestors that time is basically halved towards the most recent common ancestor, which puts it back somewhere in the mid 2000s. When evolving in parallel, within different species, the divergence grows really quick. Also when viruses jump species the mutation rate skyrockets at the beginning[0][1] to adapt to the novel host, which could easily account for most of the difference between RaTG13 and Wu-1 anyway.

[0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223060/

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3714272/

> After serial passage through some large fraction of a billion humans

Wouldn’t this count as parallel passage though? Sure there’s more variability and evolutionary pressure on the mutations, but the speed of evolution (the number nucleotide mutations) is the same over the same period of time regardless of how many billions of people it infects in parallel.

Well said, also you have little control over which colonies will take over.

Then 'it was not serial passage' theory is unfalsifiable (sorry for the double negation):

* If a wild strain is too far away from covid, then it would have taken too long to do the passage.

* If a wild strain is almost identical to covid, then obviously covid derived from that without seeing the interior of a lab.

Under what circumstances would you consider that serial passage work done in a lab might have had something to do with covid?

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