the "gain-of-function" experiments - ie. increasing the deadliness and transmissibility of a virus - doesn't seem to require any meaningful technology, at least not the way it was done in the Wuhan labs to the coronavirus[1]. Such "improved" virus wouldn't look like a "lab made". In theory similar gain-of-function experiments could have resulted in the human transmissible HIV back then.
Those gain-of-function experiments were done at the University of North Carolina.
But we know for certain that SARS-CoV-2 was not created through gain-of-function experiments. It doesn't use any of the standard viral backbones used in such experiments, it has a receptor binding domain that computational chemistry algorithms would not have predicted to work (meaning that nature "invented" it, not scientists), and the virus contains seemingly random differences throughout its genome from all known viruses - that would not be the case for a lab-created virus.
The boring answer is the correct one: this virus evolved in nature, and then spilled over into the human population late last year.
Your statement contradicted itself in several places: a "gain of function" virus would contain random differences, and would look indistinguishable from something "created by nature." Effectively that's how nature makes more virulent viruses; the more virulent examples reproduce more effectively. Just like that's how nature/bakeries makes yeast that works better on flour. No genetic engineering involved.
I don't think there is any evidence of this, despite the usual suspects (neocon types on our side, and militarists on the Chinese side) ginning up the case for an "escape from lab" casus belli, but let's get the facts straight.
> a "gain of function" virus would contain random differences, and would look indistinguishable from something "created by nature."
No, a chimeric virus created in a gain-of-function experiment would look extremely similar to known viruses, because these chimeras are created by combining elements of known viruses. It would not be 4% different from the closest known natural virus. Accumulating thousands of mutations throughout the entire genome takes decades of evolution. In the wild, that means thousands of generations of hosts.
A virus created in a gain-of-function experiment would also use a well-known backbone. It would not be based on some virus that nobody had ever heard of.
I don't know what your purpose is in regurgitating verifiable but admittedly realistic-sounding bullshit on hacker news, but virtually every statement you have made here is obvious bullshit.
I don't even particularly believe the "possibly released from a lab" meme, and am generally against the shadowy dipshits that push it. But you're not helping here.
does gain of function require directly engineering the sequence? i saw one gain of function expeeiment where a cat virus was exposed to mouse material, and underwent zoonosis on its own
additionally the sequence can just be manually copied over
that paper for some reason ignores plausible alternative approaches to creating viruses in the lab
The problem with that theory is that the virus contains thousands of mutations throughout its genome, which would take decades of evolution to accumulate. In the wild, this virus jumps to a new host every few days, meaning that decades of evolution amount to thousands of generations of virus. No lab has the time to pass virus through so many animals.
i dont understand why it would have to jump through a bunch of animals first. cant it go from bat to human?
fauci was conducting coronavirus gain of function experiments in wuhan in 2019 trying to go from bat to human, so at least some scientists didn't consider the evolutionary distance to be so great
That is the answer you get from the experiments, if it jumps then it can, if it doesn't jump, keep trying different strains and generations selectively bred in mice/ferrets/etc. (in addition to using human cells in vitro to filter the candidates at various stages, an interesting modern possibility is to use mice seeded with human cells with the receptors of target type like ACE2 in this case and/or with human cells from respiratory surfaces). In general it is like you'd selectively breed new type of apple or grain, condensing the decades of chaotic natural selection into managed selection over few years or even months when it comes to fast iterating objects like for example viruses and bacteria.
So far it looks like the experiments did succeed. China is a country where prison inmates voluntarily donate organs while still alive, and in general it sounds like their prisons are very harsh, comparable or even worse than for example in Russia. Compare to that getting infected with a flu and spending few weeks in a nice lab hospital being well fed and relieved from the hard labor and abuse by the guards and other prisoners - i suspect there would be a line to sign up for those experiments.
So I'm still not following. You say it is infeasible for a lab to generate sars2, yet it seems Fauci thinks it is feasible enough to fund an attempt.
If I understand your argument, you claim sars2 is too genetically different from the closest public sequences to have been lab engineered. But, what precludes a lab from discovering a virus in the wild that is close to making the jump, and then pushing it the rest of the way? I am not understanding the argument that we have to limit the range of possibility to only the publicly disclosed virus sequences.
For example, if you line up the ace2 site between sars2 and sars, they have a lot of similarity. This author claims the section is essentially copied over, although I don't know if it is statistically significant enough to not just be an accident.
https://nerdhaspower.weebly.com/blog/scientific-evidence-and...
So, a "lab origin" theorist could say they isolated a virus in the wild, and copied over the ace2 section from sars, and then ran it through human tissue until it gain enough function to spread effectively in the human population. Is that less or more likely than a coronavirus in the wild mutating enough to make such a lethal jump to humans? Is there any way to put a probability on the two theories?
> You say it is infeasible for a lab to generate sars2, yet it seems Fauci thinks it is feasible enough to fund an attempt.
Saying they were trying to generate SARS-CoV-2 in a lab is a very polemical way of saying that they were studying viral transmission in cell culture. They didn't create SARS-CoV-2. They created viruses that are extremely different from SARS-CoV-2.
> But, what precludes a lab from discovering a virus in the wild that is close to making the jump, and then pushing it the rest of the way?
The Wuhan Institute of Virology publishes identifying genetic sequences of the viruses it samples from the wild. SARS-CoV-2 is not among those viruses. The closest virus (RaTG13) that the WIV found before the pandemic was 4% different from SARS-CoV-2. If SARS-CoV-2 were engineered from RaTG13, then the two viruses would be virtually identical throughout most of their genome. The only differences would be those introduced by the researchers. Yet the two viruses have seemingly random differences throughout their genomes - the types of differences you would not get in gain-of-function experiments. A 4% difference corresponds to many years of divergent evolution. The two viruses might have split as far back as the late 1800s.
So it's certain that SARS-CoV-2 is not engineered on the basis of RaTG13. If you want to claim that the WIV secretly found a different virus, then for unknown reasons didn't publish about that virus, and then started doing gain-of-function experiments on it without telling anyone (including their American scientific collaborators), you're just so far out in the realm of evidence-free conspiracy land that it's not worth responding to.
> copied over the ace2 section from sars
The receptor binding domains of SARS-CoV and SARS-COV-2 are very different from one another. The blog you're looking to is nonsense.
Listen to actual experts, like the virologists at This Week in Virology, not bloggers making wild claims.
regarding the binding sites, clearly they are quite different. but, the similarities seem greater than possible by chance, and i am not sure how that could happen. maybe a variant of sars mutated into sars2?
the sites are at least similar enough that researchers are trying to use sars vaccines to engineer sars2 vaccine
What do you mean that they're more similar than is possible by chance?
Instead of reading conspiracy blogs, go read scientific papers. If you don't understand them, then there is really good introductory course material on virology available from several universities.
Looking at the ACE2 alignment from the article, it looks like there are 55 spots where the sequences have different proteins. Of those 55 spots, 7 of them are identical between the bat and sars2. On the other hand, I count 20 matches between sars and sars2.
Using a uniform distribution over the 20 proteins, and saying the probability of two proteins matching is 1/20, then the binomial probability of getting 7 or more matches out of 55 is 0.02, whereas the probability of getting 20 or more matches is less than 0.000001.
I can see 0.02 being achieved by chance, but 0.000001 seems pretty unlikely to happen by accident. So, there is some sort of non accidental relationship between sars and sars2. Maybe 1) sars2 is descended from sars, or maybe 2) it is lab engineered.
If the bat coronavirus is likely the more proximate ancestor to sars2 than sars, then #1 seems unlikely, which makes #2 the more plausible hypothesis.
Also, to return to your argument about restricting our 'lab origin' hypothesis to known viruses, it seems that if WIV found a very effective bat coronavirus, and intend to create a bioweapon from it, this is exactly the situation when they would not share the sequence. I do not understand why you think people creating a bioweapon would want to share their materials with the world.
> So, there is some sort of non accidental relationship between sars and sars2.
Yeah, they're both betacoronaviruses. You've just discovered something called "common descent." Charles Darwin published about it in 1859.
I'm sorry, but this is getting comical. You really have to step back and learn some basics about biology before you go on this dive into conspiracy theories.
Hmm, still not following. Why would the fact both are betacoronaviruses entail ace2 is conserved? Is human binding ace2 a common feature of betacoronaviruses? Are you arguing that sars is the more recent ancestor than ratg13?
I blasted sars2 against sars and against ratg13. 88% coverage for the first and 99% for the second, so ratg13 seems to be a much more recent ancestor.
Why would ace2 be much better preserved between sars2 and sars than between sars2 and ratg13?
Apologies for being dense :) As you notice, I'm pretty new to bioinformatics. Just trying to understand what your argument is.
UPDATE:
Sorry, I see a mistake I've been making that is confusing. I should be referring to Bat_CoV_ZC45 and Bat_CoV_ZXC21, not ratg13. ratg13 is the one that also has a close match to ace2, but the author claims is a forgery. The bat coronaviruses also seem to be more evolutionarily close to sars2 than sars, and they don't have the ace2 binding sites.
> Why would the fact both are betacoronaviruses entail ace2 is conserved? Is human binding ace2 a common feature of betacoronaviruses? Are you arguing that sars is the more recent ancestor than ratg13?
I'm saying that it's complete nonsense to say that there's a (1/20)^7 chance of 7 amino acids matching. We're talking about viruses that are descended from a common ancestor, not random, independently distributed coin flips.
> ratg13 seems to be a much more recent ancestor.
RaTG13 is not an ancestor of SARS-CoV-2. The two viruses share a common ancestor.
> Why would ace2 be much better preserved between sars2 and sars than between sars2 and ratg13?
ACE2 is a human protein. Neither SARS-CoV-2 nor SARS-CoV have ACE2. If you're talking about the RBD of the S protein, then note that the RBDs of SARS-CoV-2 and SARS-CoV are only 73% homologous, which is a pretty massive difference.
Stepping back for a second, you're diving down the conspiracy-theory rabbit hole with very little prior knowledge of the subject. That's just going to make you easy prey to a lot of nonsense. Really, instead of reading blogs that claim to have found the secret truth about SARS-CoV-2, listen to what respected virologists have to say about it. Do some basic background reading on virology and coronaviruses. Read some review articles from scientific journals.
I've done a bit of reading from the experts. I read the main debunking article about this lab theory, and personally did not really understand why the authors were so confident their evidence eliminated the lab theory.
1) ace2 binding is much better than humans can engineer with computer simulations
2) virus does not come from any known backbones
Regarding #1, I've found another article where the author was able to induce zoonosis from a feline coronavirus to a mouse by exposing the virus to mouse genetic material. So, the fact humans cannot directly engineer zoonosis very well does not preclude lab induced zoonosis.
Regarding #2, as I mentioned before, it seems this line of reasoning is a non sequitur. A virus backbone used to create a bioweapon is exactly the sort of sequence you are not going to upload to NCBI.
The fact the reasoning does not seem very solid in what is considered the official and definitive debunking of the conspiracy theory is itself odd.
So, it is my reading of some respected virologists that in part motivates me down this rabbit hole.
Anyways, I greatly appreciate your feedback. I'll keep learning more about virology, and hopefully get some clarity on the whole matter.
The WIV is not a bioweapons laboratory. It's an academic research institution. Any gain-of-function experiments they would do would be aimed at understanding viruses, not creating weapons. They would use known backbones, not a virus nobody has ever heard of, that they've never even uploaded to a database.
I'm going to suggest to you that the reason you don't find the reasoning in the debunking to be solid is that you don't understand the field very well. I don't know what your specialty is, but imagine someone who has no experience in it. They might have a lot of weird conceptions about your specialty, they might have no idea how things work in your field, they might find a lot of things surprising. Things that you find obvious might seem dubious to a novice. The arguments made in the debunking are considered very strong by experts in the field. That's what matters.
[1]https://www.newsweek.com/dr-fauci-backed-controversial-wuhan...