This market resolves once we have a definitive answer to this question. (i.e. "I've looked at all notable evidence presented by both sides and have upwards of 98% confidence that a certain conclusion is correct, and it doesn't seem likely that any further relevant evidence will be forthcoming any time soon.")
This will likely not occur until many years after Covid is no longer a subject of active political contention, motivations for various actors to distort or hide inconvenient evidence have died down, and a scientific consensus has emerged on the subject. For exactly when it will resolve, see /IsaacKing/when-will-the-covid-lab-leak-market
I will be conferring with the community extensively before resolving this market, to ensure I haven't missed anything and aren't being overconfident in one direction or another. As some additional assurance, see /IsaacKing/will-my-resolution-of-the-covid19-l
(For comparison, the level of evidence in favor of anthropogenic climate change would be sufficient, despite the existence of a few doubts here and there.)
If we never reach a point where I can safely be that confident either way, it'll remain open indefinitely. (And Manifold lends you your mana back after a few months, so this doesn't negatively impact you.)
"Come from a laboratory" includes both an accidental lab leak and an intentional release. It also counts if COVID was found in the wild, taken to a lab for study, and then escaped from that lab without any modification. It just needs to have actually been "in the lab" in a meaningful way. A lab worker who was out collecting samples and got contaminated in the wild doesn't count, but it does count if they got contaminated later from a sample that was supposed to be safely contained.
In the event of multiple progenitors, this market resolves YES only if the lab leak was plausibly responsible for the worldwide pandemic. It won't count if the pandemic primarily came from natural sources and then there was also a lab leak that only infected a few people.
I won't bet in this market.
1,000
3.00Here’s a thought experiment. Imagine you could stop time at the end of 2019 and do some research.
On Dec 31 2019 anyone in the world could’ve learned:
Cluster of unexplained pneumonia cases linked to Huanan Market
Credible rumors from doctors on social media that sequencing showed a SARS-like virus
Social media rumors confirmed by news reports that Huanan Market housed a black market for the live mammal trade
Live mammals mostly gone from Huanan Market by the afternoon of 31/December; one news report found one shop with unidentified mammals; other news reports noted a pile of dead animal parts (at the end of 6th street in the southwest corner of the market)
One of the preeminent labs focused on bat viruses with human/livestock spillover potential and best known for work with SARS-like viruses was in Wuhan across town from Huanan Market
The lab hosts foreign researchers in Wuhan and its projects are generally collaborations with other groups in China and around the world
In addition to identifying bat viruses closely related to SARS, the lab also identified more distantly related SARS-like viruses
The lab had grown some SARS-like viruses by passaging from samples and by reverse genetics in a system substituting spike using BsaI and BsmBI enzymes without retaining these sites in the chimeric genome
Leadership at the lab’s institute had published articles discussing challenges constructing biosafety labs in China and advocated more effective biosafety regulation; international collaborations for biosafety training
Novel, SARS-like virus recently reported in sick pangolins confiscated from traffickers in Guangdong province
Novel, SARS-like virus recently reported in bats Zhejiang province, sequenced, and used in an animal infection experiment
What was knowable from information that wasn’t yet public (this doesn’t necessarily mean the dots had been connected in private):
One nearly complete SARS2 genome had been sequenced and submitted by China CDC to US GenBank database
Samples from late December patients had been split four ways and distributed to multiple labs in China to analyze in parallel
Sequencing and other work in 2019 already involved government, university, and commercial laboratories
Wuhan lab had sampled one virus that was, at the time, the one most closely related to SARS2
Wuhan lab had eight other samples that were nearly identical to each other and very similar to SARS2 over a short sequence
Pangolin virus found in Guangdong and bat virus found in Zhejiang were also two of the sequences most closely related to SARS2
All three of these viruses shared common ancestry with SARS2, but none were plausible progenitors in a lab or in nature
A survey had identified four public markets in Wuhan trading live, mammalian wildlife including species associated with SARS in 2003. Huanan Market was the largest. This was supported by earlier observations.
Imagine you knew all of that. Then answer these questions if you like:
On 31/Dec/2019, was a lab leak origin more likely than not?
Specifically, what was the strongest piece of evidence that supports a lab leak origin at that time? Please add to the list if I missed anything.
Specifically, what’s the strongest piece of evidence unknown in 2019 that supports a lab leak origin?
A lot of people have not voted here: https://manifold.markets/KeenenW/did-covid19-come-from-a-laboratory-8d38660948d1
@LukeShadwell How is it not concrete? Look at what passed for evidence of lab leak in this thread.
Ironically it’s primarily stuff that has nothing to do with Wuhan and undercuts the only evidence there is: the coincidence of starting in Wuhan.
@LukeShadwell The person who decides this market is on the fence about Lyme disease as a lab leak, which certainly was not a lab leak.
@zcoli The resolution criteria of this market make me quite confident that it'll be resolved properly, never mind that evidently others have much more faith than I do having put 100s of thousands of mana in. It seems like you believe this market should be resolved as a NO, despite the fact that it's clearly controversial and there is not sufficient evidence. I wouldn't want you to be the one resolving this question much more than someone who is just "on the fence" about lyme disease
@LukeShadwell The first thing you’ll find searching for how old Lyme disease is an example thousands of years old.
As far as the mad scientist variations of lab leak theory go that you see here: I’m just as certain those didn’t happen as a lab leak over 5000 years ago, because both are impossible.
I’m less certain there wasn’t the boring kind of lab leak — investigating why an animal was sick followed by a very unlikely string of coincidences that give the observed evidence — but it’s 0% to very close to 0%.
There’s just no evidence other than a location coincidence that’s not nearly as strong as it seems (many equivalent coincidences could’ve happened) and, regardless, is trumped many times over by zoonosis evidence. It’s worth a thought experiment placing yourself in Dec 31 2019, considering all of the evidence then available, and trying to blind yourself to what comes next and making hypotheses that could be supported or not by data that might be published or not.
One thing you’ll find doing that is that all the “new” evidence about the type of work at WIV and about biosafety concerns at WIV isn’t new. You can read about it in papers that were already published at the time and it’s already baked into the location coincidence.
FYI, looking at what’s trending on X, the most important thing at the moment for the people who are at the other side of George and Mike P.’s links is that the a very serious and legitimately intellectual abstract from Hideki Kakeya was rejected for a scientific meeting.
The conclusion of that work was that Omicron sublineage BA.1.1 spread in the USA was driven by unexplained, unnatural transmission.
This followed a paper that said the same thing about BA.1.
This followed a paper that said Omicron was a lab leak in the first place (presumably in South Africa). The preprint for that one notably said “we neglect natural selection.”
He’s also a huge anti vaccine voice in Japan. To my knowledge no one in the “lab leak” community has criticized any or this.
That’s the degree of rationality behind the “lab leak” theory in a nutshell.
@zcoli Update: the most important thing in the world has now changed to be whether or not documents at the Universiry of North Carolina should be released under open records acts. Keep this in mind every time someone cites the weird coincidence of a pandemic in Wuhan as their best evidence of a lab leak. North Carolina: notably not very close to Wuhan. These documents: known to many people who are in on the cover up if they’re relevant to finally revealing evidence of a lab leak.
If someone can explain how this is at all different from any other theory in which the truth would be known were it not for a conspiracy at the highest levels of government spanning both major political parties in the USA plus governments in adversary countries… an explanation would help.
For example... thinking the truth about the lab leak will be unveiled here were it not covered up by China and a bipartisan effort in the USA with cooperation by UNC is only different from similar claims from David Grusch last year in that the Vatican isn't in on the imaginary cover-up yet.
In case it's not clear what imaginary crime Ebright is talking about:
@zcoli Today’s update on the evidence supposedly covered up in North Carolina that’s going to crack the case in Wuhan for sure: $284M that Ebright knows includes search results for “hypo-Baric”, double counts tens of millions of dollars, and counts chemistry and other core funding at UNC as paying off Ralph Baric to cover up a crime.
My explanation for the same set of facts: Ebright doesn’t mind lying about his scientific enemies to hurt them. Seems to check out with the facts? Something to consider when his wisdom is cited here on how the pandemic originated.
https://biosafetynow.substack.com/p/richard-ebrights-testimony-on-the
Richard Ebright's Testimony on the Origins of COVID-19
For the US Senate Hearing "Origins of COVID-19: An Examination of Available Evidence"
Below is oral and submitted testimony given by Richard Ebright for the US Senate Hearing "Origins of COVID-19: An Examination of Available Evidence.” Prof. Ebright is Board of Governors Professor of Chemistry and Chemical Biology at Rutgers University and Laboratory Director at the Waksman Institute of Microbiology.
Synthesizing and characterizing, consensus sequences has been a standard experimental approach across molecular biology for four decades (34-41).
Ebright cites himself for, if I recall correctly, all but one of these citations. In every case it is a different definition of "consensus sequence" than he's using for SARS-CoV-2 as a hypothetical "consensus sequence" of bat coronavirus genomes. He knows the citations are totally irrelevant and that he's misleading Congress with this; apparently he thinks that's worth it.
Ebright's consensus sequences: the consensus of short, repeated elements in a single genome (e.g. motifs recognized by a DNA-binding protein).
The consensus sequences he is referring to in virology: the consensus of full genomes that are nearly identical to each other.
This interpretation of "consensus sequence" is something he invented a long time ago after he gave up claiming that SARS-CoV-2 could've resulted from serial passage of RaTG13 and instead invoked someone engineering a "consensus" of RaTG13 with distantly related viral genomes. SARS-CoV-2 is definitely not this, and anyone trying to make this would be doing a massive loss of function experiment.
Not a super new paper, but relevant since the S1/S2 cleavage site God of the gaps argument is back in style again. This isn't the only example out there. If a virus gets a toehold in a new species, further adaptation at S1/S2 and/or S2' is unsurprising.
In addition, we predicted a potential furin protease cleavage site (RQQR) in S protein subdomain 1 (SD1) in all MjHKU4r-CoV genomes that is similar to that in the MERS-CoV genome and believed to play an important role in SARS-CoV-2 transmission. However, such a cleavage site was not found in any of the publicly available bat HKU4r-CoV genomes.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9933427/
And, of course, we know that SARS2-like viruses without the SARS2 S1/S2 site had no problem transmitting between pangolins. Sampled several times independently now. This doesn't guarantee that pangolin is an intermediate species between bat and human for SARS2; just shows it's along possible pathways.
Also, no more pangolin trafficking, please.
@George Is this supposed to be a post supporting "Yes" or "No" for "Did COVID-19 come from a laboratory" ?
Here's a recent lowlight from Deigin where he supports the idea that maybe SARS-CoV-2 was synthesized in North Carolina.
Inevitably, Deigin is misrepresenting the truth here. Those "some lethal feline coronaviruses" that he's talking about? You might notice that the accession numbers are rather similar (08-153990-1, 3, and 4). That's because they are three samples from one cat: https://pmc.ncbi.nlm.nih.gov/articles/PMC3713968/ (Figure 2).
Here's how Deigin describes how "OMG" this single dead cat is the key to proving SARS-CoV-2 is synthetic; he even references the paper but helpfully doesn't provide a link.
Because, if you had the link, you'd know that authors were interested in the mutation to methionine at position P1 and not the mutation to proline at P6:
Whether or not this is a mutation in FIPV relative to the FECV that infected the cat was not known at the time (2013). Again, this is all inferred from a single cat. I'll leave going down the rabbit hole to see what got Deigin interested in "feline coronavirus" in the first place. It gets weird.
But now that we've got an example or two of PRRSRR^S as a probably functional S1/S2 site in cats, maybe that'll be enough to finally stop talking about this /s.
Corresponding paper is here if someone wants to look into the supplement and see if these two samples correspond to the likely enteric coronavirus samples or not: https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.001654
Panel 4: COVID-19 Origins and the Regulation of Virology
The stakes in the debate about the origin of the pandemic could not be higher. If the pandemic started from an inadequately regulated wildlife trade or zoonoses, reforms to reduce the likelihood of human contact with wild species is vital. On the other hand, if the pandemic started due to dangerous laboratory experiments and inadequate protocols to prevent leaks, then more stringent regulation of such experimentation is warranted. What is the evidence on these topics, and what is the path forward?
@George So I read a transcription of this. They don’t really talk about the first half subject at all other than Alex Washburne explaining the paper he jumped on after the work was done; his contribution was reverse p hacking to bring the first author’s “1 in 10^20” probability of being natural up a bit to not so obviously be cherry picked fraud. A paper that was disproven a month before the preprint came out and before Washburne joined the project.
Gupta makes a few arguments against the Intelligent Design case for lab leak in general but the conversation doesn’t touch on any relevant information that’s been learned since roughly the second week of January 2020 (yes I’m including the unfunded research proposal as irrelevant information here).
Rather, the panel spends 95% of the time on the second half of the topic. Gupta argues regulation as is is fine and that it’s unreasonable to think scientists are going to evolve novel pathogens more effectively than is already happening in the wild. Everyone else disagrees. When the argument touches on the risks of resurrecting extinct pathogens, no one mentions the most obvious counter example.
850 bats in Laos/Vietnam near Chinese border. Only more questions and no answers on how, when and where SARS-COV-2 acquired its FCS.
“Importantly, none of these sarbecoviruses harbor a furin cleavage site, indicating that the enteric tropism of these viruses in bats does not require such site.
Then, we studied the pathogenicity of BANAL-236 virus (a Laotian R. marshalli sarbecovirus) in human-relevant animal models. We demonstrated that this bat sarbecovirus efficiently replicates in enteric tissues, does not cause major symptoms in humanized mice and macaques; and that serial passages on intestinal cells or humanized mice do not select for viral populations harboring the furin site, nor alter the tropism and virulence of the new strain.
This enterotropism may account for the lack of serological detection of past infection by bat sarbecoviruses of human populations highly exposed to bat guano.
This suggests that bat/human spillover infections of sarbecoviruses, if they occur, are rare; and that the acquisition of a furin site was not selected through a clinically silent circulation of bat sarbecoviruses in humans.
The acquisition of such cleavage site through recombination from a donor organism remains hypothetical regarding the origin of the donor sequences, the host harboring this recombination event and its positive selection."
https://x.com/ydeigin/status/1845668157639282940?t=QEYzdhqS_EsvBTsn-503HA&s=19
@MikePa67d The S1/S2 sequence in one of the pangolin sarbecoviruses is very different from anything found in a bat.
Where are the intermediates in bats? Other animals?
If you have no answer for this, it’s admitting that the S1/S2 insert for SARS2 is the tiniest God of the gaps in the history of Intelligent Design.
@zcoli not sure what your point is here. I don't think anyone has said it's impossible for the FCS to have arisen naturally.
@MikePa67d My point is that this is an argument straight from Intelligent Design unless you are just posting it here out of general interest and agree it's irrelevant to the question.
@zcoli Intelligent Design seems like an unhelpful and bad faith comparison when there are several ways SARS-COV-2 may have arisen via research activities.
@MikePa67d Intelligent Design appeals to both gods and aliens to explain the gaps so it's not just one way to fill the gap there, either. Everyone is aware that the lab leak theory is too vaguely defined to be testable.
With rare exceptions... the most recent mention of "enzyme" in this comments section is you invoking one of the few lab leak theories specific enough to be testable and it failed. Believing a hyper-specific genetic engineering theory emerged from a specific research proposal and then falling back to "several ways SARS-CoV-2 may have arisen via research activities" is how conspiracy theories operate. If it's not this scenario, it's another totally unrelated scenario, but you're certain that it's a scenario that involves mad scientists somehow. All to explain all of 12 nucleotides of adaptation at one of the most variable sites in the genome.
Isn't one argument that the DEFUSE proposal details match SARS-CoV-2 on many dimensions: genome about ~20% away from SARS1, divides into 6 fairly even segments with 2 most popular Type IIS restriction enzymes, and has a furin site at S1/S2 (first known SARS-like virus with this).