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What is often missed is that chimeric viruses are easy to detect. The viral genome will show clear evidence of manipulation from random base insertions and clea

What is often missed is that chimeric viruses are easy to detect. The viral genome will show clear evidence of manipulation from random base insertions and clear homology with all the ancestral viruses. Hiding the signs of manipulation would either require vast amounts of time and resources (the expense and man power would make it very difficult to hide) or straight up science fiction technology. The chimeric origin hypothesis is not a plausible explanation for the origin of sars-cov2, which means the nature link is not relevant. The other lab leak hypothesis is that a specimen collected and cultured by scientists, infected a lab employee and this patient zero then transmitted the virus to others. This is a plausible option, and it is being researched. However it is less plausible than wild transmission based on a simple numbers game. What is more likely, a breakout infection cause by a dozen scientists specifically trained and equipped against this possibility, or a transmission to one of the millions of other people who routinely interact with these bat populations? Both are possible, but one is much more likely. Before covid19, WIV had published research indicating that novel coronaviruses routinely jump from bats to humans in that part of the world. Most of these viruses aren't don't last in human hosts, but it's clear that it was only a matter time before something nasty got through. After all, it's already happened once before. The real nail in the coffin is that research[0] has shown that there were at least two, independent transmissions of sars-cov2 to humans. For this to happen as part of a lab leak it would require WIV to have found and cultivated 2 different strains of sars-cov2, and then each of those strains would have to escape the lab. [0] https://www.science.org/doi/10.1126/science.abp8715 https://www.science.org/doi/10.1126/science.abp8715

forgotpwd16 4y ago
That's a much better counter argument to the lab-origin. The >The chimeric origin hypothesis is not a plausible explanation for the origin of sars-cov2, which means the nature link is not relevant. seems to be incorrect. By a simple search: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744920/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744920/ Now the two distinct genomic lineages seem to indeed present a challenge to lab-leak hypothesis. It's explained in the original study[0] that the second lineage B came from A by intra-host evolution. Due to the molecular clock of the virus the single-introduction origin of the pandemic from a lineage A can be ruled out. [0]: https://www.science.org/doi/10.1126/science.abp8337 https://www.science.org/doi/10.1126/science.abp8337
- tripletao 4y ago
  Have you looked at Pekar's full model, as described mostly in the supplementary materials? A typical molecular clock approach wouldn't give anywhere near the accuracy necessary to exclude evolution of lineage B (just two SNPs away) in humans. Pekar instead builds layer upon layer of complexity, with dozens of reasonable but somewhat arbitrary judgment calls, in the same general direction as econometrics. From the shape of the resulting modeled phylogenetic tree, he purports to exclude a single introduction into humans. I'm not aware of any case where any similar model has been shown to have predictive power, and there's inherently no way to validate this one against any physical data. So I believe this result has been grossly oversold, per my comments and links at https://news.ycombinator.com/item?id=32740568 https://news.ycombinator.com/item?id=32740568
  - oasisbob 4y ago
    > A typical molecular clock approach wouldn't give anywhere near the accuracy necessary to exclude evolution of lineage B (just two SNPs away) in humans You're ignoring other data which is counter to the idea of B evolving from A in humans. Pekar's models are not the only evidence. - Early cases were predominantly B - A shows less generic divergence than B, this is what Pekar is talking about with regards to the discontinuity in the early clock. When we first started discussing this - I spoke up because I was annoyed by you trashing peer-reviewed papers when it was obvious you weren't even attempting to grok the phylogenetics involved. Still annoyed. It's been genuinely interesting watching the scientific debate to root the SC2 tree over the past few years because of the involved paradoxes. "Just a few SNPs" is just such a silly argument when stacked against peer-reviewed phylogenies in high-impact publications.
    - tripletao 4y ago
      Have you looked at Pekar's full numerical stack yourself, as described in their supplemental materials? If yes, then why are you confident that their choice of the Barabasi-Albert algorithm to generate a fixed infection network correctly models the earliest spread of SARS-CoV-2 in humans? In particular, why choose to study robustness against doubling time (which seems intuitively like it wouldn't affect the shape of the tree much), but not robustness against that connectivity (which seems intuitively like it would)? The rest of their arguments depend fundamentally on the polytomy thing, because nothing else excludes an earlier (even September) first introduction into humans. With an earlier introduction and thus more extensive unsampled spread, it's much harder to insist that A and B would be first sampled in the same order in which they evolved in humans, or make any similar early claims with confidence. You are correct that I hadn't fully understood their polytomy argument before you brought it up, and I appreciate you bringing it to my attention. I still don't think it's very good, though. I later found Erik van Nimwegen's criticisms, which roughly followed my own; so I don't think I'm taking a fringe position here. Indeed, I've never seen anyone citing or defending Pekar engage in any way with the numerical complexity of that model. It seems like anyone who's looked inside the box becomes a critic, thus my hope that you'll do so. High-impact publications have shown unfortunate willingness to publish low-quality work that would exclude research-related origin of SARS-CoV-2. For example, I assume you followed Nature's publication, editor's note, and ultimate extensive correction of their pangolin paper, and that you agree pangolins aren't the proximal host. This makes me less inclined to trust in their reviewers here, and more inclined to trust my own judgment (or that of the two Twitter threads I've linked elsewhere).

forgotpwd16 4y ago

That's a much better counter argument to the lab-origin. The >The chimeric origin hypothesis is not a plausible explanation for the origin of sars-cov2, which means the nature link is not relevant. seems to be incorrect. By a simple search: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744920/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744920/ Now the two distinct genomic lineages seem to indeed present a challenge to lab-leak hypothesis. It's explained in the original study[0] that the second lineage B came from A by intra-host evolution. Due to the molecular clock of the virus the single-introduction origin of the pandemic from a lineage A can be ruled out. [0]: https://www.science.org/doi/10.1126/science.abp8337 https://www.science.org/doi/10.1126/science.abp8337

tripletao 4y ago
Have you looked at Pekar's full model, as described mostly in the supplementary materials? A typical molecular clock approach wouldn't give anywhere near the accuracy necessary to exclude evolution of lineage B (just two SNPs away) in humans. Pekar instead builds layer upon layer of complexity, with dozens of reasonable but somewhat arbitrary judgment calls, in the same general direction as econometrics. From the shape of the resulting modeled phylogenetic tree, he purports to exclude a single introduction into humans. I'm not aware of any case where any similar model has been shown to have predictive power, and there's inherently no way to validate this one against any physical data. So I believe this result has been grossly oversold, per my comments and links at https://news.ycombinator.com/item?id=32740568 https://news.ycombinator.com/item?id=32740568
- oasisbob 4y ago
  > A typical molecular clock approach wouldn't give anywhere near the accuracy necessary to exclude evolution of lineage B (just two SNPs away) in humans You're ignoring other data which is counter to the idea of B evolving from A in humans. Pekar's models are not the only evidence. - Early cases were predominantly B - A shows less generic divergence than B, this is what Pekar is talking about with regards to the discontinuity in the early clock. When we first started discussing this - I spoke up because I was annoyed by you trashing peer-reviewed papers when it was obvious you weren't even attempting to grok the phylogenetics involved. Still annoyed. It's been genuinely interesting watching the scientific debate to root the SC2 tree over the past few years because of the involved paradoxes. "Just a few SNPs" is just such a silly argument when stacked against peer-reviewed phylogenies in high-impact publications.
  - tripletao 4y ago
    Have you looked at Pekar's full numerical stack yourself, as described in their supplemental materials? If yes, then why are you confident that their choice of the Barabasi-Albert algorithm to generate a fixed infection network correctly models the earliest spread of SARS-CoV-2 in humans? In particular, why choose to study robustness against doubling time (which seems intuitively like it wouldn't affect the shape of the tree much), but not robustness against that connectivity (which seems intuitively like it would)? The rest of their arguments depend fundamentally on the polytomy thing, because nothing else excludes an earlier (even September) first introduction into humans. With an earlier introduction and thus more extensive unsampled spread, it's much harder to insist that A and B would be first sampled in the same order in which they evolved in humans, or make any similar early claims with confidence. You are correct that I hadn't fully understood their polytomy argument before you brought it up, and I appreciate you bringing it to my attention. I still don't think it's very good, though. I later found Erik van Nimwegen's criticisms, which roughly followed my own; so I don't think I'm taking a fringe position here. Indeed, I've never seen anyone citing or defending Pekar engage in any way with the numerical complexity of that model. It seems like anyone who's looked inside the box becomes a critic, thus my hope that you'll do so. High-impact publications have shown unfortunate willingness to publish low-quality work that would exclude research-related origin of SARS-CoV-2. For example, I assume you followed Nature's publication, editor's note, and ultimate extensive correction of their pangolin paper, and that you agree pangolins aren't the proximal host. This makes me less inclined to trust in their reviewers here, and more inclined to trust my own judgment (or that of the two Twitter threads I've linked elsewhere).