> IMO The only "lab leak" hypothesis that makes any sense at all, was that someone just *ked up, the dice rolled horribly badly (like the worst outcome out of 10^64 possible outcomes), and it all went pear shaped.
This is really not that unlikely. Probably someone designed something like 2^10-ish different recombinant grafts from related coronaviruses, with various design parameters, and the selective pressure was "oh it was actually infectious enough to infect the careless postdoc pulling the 100 hour workweek". Surely 1 out of 2^10 is likely to be more transmissible than the parent bat strain.
These days (aka 10 years ago) with molecular biology, 2^6 is not unreasonable to do by hand, by a well-trained undergrad intern, in three months. Oh and hey... out of 2^6 we discovered one GOF with higher normalized output than its parent. Citation (disclaimer, I supervised the intern, so it's possible I'm a three-sigma-above-median intern manager): https://bmcbiochem.biomedcentral.com/articles/10.1186/1471-2...
This is really not that unlikely. Probably someone designed something like 2^10-ish different recombinant grafts from related coronaviruses, with various design parameters, and the selective pressure was "oh it was actually infectious enough to infect the careless postdoc pulling the 100 hour workweek". Surely 1 out of 2^10 is likely to be more transmissible than the parent bat strain.
These days (aka 10 years ago) with molecular biology, 2^6 is not unreasonable to do by hand, by a well-trained undergrad intern, in three months. Oh and hey... out of 2^6 we discovered one GOF with higher normalized output than its parent. Citation (disclaimer, I supervised the intern, so it's possible I'm a three-sigma-above-median intern manager): https://bmcbiochem.biomedcentral.com/articles/10.1186/1471-2...