Good points, and I tend to think the 'escaped from a lab' case is at least as strong as the zoonotic one.

A small counterpoint though -- the market is the Huanan market, i.e. specialising in south china sourced or styled food. I would not be surprised if some exotic animals were there but never admitted to.

Although reasonable, one theory ("the bat coronavirus was transported by scientists to the lab that studies bat coronaviruses") involves no illigal activity. On the other hand the counter-theory ("there was illegal bat trafficking from a small mine in Yunnan") involves speculation that something happened that we don't know about. Strictly speaking, the lab leak theory has more observed evidence. Presumably the Chinese government would have identified and explained if they found bat traffickers.

We know the lab was aware of RaTG13 - they produced a sequence quickly that no-one else had seen. I know nothing about the situation but it would be interesting to know where exactly the sample was being sequenced. I doubt they did it in the mine, samples must have been transported to some lab.

I used to think 99% chance zoonotic, but the fact the similar virus was known to the lab was enough to drag me to thinking it is probably a toss up. Lab leaks do happen, this lab was studying bat coronaviruses. It is possible.

> On the other hand the counter-theory ("there was illegal bat trafficking from a small mine in Yunnan")

One theory is that people mine bat guano from caves, so there's no need for them to ever touch a dead bat.

>he similar virus was known to the lab was enough to drag me to thinking it is probably a toss up.

A human generated virus wouldn't be similar in this way to a wild one. You would take a candidate virus and splice in genetic material from a different one. The new virus would match 100% in most places and then be completely different in a few places.

This is not how they conduct gain of function research. It's uses serial passage (using biological hosts and the virus's own variations). This produces vary little evidence of manipulation.

> The question of how it got to Wuhan all the way from Southern China remains unanswered.

It's also important to remember that the related virus we're talking about in southern China was identified in 2013. More than six years before the outbreak.

It didn't stay still. It hopped around, bat to bat, maybe to other animals. We don't have the history of the virus since then. It could have very well made the jump the humans or some other animal, years ago but only recently made the last few mutations to become the beast it is now.

Plus, it's a virus. It didn't take one path, it took all of them that it could. Each virus created a million more, repeat ad-infinitum.

So the idea that there's some mystery to how it traveled to Wuhan doesn't bother me. Viruses get around.

>>"The virologists working in Wuhan did travel all the way to Southern China to collect bat coronavirus samples and they did perform gain-of-function experiments. Viruses - even highly pathogenic ones - have escaped labs on numerous occasions. There is a plausible scenario here."

Another plausible scenario, in my opinion, is that the virus was brought to Wuhan by the virologists (in the virologist or their helpers) but never escaped from the lab itself.

If you have a bunch of people periodically going to interact with the bats, how improbable is that they get infected of something (unknowingly) on site?

It's very unlikely that you'd get a one step transfer from a bat that yielded a spike protein with the level of affinity it has for human ACE2. If you look at that protein alone, the most-likely proximal hosts are primates. If we seriously believe in zoonotic transfer, we should be looking at those populations, and understanding how orangutans and bonobos infiltrated Wuhan and transmitted the virus to unwitting humans.

The other recent coronavirus spillovers actually have rather low infectivity that increases with the course of the epidemic through adaptive mutations. But amazingly, with SARS2, it appeared already fully adapted.

The phylogenetic tree makes a clear statement about how long SARS2 has been circulating in humans. At the publication of the genome sequence there were only a handful (~4?) of mutations known and most SARS-CoV-2 genomes were, incredibly, nearly identical. See https://nextstrain.org/ncov/global. If we tend to see one mutation per transmission, that would mean that the spillover happened in October or November 2019, and almost certainly in Wuhan. All SARS-CoV-2 we've observed fits into this single tree, and there is no evidence of any previous progenitor strains. This means that SARS-CoV-2 was fully-adapted from its most-recent common ancestor. What are the odds of that happening directly from a bat?

We're only now seeing, with b1117, a big phenotypic jump related to changes in the spike protein. It has arisen in a context that suggests that it may also be the result of strange environmental conditions for the virus that are capable of accelerating its exploration of the solution space. A widely-considered hypothesis is that it arose in an immunocompromised patient receiving antibody treatment and convalescent plasma, both standard practice in the UK. In this context the virus could have achieved extremely high population (~ many candidate solutions, faster evolutionary computation) and feedback about the immune response of the entire population (to the degree that they would have received multiple donations of plasma).

The only thing we REALLY know is that these types of coronaviruses originate in Southern China and somehow got to the point of being suspiciously well adapted to ACE2 by the time it exploded in Wuhan.

That, however, can also be achieved purely by natural causes over a long time - not just in a lab. Maybe Wuhan is simply the point at which the first very infectious form of SARS-CoV-2 occurred - not the first overall occurrence of any SARS-CoV-2 variant. And it provided a perfect environment to spread at its wet markets. If the virus originated in the West, maybe we would be shitting all over meat processing facilities now?

So, how many people would need to get infected to facilitate these mutations? We could possibly have missed SARS-CoV-2 infections with earlier virus strains that were vastly less infectious. It would take quite a lot of people to raise suspicions of anything other going on than nominal incidents of flu-like symptoms. So maybe the initial SARS-2 was basically SARS-1 with much less incidence of severe symptoms - so it slipped under the radar until it mutated, exploded in incidence and suddenly produced overwhelming hospitilization rates.

It's plausible, and could be proven very easily that this happened. Presumably, some progenitor strain is out there, spreading more slowly and making less of a mess. Eventually, a SARS-CoV-2 screen will turn it up and we'll sequence it. Then we will see a strain that's diverged from all other sequences in the phylogenetic tree, with a common ancestor back further than ~1ya.

But this depends on catching that strain and evolution has likely led to its near full displacement by more infectious strains at this time.

>>"It's very unlikely that you'd get a one step transfer from a bat that yielded a spike protein with the level of affinity it has for human ACE2. If you look at that protein alone, the most-likely proximal hosts are primates"

I'm not qualified to have an opinion about that, but it seems to me that if we accept that premise, and the primate jump looks improbable, the conclusion is that the virus have to come from a lab where it has been modified.

On the other hand, many experts are saying "we don't know, it's probably natural". So, it seems to me that the scientific consensus is giving different prior probabilities to zoonotic transfer that you gave in that statement.

This is an anonymous appeal to authority, but FWIW I am a biologist and I am not convinced of any origin story. We lack evidence in every direction. Although our prior is that it's zoonotic, other experts I know acknowledge the possibility that we are looking at a lab leak. We simply don't have enough information to say.

However, there is very strong pressure to reassure the public that it's not lab-based, which would look bad for scientists and our generally pro-social efforts to help the world. I think this is misguided, because people are not stupid. They also can also observe the profound lack of evidence for zoonotic transfer, which frankly makes these assertions look like a coverup. It would be helpful if the scientific community were more honest and scientific about this issue. We should not jump to conclusions without evidence.

Yeah. Unfortunately public health researchers/biologists have very little credibility at this point so appeals to their authority won't work. In particular arguments of the form "we need more evidence" look weak given how many enormous leaps of faith the supposedly scientific establishment has been willing to make on the basis of no evidence at all for the past year, e.g. masks, lockdowns, asymptomatic infection (apparently now contradicted by a large study of >90% of the entire population of Wuhan!), now vaccines are being advertised as totally safe even though trial protocols are being abandoned left and right.

Public health research is really worrying, frankly. The quality gap between epidemiology papers I read in the last 12 months and computer science papers are shocking. Epidemiology routinely publishes papers that contain major errors that the authors clearly knew about and chose to ignore or cover up. The Flaxman paper is an example of how absurdly fraudulent it can get, yet we're told constantly that the "experts" have reached a "consensus" that isn't to be questioned.

At this point I'm pretty much ready to believe it came from a lab simply because scientists are claiming it didn't. My prior for public health researchers being honest has dropped through the floor.

I just indicated that I have spent much of my life thinking about these things. You don't have to believe that this gives me any insight, but like I said it might help you understand that I'm not just parroting some theory I've read, I'm working on it directly.

I understand your concerns about public health research. Have you thought about it could be done better? Curious what you think.

Computer science papers have their own quality problems. A shocking percentage of them don't include source code even when they describe experimental results. Here you have a field that could realize an ancient dream of perfectly describing their work, and yet they fail to do it. This is an obvious way that it could improve. What's the equivalent for epi?

Not reliably sharing source code is a big problem in health modelling too, it's an issue across academia. The last set of CS papers I read did all publish their code though, at least for the ones where I cared to look. Perhaps this problem is fading away with time.

Yeah, places like DeepMind or OpenAI don't, partly because their papers are extended press releases rather than precise descriptions of how to recreate their results. OK, that's fine, they aren't academia so they're paying for their own work. If they choose to write a paper at all it's a pure bonus over what's basically expected of them. For government funded research it's different of course.

I've spent a lot of time thinking about what could be done better and how. The problem is there's this overwhelming number of problems that track back to a few root causes that are basically intractable in the current social environment. Take bogus citations, or use of obsolete data. Completely standard in epidemiology to write papers that use values for IFR or other key variables that are 8 months old when far more up to date data is available. Or what about claims with citations in which the cited paper doesn't support the claim being made, or even contradicts it. I never see this in CS papers. I've seen it regularly whilst reading epi papers. Or papers where the key claim in the abstract is just fraudulent, like the Flaxman claims about the efficacy of lockdowns which just assumed its own conclusions in the construction of the model, and relied on assigning Sweden a ludicrously huge country-specific fudge factor in the model (4000x). Right, and the fact that this was done wasn't mentioned anywhere in the paper nor supplementary materials ... you had to read the code to find it (at least the code was open that time!).

You can tut and say well that shouldn't have happened, but of course there will be people who are tempted to dress up their chosen conclusion in the clothes of science. The question is really what mechanisms are responsible for detecting and preventing a fall in standards. But in science the only such mechanism is peer review and journals, which are hardly effective. Everyone is a part of the same system with the same incentives and there are no penalties for incorrect work, so bad papers are getting published in Nature and Science all the time, especially when aligned with the prevailing ideology of these institutions. University administrators are responsible in theory, or maybe granting bodies, but same problem: none of them have any stake in output quality. Ultimately to fix these problems you need to tie the rewards in academia to the correctness of results, but academia isn't culturally anywhere near ready to even think about that. Academic freedom implies the freedom to be wrong your entire career, of course.

A friend of mine who once lived in China quipped that maybe some low-level tech from the lab was selling animals from the lab at the wet market. Not likely, but he says given what he saw in China it would not surprise him much.

The famous lab animal selling was "A top academician at the Chinese Academy of Engineering earned 10.17 million yuan ($1.46 million) by illegally selling off lab animals" rather than a low level tech. Pigs though. Still it suggests standards may be a bit variable.

> The question of how it got to Wuhan all the way from Southern China remains unanswered.

There are coronavirus-carrying bats in Hubei province.