5 ms·

>>"The virologists working in Wuhan did travel all the way to Southern China to collect bat coronavirus samples and they did perform gain-of-function experiment

>>"The virologists working in Wuhan did travel all the way to Southern China to collect bat coronavirus samples and they did perform gain-of-function experiments. Viruses - even highly pathogenic ones - have escaped labs on numerous occasions. There is a plausible scenario here." Another plausible scenario, in my opinion, is that the virus was brought to Wuhan by the virologists (in the virologist or their helpers) but never escaped from the lab itself. If you have a bunch of people periodically going to interact with the bats, how improbable is that they get infected of something (unknowingly) on site?

inciampati 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. 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.
api 6y ago
A friend of mine who once lived in China quipped that maybe some low-level tech from the lab was selling animals from the lab at the wet market. Not likely, but he says given what he saw in China it would not surprise him much.
- tim333 6y ago
  The famous lab animal selling was "A top academician at the Chinese Academy of Engineering earned 10.17 million yuan ($1.46 million) by illegally selling off lab animals" rather than a low level tech. Pigs though. Still it suggests standards may be a bit variable.

inciampati 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. 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.

api 6y ago

A friend of mine who once lived in China quipped that maybe some low-level tech from the lab was selling animals from the lab at the wet market. Not likely, but he says given what he saw in China it would not surprise him much.

tim333 6y ago
The famous lab animal selling was "A top academician at the Chinese Academy of Engineering earned 10.17 million yuan ($1.46 million) by illegally selling off lab animals" rather than a low level tech. Pigs though. Still it suggests standards may be a bit variable.