There's no question that SARS-CoV-2 evolved mostly in bats. The debate is whether its path to humans involved a research accident. That accident could involve genetic engineering, which would potentially leave genomic evidence but wouldn't necessarily. It could also involve collection (and accidental release) of a novel naturally-evolved virus. This was a major part of the WIV's research, visiting remote caves that no other humans routinely entered, and would leave no genomic evidence at all. So there is no way to distinguish the origin of the virus solely from genomic evidence.

The WIV handled those novel viruses at BSL-2, not BSL-4. Dr. Shi acknowledged this explicitly in her interview with Science, linked below. Even Ralph Baric (who originated many of the techniques that the WIV scaled up, and whose own research was controversial long before the pandemic) has said that was an unacceptable risk.

https://web.archive.org/web/20210727042832/https://www.scien...

If SARS-CoV-2 arose from a research accident, then it was probably from an American-funded Chinese lab, using techniques developed primarily by an American. So I don't see the political benefit to either country in entertaining that possibility, though I do see a benefit to both countries to downplaying it (as seems to have occurred).

Long before the pandemic, a small subset of virologists and adjacent scientists advocated strongly for certain high-risk research on potential human pandemic pathogens, including laboratory enhancement of existing viruses (gain of function) and hunting of novel viruses from nature. That work was highly controversial, to the point that a three-year moratorium on funding was imposed, ending in 2017. Racaniello was among those advocates; so while he's certainly better-informed than the average person, he also faces a massive conflict of interest. I don't see why you'd trust him over the countless well-credentialed scientists who consider the origin of SARS-CoV-2 to be an open question.

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/

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.