There's a bit of a fuzzy overlap between "man made" and "lab leak".

Specifically, the lab leak theory more or less assumes that the virus was collected from the mine, taken to Wuhan, and some research and experiments were done on it, resulting it some changes. Certainly the lab was doing research; there's an ongoing debate over what they did, who funded it, whether what they did technically qualifies as "gain of function" research, what practical impact the research could reasonably have been predicted to have, etc.

Still, if your theory is that the lab took a bat virus, performed some research on it such as "serial passaging" to determine if it could mutate to become more infectious to humans, the virus does mutate (thus proving the hypothesis), and then a sample of the mutated virus is accidentally leaked...

...that seems like a plausible theory, and it's now showing up in mainstream discussions; eg, https://nymag.com/intelligencer/article/coronavirus-lab-esca.... But I could easily imagine that being considered a suggestion the virus was "man-made", and censored.

> Specifically, the lab leak theory more or less assumes that the virus was collected from the mine, taken to Wuhan, and some research and experiments were done on it, resulting it some changes.

I disagree, the lab leak hypothesis is independent from the lab [inadvertently or deliberately] mutating the virus. The lab may have merely possessed the virus, having made only the mistake of transporting the virus from a remote region into the middle of a city and then subsequently losing control of it.

That would help explain how the virus got from the mine to Wuhan; it does not help explain how the virus mutated from a bat virus unable to infect humans to a virus that was extremely good at infecting humans with, so far, no intermediate stages identified.

Much of the problem with the zoonotic explanation is that no evidence of the process has been found. Was a third virus involved? We haven't identified it. Was a third host species involved? We haven't identified one. Were there any half-way variants that were slightly capable of infecting humans, and then mutated further to reach their final form? We haven't identified any. There was some initial speculation about the wet market, but that hasn't panned out. Pangolins were briefly considered as a possible intermediate host, but I think that's also been ruled out.

So if the lab collected the virus, flew it to Wuhan, stored it, and then accidentally leaked it in its original form, we still have no idea what happened next. It's a bat virus, so it infected a local Wuhan bat, and then what? And whatever the theory is, why have we been unable to find any evidence of it so far?

Assuming RaTG13 was indeed the source of COVID-19, the question of "how it got to Wuhan" is, I think, much less interesting than "how did it mutate into COVID-19" (and "why can't we find evidence of that process?"). And I think when people talk about "lab leak" versus "zoonotic", they're generally focused on the latter questions.

I generally agree with you, my guess is the virus was messed with and accidentally got out. However I don't feel comfortable ruling out alternative scenarios, such as:

1) The sample the lab received was from the 'third host' and not from a bat; e.g. a field researcher mailed the lab a slice of pangolin.

2) A guano miner or lab researcher received a massive viral dose and inadvertently became a one-man walking "GoF lab"

> Assuming RaTG13 was indeed the source of COVID-19, the question of "how it got to Wuhan" is, I think, much less interesting than "how did it mutate into COVID-19" (and "why can't we find evidence of that process?").

'Interesting' is subjective, but I think both questions are important. Particularly, the wisdom of locating a lab like this inside a city should probably be called into question. Whether the lab was doing GoF research on this virus prior to outbreak is certainly an important question; arguably the more important of the two. But unless we are dealing with 'zero-sum importance', that does not diminish the importance of figuring out why and how the virus was transported into a city.

> However I don't feel comfortable ruling out alternative scenarios

I haven't suggested we should, not do I think that would be wise. We're in the uncomfortable position of having effectively no evidence in favour of any theory of COVID-19s origin, so we're reduced to trying to imagine which bits of missing evidence are the least likely to have been missed.

It seems true that Wuhan is outside the flight range of the horseshoe bats living in the mine, and that a sample of RaTG13 was brought from the mine to the lab in Wuhan. If RaTG13 was a direct predecessor of COVID-19 (likely), and if the lab in Wuhan was the direct source of the initial infections in Wuhan (hard to estimate), then I think Occam's Razor suggests we have a good enough explanation for how RaTG13 got to Wuhan. It would be a remarkable coincidence if a sample of RaTG13 was in Wuhan to be studied, then RaTG13 independently mutated into an unknown COVID-19 precursor outside of Wuhan, then the precursor was separately brought to Wuhan to be studied, then the precursor leaked and became COVID-19!

...but as ever with this mess, I don't know of a reason we could rule it out. At most we can try and estimate the odds of the lab having a closer precursor than RaTG13 but not realising or, if they realised it, not admitting it, but I'm not sure how to even start evaluating that scenario, so...

We haven't found any evidence about what happened in the lab...because China barred WHO researchers from visiting the lab do look for that evidence.

"China barred WHO researchers"...

and the WHO researchers themselves engage in (and fund) the same type of experiments as the Wuhan lab (and the Wuhan lab itself), and so had very little incentive to investigate or implicate themselves either...

and further, there actually is evidence of what went on in the Wuhan lab, see https://yurideigin.medium.com/lab-made-cov2-genealogy-throug...

So here's the thing: the more improbable thing about the lab leak hypothesis is that the lab would even have had enough virus, in virion form, to cause even 1 human infection.

Biological materials are hard to grow and store. Very few people have ever been infected from handling corpses from much more pathogenic viruses (i.e. the black death was one of the only significant ones, and that's because it's a bacterium). And that's about 70kg and trillions of bacteria to "maybe" end up contaminated.

In-vitro scale research on viruses has been going on for a long time, in BSL2 facilities (your university bio-labs for students probably met this standard), and people getting infected from much more contagious human-viruses in those settings just doesn't happen.

The scale of difference in quantity between a smear of virus particles on a petridish (pretty much immobilized, and, as we know, at serious risk of being destroyed by the trace UV from fluorescent lighting) and the quantity from an active infection in a human cough is multiple orders of magnitude (also a massive difference in exposure path: COVID spreads principally by going in through mucus membranes as aersolized droplets - dead tissue doesn't produce these, neither do immobilized particles).

No one pushing "lab leak" has ever proposed a mechanism by which it happened - they just assume it can, because they don't work in a biology lab and have no idea about what biological research actually looks like.

> So here's the thing: the more improbable thing about the lab leak hypothesis is that the lab would even have had enough virus, in virion form, to cause even 1 human infection.

I reject that. Lab leaks have been known to occur, with human casualties:

> "After the outbreak of SARS in 2003, labs around the world began studying the virus, which had come perilously close to causing a global pandemic. Since that time, there have been no less than six lab leaks of SARS. The first took place in at the National University of Singapore, where a graduate student contracted the disease from a contaminated sample. This was followed by an incident in Taiwan, when a researcher contracted it, most likely during a botched decontamination of laboratory waste. Then several leaks took place at China’s National Institute of Virology. In one case, a researcher passed the infection to her mother, who died of SARS. In each case, human error, most likely exacerbated by inadequate safety protocols, accounted for the leaks."

https://www.bloomberg.com/opinion/articles/2021-05-27/covid-...

Safety incidents happen a lot.

> By 1960, hundreds of American scientists and technicians had been hospitalized, victims of the diseases they were trying to weaponize. Charles Armstrong, of the National Institutes of Health, one of the consulting founders of the American germ-warfare program, investigated Q fever three times, and all three times, scientists and staffers got sick. In the anthrax pilot plant at Camp Detrick, Maryland, in 1951, a microbiologist, attempting to perfect the “foaming process” of high-volume production, developed a fever and died. In 1964, veterinary worker Albert Nickel fell ill after being bitten by a lab animal. His wife wasn’t told that he had Machupo virus, or Bolivian hemorrhagic fever. “I watched him die through a little window to his quarantine room at the Detrick infirmary,” she said.

> In 1977, a worldwide epidemic of influenza A began in Russia and China; it was eventually traced to a sample of an American strain of flu preserved in a laboratory freezer since 1950. In 1978, a hybrid strain of smallpox killed a medical photographer at a lab in Birmingham, England; in 2007, live foot-and-mouth disease leaked from a faulty drainpipe at the Institute for Animal Health in Surrey. In the U.S., “more than 1,100 laboratory incidents involving bacteria, viruses and toxins that pose significant or bioterror risks to people and agriculture were reported to federal regulators during 2008 through 2012,” reported USA Today in an exposé published in 2014. In 2015, the Department of Defense discovered that workers at a germ-warfare testing center in Utah had mistakenly sent close to 200 shipments of live anthrax to laboratories throughout the United States and also to Australia, Germany, Japan, South Korea, and several other countries over the past 12 years. In 2019, laboratories at Fort Detrick — where “defensive” research involves the creation of potential pathogens to defend against — were shut down for several months by the Centers for Disease Control and Prevention for “breaches of containment.” They reopened in December 2019.

From https://nymag.com/intelligencer/article/coronavirus-lab-esca..., many links to sources and more details in the original. The USA Today story is particularly interesting though (https://www.usatoday.com/story/news/nation/2014/08/17/report...).

Humans make mistakes. Accidents happen. And even at the most secure labs in the US, sometimes people die. Yes, we (hopefully) learn from our mistakes; a fatal accident in the 50s or 60s doesn't mean these things still happen today. Maybe (hopefully!) all those recent breaches and safety incidents were relatively minor. Perhaps China is much better about such things than other nations. And even if mistakes can happen that doesn't mean a mistake happened here, in this instance!

But if your prior is just "BSL-2 and higher labs are safe, they would never have a containment failure" I think you may want to re-evaluate it.

Your first example there is literally an attempt to mass produce live virus for biological weapons, with human infectious viruses. As are most of your examples. This all changes if the literal goal of research is "mass produce liters of viable virus".

But viral research in general doesn't do that, because it's a huge hazard, and unnecessary (and expensive, labor intensive etc.)

What I am drawing contention on is what physically would have to happen for a lab leak to occur (and the other side problem: if it's a natural borne virus already capable of human infectivity...then it was already in the wild).

Take the 1977 issue: the suspicion is not that it was an accident with a preserved sample. The suspicion is that the Russians were actively growing up the virus (a human infectious virus) - for some type of work, probably a vaccine trial.

So we've got two basic problems: why would the Wuhan lab be growing up large quantities of this specific virus (and is there evidence they were?)...and if it was already human infectious though, why is it more likely it escaped the lab, when such a thing would already have to be in the wild to have been recovered?

There'd be no reason, having discovered COVID-19, to start growing up the virus before it had been sequenced. And there'd be no reason, without already knowing what it does, to not publish a paper describing the act of isolating and sequencing a new coronavirus, which is the type of research the Wuhan lab put out all the time. Researcher's operate on publish or perish, and Chinese researchers publish everything they can.

Those are good questions, but I think the link I provided gives some decent potential answers.

I don't know, and I'm not asserting, that any of this is true. But given what is known about the types of research being done, this doesn't seem like something we can rule out either.

For one example, the article quotes Shi Zhengli, a lab director at the Wuhan Virology Institute, who had been doing research on RaTG13, and who upon realising COVID-19 was related to RaTG13 was immediately was concerned it had leaked from her lab. According to the article, she lost sleep over this, and was enormously relieved when she could prove that the outbreak in Wuhan was not any strain that the lab had a record of storing.

I find it surprising that you are so much more convinced than a lab director of the lab in question that no such leak was possible. To be sure, perhaps she was suffering from an excess of caution...but if she found the thought plausible enough that she lost sleep over it, perhaps we, vastly further away and with much less information, should not rule the risk out entirely?

In any case, if you feel comfortable, based on your knowledge, concluding that you can rule out the lab leak hypothesis, that's great, but it does seem to put you at odds with basically every expert I've seen quoted so far.

> I find it surprising that you are so much more convinced than a lab director of the lab in question that no such leak was possible.

> when she could prove that the outbreak in Wuhan was not any strain that the lab had a record of storing.

You answered your own question. That's the point here: the evidence does not point to a lab leak.

So the director of one lab, hearing about COVID-19, apparently went "oh shit, that could have come from MY lab!" Later, she publicly announced that it's fine, it didn't come from her lab after all, then the lab was shut down, all records suppressed, and China has prevented any independent investigation.

Even if we take this at face value, and the denials were fully truthful, this tells us that:

1) it didn't leak in that form from that specific lab (of the several operating at the Virology Institute), assuming they had good record keeping. But it might have leaked from a different lab, or it might have leaked from her lab and then mutated prior to being discovered. (And, while it might seem unlikely that it mutated without any trace of intermediate forms being found, that's the exact assumption the zoonotic theory already requires...)

2) Someone in a position to know believed that a leak was plausible based on her knowledge of the types of research being performed, the quantities of material they had on hand, the safety protocols they were following, etc.

I suppose I just find that less reassuring than you do. :)

SARS 1, which is far less infectious, escaped from labs multiple times.

> Biological materials are hard to grow and store. In general, many diseases are highly species specific and/or affect only certain cell types. When you don't have a suitable cell line, the only real option is to keep live hosts. But these hosts could cross-contaminate other species/cell lines within the lab facility. Bat physiology is very different from most other mammals. If you want to study viruses in bats, it makes sense to use real animals, because you can be certain that the virus replicates in vivo, but it can be difficult to find a good in vitro environment.

The whole purpose of the lab was to grow and study these viruses, and to promote their growth in order to study how they might grow. Hard to understand how they would not have had enough virus, as you say.

Indeed, a lab leak includes all of these possible priors of how the virus ended up in the lab in the first place.

But the only serious contender for the prior hypothesis is that the researchers produced a highly infectious chimeric coronavirus through gain-of-function/serial passage.

At least one researcher who has worked with the head of the Wuhan lab has accused her of shoddy adherence to safety practices, so it's also quite possible that simple negligence led to cross-contamination and subsequently to human exposure.

It would certainly explain how the predecessor candidates simultaneously acquired all of the necessary mutations: all of the most genetically similar coronaviruses were all being studied in the lab; if precautions were not taken to avoid cross-contamination then they could picked up the mutations in a relatively benign environment without external stressors. (One of the initial reasons given for the man-made theory was due to the fact that COVID19 was unlikely to arise naturally in the wild because any combination of mutations among the predecessor strains short of the entire package of mutations that ended up in COVID19 would have resulted in a strain less able to reproduce than existing competing strains.)

Similarly, lax attention to safety practices would also explain why the first known cluster of COVID19 cases occurred among Wuhan lab workers.

Stored in what form.

A lab having a bunch of samples in a refrigerator doesn't mean that a spill causes them all to spontaneously recombinate.

while you are correct that lab-leak is "theoretically" a distinct hypothesis, in this specific case the apparent splicing of pangolin virus parts together with bat virus parts is a highly suggestive smoking gun for man-made, especially when you consider that this lab does splicing experiments

From what I understand, this lab and those like it likely have/had a large backlog of samples they had received from field researchers but had not yet had an opportunity to identify, sequence, or otherwise mess around with. A procedural error in handling a sample in that backlog could have occurred, at least in theory.

What’s the difference? I suppose it is possible that the Wuhan bat hunters found this virus occurring naturally and just, you know, kept it around without telling anyone...

There is a huge difference! For one, suggesting it was man-made lends credibility to the conspiracy theory crowd ("plandemic", "they manufactured it to enslave you", etc), which is probably why the press over-indexed on debunking it. Also, it could imply that there was some intent behind it appearing when and where it did, when there may have been none (Hanlon's razor applies until a proof to the contrary appears). My understanding was that the theory that the virus was man-made was debunked, but I have not been paying much attention to what was happening to the stories saying it may have been an accidental leak from a lab, and given China's record, I wouldn't be too surprised to learn that there was research happening on it, it got out, and that was then covered up.

If the virus was man-made, then its release was either accidental or deliberate. Both of these possibilites need to be allowed until disproven. If it was deliberate, then why?

It'd be pretty stupid for them to deliberately release it right next to the lab.

This seems obvious. I don't think it was deliberate. But whether deliberate or not, the virus achieved many policy goals for the ccp.

Firstly it got rid of Trump who was before covid in charge of one of the best economies in the USA and would have had an easy path to reelection. The virus was a black swan event that caused that to go away and trump.to make several mistakes. It also got joe biden elected which we know the CCP preferred.

Secondly, it embarrassed america on the world stage while china came away initially looking very good. China's centralized government came out looking better than the chaotic american way. This helps China's foreign investment image. Wouldn't you rather do business with stable countries?

Finally, of all countries, china had the best economic outcome. It's economy was never totally shut. They continued to profit from masks and other PPE.

Basically, the virus was a clear win for the ccp.

Personally my belief is that whether the virus is natural, a leak, or a man made weapon, once it was out, the ccp clearly weaponized the pandemic to effectively achieve several policy goals.

> Firstly it got rid of Trump who was before covid in charge of one of the best economies in the USA and would have had an easy path to reelection. The virus was a black swan event that caused that to go away and trump.to make several mistakes. It also got joe biden elected which we know the CCP preferred.

This sounds super far fetched. When Covid began to spread the democratic candidate wasn't chosen yet and this theory completely relies on the Trump administration to completely screw up in the eyes of the public. I don't have a high opinion of Trump, but the US government is a lot larger than him.

And then if they're caught it turns the entire planet against them. It sounds like a massive risk just to get rid of a somewhat annoying president 4 years early, it's not like he was threatening war or anything like that.

There’s only a spec of difference. I don’t know anyone suggesting that the lab leak was of a natural origin. The theory is that the lab created the virus and it leaked.

I think there’s some nuance here. The virus could have a perfectly natural origin in bats, but not be able to infect humans in its original form. There are many ways the virus could have come to infect humans, such as by manipulating it directly, via gain of function research, or even just by a random mutation that managed to infect a lab worker (seems unlikely since it’s alleged there may have needed to be an intermediate species). Whether you could consider the virus “lab created” or “man-made” at that point is maybe a matter of debate. Even the Guardian article on Facebook’s policy changes seemed to conflate these scenarios, so I’m not entirely sure what the changes were.

But they’re all a far cry from the more extreme narrative of “this was deliberately engineered to infect humans and/or as a bioweapon”, which is not what is being suggested here (nor, it seems, was that ever what Tom Cotton suggested).

I know I got downvotes already but I guess that’s what I meant, that in a lab setting human researchers would have been manipulating the virus. I meant that I don’t think anyone is saying that researchers captured a novel COVID variant in nature and just held it in a lab until it leaked.

If the lab theory holds any water, it’s almost certain that humans were manipulating the virus in some form.

That’s why I don’t see much of a distinction between a lab leak theory and a human-made or human-manipulated virus.

Well, I report the opposite. I guess the data is useless.

I think there's a genuine spectrum between man-made bio-weapon (not very believable IMO), through gain of function research (I've read enough that - if true - the RNA evidence suggests that it probably wasn't this), through to leak from animal studies.

Gain of function, if it isn't ruled out by RNA or other approaches, isn't quite man-made and is at least somewhat plausible. Gain of function research on the flu is (as I understand it) how the flu vaccine is created ahead of the season.

https://jme.bmj.com/content/41/11/901

Evans NG, Lipsitch M, Levinson M The ethics of biosafety considerations in gain-of-function research resulting in the creation of potential pandemic pathogens

Journal of Medical Ethics 2015;41:901-908.

This paper proposes an ethical framework for evaluating biosafety risks of gain-of-function (GOF) experiments that create novel strains of influenza expected to be virulent and transmissible in humans, so-called potential pandemic pathogens (PPPs). Such research raises ethical concerns because of the risk that accidental release from a laboratory could lead to extensive or even global spread of a virulent pathogen.

Some techniques of manipulating the virus would leave "fingerprints". Others would not. My understanding is that the sweeping assertions that COVID-19 would show clear signs of being manipulated have been largely debunked. Many ultimately traced back to a letter written by a group of virologists led by Kristian Andersen and published in Nature, but all that letter did was assert that some techniques (not all!) were unlikely (but even then, not impossible).

I'm unaware of any reputable experts who are willing to assert that manipulation via, eg, serial passaging, can be ruled out. The closest you'll get is assertions that a natural zoonotic origin is, in their estimation, more likely.

See, eg, https://nymag.com/intelligencer/article/coronavirus-lab-esca... and https://nicholaswade.medium.com/origin-of-covid-following-th....