0% chance of a Wuhan emergence under the lab leak theory! You should tell that to the government agencies that favor lab leak over zoo origin.
Gee, the ID creationist lab leak conspiracy theorist totally misses the point. What were the odds on that?
And you should email all the Washburne blog posts to the government agencies that favour a zoological origin over a lab leak. Itâs almost as though these agencies are made up of fallible human being with biases and blind spots.
As @Faizal_Ali said, I donât think you are getting my drift, @Giltil. My comments do not relate to any discussion of actual SARS-CoV-2 origins, but rather to Washburneâs badly-flawed âanalysisâ.
Stated another way, @Giltil, if you buy Washburneâs âBayesian approachâ, you are obliged to conclude that the lab leak theory is wrong.
Of course, Washburneâs âBayesianâ method is garbage. No problems here if you figure this out and discard this particular argument.
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Based on a Bayesian analysis (for which I will not provide priors, and how dare you ask!) the odds are great!
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Regarding the origin of SARS2, there is a vigorous debate between proponents of the zoonotic and lab leak theories. In order to defend their thesis and to confound their opponents, the proponents of the zoonotic theory are waving two publications (Worobey et al, 2022 and Pekar et al, 2022). However, the lab leak proponents dispute the validity of these two publications. For example, it is the case of Jonathan Latham and Allison Wilson in the piece below, where they argue that a new method in virology called Mutational Order Analysis (MOA)is superior to the method used by Pekar et al to investigate the origin of SARS2.
The following are the main conclusions that can be drawn when applying MOA to SARS2:
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MOA identifies just one root virus (when Pekar et al identify two)
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The root virus identified by MOA predates all the root viruses identified by Pekar and Worobey, pushing back the predicted date of SARS-CoV-2 emergence into September, 2019
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The earliest viruses were highly adapted to human, which, if true, provides nearly incontrovertible evidence for the lab leak hypothesis.
Not being versed in phylogenetics, I cannot really comment on the superiority or not of the MOA over the method used by Pekar et al. But perhaps some experts here such as @John_Harshman or @Joe_Felsenstein may help.
Here is the piece by Jonathan Latham and Allison Wilson.
And here are the two publications by the authors who applied MOA to the origin of SARS2
I think youâll find that most scientists are looking for evidence instead of debate.
I looked at Latham/Wilsonâs article.
This caught my eye:
A Huanan market origin has officially been dismissed by the authorities in China.
But checking their cited source uncovers the exact opposite:
Liang Wannian, team leader of the Chinese side of the WHO-convened joint expert team on origins tracing, told the briefing that scientists reached in the joint report the consensus of âextremely unlikelyâ after a thorough study in Wuhan on the lab leak hypothesis, a conclusion that should not be ignored.
Yuan Zhiming, director of Chinaâs National Biosafety Laboratory and professor at Wuhan Institute of Virology, also refuted the lab leak rumors at the briefing. He said the latest US Republicansâ virus origins report is a âHollywood movie scriptâ which is ridiculous and has nothing to do with science.
In fact, the next phase of study should be carried out in multiple places worldwide covering countries where the horseshoe bat and pangolins reside, and countries that lack sufficient testing, those with virus-positive animal data and who supplied the Wuhan Huanan market through cold-chain logistics, Liang said.
Their source actually says that instead of rejecting the Huanan market origin, the Chinese authorities reject the lab leak claim and want future investigation to focus on routes into the Huanan market.
Iâm not going to bother reading the rest of that article.
@Giltilâs other âfactsâ have been addressed already, so Iâll just comment on this one:
That would be expected even if the pandemic originated at the market, since most of the animal sellers would have no more link to the virus than the vegetable sellers.
What would be expected if the pandemic originated at the market, but not if it originated with lab workers visiting the market, is that stalls from one area of the market showed higher positivity than stalls elsewhere, due to proximity to the source, regardless of what they were selling. That is what has been reported.
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Why would someone believe that? Is it surprising that a virus that was highly contagious to humans would appear to be âhighly adaptedâ to infecting humans? I canât see how it could be otherwise.
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See my post at 126
Because he would be educated in virology
Do you think vulgarity helps your case?
Does virology teach that pandemics in humans, that spread with such rapidity that a large percentage of the worldâs population is infected within a matter of weeks, happens if the virus is poorly adapted to infecting and being transmitted by human hosts? If so, could you provide a reference that teaches this?
Firstly, this makes it sound as if the MOA method followed-up after Worobey et al. 2022 and Pekar et al. 2022. In fact, it was the other way around. The two studies that you linked (Kumar et al. 2021 and Caraballo-Ortiz et al. 2022) were published before the former two. In fact, Pekar et al. 2022 disputes the latter two in the following:
The A.1 and A+C29095T proposed ancestral haplotypes were strongly rejected by all the phylodynamic analyses, even when rooting with recCA or bat sarbecovirus outgroups, which include both C18060T and C29095T (Table 1 and data S3). Hence, WA1-like and 20SF012-like haplotypes cannot plausibly represent the MRCA of SARS-CoV-2 as previously suggested (19â21); the similarity of these genomes to the recCA is due to C-to-T reversions. Haplotypes not reported in Table 1 were similarly rejected (data S3).
Note: [citations 20 and 21 are Kumar et al. 2021 and Caraballo-Ortiz et al. 2022]
Thatâs not the case. Pekar et al. 2022 also finds ONE root. What they disagree on is where the root of all SARS-CoV-2 variants is. Pekar et al. propose the following phylogeny, with two lineages (A and B) splitting off from each other around 11 December 2019 with a 95% highest posterior density (HPD) interval between 25 November to 12 December.
They also claim that the specific structure of this phylogeny, specifically the âexplosiveâ radiation (polytomy) within each of these A and B lineages, suggests that each respective base of lineage A and B represents two seperate spillover events, both occurring at the Wuhan market.
Lineages A and B comprise 35.2 and 64.8% of the early SARS-CoV-2 genomes, respectively, and each lineage is characterized by a large polytomy (many sampled lineages descending from a single node on the phylogenetic tree), with the base of lineages A and B being the two largest polytomies observed in the early pandemic (Fig. 1). Furthermore, large polytomies are characteristic of SARS-CoV-2 introductions into geographical regions at the start of the pandemic (for example, fig. S23) (11, 27â29) and would similarly be expected to occur after a successful introduction of SARS-CoV-2 into humans. Congruently, the most common topology in our simulations is a large basal polytomy (with â„100 descendent lineages), which is present in 47.5% of simulated epidemics (Fig. 2A).
This is mostly right what I can tell. Kumar et al. 2021 and Caraballo-Ortiz et al. 2022 propose a root that lies somewhere within lineage A (which would mean lineage B is descended from A, not sisters). From this rooting, the common ancestor is reckoned to be older, around September to October 2019. This means that the virus had likely circulated a long time before arriving in the Wuhan market, making it more likely a superspreader rather than the site of original spillover.
It should also be noted that (regardless what the piece written on the âindependent science newsâ website says), Kumar et al. 2021 nor Caraballo-Ortiz et al. 2022 propose a lab leak scenario and explicitly entertain zoonosis. I also donât see how these different rooting of the phylogeny would tip the balance away from zoonotic origin in either case. Either the zoonosis happened later in Wuhan (twice) according to Worobey et al, 2022 and Pekar et al, 2022, or zoonosis happened earlier prior to the Wuhan outbreak according to Kumar et al. 2021 and Caraballo-Ortiz 2022.
I donât see any reason why this would suggest âincontrovertibleâ evidence for lab leak. This is also what you would expect from zoonotic spillovers that lead to outbreaks. What happens when a virus that isnât âwell adaptedâ to survive in humans comes into contact with a human? It wonât do anything. At the most, it will cause a few infections but itâs not able to transmit itself among humans very effectively. The R0 is below 1.0, which means the virus fizzle out very quickly. Itâs likely that many spillover events end like this. Appearing and going away too quickly to be noticed. The ones that we do notice (or at least the ones that cause major epidemics/pandemics) are the ones that experienced mutations which enabled them to effectively transmit among us PRIOR to the spillover.
How host genetics dictates successful viral zoonosis - PMC
Work in molecular virology has revealed why virus replication tends to be so specific for particular host species (Box 1). Viruses replicate themselves inside the cells of their hosts, and to do so, they must correctly execute tens to hundreds of proteinâprotein interactions. For instance, HIV is thought to interact with as many as 400 proteins in human T cells [13]. Animal viruses will replicate in human cells when they can interact with all of the useful host proteins that they need and simultaneously avoid interaction with all of the immunity proteins that will destroy them. Viruses might not interact correctly with host proteins in a new species (binding to useful proteins, avoiding immunity proteins) because of differences in the primary sequences of these proteins in the new species. Even small primary sequence differences between orthologs of a host protein can change the virus interaction surface, either directly or by changing the structure or pattern of post-translational modification, such as the addition of glycans. While an animal virus could be selected for perfecting interactions with human proteins (enhancing interaction with useful host proteins and avoiding interaction with antiviral proteins), the conditions for human adaptation will not exist until after viral replication in a human has commenced. Instead, only âalive-on-arrivalâ animal viruses, meaning those already able to launch replication cycles upon encountering a human, will have any opportunity to further optimize themselves for the human host. (Alive-on-arrival viruses have also been referred to as âoff the shelfâ [1].) Stated another way, zoonosis requires that human-compatible viral variants pre-exist in the animal reservoir, arising before these viruses have ever even experienced the selective constraints of the human body. For the vast majority of animal viruses in nature, there are just too many proteinâprotein interactions to master by chance in a random encounter with humans.
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Well I think the idea is that the fact that it was already highly contagious in the earliest known cases is what is supposed to be a surprising and unusual fact, in need of explanation, on a zoonotic origin. As I understand this argument they are saying when zoonoses happen the viruses are claimed to typically begin as considerably less contagious in their new hosts compared to SARS-Cov2, and then have to gradually evolve higher transmissibility before it gains the ability to so easily jump from person to person.
But that here the first known cases already had unusually high transmissibility, and showed essentially no gain in that for a long time. This very good initial transmissibility combined with lack of further gains early in the pandemic, they argue, shows that the virus had already adapted to effective replication and transmissibility in human hosts (and that this had presumably occurred in human cell culture, or humanized mice or similar).
I think another prong of this argument is that whatever gains has since occurred in the virusâs transmissibility came from immune escape, rather than things like improved receptor binding, gains in intracellular replication, and stuff like that.
Doesnât this then imply that the fact that the market was a superspreader event is less relevant as evidence that the virus began with a natural zoonotic spillover?
I believe I see some tension between invoking SARS-Cov2 positive samples collected at the market, as evidence for a natural zoonotic transmission because they sell wild animals some of which are known to harbor coronaviruses - yet at the same time saying these detections of SARS-Cov2 at the market arenât actually the site of initial spillover, rather just a first known super-spreader event and that the actual zoonosis could have happened elsewhere?
Youâre mostly right. In a nutshell, in nature, when a virus enter a new host population, it is supposed to evolved rapidly, ie, to rapidly accumulate a set of adaptive mutations, in order to shrive in its new environment. But according to the phylogeny provided by MOA, no such thing happened in the early days of the pandemic. In fact, it was not until the 8th mutation that an effect on fitness occurred. This is not normal for a zoonotic spillover.
Okay. But Iâm highly skeptical that those statements are true.
First of all is it true that this isnât normal? What do we know about what happens during influenza pandemics for example? How much adaptation happens early, there, as in do we have any good grasp of how long it takes for mutations to show fitness gains? And how does that compare to SARS-Cov2?
I have a strong suspicion thereâs actually a lot more uncertainty about this than the characterization that weâre offered by lab-leak proponents.
I would also want to have it substantiated that no fitness gains occurred until the 8th mutation during the SARS-Cov2 pandemic. Can we really say we know that? What do we know about this?
The earliest viruses were adapted, cleavage sites and all, to all sorts of mammals - you could fill a zoo. This is incontrovertible evidence that the virus was adapted to all sorts of mammals.
I would not say highly adapted, as that adjective would prove false relative to mutations in variants to come.
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