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.
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.
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.
> 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.
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.
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.
>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.
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.
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.
> 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.
exactly the top comment of this reply/thread, that's why i wrote such comment on it.
"As someone who was a genetic engineer for a long while, watching HN talk about dodgy papers like this is painful."
Understand: "as a great scientific with long career, i feel depressed to see so much stupidy."
Trying to attract my sympathy for his "painfull feeling", therefore trying to positively bend my opinion in his favor.
"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."
Im not a specialist here, but this babbling just suggest me someone unable to think out of the box, restricting all possibles to only what he can master.
"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."
"would leave" - "it would" - To me this is legalist wording. A way to suggest something without actually affirming it. cause the dude is not sure at all in fact.
So may be the core idea of his message is scientifically groundede and valid, but the way he expresses it is far more closer to the 'trust me bro' stance than critical neutral scientific phrasing.
> Im not a specialist here, but this babbling just suggest me someone unable to think out of the box, restricting all possibles to only what he can master.
This is a prime example of Asimov's quote: "Anti-intellectualism has been a constant thread winding its way through our political and cultural life, nurtured by the false notion that democracy means that 'my ignorance is just as good as your knowledge.'"
Well, at which extent this applies to our current case ?
Or is it just a way to look smart, by just citing a famous reference without contextualising to our current issue ?
Alevskaya talks about their experience as a biologist, and what their take is on this paper. And your response was, “I don’t understand any of that, so there’s probably nothing there to understand”.
This is not what i said. i suggest you to understand what you read.
first the guy claims he is a scientist and continue with some obfuscated babbling mixing emotional tone and hazardous outcome. Which at first and second read, isnt a scientific neutral analysis and critics.
Therefore it left only the "trust me bro" posture. Which is far from beeing efficient at all.
This discussion at virological.org is where virologists themselves are discussing issues around analysis of viruses in general. It is referring to ancestry and the likely host organism(s)
Horseshoe bats are the likely reservoir of sarbecoviruses (1), including SARS-CoV-1 and SARS-CoV-2 (2–4). Since the emergence of SARS-CoV-1 in 2002 and SARS-CoV-2 in 2019, there has been an increase in the sampling of sarbecoviruses in bats, which can reveal how recently SARS-CoV-1-like and SARS-CoV-2-like viruses sampled in bats shared a common ancestor with, respectively, SARS-CoV-1 and SARS-CoV-2 (jointly referred to as SARS-CoVs)
It may lie to one side of a debate about "engineering" but I take heart from the virologists doing the ongoing detective work to unpack what we can know about this disease and its vectors.
(I posted this to HN directly before. It got very little traction which I doubt means very much)
The origin of SARS-CoV-2 is kind of irrelevant, since both proposed origins could cause future pandemics and so we need to prepare for both kinds. Bump up all animal virus research to BSL4 and mitigate/reduce interaction between humans and wild animal populations.
I agree, do not understand the downvotes. What budget would evil organisation need to create dangerous virus similar to SARS-CoV-2? Is there a chance it may happen again?
I'd guess someone with the right skills could cook up a new human disease for about $10K. I might be off by a factor of ten (in either direction).
I imagine getting the balance of R value and virulence just right would be difficult; I didn't include that in my estimate.
Pandemics come along every hundred years or so, so this will happen again unless we hurry up and exterminate all mammals (humans included).
Alternatively, people could stop panicing. As pandemics go, Covid was extremely mild, and tools like contact tracing and mRNA vaccines will help us reduce the impact of the next one.
I can believe that - after the Snowden revelation on BigTech's close ties with the US Intelligence service, the increasing public awareness to invasive data collection and governments creating privacy focused legislation to minimise said data collection and enforcing data localisation laws that would make it illegal to store and process personal data in foreign countries, an artificially created pandemic that necessitated people to quarantine themselves and force all services through the internet / BigTech could indeed be a partial last ditch effort to force countries to create better internet infrastructure and collect commercial, personal and government data on every global citizen, from every country. China and US are possible suspects, with US being the most likely one.
I have made some analyses on coronavirus sequences.
To be honest I simply don’t understand those experts who are adamant about a likely natural origin of Covid-19.
Let’s talk about the controversial furin cleavage site in the gene of the spike protein.
Apart from this sequence motif, there is not a single(!) insertion or deletion along the entire spike protein between Covid-19 and RaTG13 (more than 3900 nucleotides). All the differences are substitutions, i.e. point mutations.
In other words, every single nucleotide has its equivalent in the parallel sequence. (as opposed to this, more than five hundred different InDels were discovered in different variants after less than four years of evolution in humans)
Covid-19 and RaTG13 have 96% of homology, which could be translated to about 50 years of divergent evolution. (that’s a popular argument of why RaTG13 couldn’t have evolved into Covid-19 during the several years after its discovery. (that’s not entirely true because the rate of the evolution is not constant, it can be accelerated for shorter periods, but let’s accept it for now)
That means that RaTG13 and Covid-19 must have had a common ancestor at about 50 years ago. That either had or had not the furin site. If it had then RaTG13 lost it some time during the following years, if it hadn’t then Covid-19 acquired it.
The first scenario is very unlikely because the furin cleavage has known to provide strong evolutionary advantage so in the presence of the bulk un-mutated viruses in the same cells, the new mutant must have been selected out and disappeared fast, right after its emergence.
So Covid-19 acquired it. The question is only, how? If it were not an insertion then I could accept that it occurred step-by-step by consecutive single mutations such as evolution is known to work. First a very weak site being formed and then it becames stronger and stronger by each additional point mutation, driven by the selection force. But not in the case of an insertion, it must have happened in one single step. In the nature, Covid-19 could have acquired it only from another bat coronavirus by recombination (or more exactly by template switching).
However there is no known member of the family of betacoronaviruses (where Covid-19, SARS and MERS belong) which contains furin site. Nor bat viruses and neither in other species.
There is furin cleavage site in the spike protein of several alphacoronaviruses but their sequences are too different from Covid-19 to be able to recombine with it. Also, the furin site sequence in those bat viruses is very different from the one in Covid-19, even on protein level, let alone on RNA level. You can find similar sequences only in feline and canine coronaviruses. The site in Covid-19 looks to have optimized codon usage for human (or mouse) cells and highly suboptimal for protein translation in bats. (especially for those often mentioned Arginine codons)
All these considerations taken together with the proven fact that Eco Alliance and Dr. Baric at University of North Carolina at least considered inserting a furin site into a bat coronavirus (see the links) strongly argues for the laboratory origin of Covid-19.
https://theintercept.com/2021/09/23/coronavirus-research-gra...https://theintercept.com/2021/10/06/intercepted-covid-origin...
I cannot render a percentage number to this probability but in my mind it’s close to certainty.
the title of this article is not clickbait. not any kind that is manipulative, anyway.
it is a headline designed to get you to read an article, yes, and in that way most headlines are "bait" for someone, but clickbait headlines specifically use manipulative techniques to both avoid telling the nature of the article at all, and still prey on a reader's curiosity, both of which encourage the reader to load the article page, often to see that the article itself isn't something the reader cares about. clickbait headlines and articles are both designed solely to create revenue from advertisement impressions.
this article headline is accurate and complete, and the article is exactly what the headline said it would be.
Meh no biggie. Might be wrong word choice for what is still a reasonably good point; the choice to publish about an extremely controversial paper that has not even been reviewed? It is, in fact, manipulative. It is stirring drama for the purpose of increasing readership.
When I Google “What is click bait?” I get this definition: “(on the internet) content whose main purpose is to attract attention and encourage visitors to click on a link to a particular web page.”
This article kinda does actually fit that definition. Not with manipulative wording in the title, but with choice of topic and (to parent’s point) highlighting an outlier and lacking representation for the general trends.
