zlacker

>>todd8+(OP)
The evidence is circumstantial, but there has yet to be any evidence ruling it out. To be clear, the lab leak hypothesis is always possible. Things can always leak out of labs, let's not kid ourselves.

Some things (going by memory here) that seem to support the hypothesis:

1) Major point of differentiation for this virus is that compared to it's closest known relatives, it has acquired a furin site (eukaryotic protein cleavage site) that enhances its virulence.

2) That furin site RNA contains a non-canonical amino acid codon

3) That non-canonical codon contains a restriction site that could easily be used to track, whether, say, your added furin site is surviving multiple cell passages, by performing a restriction digest and running the fragments on a cell.

Like I said above, it's circumstantial, but this is all very normal. Both adding the furin site (how does coronavirus evolve into something more virulent?) and tracking it that way. Then all it takes is someone to get infected (EVERYONE working in biology has broken at least one lab safety rule in their life, even in BSL4) and either not be symptomatic and realize, or not say anything.

>>COGlor+lE
Furin cleavage sites very similar if not largely identical to this one have also been found in nature, and have been generated in nature in very short spans of time (on the order of a few decades, which is what is suspected to have happened with SARS-CoV-2).

I describe the evidence in detail in this detailed longform post I wrote on reddit a few months back: Hi, I have a PhD in virology focused on emerging viruses, and a few months back I wrote a very lengthy and involved piece full of sources.

And in there, I describe exactly how wrong your point 1 is. And how misguided your point 3 is.

The post also won a "best of r/science 2020" award!

You can find it here: https://www.reddit.com/r/science/comments/gk6y95/covid19_did...

See under "Addendum to Q2"

>>jedueh+u41
I read through your post and it was incomplete and hand wavy, although that makes sense because it was written for Reddit. The bias was also obvious, and remarkably unscientific in how you approached the "problems" in a deterministic manner. You cherry picked examples (for instance, saying we can detect Cas9 mutations) that make no conclusive point (for example, there are a variety of ways to add a furin site to a genome that don't involve Cas9) but are indistinguishable as proof by the Reddit audience. The bottom line is, though, you are cherry picking arguments that lay people are more or less too unaware of their cherry picked status to argue with.

As a virologist, who "engineers viruses", I also take some offense to this line: >The virus itself, to the eye of any virologist, is clearly not engineered.

I also suspect that the viruses referenced in the featured article would object to that line as well.

>>COGlor+Yf1
I agree with you that I am uncomfortable with the "hand-waviness" of the OP's response. If you are a virologist, I would really like your opinion on the science of the following document:

https://onlinelibrary.wiley.com/doi/pdf/10.1002/bies.2020002...

Like you, I don't enjoy when facts I post are de-railed without actually addressing any of them. It happens a lot, but I try my best to not let them be the last word.

There is plenty of factual information out there that makes an accidental lab-leak hypothesis strong.

>>EMM_38+gE1
I'm unfortunately going to give an equally hand-wavy response. There's nothing in there that strikes me as factually incorrect (I could be wrong though because I am not an expert on these viruses). I did a brief genome analysis myself - only ~5% of the arginines are encoded by the CGG codon. It's also true that those two introduce the furin site, and it's hypothesized that the furin site is critical to the viruses ability to enter the human cell. It's also true that it's a large difference between the closest variant and SARS-CoV 2. There's also the fact that it's an insertion, not a mutation. i.e. the gene acquired extra amino acids, not just changing the new ones (that's one point I think is hand-waved over in the OP's comment, as he points out that there are many mutations between SARS-2 and the closest relative - which is true, but there is (to my knowledge and I'm happy to be corrected on this) only one insertion, and that is the furin site bearing two adjecent non-canonical arginine codons next to each other that also introduce a restriction site.) However, I do believe the insertion is out of frame, which is odd. If I was engineering the protein, I'd probably make the insertion in-frame to reduce variables as much as possible. So that's a point against. The paper also just glosses over that.

The restriction site is interesting because to my knowledge, mammals don't produce the protein that would normally digest it (which implies that it's probably rare among infectious eukaryotic viruses), but again, I could be wrong there and am happy to be corrected. Typically, a restriction enzyme will, under the right conditions, cut the DNA (or RNA) at the restriction site. One of the interesting things here is that if I was introducing a restriction site to track GoF research, adding it directly in the thing I added greatly simplifies my life. If that restriction site goes away, I know I lost my insert. It's also nicer to use a restriction site because I can do the digest in 30 minutes on a benchtop, run an agarose gel in an hour, and know if I still have it after passaging the virus, vs say, sequencing, which is usually more expensive and takes longer. Especially if it's BSL2+ because now I need to put it over a BSL2+ sequencer.

It's a hypothesis. We'll never know. There's no conclusive evidence either way, and it's absolutely something we should all be talking about, and the scientists among us should be trying to properly falsify it to the best of our ability.