[daly]

Your linked article claims it was not a lab leak.

re: BSL-2 vs BSL-4 ... Assuming it WAS a lab leak, was there an a-priori reason to believe that among the many different naturally occurring viruses under study that SARS-CoV-2 would cause a worldwide pandemic? Bats are known to have hundreds of different viruses. Ebola and HIV seem to have been spread widely without a lab connection.

As for gain-of-function studies, they might be beneficial. One might, for example, modify a DNA-modifying virus to add a gene for expressing insulin, providing a cure for diabetes. A DNA-modifying virus provides an ideal whole-body carrier for genetic disorder correction. Indeed this hackernews post (https://news.ycombinator.com/item?id=40307138) today shows a deaf girl cured through genetic manipulation. See https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786910/

[tripletao]

My linked article is an interview with Dr. Shi. Are you expecting that she'd just say "yeah, it was probably us"? Very few people, no matter how honorable, would voluntarily take the blame for millions of deaths. Even if she did wish to, she and her family are under the physical control of a government that has routinely (Xinjiang etc.) wielded some pretty unpleasant tools to control its subjects. She wouldn't necessarily know herself without specific effort, since it's possible for a virus to leak before it's sequenced. (If you were her, would you want to know?) All that gives her extraordinary incentives to downplay the risk of a research accident, regardless of the truth.

SARS-CoV-2 is a novel sarbecovirus, differing from SARS-1 in the spike by about 20%, with an FCS. The WIV proposed in DEFUSE to study viruses with exactly those properties, by collection from nature followed by laboratory manipulation. That proposal wasn't funded, but leaked documents claim the work proceeded with other funders. No other site anywhere in the world has been known to conduct or propose such research; refutations like "lots of big cities have virology labs" miss the uniqueness. Dr. Shi herself did not expect natural spillover in Wuhan, far from the caves established (mostly by her team) to carry the greatest diversity of similar viruses.

None of the biological therapeutics that you mention are scientifically controversial. (Some aspects e.g. of flu vaccine manufacturing get closer to the edge, but not too close.) The concern is the deliberate search--whether in remote areas of nature, or by laboratory manipulation--for deadlier and faster-spreading human pathogens, which are deliberately just one containment failure away from a novel pandemic. It's unfortunate that the unqualified phrase "gain of function" has become publicly associated with such work, since many harmless or beneficial genetic changes can also be described as a "gain of function". The professional term of art is "enhanced potential pandemic pathogens" (ePPP), which is much clearer.

Whatever the name, no such research has ever delivered any public benefit. Its supporters are a tiny subset of virologists, but a particularly vocal subset given what's at stake for them (funding, reputation, etc.) personally. I hope you won't listen only to them, and I particularly hope you won't let them conflate their narrow domain with the whole of modern virology. They're hoping to cloak their risky and speculative experiments in the benefits provided by the rest of the field; but I'm afraid they're more likely to induce a political overreaction in which lifesaving research is banned.