Astral Codex Ten

MERS

38 min read

MERS

Article

MERS is a recurring concept in the Astral Codex Ten archive, appearing 2 times across 2 issues between July 30, 2022 and April 09, 2024. The archive places it in contexts such as “previous coronavirus outbreaks … MERS (2012)”; “PLA involvement at WIV and MERS research prior to SARS-COV-2”. It most often appears alongside BANAL-52, Canada, China.

Metadata

  • Category: Concepts
  • Mention count: 2
  • Issue count: 2
  • First seen: July 30, 2022
  • Last seen: April 09, 2024

Appears In

Source Context

Recovered passages from the original issue text. When the raw archive preserved outbound links inside the source passage, they are listed directly under the quote.

Your Book Review: Viral
July 30, 2022 · Original source
The main case for the natural origins hypothesis is that it should be our default belief, in the absence of convincing evidence otherwise. The vast majority of disease outbreaks like this, including previous coronavirus outbreaks SARS (2003) and MERS (2012), came from nature, not from a lab. So, before examining the evidence, we should begin with a strong prior in favor of natural origins.
However, what’s still missing is any direct evidence for an animal source of SARS-CoV-2. Chan and Ridley note that during the SARS (2003) and MERS (2012) coronavirus outbreaks, the animal sources were discovered relatively quickly. But with COVID-19, now more than 2 years into the pandemic, an animal source still has not been identified, despite the fact that we now have access to better investigative tools, like faster and cheaper genome sequencing compared to the SARS and MERS investigations.
Highlights From The Comments On The Lab Leak Debate
April 09, 2024 · Original source
This alone isn’t fatal to lab leak. It’s perfectly possible for the lab to leak (let’s say) November 5th, the virus spreads a bit, and then a month later someone goes to the wet market, coughs on a vendor, and starts the officially recognized pandemic. But if that were true, you’d expect (let’s say) 30 cases by early December. Let’s say the wet market vendor was exactly Case # 30. She infected the other wet market vendors, starting a pandemic with an obvious center at the wet market and lots of infected wet market vendors and patrons. What about Case # 29? If they were (let’s say) a barista, how come they didn’t infect people at their coffee shop? How come there wasn’t a second obvious cluster radiating out from a coffee shop, lots of coffee-shop-linked cases, etc? How come there weren’t 30 equally-sized clusters? In order to avoid this, you either need to claim that the wet market was a perfect superspreader location, or that the pattern with lots of cases in the wet market and few-to-none anywhere else was a result of ascertainment bias. Saar made both those arguments during the debate, but I thought Peter rebutted them effectively. 1.4: COVID in Brazilian wastewater Nicholas Halden (blog) writes: What should we make of this study, which found the presence of covid in Brazilian wastewater in late 2019? Consider the doubling times. The study says that scientists working in late 2020 found COVID in samples of Brazilian wastewater from November 27, 2019. This was long before the first detected case of transmission in Brazil on March 13, 2020. Between November 27, 2019 and March 13, 2020 is about 16 weeks, so 32 COVID doubling times. 32 doubling times with no lockdown is enough time for COVID to infect every single person in Brazil. If COVID had infected everyone in Brazil before the first recognized case, we would have noticed. (again, COVID doubling time isn’t exactly invariably 3.5 days, but here we’re talking about numbers big enough that the exact details don’t matter very much) So if COVID was in Brazil on November 27, it must have fizzled out instead of going pandemic. How likely is that? If one person had COVID, it’s not too unlikely - not all COVID cases transmit it forward. If (let’s say) twenty people had COVID, it’s very unlikely - at that point, the law of large numbers takes over; in a freak coincidence, every single patient would have to fail to infect anyone else. So almost certainly fewer than 20 people in Brazil had COVID in November 27. So which is more likely - that somehow 20 people had COVID long before the virus was officially detected, and on a totally different continent, yet somehow a scientist looking through wastewater found the water from exactly those people and managed to detect the virus? Or that there was a sampling error, which happens all the time in these kinds of things? Peter wrote a blog post on some of these issues. He found that there were positive tests from wastewater samples as early as March 2019, which doesn’t fit anyone’s timeline, including lab leakers’. And most of these positives (including the Brazilian sample) contained later strains of the virus with mutations it picked up late in 2020. So these were almost certainly false positives from contamination. 1.5: Biorealism’s 16 arguments Biorealism has a list of sixteen arguments, which he liked so much that he posted it three times in the ACX comments, twice on Less Wrong, twice on Manifold, and about a dozen times on Twitter under multiple account names. Some posts were slightly different from others, but a typical version is: Importantly, Miller incorrectly claimed the N501Y mutation would result from passage in hACE2 mice (mixed them up with BALB/c mice). The major papers Miller relied on have been seriously challenged since the debate. See Stoyan and Chiu (2024), Weissman (2024), Bloom (2023) and Lv et al (2024). Overall the circumstantial evidence makes lab v plausible: Peter admitted getting this wrong during the debate. I think this very minor point about mice mutations was approximately his only mistake in 15 hours of debating, and he admitted it as soon as he noticed. Biorealism somehow heard about this (obviously not through watching the debate, as we’ll see in a moment), then left about 20-30 comments starting with it, under various accounts, on various platforms, as if it somehow discredited Peter. This is making me somewhat less charitable to him and his 16 arguments than I would be otherwise. 1. Chinese researchers Botao & Lei Xiao observed lab origin was likely given the nearest known relatives to SARS-CoV-2 were far from Wuhan. Wuhan Institute of Virology (WIV) sampled SARS-related bat coronaviruses where the nearest relatives are found in Yunnan, Laos and Vietnam ~1500km away. They refuse to share their records. The ancestral viruses of SARS were found equally far from where SARS spilled over into humans, so we know it’s possible (and likely) for viruses to travel that far. 2. Patrick Berche, DG at Institut Pasteur in Lille 2014-18, notes you would expect secondary outbreaks if it arose via the live animal trade. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10234839/ There are constant outbreaks of weird coronaviruses in animal handlers. See eg this paper, which estimates about 60,000 of these per year. None of these ever go anywhere, because the farmers are in rural areas that aren’t dense enough to sustain a high R0, and the epidemic fizzles out after a single digit number of cases. Any early outbreaks of COVID would have vanished into this long and mostly unnoticed list. 3. Molecular data: Only sarbecovirus with a furin cleavage site. Well adapted to human ACE2 cells. Low genetic diversity indicating a lack of prior circulation (Berche 2023). Restriction site SARS-CoV-2 BsaI/BsmBI restriction map falls neatly within the ideal range for a reverse genetics system and used previously at WIV and UNC. Ngram analysis of the codon usage per Professor Louis Nemzer https://twitter.com/BiophysicsFL/status/1667232580255490053?t=IJgitS5cw364ioclzVWxaA&s=19 The SARS2 backbone is very low in CG and CpG. While the 12-nt insert that gives it the FCS is extremely high in both. Almost as if it was some kind of chimera of a consensus sequence and a codon-optimized polybasic cleavage site? https://twitter.com/BiophysicsFL/status/1752800486837678377?t=EpIRgyybJVaPgeMP5xdstA&s=19 https://www.biorxiv.org/content/10.1101/2022.10.18.512756v1 https://link.springer.com/article/10.1007/s10311-021-01211-0?fbclid=IwAR1HMUMtLIAFOFppVasQDeoIAYrVhP8j4YoPO4wnaTOUiKLsllZl_oKryOw Most of this was discussed extensively in the second session of the debate, which I recommend. The CGG-CGG arginine codon usage is particularly unusual but used in synthetic biology. I asked a synthetic biologist about this. He said: » “Nope. I would literally never do this if I was designing a small insert (maybe I wouldn't notice if it happened by chance with ~1 in 25 odds in a naive codon optimization algorithm as part of a larger sequence). High GC% is bad. Tandem repeat is worse. Several other perfectly fine arginine codons. And I wouldn't engineer a viral genome using human codon usage. An engineer would not do it.” 4. DEFUSE full proposal: virus 20% different from SARS1, consensus seq assembled with 6 segments, without disrupting coding seq, BsmBI order, FCS. SARS2: 20% different than SARS1, 6 evenly spaced fragments w BsmBI and BsaI restriction sites, FCS. Jesse Bloom, Jack Nunberg, Robert Townley, Alexandre Hassanin have observed this workflow could have lead to SARS-CoV-2. Work often begins before funding sought or goes ahead anyway. Re: 4 - Also scattered across second section of debate, also not going to retread 5. Market cases were all lineage B. Lv et al (2024) indicates there was a single point of emergence and A came before B. So market cases not the primary cases. See also Bloom (2021), Kumar et al (2022). Peter Ben Embarek said there were likely already thousands of cases in Wuhan in December 2019.https://t.co/50kFV9zSb6 https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/34398234/ https://academic.oup.com/bioinformatics/article/38/10/2719/6553661 There was a Lineage A sample in the market, lab leak proponents just try to ignore/dismiss/conspiracize it away. The first two known Lineage A cases were very close to the market. Lv (is this even a real name? It sounds like Roman numeral? But I guess that’s what you expect in a country ruled by someone named Xi) found some weird COVID variants in Shanghai that might or might not mean anything; you can see some discussion of the implications here, but I don’t think they’re strong evidence either way. If A was first, it means some really weird stuff coincidences have to happen to give us the spread rates and genetic clock data we get, but they’re not necessarily weirder in the zoonosis hypothesis than the lab leak one. The claim that there were “thousands of cases in Wuhan in December 2019” is very easy to disprove by doubling rate arguments like the one above, by the blood bank study mentioned above, by the WHO’s failed case search, and by many other lines of argument. 6. Evidence for lineage A in the market is based on a low quality sample according to Liu et. al. (2023). I really think lab leakers need to decide whether they think China is a sinister actor trying to cover up the truth, or whether they should trust every offhand comment by Chinese government officials as gospel. Dr. Liu doesn’t explain in what sense he thinks the Lineage A sample is “low-quality”, and the Western scientists who I asked about this said they didn’t understand this complaint and that the sample was fine. A Western team re-analyzing the same sample describes it as “conclusively contain[ing] Lineage A.” I think most lab leakers have switched from trying to deny the genetics to claiming that this was “contamination”, which also doesn’t make sense (the sample is genetically very early). Note that aside from this sample, the first two Lineage A cases discovered were both very close to the wet market. 7. Bloom (2023) shows market samples do not support market origin. There is also no evidence of transmission in the claimed susceptible animals elsewhere. https://academic.oup.com/ve/advance-article/doi/10.1093/ve/vead089/7504441 Discussed extensively in my article as well as the first section of the debate. 8. Lineage A and B only two mutations apart. François Ballox, Bloom and Virginie Courtier-Orgogozo note this is unlikely to reflect two separate animal spillovers as opposed to incomplete case ascertainment of human to human transmission (Bloom 2021). Discussed extensively in my article as well as the first section of the debate. 9. Sampling bias. George Gao, Chinese CDC head at the time, acknowledged to the BBC stating they may have focused too much on and around the market and missed cases on the other side of the city. David Bahry outlines the documented bias. Michael Weissman has shown this mathematically. https://journals.asm.org/doi/10.1128/mbio.00313-23 https://academic.oup.com/jrsssa/advance-article-abstract/doi/10.1093/jrsssa/qnae021/7632556 Re: Dr. Gao, see above comment about Chinese officials. See the section Ascertainment Bias below for why I disagree with this specific claim, which also addresses the Michael Weissman argument. 10. Spatial statistics experts show the Worobey claim the market was the early epicentre was flawed. https://academic.oup.com/jrsssa/advance-article-abstract/doi/10.1093/jrsssa/qnad139/7557954 Re: 10 - See Confirmation Of The Centrality Of The Huanan Market Among Early COVID-19 Cases, a response to the paper you cite: The centrality of Wuhan's Huanan market in maps of December 2019 COVID-19 case residential locations, established by Worobey et al. (2022a), has recently been challenged by Stoyan and Chiu (2024, SC2024). SC2024 proposed a statistical test based on the premise that the measure of central tendency (hereafter, "centre") of a sample of case locations must coincide with the exact point from which local transmission began. Here we show that this premise is erroneous. SC2024 put forward two alternative centres (centroid and mode) to the centre-point which was used by Worobey et al. for some analyses, and proposed a bootstrapping method, based on their premise, to test whether a particular location is consistent with it being the point source of transmission. We show that SC2024's concerns about the use of centre-points are inconsequential, and that use of centroids for these data is inadvisable. The mode is an appropriate, even optimal, choice as centre; however, contrary to SC2024's results, we demonstrate that with proper implementation of their methods, the mode falls at the entrance of a parking lot at the market itself, and the 95% confidence region around the mode includes the market. Thus, the market cannot be rejected as central even by SC2024's overly stringent statistical test. I think this response is pretty strong. In one analysis, they show that even though the other paper’s methodology is worse than theirs, if you apply it correctly (instead of inappropriately excluding various cases like the paper’s authors did), the center of all early cases in Hubei province lands on the wet market parking lot. In another analysis, they show that the other paper’s recommended tests wouldn’t have correctly pointed to the offending water pump in the famous John Snow cholera outbreak, but theirs would have. Still, I think it’s useful to supplement fancy statistics with normal common sense, so I recommend just looking at the map of early cases: …and deciding whether you think the assumptions behind a specific statistical test are likely to debunk the idea that cases are centered around the wet market. 11. Wuhan used as a control for a 2015 serological study on SARS-related bat coronaviruses due to its urban location. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178078/ I don’t know why this point is supposed to matter. If you mean that Wuhan isn’t directly exposed to bats, nobody ever said it was. The zoonotic theory is that wildlife carted in from other areas of China started the pandemic in the wet market. 12. Superspreader events also seen at wet markets in Beijing and Singapore (Xinfadi and Jurong). This was discussed very extensively in the debates, both in section 1 and section 3. Wet markets weren’t “superspreader locations” - in fact, the disease spread no more quickly there than anywhere else. They were the first place in those cities that the pandemic started, due to contaminated animal products. If anything, this supports zoonosis. See also my discussion with Saar on this point below. 13. WIV refuse to share their records with NIH who terminated subaward in 2022. Wider suspension over biosafety concerns. https://www.bloomberg.com/news/articles/2023-07-18/us-suspends-wuhan-institute-funds-over-covid-stonewalling Although WIV has not been especially forthcoming, some of their databases were leaked in various ways and showed that they did not have any viruses capable of transforming into COVID. 14. PLA involvement at WIV and MERS research prior to SARS-COV-2. MERS features several similarities with SARS-CoV-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022351/ I can’t even tell what conspiracy theory you’re trying to propose with this one; if you spell it out I can try to explain why it might be false. 15. SARS1 leaked several times and SARS-COV-2 has leaked from a BSL-3 lab in Taiwan. Agreed that SARS leaked several times. It also spilled over from animals several times. During the debate, a lab leak rate of once per lab per 500 years was proposed (everyone agreed to steelman this by 10x for WIV numbers); I would be interested to know whether anything about the study of SARS challenges that number. 16. Unpublished infectious clone identified from Wuhan contradicting arguments such reverse genetics systems would be published. https://www.biorxiv.org/content/10.1101/2023.02.12.528210v1.full I asked some scientists about this paper and here’s what they told me. Wuhan University sequenced some rice. In the middle of the sequence, there’s an unexpected sequence from a common coronavirus, HKU4. The most likely explanation is that someone else in Wuhan was working on the coronavirus and there was cross-contamination. Plausibly this is Wuhan Institute of Virology, who is known to work with coronaviruses. This is cool detective work, but it’s not clear what it’s supposed to prove. I think some lab leakers are using it to prove that WIV can do reverse genetics, but they admitted this already in a published paper so that’s not too helpful. I think others are using it to prove WIV had “secret viruses” in their catalogue, but the rice virus wasn’t secret, it was HKU4, which is common and which WIV has already published papers about. 1.6: DrJayChou’s 7 Arguments Once again, I cannot stress enough how much better a take you might have on this debate if you watch it. “The first known case predates the market outbreak by a month” - this is not the consensus position. I cannot say for sure what Dr. Chou means by this, but I suspect he’s referring to one of the many claims to this effect that Peter effectively debunked during the debate (Connor Reed, Mr. Chen, the 92 cases, Brazil, etc).
Inline links: blog, writes, this study, wrote a blog post on some of these issues, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10234839/, this paper, https://twitter.com/BiophysicsFL/status/1667232580255490053?t=IJgitS5cw364ioclzVWxaA&s=19, https://twitter.com/BiophysicsFL/status/1752800486837678377?t=EpIRgyybJVaPgeMP5xdstA&s=19, https://www.biorxiv.org/content/10.1101/2022.10.18.512756v1, https://link.springer.com/article/10.1007/s10311-021-01211-0?fbclid=IwAR1HMUMtLIAFOFppVasQDeoIAYrVhP8j4YoPO4wnaTOUiKLsllZl_oKryOw, https://t.co/50kFV9zSb6, https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/34398234/, https://academic.oup.com/bioinformatics/article/38/10/2719/6553661, here, describes it as, https://academic.oup.com/ve/advance-article/doi/10.1093/ve/vead089/7504441, https://journals.asm.org/doi/10.1128/mbio.00313-23, https://academic.oup.com/jrsssa/advance-article-abstract/doi/10.1093/jrsssa/qnae021/7632556, https://academic.oup.com/jrsssa/advance-article-abstract/doi/10.1093/jrsssa/qnad139/7557954, Confirmation Of The Centrality Of The Huanan Market Among Early COVID-19 Cases, https://substackcdn.com/image/fetch/$s_!BNAm!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2Fffd4cddb-6e3e-41f5-8ef6-ec0b27bec600_626x426.webp, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178078/, https://www.bloomberg.com/news/articles/2023-07-18/us-suspends-wuhan-institute-funds-over-covid-stonewalling, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022351/, https://www.biorxiv.org/content/10.1101/2023.02.12.528210v1.full, a published paper, has already published papers about, https://substackcdn.com/image/fetch/$s_!yA9U!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F467dd304-190a-4437-8920-d498c433dffb_1600x960.jpeg
…and deciding whether you think the assumptions behind a specific statistical test are likely to debunk the idea that cases are centered around the wet market. 11. Wuhan used as a control for a 2015 serological study on SARS-related bat coronaviruses due to its urban location. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178078/ I don’t know why this point is supposed to matter. If you mean that Wuhan isn’t directly exposed to bats, nobody ever said it was. The zoonotic theory is that wildlife carted in from other areas of China started the pandemic in the wet market. 12. Superspreader events also seen at wet markets in Beijing and Singapore (Xinfadi and Jurong). This was discussed very extensively in the debates, both in section 1 and section 3. Wet markets weren’t “superspreader locations” - in fact, the disease spread no more quickly there than anywhere else. They were the first place in those cities that the pandemic started, due to contaminated animal products. If anything, this supports zoonosis. See also my discussion with Saar on this point below. 13. WIV refuse to share their records with NIH who terminated subaward in 2022. Wider suspension over biosafety concerns. https://www.bloomberg.com/news/articles/2023-07-18/us-suspends-wuhan-institute-funds-over-covid-stonewalling Although WIV has not been especially forthcoming, some of their databases were leaked in various ways and showed that they did not have any viruses capable of transforming into COVID. 14. PLA involvement at WIV and MERS research prior to SARS-COV-2. MERS features several similarities with SARS-CoV-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022351/ I can’t even tell what conspiracy theory you’re trying to propose with this one; if you spell it out I can try to explain why it might be false. 15. SARS1 leaked several times and SARS-COV-2 has leaked from a BSL-3 lab in Taiwan. Agreed that SARS leaked several times. It also spilled over from animals several times. During the debate, a lab leak rate of once per lab per 500 years was proposed (everyone agreed to steelman this by 10x for WIV numbers); I would be interested to know whether anything about the study of SARS challenges that number. 16. Unpublished infectious clone identified from Wuhan contradicting arguments such reverse genetics systems would be published. https://www.biorxiv.org/content/10.1101/2023.02.12.528210v1.full I asked some scientists about this paper and here’s what they told me. Wuhan University sequenced some rice. In the middle of the sequence, there’s an unexpected sequence from a common coronavirus, HKU4. The most likely explanation is that someone else in Wuhan was working on the coronavirus and there was cross-contamination. Plausibly this is Wuhan Institute of Virology, who is known to work with coronaviruses. This is cool detective work, but it’s not clear what it’s supposed to prove. I think some lab leakers are using it to prove that WIV can do reverse genetics, but they admitted this already in a published paper so that’s not too helpful. I think others are using it to prove WIV had “secret viruses” in their catalogue, but the rice virus wasn’t secret, it was HKU4, which is common and which WIV has already published papers about. 1.6: DrJayChou’s 7 Arguments Once again, I cannot stress enough how much better a take you might have on this debate if you watch it. “The first known case predates the market outbreak by a month” - this is not the consensus position. I cannot say for sure what Dr. Chou means by this, but I suspect he’s referring to one of the many claims to this effect that Peter effectively debunked during the debate (Connor Reed, Mr. Chen, the 92 cases, Brazil, etc).
Inline links: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178078/, https://www.bloomberg.com/news/articles/2023-07-18/us-suspends-wuhan-institute-funds-over-covid-stonewalling, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022351/, https://www.biorxiv.org/content/10.1101/2023.02.12.528210v1.full, a published paper, has already published papers about, https://substackcdn.com/image/fetch/$s_!yA9U!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F467dd304-190a-4437-8920-d498c433dffb_1600x960.jpeg
This collapses the ‘extreme coincidence’ claim, which as explained above, turns lab-leak into the leading hypothesis. My strongest disagreement is with his Point 3 - the inference from other seafood-market-based COVID spread events. Saar writes: A common objection to this method is that these outbreaks are caused by cold-chain products brought into these markets. However, this still fails to explain why markets form these early clusters and not the many other places where cold chain products are delivered to. Additionally, this only demonstrates the importance of cold wet surfaces in preserving SARS2 infectivity, further strengthening the hypothesis in method 1 that a crowded location with many wet surfaces like HSM is highly conducive for rapid SARS2 spread. Last, it also opens the possibility that the HSM outbreak was also caused by cold-chain products. This would reduce the significance of Wuhan being the outbreak location (as the product could have come from anywhere), but since the other evidence for lab-leak is so strong, Wuhan can be given no weight and still lab-leak would be highly likely – Rootclaim’s conclusion will only drop from 94% to 92%. Most of these outbreaks have been traced back to either a migrant worker (eg a fisherman from a country with COVID sells fish at the market of a country with Zero COVID) or a cold chain product. For example, here’s Dai et al on the Xinfadi outbreak, the most important event of this type: According to a joint publication by the Beijing CDC and 13 research institutions, the outbreak at Xinfadi Market was likely to be initiated by fomite transmission from contaminated foods imported via cold-chain logistics (Pang et al., 2020; Beijing Daily, 2020b). Based on the epidemiological investigations at the Xinfadi Market, the researchers preliminarily concluded that booth #S14 in the aquaculture product selling area on the basement floor of the primary trading hall was the source of the initial transmission. Specifically, five customers were tested positive for IgG/IgM antibodies against SARS-CoV-2 in serological screenings, all of whom visited booth #S14 on May 30 and 31, 2020. On May 30, 2020, the owner of booth #S14 procured imported and fully packaged salmon from a company's cold storage warehouse, then cut and processed the salmon for sale at the Xinfadi Market. Laboratory tests showed that sample swabs from five salmon fish from this supplier were tested positive by examining all salmon in the original sealed packages (n = 3582) in the cold storage facility. Viral genome sequencing showed that the viral strain isolated from one of the positive salmon swabs was homologous to that isolated from the infected persons and environmental samples at the Xinfadi Market (Beijing Daily, 2020b). The joint study reported that an ancestral strain isolated from the Xinfadi Market in Beijing was markedly different from the strains identified in two preceding outbreaks in China and the sequences obtained in March 2020 in Beijing. Phylogenetic analysis assigned the ancestral Xinfadi strain to clade B.1.1. Given the fact that the ancestral sequences were mainly identified in Europe, the strain was more likely to be imported to Beijing rather than derived from strains previously circulating in China (Pang et al., 2020). I know China has a bias towards believing frozen food COVID explanations, but this all sounds pretty convincing to me. Why is it more often markets than other places with cold chain products? Partly it’s the migrant workers - a lot of seafood markets are right next to seaports, and the contact tracing eventually traces back to a fisherman who came in through the seaport - I don’t think this is any more mysterious than epidemics often starting via airport or any other transportation hub. But even just keeping the focus on cold chain products, - there have also been outbreaks in seafood distribution warehouses, on docks, and in a seafood processing work area. Markets have many more people than any of those locations, and maybe (total speculation) cutting on cutting boards could aerosolize bits of fish. The strongest evidence that the Wuhan / Huanan Seafood Market epidemic wasn’t caused by migrant workers or imported seafood products is that there was no previous COVID-infected source of workers or seafood. If there had been, we would have noticed when the outbreak there spread (see Section 1.4 on Brazil). Responses to a few of Saar’s other points below: How many locations other than markets provide an interface with wildlife? Were markets actually identified in advance to be high-risk spillover locations or only in retrospect? I think scientists had called wet markets as an especially dangerous potential transmission location in advance. See for example Infectious Diseases Emerging From Chinese Wet Markets, published in 2006, which says: » “In Chinese wet-markets, unique epicenters for transmission of potential viral pathogens, new genes may be acquired or existing genes modified through various mechanisms such as genetic reassortment, recombination and mutation. The wet-markets, at closer proximity to humans, with high viral burden or strains of higher transmission efficiency, facilitate transmission of the viruses to humans.” In 2004, a paper on an emerging bird flu expressed hope that it would not spread too widely, but concluded that: » “Even in the event of yet another lucky escape, more measures must be taken to limit the amplification of viruses with pandemic potential in the wet markets around the world.” In 2007, Reuters published an investigation: Chinese Markets May Be Breeding Ground For Deadly Viruses, which said things like: » “We face similar threats from other viruses and such epidemics can happen because we continue to have very crowded markets in China," said Lo Wing-lok, an infectious disease expert in Hong Kong. "Even though official measures are in place, they are not faithfully followed. We are not talking about just civet cats, but all animals," he added.” Wet Markets, A Continuing Source Of SARS And Influenza, published 2004, is admittedly focusing on the next SARS1 outbreak instead of on SARS2, but gets bonus points for mentioning both wet markets and labs as likely causes of the next pandemic: » “Will SARS reappear? This question confronts public-health officials worldwide, particularly infectious disease personnel in those regions of the world most affected by the disease and the economic burden of SARS, including China, Taiwan, and Canada. Will the virus re-emerge from wet markets or from laboratories working with SARS CoV, or are asymptomatic infections ongoing in human beings? Similar questions can be asked about a pandemic of influenza that is probably imminent. Knowledge of the ecology of influenza in wet markets can be used as an early-warning system to detect the reappearance of SARS or pandemic influenza.” Saar mentions that there are several other possible sources like restaurants or farms. I think Peter demonstrated during the debate that pandemics are unlikely to start in rural areas, so farms aren’t that important. Restaurants mostly source their products from wet markets. During SARS1, some pandemics started in restaurants because they kept the civets in cages next to the diners (like how some Western restaurants keep lobsters). After SARS1, restaurants stopped doing that and became a less likely spillover location. Saar again: Scott quotes Peter, who implies that under the lab-leak hypothesis, we would expect the confirmed early cases to be centered around the WIV. However, cases are not expected to center on the lab. The lab is not spraying viruses into the air or hosting thousands of locals daily. If a worker gets infected, they spread the virus to their friends and family at completely different locations. In most places with an outbreak of known origin, epidemics show some geographic clustering. This has been true ever since the very beginning of epidemiology, when John Snow successfully traced a cholera outbreak back to its origin at a contaminated water pump by taking the center of the map of cholera cases. This isn’t a 100% law of nature; an infected lab worker might get lucky and not pass it to any of his lab co-workers. Still, we might expect him to infect his family, the stores he went to, or the restaurants he went to. If he lived near his workplace, these might also be near the lab. If he didn’t - let’s say he lived on the other side of town and had a long commute - he would start a cluster near his house, or his favorite store, or his favorite restaurant. Then the people there would infect their families/co-workers/stores/restaurants. The cluster would start somewhere! Sure, some people would infect nobody close to their work or home, and instead just infect one person a hundred miles away who they breathed on during a trip - but this is the exception, not the rule. So you wouldn’t expect a totally random distribution of cases all around Wuhan. There would be one center, or maybe several centers. But none of the claims that COVID was quietly spreading for months before the wet market have pointed to some alternate center of cases. If COVID was spreading for months before the lab, it somehow spread in a completely diffuse geographical pattern, with people exactly as likely to infect people far away from them as close to them - until it reached the wet market in December, and then spread in the normal center-radiating-outward way that every other infection spreads. All the evidence trying to support a spillover at the market is based on complex models with many single points of failure, built from unreliable and biased data. Therefore, it is difficult to give this evidence significant weight as there is always a possibility of errors in the data or its interpretation. More on this in the UFO comment below. Disagree. “First known case was at a wet market” is as simple as it comes. Certainly it’s less complex than “the virus has a 12 nucleotide insertion at the furin cleavage site, and even though those sometimes happen by natural recombination probably this one didn’t, and even though it looks out of frame maybe there was some weird thing going on with serine that made it in frame this one time only”, which is Saar’s star piece of evidence. I understand Saar thinks he can come up with lots of objections to “seen near wet market is suspicious for wet market origin”, then claim that getting over those objections requires “complexity”. But if Peter had no dignity, he could also come up with lots of objections to “seen in same city as Wuhan Institute of Virology is suspicious". He could say that maybe the civet farms of Hubei province were uniquely blah blah blah, and then Saar would have to prove that the civet farms weren’t uniquely blah blah blah, and then he could say “Oh, sure seems like you have a complex model with lots of unique points of failure, it all depends on fifty facts about the regulation of civet farms.” To illustrate what a market looks like in a real zoonotic pandemic, consider this study from SARS1. The researchers went to a random market and sampled the wildlife sold there. 4 of 6 civets sampled were positive, and 3 of them were phylogenetically distinct (i.e. infected in completely different places). A scientist I talked to says the 3 phylogenetically distinct lineages were most likely sampling errors. Still, this seems irrelevant to me since, again, no raccoon-dogs were tested. Scott explains that Covid’s closest known relative, BANAL-52, is rare and so it’s highly unlikely the WIV would’ve had it available as the starting point to engineer Covid . . . This is a basic mistake. SARS2 is not based on BANAL-52 but a relative of it. There is nothing unlikely here. No BANAL-52 relative close enough to create COVID from has ever been discovered. By mentioning BANAL-52, I was trying to be maximally charitable to the lab leak side. In order to create COVID, they would need a virus very close to COVID. But in years and years of searching, nobody has ever discovered a virus like this. Therefore it must be rare. As a way of bounding how rare, let’s see how rare the closest virus ever discovered is. That’s BANAL-52. It is very rare. Therefore, the COVID ancestor must be rarer than that. I don’t know how strong this argument is, because maybe there are millions of rare viruses capable of becoming pandemics, such that getting any one of them is very easy, even though each one individually is rare. The version of this I find convincing is that it should be a probabilistic cost to say that WIV did gain-of-function on a seemingly undiscovered and so-far-very-hard-to-discover rare virus instead of on any of the usual SARS-like viruses that people do their gain-of-function research on. Overall, all attempts to portray [Connor Reed] as an unstable, delusional person were unsuccessful. He is an ordinary person who very accurately described Covid-19 symptoms in real-time and claims to have received a positive test result. The timing and location matches the lab leak hypothesis and is impossible for the HSM claim. Therefore, they must discredit him. It is worth noting here the biased evidentiary standards used by zoonotic proponents. Reed’s testimony about his sickness, given on camera to multiple outlets, is deceitful and should be ignored. Yet, an anonymous voice testimony in one Chinese publication is definitely identified as Mr. Chen (another possible pre-HSM case) and should be considered reliable. See above for why I don’t trust Connor Reed. I’m not sure why Saar attributes Mr. Chen to “an anonymous voice testimony in one Chinese publication”. When I looked for Chen information, I got this thread, where it’s attributed to two Chinese hospital doctors, cross-checked with the Chinese COVID data repository, and double-cross-checked with the supplementary table in a peer-reviewed paper published by a team of Wuhan doctors. To understand how ridiculous the claim is that the HKU1 insertion looks just as engineered as SARS2’s, here are their alignments. Hopefully that should be enough. COVID: HKU1: I’m not a virologist, but I question how this comparison works. Surely HKU1 got its insert on some specific day. If you take the virus the day before, and then the other virus the day after, there will be no differences except the insert, and it will look just like COVID (ie an insert without many other mutations). The fact that the COVID comparison has few mutations, and the HKU1 insert has many mutations, just shows that whatever older virus we chose to compare HKU1 to is more distant from HKU1 than BANAL-52 (or whatever) is from COVID. Or am I missing something here? [The evidence that China tried to cover up zoonosis from the start] is untrue. They clearly said from the start this is a zoonotic spillover at HSM, and at least part of the government went to immense efforts to identify the animal, close farms, etc. (and of course couldn’t find any infected animal). Only in late 2020 did they start suspecting an import from cold-chain products after having multiple outbreaks that seem related to cold-chain products. From a Vox article from March 2023: From the start, the Chinese government interfered with efforts by both Chinese and international experts to study the pandemic, including its origins. Reporting by the AP found that even as WHO officials were publicly praising China’s cooperation, behind the scenes they were complaining about lack of access and a refusal to share data. Within months of the beginning of the pandemic, the Chinese government imposed restrictions on academic research into the origins of the novel coronavirus … China’s intransigence wasn’t unusual — countries are rarely eager to confirm that they’re the source of a deadly disease — but it went beyond the norm. International investigators weren’t permitted to see the market until more than a year after the pandemic began and a WHO-affiliated team was allowed a highly choreographed and controlled visit. The resulting report that came out of the Wuhan visit, which dismissed the possibility of a lab origin, pointed the finger at some kind of zoonotic spillover while concluding that it was unlikely that the spread started at the market, which surprised many experts. It also found that it was “possible” that the virus had been introduced via contaminated frozen food products from abroad. While few experts took that possibility seriously, it fit a narrative the Chinese government had been pushing, against nearly all evidence, that the pandemic had in fact not originated in China. “China just doesn’t want to look bad,” Filippa Lentzos, a biosecurity expert at King’s College London, told Science last August. “They need to maintain an image of control and competence. And that is what goes through everything they do.” […] it seems clear that with more cooperation, scientists could have been looking at raccoon dogs a year or more ago. “The big issue right now is that this data exists and that it is not readily available to the international community,” Maria Van Kerkhove, the WHO’s Covid-19 technical lead, told reporters on Friday. “This is first and foremost absolutely critical, not to mention that it should have been made available years earlier, but that data needs to be made accessible to individuals who can access it, who can analyze it and who can discuss it with each other.” The irony is that by making it so difficult to properly investigate a zoonotic origin of Covid, the Chinese government has created a vacuum that has been filled by claims on all sides, including the much more damning accusation that the pandemic was the result of a lab error at the Wuhan Institute of Virology. For what it’s worth, my timeline of Chinese denials and coverups looks like this: December: COVID doesn't exist, it's all lies Early January: Fine, it exists, but it’s just some wet market thing that can't spread from person to person Late January: Fine, it can spread from person to person, but we’ve got it under control now. February: Fine, it’s out of control, but you would not believe how great our response was. We're basically heroes. March: COVID was a US bioweapon, or possibly came from Italy. April: Chinese people are banned from researching the origins of COVID without government permission. 2: Comments Arguing Against Lab Leak 2.1: Is the pandemic starting near WIV reverse correlation? randomstringofcharacters wrote: Isn't [the pandemic starting near the lab] a reverse correlation issue? The lab is situated there because it's an area where coronaviruses were found in the past. Many people had this question, but Wuhan Institute of Virology was founded in 1956, didn’t originally focus on coronaviruses, and isn’t in a coronavirus hot spot. Most of WIV’s coronavirus samples come from Yunnan, about a thousand miles away. COVID’s closest relatives were found in Laos, almost two thousand miles away. During the debate, both Saar and Peter calculated the odds of a natural pandemic arising in Wuhan by dividing the population of Wuhan by the total urban population of East Asia (Saar) or South China (Peter). Saar got 1.5%, Peter got 3% (he later said this could be as high as 10% because it was a central hub in the wildlife trade). This isn’t an Official Position and I don’t think anyone else shares it, but during the debate Peter pointed out a few times that there are plenty of disease-ridden bats in Hubei (the province Wuhan is in), and that it’s not impossible that a bat virus currently known only in Laos could be active in Hubei. Still, this is the minority viewpoint and most scientists just think it involved something about the wildlife trade. 3: Other Points That Came Up 3.1: Apology to Peter re: extreme odds quiet_NaN wrote: Hot take: Peter clearly failed to convince anyone. The lab leak odds, in log10 (i.e. orders of magnitude are): Peter -20.7 Saar 2.7 Eric -3.1 Will -2.5 Scott -1.2 Daniel -1.4 One of these numbers is clearly an outlier. Scott mentions it and calls it "trolling", I would argue that it is debating in bad faith. 2e-21 is a ratio which is just silly. For one thing, the gain of function at WiV pathway is not the only pathway towards a lab leak. The WIV could also have released a naturally occurring coronavirus at the wet market. At 2e-21 odds, we would probably have to consider the possibility that the WIV built a time machine and went back in time to infect the wet market. I might have screwed up here - or at least I should have emphasized the “trolling” part. Peter complained about my presentation of his extreme-odds slide, saying: This is basically accurate. During the debate, Saar gave lots of different numbers. I don’t want to say exactly what the different numbers meant, because in earlier drafts of my post, Saar said I misunderstood them. My impression were that some of his numbers were conservative, others were central, others were extreme, others were adjusted-for-out-of-model-error, others were not-adjusted, etc. In an early draft of the post, I gave higher numbers for Saar. Saar asked me to replace them with the numbers I ended up using. I decided to agree, because I wanted to represent Saar fairly with the numbers he most centrally believed, but also because these were closest to the numbers on his Rootclaim site so it wasn’t like he was making them up just to fool me. Peter didn’t argue quite as hard, and also he didn’t have anything like the Rootclaim site, so I just took his first set of numbers. Trying to piece things together, I think a reasonable summary would be: During the debate, Saar mentioned 700-million-to-one odds in favor of lab leak, not because he thought this was plausible, but just as a discussion of where the situation would end up if you didn’t adjust for human fallibility.
Inline links: Dai et al, Pang et al., 2020, Beijing Daily, 2020b, seafood distribution warehouses, on docks, a seafood processing work area, Infectious Diseases Emerging From Chinese Wet Markets, a paper on an emerging bird flu, Chinese Markets May Be Breeding Ground For Deadly Viruses, Wet Markets, A Continuing Source Of SARS And Influenza, this study from SARS1, this thread, https://substackcdn.com/image/fetch/$s_!dcI7!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2Fc5aabd26-d70b-4f35-97cb-96d351bb52fd_552x920.png, https://substackcdn.com/image/fetch/$s_!UQ14!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F2411167c-1405-4fde-914b-6388ee498523_935x851.jpeg, a Vox article, wrote, wrote, https://twitter.com/tgof137/status/1773797640607850745