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Comment by ttul | Hacker News Reader

The This Week In Virology podcast has been talking about the lab leak concept since the early days of the pandemic, with various experts opining on the likelihood. In [1], the expert discusses how the virus itself does not seem engineered; it’s most likely a naturally created virus.

However, this is exactly the sort of virus that they study at the BSL4 lab in Wuhan, quite legitimately - and they produce good science from this work. But because this is China, if a lab accident happened, it won’t be getting reported in the media. It’s a state secret.

The Energy Department gave a low probability to their assessment, but this is still a bombshell. Imagine the legal liability for China in international courts if the evidence is solid enough for litigation.

1. https://www.microbe.tv/twiv/tag/lab-leak-hypothesis/

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> However, this is exactly the sort of virus that they study at the BSL4 lab in Wuhan

No it isn't. The were studying SARS-CoV-1 and WIV-1.

They sequenced RaTG13 but that is too far away from SARS-CoV-2 with a thousand random mutations across its genome. And there's no evidence that they ever recovered culturable virus from RaTG13 or were able to culture it--there's a vast gap between sequencing a virus and culturing it.

We also know about their SARS-CoV-1 and WIV-1 work because they published it. Before the pandemic they had no reason to keep work on RaTG13 secret.

This is a case of Schrodinger's BSL4 lab. We know they built chimeras of other viruses because they told the world about that, we know they sequenced RaTG13 because they published that sequence, but there's a SARS-CoV-2 progenitor backbone that they found, which for some reason they picked to be the backbone in a new set of experiments, which they had perfect secrecy over and nobody has ever found any evidence of it.

The obvious solution for this conundrum is that they did study it, but didn't publish it because the screw-up happened and all evidence was promptly destroyed. In a totalitarian state, the secrecy is the default mode. You can get exceptions and publish stuff, sure, but only once you asked and received permission. If you didn't - or in the period between you asking and permission being issued something happened - no evidence will be seen by anybody.

Perfect, then it's unfalsifiable.

Unfortunately, unless whoever destroyed evidence screwed up (happens all the time, security services have enough idiots and slackers), or somebody kept some evidence and then will defect, yes, it is likely we'll never have the proof. That's why they do it.

Maybe we should stop supporting the study of dangerous viruses in facilities that don't maintain adequate levels of transparency.

Regardless of what actually happened in this case (FWIW I still believe a natural origin was most likely), the Chinese authorities covered up everything to do with the lab and destroyed potential evidence before a proper investigation could take place. In court cases we have a norm that evidence you destroy is treated as evidence against you, for good reason.

I'm not making an argument regarding this instance, but to have a theory that you can't disprove really makes it not a theory and impossible to engage with.

> In court cases we have a norm that evidence you destroy is treated as evidence against you, for good reason.

Destruction of evidence is considered only evidence of consciousness of guilt and cannot be used to prove guilt alone. The court also has to consider that an innocent person may commit destruction of evidence to avoid wrongful prosecution from situations that look damning.

Another point is that in the SARS-CoV-1 outbreak in 2002-2004 the Chinese government acted similarly:

> Early in the epidemic, the Chinese government discouraged its press from reporting on SARS, delayed reporting to WHO, and initially did not provide information to Chinese outside Guangdong province, where the disease is believed to have originated.[19] Also, a WHO team that travelled to Beijing was not allowed to visit Guangdong province for several weeks.[20] This resulted in international criticism, which seems to have led to a change in government policy in early April.

https://en.wikipedia.org/wiki/2002–2004_SARS_outbreak

There was no BSL4 lab in Guangzhou and they didn't sterilize the market there right away, so in that case they were able to eventually track the virus to its origins--yet the reaction of the Chinese government was basically the same.

Americans have a fairly severe problem with assuming that other nations and people's will react with transparency to the US if they have nothing to hide. This is the same problem we saw with Hussein and the way that he tried to block the weapons inspectors and it turned out by his own admission that it was due to him not wanting to appear weak in the view of Iran and Hussein was preoccupied with Iran: https://www.theguardian.com/world/2009/jul/02/saddam-hussein...

The circumstances that make the theory unfalsifiable (lack of transparency/controls in Chinese biological research) are the issue here. Due to the lack of transparency we will likely never have definitive proof for the origin one way or the other.

At a minimum the US government should not be funding any biological research in places without adequate transparency/controls.

It's not, because all it would take to falsify it would be to do an exhaustive search of the lab's documentation and a comprehensive interview of lab employees.

We can't do it because of the CCP, not because of epistemological reasons.

How would that falsify the theory? If you find no evidence you can just claim that the state destroyed it.

The effort required to culture virus like this is fairly large, and it requires them to keep it secret in 2019 before there was any need to keep it secret. Nobody talked about it to collaborators, no sequences were leaked out, etc.

They somehow had tighter controls than Apple developing a new iPhone, before they had any reason to.

Again, you think keeping something secret needs a reason. That's not how totalitarian state works. In such state, not keeping something secret needs a reason. Everything else is secret by default. And the standard mode of action on any disaster is to deny it, lie and hide the evidence. It's not special for pandemic, it happens every time. Yes they absolutely have tighter controls than Apple, and the reason is they live in a totalitarian state and Apple doesn't.

We know they constructed Chimeras of the WIV1 SARS-1-like virus because they published it:

https://www.pnas.org/doi/10.1073/pnas.1517719113

Pretty bad secrecy.

We knew WIV1 existed as well because they published it 3 years earlier:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389864/

How long had they been working on either of those before publishing? You're giving the end points of the research, the person you're replying to is saying the end point wasn't reached, hence it was still secret.

See if you can determine that for yourself by e.g. reading the second paper as far as the first sentence of the second paragraph and then looking at the publication date.

I'm not interested in reading those papers, especially as what's relevant are the dates, which means the burden is on the person presenting them to get the dates right, no one else. More importantly, they were missing the point, which was my point.

Your point? I'm not sure if you had one. Next time, just post the date up instead of some snarky RTFM that doesn't even fit the thread.

It's not like the 2016 article was some kind of a spy leak. They were allowed to cooperate on things that lead to this publication - because in 2016, there was a reason to allow it - NIH grants alone would probably be a good reason. As soon as they learned about the screwup (that likely happened somewhere in 2019) all evidence of the works related to the leak that hasn't been published has been hidden or destroyed. Thus, we can't expect any publications about that work, at least not from 2019 onwards. You're fishing for some contradiction, but there's none - publications do not suggest absence of censorship, publications only suggest the censors had no problems with it being published. And indeed, they couldn't know in 2016 that their research in 2019 would lead to a massive screwup with a global consequences. If they were an open society, there would be a constant trail of evidence leading to the moment of the screwup - communications, orders, articles, chats, etc. In a totalitarian society, all these were under tight control by default - and as soon as it turned out they are dangerous - which became clear sometime in 2019, when the Chinese government learned about the possible leak - all this information, already tightly controlled by default anyway, was disappeared or at least made inaccessible to outsiders. It is possible it still exists somewhere in the dungeons of the Great Firewall - who knows. The point is this is why information control exists - to make such things possible. In an open society, this would be completely infeasible - tracking back everything connected to a certain research program and making it as if it didn't exist. In a closed, tightly controlled society - yes, plausible.

there are millions of people who want to know what Apple is doing

What about the request to use gain of function research to add furin sites to coronaviruses? That seems to me the smoking gun, since this lab asked for funding to do exactly that.

It’s a bit like Jaime Meitzl (sp?) said - for the first time in history you find a unicorn (furin binding site in a coronavirus) next to a lab that asked for funding to make regular horses into unicorns. But the lab says it’s “natural origin”.

The PRRAR FCS not a known FCS prior to the pandemic so it is unlikely the lab would have genetically engineered it and they would have used something like RRXRR instead.

Other coronaviruses have an FCS and they have evolved multiple different times, independently:

https://www.sciencedirect.com/science/article/pii/S187350612...

The fact that we knew that adding an FCS to a virus would likely enhance its ability to produce a pandemic really isn't a smoking gun that we actually did it, because we're just studying and copying what nature is already doing (who is actually a much better geneticist than we are, with vastly greater tools).

And since you want to talk about suspicious "unicorns" how about the idea that a lab worker was infected in the lab, and then the only thing that they did was visit the wet market. They didn't infect anyone they lived with, or go to any restaurants, or go visit grandma and this Typhoid Mary/Mike has no existence outside of working in the lab and visiting the wet market. And this idea gets worse if you include more workers in WIV having supposedly been exposed.

What fits with the facts better is that they genetically engineered the virus in perfect secrecy and deliberately let it loose in the wet market, which is just insanity--nobody gains anything from doing that, but it is also impossible to argue against.

Why would it have happened only in the market? Seems to me that it’s plausible they just managed to cover up other points of origin for the pandemic in Wuhan and that the market was the first super spreading event.

If your only defense is that this is not the most commonly used way to add a FCS to coronaviruses, that seems pretty thin.

And the evidence of the cover up is that there's only evidence at the wet market?

You realize that is going to rapidly descend into circular logic.

The argument "they would have used a published backbone and reverse genetics system" is wishful thinking.

You might interested in this paper: https://www.biorxiv.org/content/10.1101/2023.02.12.528210v2

"Discovery of a novel merbecovirus DNA clone contaminating agricultural rice sequencing datasets from Wuhan, China"

MERS is really nasty, this is clearly evidence of engineering, and guess what the system is unpublished.

Personally I suspect this paper (which came out a while ago but got "boosted" recently) could be the reason for DOE "confidence update".

Media have not reported on this and "the usual" zoonosis advocates have been remarkably silent about it.

HKU4 contamination in agricultural samples in the Country that HKU4 was discovered in does not pose a particularly controversial question as to how it got there.

While it is in the same group of beta coronaviruses that MERS is in, the HKU4 virus was first found in Kowloon and the "HK" stands for "Hong Kong" (although it would be a mistake to assume that says much more than where it was found and not what its range is throughout China)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111821/

And coronaviruses undergo recombination (XBB.1.5 is a recombinant which is all over the news) and that produces "Chimeric" viruses in nature. Finding evidence of "gene splicing" in samples and determining it must be humans ignores the fact that nature does it better than we do, and really points at how politically biased that article is.

They want you to believe that WIV imported MERS-like viruses from Saudi Arabia and were fucking around with them in the lab, and not that those viruses are found all over China naturally and nature fucks around them constantly in much higher volume than we can.

Did you notice the bit where it's a cDNA clone of an RNA virus and do you understand the implications of that?

This is an engineering product.

As for politics, sure there is a lot of that going around but you can verify this finding yourself with freely available software using the published sequences.

That preprint is now starting to get slaughtered in the Disqus comment section associated with it.

I don't think much of the "takedown" so far. Interested to discuss specifics if I'm not getting something.

Cadhla (who works for EcoHealth alliance BTW) points out that it was Wuhan University who registered the rice sequence bioproject PRJNA601977 - which is not hugely relevant since the source of the contamination could be from anywhere (that happened to have a HKU4 reverse genetics system...).

Andreas points to incomplete sequence coverage (not unusual in a contamination scenario) and claims it might be "not dangerous work" because the sequence gap leaves open the possibility that the missing bit was non-functional. True but weak. It's 33 NTs of highly conserved sequence, what does he really think was in that gap? I know what Fat Tony would say.

Flo's comments seem to be claiming that https://www.biorxiv.org/content/10.1101/2023.02.12.528210v2 is plagiarizing https://europepmc.org/article/ppr/ppr353109 (the team's earlier paper which included a similar finding).

Her claim that a reverse genetics systems for HKU4-like COVs was previously disclosed seems weird since AFAIK it was this team that had previously disclosed it. It's possible I am not understanding what she is saying as it makes no sense to me.

Earlier in the pandemic I read a report talking about the possibility of the virus being something they sampled, and that it leaked when they accessed the sample presumably to start sequencing/analyzing it.

The theory was that it was a virus they'd have sampled from immunocompromised miners working in the same caves that the bats with the most closely related viruses inhabit. They had some references to a report with something like that happening some time prior.

It's so far the only theory I've read that seems to match the evidence.

The evidence doesn't seem to indicate that it was engineered, or that it was a product of gain of function research on animals. I think there would have been more solid evidence pointing in that direction by now, if that was the case. They would have published something related to it, or non-Chinese researchers connected to the lab would have known something.

Yet there's no evidence of any related animal resorvoir, and the virus was very well adapted to humans from the very start. And everything points to the virus passing through the lab somehow. Those things put together seems to point at them having sampled a virus that already made the jump to humans, and that somehow during the sampling, or retrieving the sample from storage, the virus escaped.

There's many thousands more contact between bats and humans involved in mining (literally how RaTG13 and the Mojiang mine, bat guano collection for farming and just tourism:

https://www.sciencetimes.com/articles/33905/20211012/china-r...

There's a lot of economic activity in China that is close to bat habitats and there's evidence that cross reactivity to sarbecoviruses exists in a significant amount in rural china.

The researchers collecting samples were a very tiny slice of the human-to-bat-virus exposure that is going on in China all the time.

And we know that SARS-CoV-2 doesn't last very long on surfaces, it isn't transmitted by fomites. It needs to be aerosolized and breathed in. It isn't likely that the researchers were collecting live viable virus in the samples that they brought back to the lab. What they were sequencing was overwhelmingly going to be "dead" mRNA.

The idea that the lab researchers were the initial Typhoid Mary of the pandemic is also simply not believable because it requires one to believe that they lived within a bubble EXCEPT for one trip to the wet market where the outbreak happened. They didn't start spreading it around their apartment building, they didn't infect people in restaurants, didn't infect elderly relatives who wound up in the hospital, etc.

It makes "more" sense that they deliberately genetically engineered the virus and released it in the wet market entirely on purpose.

> The idea that the lab researchers were the initial Typhoid Mary of the pandemic is also simply not believable because it requires one to believe that they lived within a bubble EXCEPT for one trip to the wet market where the outbreak happened.

Except that SARS-CoV-2's epidemiological dynamics are well-known to be overdispersed? Almost all lineages die out, and a few explode due to repeated super-spreader events. It's therefore unlikely that the first cluster will be discovered at the site of introduction. For example, SARS-CoV-2 was presumably first introduced to other continents at airports and seaports; but that's not where the first clusters were found.

Explain the coincidence of why it happened to be in a wet market and not a restaurant or other gathering where people congregate. Just happened to be the one place to make it look exactly like zoonosis and extraordinarily similar to SARS-1.

If you think SARS-CoV-2 arose naturally in the same city as the world's biggest laboratory collection of sarbecoviruses (which I do agree is possible), then you must agree that weird coincidences do happen sometimes? A wet market is crowded and poorly-ventilated, so it's a great place for a respiratory virus to spread, regardless of how it got introduced.

There's also the question of ascertainment bias, whether cases were found in the wet market simply because that's where the authorities looked. I assume you've seen those endless debates, which seem basically unresolvable to me given the limited information available.

The pandemic happening in the same city as WIV isn't really that much of a coincidence. The virus needed a large densely packed city to really take off. Wuhan is the biggest city in central China. The catchment area around Wuhan for where a virus would follow the animal trade to the city is probably large. Wuhan is also a good candidate for a centrally located lab. That only seems like a 5-10% low probability chance, which happens (it is also the second time it happened in China and the first time looked like this one, only it hit Guangzhou where there was no lab).

The infected lab worker causing exactly one massive superspreading event in the wet market without infecting anyone else, making it look exactly like zoonotic spillover, without leaving any other contacts around Wuhan is much less believable to me. That sounds like a thousand to one odds or much worse.

> The infected lab worker causing exactly one massive superspreading event in the wet market without infecting anyone else,

That's indeed unlikely, but it's a strawman. As I've noted repeatedly above, most lineages die out. If the introduction into humans occurred outside the market (naturally or otherwise), then it's quite likely that patient infected others outside the market; those lineages just died out. I remember Trevor Bedford showing genomic evidence of all the failed introductions into Seattle before the spread finally went exponential, early in the pandemic.

Pekar et al. is basically a more sophisticated version of your argument, with numerical models of the phylogenetic and epidemiological dynamics. I don't think it's convincing (since they chose their power law pretty arbitrarily), but at least they acknowledge and purport to model that stochasticity.

If you are not a native English speaker, you may want to know that you are pretty drastically misreading parents comment. He is not saying "I know this specific virus is present" but "the lab studied SARS related coronaviruses" which you in fact seem to agree with.

They're not related enough to matter.

I've lived in the United States all my life, you're just missing the point.

they collected dozens if not hundreds of samples of various viruses. not all the work gets published. in fact majority of scientific effort doesn't get published. experiments either don't work or you don't get interesting results etc... doubly so if a global pandemic started before you were done with your current project

> However, this is exactly the sort of virus that they study at the BSL4 lab in Wuhan, quite legitimately

Bat coronavirus work including chimera creation was done at WIV at BSL-2, not BSL-4.

This is the real scandal.

It’s weird you mention BSL4 and use present tense about Wuhan when discussing covid origins.

The Coronavirus work at Wuhan was done in BSL2 environment; the BSL4 lab was still being built at that time.

> it’s most likely a naturally created virus.

The lab leak hypothesis doesn't even rule out that it was a natural virus. It just says that the virus leaked from the lab. It could have been:

- deliberately created in the lab (gain on function)

- accidentally created in the lab through repeated cross-species contamination of lab animals

- just stored in the lab from a natural sample

- or even not deliberately stored in the lab but acquired through infection of a researcher on a collection mission.

Governments cannot be sued in foreign courts, so there’s no liability.

Of course they can. It'll probably be a kangaroo court but you'll need a big global coalition for that.

they produce good science from this work.

Other than securing more funding for more research, and trivia for virologists, what good science has come from this lab?

I’d have to re-listen to numerous TWiV podcasts, but here is a WaPo article discussing the quality of research at WIV: https://archive.ph/2020.01.31-185716/https://www.washingtonp...

The Wuhan institute was celebrated as an improvement over the facilities at which dangerous viruses had previously been studied in China. The 2004 SARS outbreak originated in a lab: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC416634/

That WaPo article isn't about the quality of research at the WIV, it's an attempted (failed) debunking of the "fringe theory" that SARS-CoV-2 escaped from a lab. It has nothing to say on what good science they produced, perhaps because there wasn't any. Virology appears to spend its time fiddling with viruses based on the claim that doing so will help create vaccines, except, their work doesn't seem to have contributed to any vaccine development.

> their work doesn't seem to have contributed to any vaccine development.

On the contrary, look at covid aftermath — it quite did! /s

Touché!

> The 2004 SARS outbreak originated in a lab

This is news to me. The article you referenced opens by saying [0]:

> The World Health Organization has confirmed that breaches of safety procedures on at least two occasions at one of Beijing's top virology laboratories were the probable cause of the outbreak of severe acute respiratory syndrome (SARS) there last month, which infected nine people, one of whom died.

This seems to be saying they traced the illness in nine people there at the lab back to two leaks at the lab, not that the entire disease outbreak originated in a lab.

There a lot of other studies, referenced in this wikipedia article [1], which explain that the first SARS virus originated in bats:

> Phylogenetic analysis of these viruses indicated a high probability that SARS coronavirus originated in bats and spread to humans either directly or through animals held in Chinese markets.

> In 2004, scientists from the Chinese Center for Disease Control and Prevention of the University of Hong Kong and the Guangzhou Center for Disease Control and Prevention established a genetic link between the SARS coronavirus appearing in civets and humans, confirming claims that the virus might have transmitted from the animal species to humans.

In the last 15 years people have fallen ill of the plague, cowpox, meningococcus, h5n1, anthrax, and zika due to lab leaks in the Unites States [2]. These are just the leaks where people got sick and/or died, all lab workers I believe. There were others affecting animals, and others where nobody got sick. None of that means these labs originated these diseases. The origin of a disease is separate from a localized outbreak.

[0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC416634/

[1] https://en.wikipedia.org/wiki/SARS-CoV-1#Origin_and_evolutio...

[2] https://en.wikipedia.org/wiki/List_of_laboratory_biosecurity...

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