4 ms·

It's very unlikely that you'd get a one step transfer from a bat that yielded a spike protein with the level of affinity it has for human ACE2. If you look at t

It's very unlikely that you'd get a one step transfer from a bat that yielded a spike protein with the level of affinity it has for human ACE2. If you look at that protein alone, the most-likely proximal hosts are primates. If we seriously believe in zoonotic transfer, we should be looking at those populations, and understanding how orangutans and bonobos infiltrated Wuhan and transmitted the virus to unwitting humans. The other recent coronavirus spillovers actually have rather low infectivity that increases with the course of the epidemic through adaptive mutations. But amazingly, with SARS2, it appeared already fully adapted. The phylogenetic tree makes a clear statement about how long SARS2 has been circulating in humans. At the publication of the genome sequence there were only a handful (~4?) of mutations known and most SARS-CoV-2 genomes were, incredibly, nearly identical. See https://nextstrain.org/ncov/global https://nextstrain.org/ncov/global. If we tend to see one mutation per transmission, that would mean that the spillover happened in October or November 2019, and almost certainly in Wuhan. All SARS-CoV-2 we've observed fits into this single tree, and there is no evidence of any previous progenitor strains. This means that SARS-CoV-2 was fully-adapted from its most-recent common ancestor. What are the odds of that happening directly from a bat? We're only now seeing, with b1117, a big phenotypic jump related to changes in the spike protein. It has arisen in a context that suggests that it may also be the result of strange environmental conditions for the virus that are capable of accelerating its exploration of the solution space. A widely-considered hypothesis is that it arose in an immunocompromised patient receiving antibody treatment and convalescent plasma, both standard practice in the UK. In this context the virus could have achieved extremely high population (~ many candidate solutions, faster evolutionary computation) and feedback about the immune response of the entire population (to the degree that they would have received multiple donations of plasma).

neuronic 6y ago
The only thing we REALLY know is that these types of coronaviruses originate in Southern China and somehow got to the point of being suspiciously well adapted to ACE2 by the time it exploded in Wuhan. That, however, can also be achieved purely by natural causes over a long time - not just in a lab. Maybe Wuhan is simply the point at which the first very infectious form of SARS-CoV-2 occurred - not the first overall occurrence of any SARS-CoV-2 variant. And it provided a perfect environment to spread at its wet markets. If the virus originated in the West, maybe we would be shitting all over meat processing facilities now? So, how many people would need to get infected to facilitate these mutations? We could possibly have missed SARS-CoV-2 infections with earlier virus strains that were vastly less infectious. It would take quite a lot of people to raise suspicions of anything other going on than nominal incidents of flu-like symptoms. So maybe the initial SARS-2 was basically SARS-1 with much less incidence of severe symptoms - so it slipped under the radar until it mutated, exploded in incidence and suddenly produced overwhelming hospitilization rates.
- inciampati 6y ago
  It's plausible, and could be proven very easily that this happened. Presumably, some progenitor strain is out there, spreading more slowly and making less of a mess. Eventually, a SARS-CoV-2 screen will turn it up and we'll sequence it. Then we will see a strain that's diverged from all other sequences in the phylogenetic tree, with a common ancestor back further than ~1ya.
  - neuronic 6y ago
    But this depends on catching that strain and evolution has likely led to its near full displacement by more infectious strains at this time.
RobertoG 6y ago
>>"It's very unlikely that you'd get a one step transfer from a bat that yielded a spike protein with the level of affinity it has for human ACE2. If you look at that protein alone, the most-likely proximal hosts are primates" I'm not qualified to have an opinion about that, but it seems to me that if we accept that premise, and the primate jump looks improbable, the conclusion is that the virus have to come from a lab where it has been modified. On the other hand, many experts are saying "we don't know, it's probably natural". So, it seems to me that the scientific consensus is giving different prior probabilities to zoonotic transfer that you gave in that statement.
- inciampati 6y ago
  This is an anonymous appeal to authority, but FWIW I am a biologist and I am not convinced of any origin story. We lack evidence in every direction. Although our prior is that it's zoonotic, other experts I know acknowledge the possibility that we are looking at a lab leak. We simply don't have enough information to say. However, there is very strong pressure to reassure the public that it's not lab-based, which would look bad for scientists and our generally pro-social efforts to help the world. I think this is misguided, because people are not stupid. They also can also observe the profound lack of evidence for zoonotic transfer, which frankly makes these assertions look like a coverup. It would be helpful if the scientific community were more honest and scientific about this issue. We should not jump to conclusions without evidence.
  - thu2111 6y ago
    Yeah. Unfortunately public health researchers/biologists have very little credibility at this point so appeals to their authority won't work. In particular arguments of the form "we need more evidence" look weak given how many enormous leaps of faith the supposedly scientific establishment has been willing to make on the basis of no evidence at all for the past year, e.g. masks, lockdowns, asymptomatic infection (apparently now contradicted by a large study of >90% of the entire population of Wuhan!), now vaccines are being advertised as totally safe even though trial protocols are being abandoned left and right. Public health research is really worrying, frankly. The quality gap between epidemiology papers I read in the last 12 months and computer science papers are shocking. Epidemiology routinely publishes papers that contain major errors that the authors clearly knew about and chose to ignore or cover up. The Flaxman paper is an example of how absurdly fraudulent it can get, yet we're told constantly that the "experts" have reached a "consensus" that isn't to be questioned. At this point I'm pretty much ready to believe it came from a lab simply because scientists are claiming it didn't. My prior for public health researchers being honest has dropped through the floor.

neuronic 6y ago

The only thing we REALLY know is that these types of coronaviruses originate in Southern China and somehow got to the point of being suspiciously well adapted to ACE2 by the time it exploded in Wuhan. That, however, can also be achieved purely by natural causes over a long time - not just in a lab. Maybe Wuhan is simply the point at which the first very infectious form of SARS-CoV-2 occurred - not the first overall occurrence of any SARS-CoV-2 variant. And it provided a perfect environment to spread at its wet markets. If the virus originated in the West, maybe we would be shitting all over meat processing facilities now? So, how many people would need to get infected to facilitate these mutations? We could possibly have missed SARS-CoV-2 infections with earlier virus strains that were vastly less infectious. It would take quite a lot of people to raise suspicions of anything other going on than nominal incidents of flu-like symptoms. So maybe the initial SARS-2 was basically SARS-1 with much less incidence of severe symptoms - so it slipped under the radar until it mutated, exploded in incidence and suddenly produced overwhelming hospitilization rates.

inciampati 6y ago
It's plausible, and could be proven very easily that this happened. Presumably, some progenitor strain is out there, spreading more slowly and making less of a mess. Eventually, a SARS-CoV-2 screen will turn it up and we'll sequence it. Then we will see a strain that's diverged from all other sequences in the phylogenetic tree, with a common ancestor back further than ~1ya.
- neuronic 6y ago
  But this depends on catching that strain and evolution has likely led to its near full displacement by more infectious strains at this time.

RobertoG 6y ago

>>"It's very unlikely that you'd get a one step transfer from a bat that yielded a spike protein with the level of affinity it has for human ACE2. If you look at that protein alone, the most-likely proximal hosts are primates" I'm not qualified to have an opinion about that, but it seems to me that if we accept that premise, and the primate jump looks improbable, the conclusion is that the virus have to come from a lab where it has been modified. On the other hand, many experts are saying "we don't know, it's probably natural". So, it seems to me that the scientific consensus is giving different prior probabilities to zoonotic transfer that you gave in that statement.

inciampati 6y ago
This is an anonymous appeal to authority, but FWIW I am a biologist and I am not convinced of any origin story. We lack evidence in every direction. Although our prior is that it's zoonotic, other experts I know acknowledge the possibility that we are looking at a lab leak. We simply don't have enough information to say. However, there is very strong pressure to reassure the public that it's not lab-based, which would look bad for scientists and our generally pro-social efforts to help the world. I think this is misguided, because people are not stupid. They also can also observe the profound lack of evidence for zoonotic transfer, which frankly makes these assertions look like a coverup. It would be helpful if the scientific community were more honest and scientific about this issue. We should not jump to conclusions without evidence.
- thu2111 6y ago
  Yeah. Unfortunately public health researchers/biologists have very little credibility at this point so appeals to their authority won't work. In particular arguments of the form "we need more evidence" look weak given how many enormous leaps of faith the supposedly scientific establishment has been willing to make on the basis of no evidence at all for the past year, e.g. masks, lockdowns, asymptomatic infection (apparently now contradicted by a large study of >90% of the entire population of Wuhan!), now vaccines are being advertised as totally safe even though trial protocols are being abandoned left and right. Public health research is really worrying, frankly. The quality gap between epidemiology papers I read in the last 12 months and computer science papers are shocking. Epidemiology routinely publishes papers that contain major errors that the authors clearly knew about and chose to ignore or cover up. The Flaxman paper is an example of how absurdly fraudulent it can get, yet we're told constantly that the "experts" have reached a "consensus" that isn't to be questioned. At this point I'm pretty much ready to believe it came from a lab simply because scientists are claiming it didn't. My prior for public health researchers being honest has dropped through the floor.