[alevskaya]

As someone who was a genetic engineer for a long while, watching HN talk about dodgy papers like this is painful.

This paper posits a completely crazy cloning strategy that makes no sense (ie doing something far more convoluted than typical bsaI/bsmbi seamless cloning workflows that breaks the whole point of "seamless" workflows), and then tries to use that to make a case for a genomic signature that we could look for. They then look at a handpicked set of viral genomes, but leave a bunch out and duplicate others (I think WIV04 and WHu are the same), and largely seem to be observing without realizing it that yes, recombination occurs among these viral lineages.

This isn't even getting into the fact that a restriction-ligation based cloning strategy would leave glaringly obvious fingerprints behind in the form of the hundreds of nucleotide differences that are present outside the cutsites across the lineages... it would be blindingly obvious if someone just cut-and-pasted sars-cov-2 from other studied genomes.

[rcpt]

They "handpicked" those because they're some of the most common. This is discussed in their paper.

The "completely crazy" strategy was state-of-the-art and published by the WIV in 2016 https://twitter.com/R_H_Ebright/status/1583868000888795137

[alevskaya]

I'm pretty tired of debating people who don't know biology here. Using seamless cloning methods is super common - but they don't work like the paper authors suggest they do. I misspent my youth doing reactions and workflows like these for over two decades.

What they're observing is homologous recombination between strains - all the sites they're claiming are found in nature.

Again - there would be a genetic signal the strength of the noonday sun burning your eyes out if sars-cov-2 was made by cut-and-paste at these sites. You wouldn't need this ridiculous circular argumentation to prove that point.

If we're linking to tweets, these two go into great depth about how ridiculous this paper is: https://twitter.com/Friedemann1/status/1583519970902048768 https://twitter.com/acritschristoph/status/15834864034169692...

[rcpt]

> the sites they're claiming are found in nature.

They're not looking for the existence of the sites they're looking at the distribution of them. Their paper shows that in natural viruses the distribution is distinct from synthetic viruses.

The proposed classifier is how uniformly distributed these sites are, not that the sites exist.

> circular argumentation

Can you elaborate? They select a site based on commonly used it is (and maybe also the fact that Baric and WIV published on it). Then they found evidence of it being used. What's "circular"?

> great depth about how ridiculous this paper is

The crux of his argument (and yours) is tweet 10/ in that thread -- "You CAN actually do it like that, but why should you?" which is pretty weak.

Often, if not most, of the time the engineering I come across hasn't been done in the slickest most optimal way. The fact that there's a better way to do something isn't proof that everyone's been doing that the whole time.

For example, WIV was using non-seamless cloning in 2016 https://twitter.com/R_H_Ebright/status/1583868088524541953

> pretty tired of debating people who don't know biology

I started my PhD in math biology but for whatever reason I just couldn't get along with the PI or any of the postdocs. I don't know what it was. I eventually switched to just math. Oh well.

I used to second guess my decision but in the nearly two decades of research since I've never come across the level of smugness and credentialism that I now see coming from that field. Every disagreement is met with remarks about "kindergarten molecular biology" or referring to other researchers diagrams as "cartoons". Now I don't second guess anymore.

Perhaps if you're so bothered by the people here you should keep your posting to virological.org or simply talk with the biology profs on Twitter directly.

[iancmceachern]

Thank you, this is why I come to HN (facts). Keep fighting the good fight.

[peyton]

Would be nice to have detailed inventory and records from the lab to corroborate your claims.

That information did exist at one point.

[alevskaya]

You don't need access to a proprietary database to refute that sars-cov-2 wasn't copy-pasted at these restriction sites. We have public sequences of the closely related coronavirus strains. The unnatural SNP pattern would be absolutely obvious if someone patched together different lineages around these specific conserved RE sites. Instead we see a set of conserved RE sites related across the publicly known strains by homologous recombination.

What I've tried repeatedly to impress upon people here is that most routine cloning strategies leave pretty clear signatures, and the idea that a lab would go so far as to eliminate these signatures for such mundane virology work is tantamount to a much more elaborate conspiracy theory.

[CodeWriter23]

Your assessment relies on two assumptions. The first being that samples from the “public sequences” are identical to the sequences China’s labs purposefully unpublished early in the pandemic. The second being the assumption there was no nefarious purpose to the well-documented gain of function research taking place in Wuhan.

I don’t need to be a biologist to call your assumptions out as junk science.

[jmeister]

>I'm pretty tired of debating people who don't know biology here

Too bad. This is a matter that affects every citizen in this country, and the experts lost their credibility a couple of years ago at least. The rubes will keep shouting their barbaric yawps over the roofs of the world.

[ggm]

No, they didn't loose their credibility. To political debate they were never granted it, and between themselves as peers it hasn't been lost.

Your perception and reality diverged and your claims they lost credibility lacks a crucial qualifier: 'to me' -which I and many many others discount, even at the volume of American science scepticism. You actually aren't a majority, anywhere and you don't define scientific credibility any more than politics does.

[tetris11]

It is weakening somewhat. The sheer volume of papers that pass in high impact journals, and then are later pulled after X years with minor repercussions, seems at least to me to be an alarming trend. That, paired with the cronyism I've personally witnessed between editors and professors... as someone entrenched in the field, I have to say, I'm surprised more people aren't jaded.

[simplotek]

> This is a matter that affects every citizen in this country, and the experts lost their credibility a couple of years ago at least.

I don't agree. What we did see is ignorance and completely absurd conspiracy theories taking the center stage while experts were being sidelined or even completely removed from the discussion.

[netmonk]

May be because of the "trust me bro, im a scientist" stance.

[simplotek]

> May be because of the "trust me bro, im a scientist" stance.

Could you please show a single example you feel demonstrates this thing you describe as "trust me bro, im a scientist" stance?

[drpixie]

Yeah - Covid seems to be one a few topics that bring out "special" opinions. It's a pity, and not confined to HN, but seems to be a sign of the times.