> Creating synthetic variants (to see if there is gain or loss in function) is very helpful in that it allows well-controlled experiments

Only if, as I responded to another post of yours elsewhere in this discussion, the experiments consist of infecting humans with different strains and seeing what happens to them. And even then there are a huge number of possible confounders.

> There have been near-misses with accidental releases of SARS-CoV-1 and Guanarito [0]; no gain of function required

Indeed. The fact that this problem has been around for a while doesn't make it any less of a problem. Plus, those releases had a much smaller impact because those previous viruses were not as well adapted to human infection when they first appeared--a feature that SARS-CoV-2 does not share (see further comments below).

> I don't know what would be different if gain of function research had been banned

If the lab escape theory is correct, we would not have had this pandemic because the lab would not have done the research in the first place. Seems like a pretty major negative consequence to me.

> On a technical and scientific level we were very well prepared for COVID-19. Its biology was well-understood almost immediately. Our failures were on the social and organizational levels.

The decision to do gain of function research in the first place, particularly in a lab in China where US officials could not hope to have any useful oversight of safety procedures, was also a social and organizational failure. (So was our failure to get a vaccine widely distributed even though, as you note, we understood the biology of the virus very quickly.) Doesn't make the pandemic any less devastating.

> they have contributed to the general knowledge base that permitted extremely rapid development of the COVID-19 vaccine

I don't know what knowledge base you're talking about. DNA sequencing technology, and generating mRNA from a given DNA sequence, which is how Pfizer and Moderna were able to produce a COVID-19 vaccine in a matter of hours, were around before any of the research you refer to was done, and that research added nothing new.

If you mean knowledge about the spike protein being important, that was known before any gain of function research was done, so I don't see how that research helps. Simple research into "how does this type of virus infect a human cell" would have been enough.

> I guess I favor a restriction on deliberately increasing pathogenicity, virulence, and transmissibility beyond levels that occur in similar natural viruses, but allowing the possibility that this could still happen unintentionally. I also think synthetic variants should be destroyed as soon as their purpose is complete, and facilities where these viruses are studied should have a test/trace/isolate plan in continuous operation.

While these are nice ideas, the problem is that they would have to be implemented with the same grossly failed institutions that got us into this mess.

To me this is similar to an argument I agree with against allowing capital punishment in our society: while I agree in principle that there can be cases where capital punishment is justified, the institutions in our society have shown that they are incapable of exercising the kind of discipline required to make sure that, when a person is sentenced to death, we know to a moral certainty that they are guilty of a crime that merits that punishment. Similarly, while in principle it might be the case that we could gain benefits from dangerous research with viruses, the institutions in our society have shown that they are incapable of exercising the kind of discipline required to do that safely.

> COVID-19 wasn't necessarily leaked from a lab, and even it was, it may be a naturally occurring variant

The fact that even the earliest samples obtained, in late 2019, were already highly infective to humans, is a huge indicator to me that this virus was not only leaked from a lab, but leaked from a lab that was doing gain of function research, not a naturally occurring variant. As I noted above, previous accidentally released viruses, which were believed to be naturally occurring variants, did not have this property, and, as we can see by comparing the respective outbreaks that followed, it makes a huge difference in the impact.