Recently you were quoted as saying: "When I first saw the furin cleavage site in the viral sequence, with its arginine codons, I said to my wife it was the smoking gun for the origin of the virus. These features make a powerful challenge to the idea of a natural origin for SARS2." Can you unpack this quote for us?
Let me be clear, even though I used the phrase "smoking gun," I don't really think there's a smoking gun in the genome itself.
Now, within the SARS-CoV-2 genome there is an insertion of 12 nucleotides that is entirely foreign to the beta-coronavirus class of virus that SARS-CoV-2 is in. There are many other viruses in this class, including the closest relative of SARS-CoV-2 by sequence, and none of them have this sequence. The sequence is called the furin cleavage site.
To back up a little bit: In order to infect a cell, the spike protein on the surface of viruses like SARS-CoV-2 needs to first be cut, or cleaved. The cut needn't be terribly exact, but it needs to be cut. Different viruses attract different kinds of cellular "scissors," so to speak, to make this cut; the furin cleavage site attracts the furin protein providing the most efficient way to make a cut. You don't need a furin cleavage site to cut the protein, but it makes the virus more efficiently infectious.
So where did it come from in SARS-CoV-2? There are other viruses that have furin cleavage sites, other coronaviruses, though not the family of beta-coronaviruses. So this sequence's nucleotides could have hopped from some other virus. No one has identified a virus that has exactly this sequence, but it could have come from something close, then evolved into the sequence that we see today.
I'm perfectly willing to believe that happened, but I don't think it's the only way that that sequence could have appeared. The other way is that somebody could have put it in there. You can't distinguish between the two origins from just looking at the sequence. So, naturally, you want to know were there people in the virology laboratory in Wuhan who were manipulating viral genetic sequences? It's really a question of history: What happened?
When I first saw the sequence of the furin cleavage site—as I've said, other beta coronaviruses don't have that site—it seemed to me a reasonable hypothesis that somebody had put it in there. Now, I don't know if that's true or not, but I do know that it's a hypothesis that must be taken seriously.