Strong claims require strong proof. Yet new preprint on Covid is making the rounds, amplified by no less than the Economist. This pape and attempts show that Covid must have come from a lab because it is “synthetic”. Covid brain trust member GM finds that the article does not deliver on its claims. However, since it “proves” what many want to believe, it’s unlikely to go away quickly.
I must confess to regarding with extreme prejudice any paper that has a prominent “Lay Summary” section. That signals that it is intended to shape popular opinion, as opposed to make its case on scientific merit.
Lay Summary To construct synthetic variants of natural coronaviruses in the lab, researchers often use a method called in vitro genome assembly. This method utilizes special enzymes called restriction enzymes to generate DNA building blocks that then can be “stitched” together in the correct order of the viral genome. To make a virus in the lab, researchers usually engineer the viral genome to add and remove stitching sites, called restriction sites. The ways researchers modify these sites can serve as fingerprints of in vitro genome assembly.
We found that SARS-CoV has the restriction site fingerprint that is typical for synthetic viruses. The synthetic fingerprint of SARS-CoV-2 is anomalous in wild coronaviruses, and common in lab-assembled viruses. The type of mutations (synonymous or silent mutations) that differentiate the restriction sites in SARS-CoV-2 are characteristic of engineering, and the concentration of these silent mutations in the restriction sites is extremely unlikely to have arisen by random evolution.
From GM via e-mail:
This one has understandably received a lot of attention, but it does not really prove what it claims because it doesn’t explain much about the observed properties of the virus.
First, there are literally thousands of restriction enzymes. They focus on just 2-3 of them because supposedly those have been used in the past to engineer CoV genomes, and then they claim that the distribution of those sites in the genome is too non-random to arise naturally.
But we have the second problem, which is that if this genome was stitched together through such a procedure, it would be stitched together from recognizable pre-existing pieces. In fact people have been doing exactly that kind of experiments ever since Omicron appeared (and even before that, but especially once we had multiple really distinct strains), in which they swap pieces from different strains/variants and study the properties. The other recent study receiving much unwarranted attention — the one about the “80% lethal” strain — also featured that kind of work.
But the SARS-CoV-2 genome does not look stitched from known previous strains, it has unique mutations all over the place.
So if we are to stick with the lab origin hypothesis, that means that one has to propose one of the following:
1) There was a vast collection of sarbecovirus strains in Wuhan that has been since then carefully hidden, and it was a stitch job from pieces that originated from various strains within that collection. And the SARS2 genome only appears to have a lot of unique mutations because we have never seen those other strains. I guess that is possible, but since the pandemic started there have been serious efforts to sequence as much of bat coronaviruses as possible, and the only thing that popped out of those was the strains from Laos with a very similar RBD to that of SARS-CoV-2. But only the RBD, the rest of the genome was much more divergent. So that possibility does not seem very likely.
2) The virus underwent prolonged evolution in the lab, through serial passaging involving some combination of cell lines and live animals. Which is how it accumulated so many mutations relative to whatever ancestors it had. This is much more likely, and even I have in fact long suspected that there might have been something of the sort involved in the origins of the pandemic. However, there would likely still be a recombination signature if there was stitching together involved, and we don’t really see that.
Sadly I can’t access the supporting tweets, but another was less kind:
Alright, I had a look last night and will quickly do a thread on it.
There are many kinds of 'wrong' in science, but this preprint is False. There are many reasons (links at end), but the main one: the “unusual” sites are all *exactly* found in natural bat coronaviruses. 1/n https://t.co/2IrCemHPG8
— Alex Crits-Christoph (@acritschristoph) October 21, 2022