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Comment by ximeng | Hacker News Reader

https://www.sciencedirect.com/science/article/pii/S187350612... Here is a paper that states that the furin cleavage site appears naturally in a number of viruses.

I looked into these lab origin theories for the furin cleavage site last year. The problem with it being a laboratory insertion was that although performing an insertion is relatively easy once you know what to insert, generally it’s beyond current science to independently create mutations for a specific purpose.

It’s a bit beyond me as a non-biologist but my feeling based on the literature was that the lab origin was unlikely. However it is pushed in certain circles partly for ideological reasons, based on evidence that is plausible at first glance but with a lot more digging not entirely convincing evidence.

However, there didn’t really seem to be much neutral expert analysis of the evidence.

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The natural origin hypothesis is also pushed for ideological reasons - at this level of meta analysis we are at a stalemate. The article was good at revealing that there is not just ideology - but also material interests involved and that the two prestigious letters that were so categorical in dismissing the lab escape hypothesis were quite a bit tainted by conflicts of interests.

I believe the lab origin theory is flawed based on the scientific reasoning, not the meta analysis. I agree that the meta analysis is inconclusive as it is not emphasising the science enough. The feeling I get is China doesn't really want to talk about it because it encourages ideologically motivated people to attack China, and serious scientists are mostly not convinced that this is a lab escape and so don't feel the need to discuss it.

At the same time, China risks looking guilty because they are defensive and try to control the information. All this leaves this kind of article with a seemingly plausible scientific and ideological basis that is difficult for laymen and even scientific journalists to evaluate due to the complexity of the science involved, and not many scientists interested in spelling out why the reasoning might be flawed.

You also see in the quote from the article:

“Yes, but your wording makes this sound unlikely — viruses are specialists at unusual events,” is the riposte of David L. Robertson, a virologist at the University of Glasgow who regards lab escape as a conspiracy theory.

The article is great at spelling a few things out, personally I feel enticed by it in some form. It is the job of other scientists to dispel any wrong or inaccurate information.

Usually the more interesting questions are of the kind of what -isn’t- being said, of what information isn’t being related or investigated.

I agree it's enticing. I tend to agree with the scientist quoted that it's a conspiracy theory, but if it is then it's a really good one, and this article is well written.

If I'm right the reason it's not being analysed or investigated is that from a scientific perspective it's just not an interesting question, rather than for a deeper ideological reason as suggested in this article.

I drew the conclusion that this furin cleavage site theory wasn't actually convincing after a few days of wading through scientific literature, but as a non-expert I was pretty disappointed that there wasn't more accessible analysis of well-written arguments as presented in the article that would put it into a more objective perspective. It would have been great if that scientist they quote would have provided a more detailed rebuttal.

The problem is it actually isn't the job of scientists to dispel wrong or inaccurate information for the most part. They do detailed esoteric studies and write them up for specialists. It's nobody's job to rebut bad arguments, and that's the problem.

Exactly, and concerning your last paragraph since nobody seems responsible (and who is able to write such a rebuttal) it isn’t done. This is a problem because sometimes it can harm the information sphere around this, which is already loaded in camps and so on. Especially when it comes to China which has a questionable track record on sharing information which doesn’t paint them in a good light.

I find it hard to take seriously any “scientist” that dismisses an idea as a “conspiracy theory” (i.e. a concept developed by the CIA specifically to discredit political opponents) as opposed to using actual rational / scientific arguments.

At best, it demonstrates intellectual laziness, at worst a political / ideological conviction, neither of which is a hallmark of a good scientist.

To be clear, the scientist is not quoted as calling it a conspiracy theory, that is the wording of the author of the article.

The scientist provides a scientific explanation (“Recombination is naturally very, very frequent in these viruses, there are recombination breakpoints in the spike protein and these codons appear unusual exactly because we’ve not sampled enough.”).

First, "conspiracy theory" these days has a wider meaning, in that it can be used to refer to pretty much any claim that goes against conventional explanations. I'm not a fan of the wide use of this term but it is what it is and it's now basically a useless term in any discussion except for manipulation.

But let's flip this round as the author here is openly heavily weighing his dismissal of scientific support for natural origin by claiming that it is supported by ideological reasons. That's exactly the same as someone dismissing the lab claim for ideological/conspiracy reasons, just the other way round. Natural origin doesn't support the author's ideology, so he dismisses it and has a bias towards evidence for lab origin. The author has previous done this exact some thing with his previous writings, taking a fringe position and dismissing scientific objection that aligns with the scientific consensus as ideology. Basically, this is a subjective opinion piece, not objective analysis.

I agree with you conspiracy theory can mean pretty much anything for example during WW2 people couldn't grasp that Nazi regime had extermination camps until Allies entered East Europe and Germany and filmed the horrors of those camps. Some people could've called extermination camps conspiracy theory and regard it as propaganda against Hitler and Nazi Germany.

When entering the camps, they made sure to document well, because they knew no one could possibly believe the extent of the atrocities without seeing themselves.

That's what I meant so that some people can not call the holocaust a conspiracy theory.

Conspiracy theories are as old as humanity: https://en.wikipedia.org/wiki/List_of_conspiracy_theories

What makes you think that they are a concept developed by the CIA?

Even the exact phrase "conspiracy theory" predates the CIA by at least 40 years. So it seems the poster's theory about the origin of the conspiracy theory is, reflectively, a conspiracy theory itself. Given that the CIA is so often the subject of such conspiracy theories, I suspect irony might have been employed.

Now I can't tell if the commenter legitimately thinks that no scientific mind would dismiss conspiracy theories or if they're making fun of people who want scientists to entertain conspiracy theories.

The problem with calling it a conspiracy theory does not hinge on whatever the CIA may or may not have used the expression for, but rather on the unassailable fact that there is no implied conspiracy in said theory. It's an accident theory, calling it a conspiracy theory is just as wrong as saying that James Dean died in a Porsche conspiracy.

But it needing a conspiracy to be kept quiet is one of the main arguments against thr lab theory.

How many people (lab technicians, doctors, 'police') would know it is from a lab and are hiding that information? If the answer is 'hundreds' then the chances of it being kept hidden are very low. That is what labeling it a conspiracy theory means.

You do realize the power of China's information control system and the level of national fervor their people have right? Any mention would be investigated, probably hidden and the person and their family disappeared.

Back in January, it wasn’t. Some Chinese friends of mine became very convinced it was a lab leak back in Jan 2020 based on rumors on WeChat. The censors cleaned that up, but I’m pretty confident that privately a lot of people in China believe the lab leak theory.

I lean towards the lab hypothesis due to China’s behavior early in the pandemic. I have a difficult time understanding why they would have been arresting doctors who were talking about the virus if it were natural.

The transition from arresting doctors to locking down cities doesn’t make much sense otherwise. You could argue they had motivation to arrest doctors talking about a natural infection if they thought they were spreading fear and disrupting lunar new year festivities, but going to locking down whole cities is about as fear inducing and disruptive as it gets. If that were the motivations for arrest, I’d expect more reluctant and less heavy handed mitigation efforts.

If this were a natural disease and the motivations were to control it as quickly as possible, I’d expect early doctors to be painted as national heroes/propagandized positively very early, similarly to the portrayal of the people that built extra hospital spaces early on.

It’s possible there were different officials involved that changed motivations halfway through, but the lab leak hypothesis offers a more consistent explanation. It makes sense that they would have tried to control the virus quietly if it were a lab leak/wanted to keep it secret, and that they would engage in drastic measures to control it when that didn’t work.

That's not enough to draw any conclusion - authoritarian governments led by a tiny few are the geopolitical equivalent of a schizophrenic. The smaller the group with absolute power, the more individual personalities, arbitrary interests, and even day-to-day mood dominate the decision making process. The more power is distributed beyond the group, the more policies return to the mean and the less it varies from day to day.

China has the added wrinkle that it's so large that national authorities policies' can vary wildly from local and regional responses for a long time while the bureaucrats play a game of telephone.

That’s a fair point. The response is not conclusive evidence.

I still think the response is more consistent with a lab leak, even when bureaucratic schizophrenia is accounted for, but that expected level of noise makes it impossible to conclude anything definitively.

> [...] China’s behavior early in the pandemic. I have a difficult time understanding why they would have been arresting doctors who were talking about the virus if it were natural.

I'm ambivalent about the two hypotheses, but China's early behaviour fits either, I think. I do think that the instinct of the regional bureaucracy is to control the flow of information, and punish those that proceed outside the party hierarchy (even if there was no foul play/bad conscience/anything to hide).

It’s plausible either way, and the behavior is by no means a smoking gun, but it seems slightly more consistent with a lab leak hypothesis. I’d expect a slightly different pattern of attempting to control information if there wasn’t any connection to the lab.

The disappearance of Huang Yan Ling is another bit of evidence that pushes me towards the lab leak.

If I were to assign a percentage to it, I’d say about 60% chance lab origin is true, 40% chance natural origin is true.

> it seems slightly more consistent with a lab leak hypothesis.

Do you actually have any evidence in which to compare and contrast how a government behaves when trying to cover up a manmade virus vs how a government behaves when trying to cover up a natural virus that has hopped species? Genuinely asking because we absolutely need to be pinning conclusions on evidence and not conjecture here.

My counterpoint is Ai Wei Wei was disappeared for barely anything at all, dude was producing art that people don’t like. And Jack Ma also disappeared for a period of time right? The Chinese government disappears people like I have coffee in the morning. I would need more evidence to presume this disappearance of a doctor is somehow more significant.

> Do you actually have any evidence in which to compare and contrast how a government behaves when trying to cover up a manmade virus vs how a government behaves when trying to cover up a natural virus that has hopped species?

I’m not GP, but GP used the term “lab escape”, not “man made”. Lab escape could just as easily apply to a naturally occurring disease that was being studied in the lab.

Yes. If you're talking about the bioweapon/artificial virus hypothesis, I am not suggesting that the virus was intentionally constructed. The lab was researching human transmissibility of bat coronaviruses and I believe there was likely some sort of accident.

The disappearance of Huang Yan Ling is significant because the Wuhan virology lab said she's fine and hasn't disappeared/is working elsewhere. Many suspected she was patient zero and died.

The CCP has a huge incentive to have her come forward and make some kind of a statement that she's fine and that the outbreak has nothing to do with the lab/those are all rumors, similar to what the lead researcher Shi Zhengli did. The expected behavior if she were the target of a rumor that she was patient zero would be to squash it immediately in the strongest way possible, whether or not it were true. Huang Yan Ling making a statement and talking about that silly rumor would be the strongest way to squash that rumor.

The fact that has not happened suggests she isn't able to because she is no longer alive.

As to more generic comparisons about behavior during a natural virus vs an accidentally released virus, I don't have anything stronger than conjecture, but think a comparison to SARS would shed some light. Again, it is my understanding that during that outbreak, in which a natural virus hopped species, there was heavy handed action and repression of information about how bad things were getting, but that was after things had gotten bad. I don't believe there were doctors that were being silenced before the outbreak got severe. If you want to prevent the severity of a natural outbreak you need and want doctors to be jumping on the issue early, and I would imagine you would want to exaggerate the effectiveness of their early intervention rather than silence doctors trying to mount an early intervention.

Arresting Drs talking about a possible repeat of SARS is something China clearly wouldn’t want out unless it absolutely had to. The effects on markets, general panic etc are not nothing issues.

Later discovering they really did have a problem and it was even worse than SARS going to a full lockdown at the main crossroads city right before Chinese New Year (the largest human migration event).

The motivation feels very normal/predicable for China. And also similar to their SARS response. So is SARS also an intentional self inflicted lab leak? And is MERS a secret belt and road initiative?

Seems weird there is a conspiracy about the third deadly coronavirus but not the first two... or the common cold for that matter? Where did that come from and was that a lab leak?

Whole thing smells of lazy arm chair enquiry with a touch of xenophobia

I don’t know why any mention of a lab escape automatically triggers people to start shouting “xenophobe”.

There’s nothing particularly new about lab escapes, they happen quite frequently. And given the presence of a bio-lab studying coronaviruses just a short distance from the site of the first reported cases, why would any rational person not consider that as a possibility?

I don’t think you even have to go down the “bio weapon” route here. It could be as simple as a worker infecting themselves with a natural sample unwittingly. Following your logic then, I think China would be incredibly unlikely to admit a lab escape of a natural sample now given the devastation it has caused. It’d be a huge loss of face and draw questions towards China’s competence.

In the context of the rest of my comment SARS, MERS... so we know that deadly variants of coronavirus break into the human population. But THIS one is the lab leak...

If this did come from a lab, it was an accident. I think it’s unreasonable to consider the spread in China intentional, as there’s no reasonable motivation to do so.

The main difference from SARS is we know there is a virology lab in Wuhan researching coronaviruses right across from the wet market considered the epicenter.

I don’t know enough about the reaction to SARS to know how similar it was, but my understanding was they were similarly draconian internally, and were trying to keep it relatively quiet, but I am not aware of any arrests of doctors early on in SARS outbreaks.

The plausibility of Covid escaping from a lab does not make all viruses plausibly escaped from labs. The reason it’s more plausible for covid are the initial reactions and the proximity of the epicenter to a virology lab studying covid.

I fail to see how it’s xenophobic to consider the lab leak plausible. If anything a natural spread relies on the assumption that the wet market was engaged in unhygienic practices and that someone foreign may have eaten an infected bat.

Setting the actual tragic pandemic to one side.

It is not true that there are never going to be reasonable motivations to deploy a virus:-

It could be viewed as a tool to alter population demographics in an ageing society.

It might be deployed against an adversary.

It might be used to reduce the human population to avoid a predicted ecological disaster.

There are probably dozens of very reasonable motivations.

That’s a stronger claim than I was making; I don’t think it’s categorically unreasonable to assume there’s motivation to intentionally release a virus.

I think it’s unreasonable to think there was a motivation to intentionally release Covid.

I don’t think there’s reasonable motivation given when and where the outbreak started, how the virus works, China’s response, etc.

I think the particular scenarios you’re painting are also quite extreme/unlikely, so any claim that a virus was released intentionally would require extraordinary evidence in most cases/I’d rarely entertain that hypothesis. There are less drastic and risky ways with less blowback of dealing with all of those issues, even if you assume a very capable bad actor and ignore the normal and expected amount of incompetence and error.

Right, I agree with you completely on Covid.

> as there’s no reasonable motivation to do so. China is the only major economy to have done well during the pandemic. Not saying that it was intentional but it seems somewhat naive to say there is no reasonable motivation to do so.

I don’t think it’s reasonable to assume they knew that would be the outcome, or that they would release it intentionally on their own population to affect the rest of the world.

“Right across from”?

If you are familiar with Wuhan, you’d know you are talking crap. The virology lab is on the East side of the river in the University sector of the city.

The market is on the west side of the river and is in the cbd sector of the city.

We are talking 10km distance apart, with a huge river between. And there are many other wet markets between that would more likely service the community closer to the lab.

That particular wet market takes a lot of shipments straight off boats and from outside the city.

But sure. If by “right across” you meant “on the other side of the CBD, across the largest river in China, and on the opposite side of the largest University campus in China” then I agree.

Map for others to reference and judge whether “right across” is a reasonable description.

https://www.breakingasia.com/wp-content/uploads/Wuhan-Virolo...

A virology lab studying the human transmissibility of bat corona viruses ~10km away from the purported epicenter of the outbreak of a bat related coronavirus is notable.

Epicentre of the outbreak != the origin. But sure... let just pretend that Wuhan is a single lab, a single road going 10km and a wet market.

How come no one at the lab? Or the University got it? How come initially it was Hankou (west side) that was locked down and not Wuchang (east side)?

Surely the folks leaking (given the equivalent of the cdc is in the same location) it would have thought of that and locked it down first?

Sorry that facts keep spoiling the juicy narrative.

>I have a difficult time understanding why they would have been arresting doctors who were talking about the virus if it were natural.

No doctors were arrested early on. Few got cold tea lectures about spreading rumors that literal SARs returned not novel SARs like virus. Signed boilerplate paperwork and was released back to work. This is generic behavior for "picking quarrels and provoking trouble" tier infractions. Not particularly heavy handed at all as far as PRC behavior is concerned. Folks get talks with cyber security for far less. Arguably warranted, had covid not been once in generation virus, spreading panic based on rumors to some critical mass before CNY is pretty egregious. The fact these doctors got slap on risk treatment shows officials were essentially oblivious of severity of novel virus. If there was foreknowledge of a lab leak, these doctors would be under surveillance and stashed away in safe house away from family/friends/work for months/years like in other politically sensitive cases.

> No doctors were arrested early on

The following happened to Doctor Li Wenliang:

> On 3 January 2020, police from the Wuhan Public Security Bureau investigating the case interrogated Li, issued a formal written warning and censuring him for "publishing untrue statements about seven confirmed SARS cases at the Huanan Seafood Market." He was made to sign a letter of admonition promising not to do it again. The police warned him that any recalcitrant behavior would result in a prosecution.

Being detained and forced to sign a letter on threat of prosecution is the practical equivalent of being arrested.

> If there was foreknowledge of a lab leak, these doctors would be under surveillance and stashed away in safe house away from family/friends/work for months/years like in other politically sensitive cases.

There is no evidence that doctors like Doctor Li Wenliang had knowledge of the origin, and were targeted for reporting on the virus.

Huang Yan Ling was a researcher at the virology lab in Wuhan that has been missing since right before the outbreak.

Since when is being brought in for questioning equivalent to being arrested anywhere? Being arrested and prosecuted is being arrested. People deliberately conflate it build narrative of PRC hiding covid origins when its generic rumor quashing behavior by PSB. Point remains, non of the doctors alleged to be part of some massive cover up by conspiracy peddlers were subject to any of the treatment PRC actually reserves for coverups.

Huang Yan Ling stopped working at WIV in 2015. The only reason she's noteworthy is conspiracy theorist tried to link her as patient 0. People have some expectation that PRC should indulge in random conspiracy theory by parading her around. Like is US going open up fort Detrick for scrutiny? No because entertaining the whims of yahoos is ridiculous.

> No doctors were arrested early on.

That's a lie.

Your first sentence is a complete lie.

" I have a difficult time understanding why they would have been arresting doctors who were talking about the virus if it were natural."

Oh that's easy: an authoritarian state would be arresting irrespective of the origin. They want to control the message , no matter what. The truth is a distraction in that case.

Once things flip, and the public becomes aware, then they can re-write history and make them national hero's. Chinese citizens are apparently skeptical of their own government, and get pissed off a lot, I suggest the Doctor who made the discovery is a little bit of a populist hero already.

The CCP's actions demonstrate they are fully authoritarian, that's about it.

My colleague, an evolutionary biologist's comment on this: the virus is unlikely to prevail if manually tweaked since evolution does such an amazing job that it's very unlikely it alone could dominate and infect large populations.

How about a virus that's just allowed to evolve inside human tissue? Not "manually tweaked" just allowed to evolve faster.

I'm not an evolutionary biologist. I merely want to pass on his comment. He studied the viral genome segments inserted in human genome. I can pass that question to him if you want.

The Coronavirus Gain-Of-Function research the Wuhan lab was doing probably wasn't manually tweaking the virus, or inserting viral genome segements.

It was more likely putting evolutionary pressure on Coronaviruses in order to change it's properties and behaviour.

'Manually tweak' is a bad word invented by me. He didn't mean it was viral segment insertion either.

Regarding selection pressure people do that all the time, in fact it is far from easy to artificially apply environmental pressure and obtain highly functional new variants. In cancer research, xenograft are extremely tricky to do with immunodeficient animal models, let alone human tissue in the lab. Sure you can have some success but it's difficult enough to reproduce. His point is that even if an artificially selected highly viable variant was obtained, it is very unlikely it can prevail in real world nature selection (large scale too). I'm no expert but happy to read about any paper if it's not the case.

If we abstract away the specific actors/motivations, this reminds me a bit of the Oumuamua debate. "Man made" and "natural" are both very broad theories that admit many details and are thus hard to falsify. But I wonder to what degree we agree about:

(1) Which category (if either) has an advantage by Occam's razor? (2) Which category (if either) is more easily falsifiable? (Meaning easier to determine improbable, since it is hard to falsify them entirely)

For me, I see neither having an advantage on (1), but on (2) there are a finite number of relevant, well-known lab techniques that could be investigated.

Just one nitpick - it does not need to be 'man made' to make a 'lab escape'.

Yeah, my spouse just hit me with the same point. I think the ["natural" process but facilitated by lab escape] branch is probably the hardest to falsify, so it's a place peoples' prior weights on that scenario are going to end up really dominating discourse.

I think that branch is past what scientific dialog really covers, and it's probably the methods and standards of proof from legal exploration that might be the way to progress the discussion. Unfortunately, the world is missing a moderator that folks would broadly trust to facilitate that conversation.

Correct, and this is talked about a good bit in the article.

> generally it’s beyond current science to independently create mutations for a specific purpose.

No it isn't.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810786/

Quite a long article, but skimming it it looks like that experiment involves applying naturally occurring mutations to an existing virus?

Yes. Gain of function research involves putting evolutionary pressure on an organism to give it certain traits that can be found in the wild, but the resulting virus is anything but natural.

I think a lot of people dismiss the lab leak hypothesis based on the idea that a lab-created virus must have an engineered genome rather than an evolved one.

> generally it’s beyond current science to independently create mutations for a specific purpose.

Labs are the places where people go to push the boundaries. If we go with lab-leak, it is extremely possible that they had figured something new out. They were doing something novel in there, because they were paid money to do novel things.

If we're going to play at paranoia and assume the virus was engineered, it doesn't necessarily follow that the release was an accidental leak.

It would be trivially easy for a hostile power to covertly release a pathogen in another country.

It would also be trivially easy to engineer simultaneous release in multiple locations.

It would be less easy but not impossible to take an existing pathogen during a pandemic, engineer a variant, and release it in another country.

There would always be ambiguity and uncertainty about the source, because there are no telltale markers that unambiguously define an origin, or even whether a pathogen is natural or man-made.

I am not suggesting any of this happened. But I am pointing out that biowarfare has some unexpected covert possibilities.

While Covid may or may not be an example - insufficient data - any defensive strategy should consider the possibility that some other pathogen might be seeded deliberately.

We are not playing paranoia. And you have a valid point that in this scenario it's not crystal clear that it was accidental.

It's true that labs were pushing boundaries, the Wuhan lab as well. But every time they succeeded in doing something novel, they were celebrating it in the media. If they really had been able to reach this major technological breakthrough, one would expect that they would have made this one public as well.

I would say that it's more likely that this was a natural mutation that got its chance to survive natural selection because of the lasting and intense contact with human researchers in the Wuhan lab. There are some media sources that show that researches didn't take too many precautions with avoiding this contact. E.g. there are pictures of researchers without wearing gloves and one that's even showing bites from bats.

It depends how quickly the mistake was made. Totalitarian states are not famous for admitting mistakes, in fact they hide them with all their tools. So I don't think your media hype story is a good explanation.

Maybe this URL makes it seem more legit than it is, but the linked article below has a "2.5" version of events that proposed that samples taken from a group with who'd been infected by a coronavirus from bats may have been released accidentally. In other words that the lab was the point of release, but that they didn't construct or alter the virus as it already had adapted to humans in an earlier time.

I've done some separate reading that this is a legitimate way that viruses can adapt to a new species, but I don't have any background to evaluate the argument much beyond face value.

Some of the adjacent comments shed some doubt there as it sounds like bats aren't a plausible source because of the spike protein genetics.

https://www.independentsciencenews.org/commentaries/a-propos...

The furin cleavage site in SARS-Cov-2 does not appear in any other SARS-related beta coronavirus (sarbecovirus).

From 2014, Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein [1]:

> Such furin-mediated activation is unusual in that it occurs in part during virus entry. Our findings may explain the polytropic nature, pathogenicity, and life cycle of this zoonotic coronavirus.

MERS-CoV uses furin cleavage of S1/S2 but it does not bind to ACE2 like SARS-CoV-2.

[1] https://www.pnas.org/content/111/42/15214

From the OP, it appears that scientists knew exactly where to insert a furin cleavage site:

>“Since 1992 the virology community has known that the one sure way to make a virus deadlier is to give it a furin cleavage site at the S1/S2 junction in the laboratory,” writes Steven Quay, a biotech entrepreneur interested in the origins of SARS2.

The problem is knowing how to put in the furin cleavage site, and generally if it's done in the lab it's done by copying a particular sequence from an existing virus as scientists can't predict how to do it themselves (without copying) with current state of knowledge.

That's such a mischaracterisation, I don't even know where to start. That Quay-guy obviously searched for "furin" on pubmed, found some papers (that don't even say that - and most definitely not for any coronaviruses) and thought it fit his thesis. If only viruses and infections were that simple!

Could you still start somewhere and explain it a bit please? Thank you very much!

he left out the most damning part:

> “At least 11 gain-of-function experiments, adding a furin site to make a virus more infective, are published in the open literature, including [by] Dr. Zhengli Shi, head of coronavirus research at the Wuhan Institute of Virology.”

Introducing mutations with purpose is beyond us, but inserting a variety of mutations randomly in areas of the proteins known to be impactful in various processes, then observing the behavior of the mutants in vivo is not. We do high throughput mutant screening all the time.

The Wu and Zhao paper [0] you cited is based on this paper [1] by Zhou et al, whose conclusions were questioned by this preprint [2].

In fact, the paper [3] cited in the top comment has the following response to the Wu and Zhao paper you cited:

> The recent acquisition of the FCS by SARS-CoV-2 via a natural insert was proposed by Wu and Zhao (2021) on the basis of the existence of FCS in other, more distant Betacoronaviruses with different loop positions to SARS-CoV-2 and the existence of a partial natural insert in the same region in RmYN02 (Zhou et al. 2020a). The reliability of the conclusions of Zhou et al. (2020a) has been questioned by Deigin and Segreto (2020), who particularly challenge the claim that RmYN02 has an insertion around the site of the FCS insertion in SARS-CoV-2 and instead point to a two amino acid deletion in RmYN02 at that locus. Therefore, RmYN02 should not be used as evidence of the natural origin of SARS-CoV-2′s FCS until its claimed insertion is properly validated.

Disclaimer: I’m no biologist/virologist.

[0] https://www.sciencedirect.com/science/article/pii/S187350612...

[1] https://doi.org/10.1016/j.cub.2020.05.023

[2] https://arxiv.org/abs/2012.00627

[3] https://link.springer.com/article/10.1007/s10311-021-01211-0

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