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> Chances of this "escaping" the lab and producing another coronavirus wave are zero because that already happened. Are you aware of any situation where the om

> Chances of this "escaping" the lab and producing another coronavirus wave are zero because that already happened. Are you aware of any situation where the omicron spike and Wuhan backbone could have recombined naturally? As far as I know, the latter was extinct in the wild by the time the former emerged. It's good that the omicron/delta variant didn't blow up in humans. The omicron/Wuhan variant seems like another throw of the dice, though, and even a very small probability times millions of potential deaths is significant.

lamontcg 4y ago
You didn't read carefully what I wrote. The T-cell epitopes in all strains of SARS-CoV-2 are not subject to immune escape and there are thousands of them. Even the neutralizing antibodies to Wu-Hu-1 spike will cross react with omicron still. Nobody at this point is immune naive to this combination. And the most recent pandemic strain of SARS-CoV-2 was Omicron. If this Omicron spike containing virus escaped into the wild then it will encounter a human race with substantial neutralizing antibody activity to this exact spike protein sequence. And there isn't any "but maybe by splicing them together it literally changes everything, you can't possibly prove that isn't true" argument. This isn't science fiction. Inside the cell all of these proteins are diced up into small hexamers and displayed on MHC and it doesn't matter what the combination of the spike and the backbone are, the T-cell epitopes are going to be the same. Omicron spike will have Omicron antibody epitopes and Omicron T-cell epitopes, doen't matter what backbone you splice it onto. If you want to create a new pandemic, particularly one with "millions of potential deaths" you need to change this virus sufficiently that it is no longer identified as SARS-CoV-2 by our T-cells and you don't get that just by combining two different variants.
- tripletao 4y ago
  If that's your argument, then what do you even need the XD strain for? You could simply assert that because natural omicron has spread widely, any lab chimera with the omicron spike must be safe. That seems remarkably cavalier though, considering that (a) natural omicron continues to spread, and kill people every day; and (b) while China's reported case counts are probably inaccurate, they probably do still have a large population that's completely omicron-naive.
  - lamontcg 4y ago
    I clearly didn't need the XD strain, I thought that would be read as supplementary. I routinely forget that no matter how clear your argument sounds to you that someone on the Internet will always misunderstand it (and pick apart a detail that has no central relevance).
    - tripletao 4y ago
      Except that natural omicron continues to kill people now? So it's empirically true that at least one backbone (i.e., the natural omicron backbone) plus the omicron spike remains able to cause significant sickness and death, despite the immunity we've built up, even outside China. So what's your argument that the risk from a different backbone is "zero"?
      - lamontcg 4y ago
        Yet more misunderstanding. First of all they used BA.1 and that spike is nearly extinct and isn't causing much sickness and death, it has been out-competed by BA.5. BA.1 is literally "last years news" and BA.5 is immune evasive against BA.1. Any BA.1 spike is going to be recognized by the same neutralizing antibodies which has suppressed BA.1 circulation in the larger population. And I should have written something like the additional risk over the existing circulating pandemic strains is zero. It could cause infections and deaths, but just like XD it would be outcompeted quickly by BA.5 and wouldn't go anywhere, and the infected people would run exactly the same risk as they would have against the existing global pandemic. There is no way you get from this lab experiment to "COVID-22", it is still all the same virus, same pandemic, and a variant of the virus which will be substantially less fit against population immunity than BA.5 or whatever new variant winds up circulating this winter.
        tripletao 4y ago
        So you're acknowledging now that the lab chimera might infect some people if it escaped, but you're saying that's okay because those people would otherwise have gotten infected with a natural variant anyways? But if the IFR for the lab chimera is higher than the IFR for natural omicron (which it was, at least in their mice), then those people are paying a higher price in mortality for the same immunity--that's the gain of function of concern. And really, is there anything in biology that we know with sufficient confidence to risk millions of lives in exchange for no immediate practical benefit? Like I guess whoever did the 1977 flu vaccine trials also assumed that if their virus escaped, it would get outcompeted by the existing natural viruses; but we know what happened there.
- alchemist1e9 4y ago
  You and Derek Lowe are at best apologists who due to your myopic perspective can’t see the obvious risks that many of us outsiders can imagine. At worst you’re part of a group for which “it is difficult to get a man to understand something, when his salary depends on his not understanding it”
  - lamontcg 4y ago
    If I wind up rotting in hell with Derek Lowe that'll be pretty good company, I think I'll take that.
- benibela 4y ago
  >Nobody at this point is immune naive to this combination. My mother did not get vaccinated and she probably was not infected
  - lamontcg 4y ago
    She's got less to fear from this lab experiment (based on variants that are existing or nearly existing) than from the ongoing natural pandemic.
Izkata 4y ago
> As far as I know, the latter was extinct in the wild by the time the former emerged. Omicron isn't a descendant of Delta. It has an odd lineage that couldn't be explained and (unless new info has come up since I last looked) it was likely a descendant of either Wuhan or Alpha that mutated hidden from most of the world - one of the theories was that Wuhan/Alpha jumped to rats, then back to humans after becoming Omicron.
- tripletao 4y ago
  I agree, but I don't think that's relevant? So I think my terminology was unclear. By "omicron/delta" I meant a recombinant of the omicron spike with the delta backbone, the one that apparently happened naturally and Derek Lowe describes as the XD strain. By "omicron/Wuhan" I meant a recombinant of the omicron spike with the Wuhan backbone, which these researchers created in their lab (and I don't believe had any opportunity to occur naturally, since the two lineages never existed simultaneously).
  - Izkata 4y ago
    > since the two lineages never existed simultaneously Some version of it would likely have existed in the rat-origin theory of Omicron as an intermediate stage, is what I meant.
    - tripletao 4y ago
      Ah, got it now. Then I guess the rats (or other cryptic hosts in which omicron evolved) might have been exposed to the omicron/Wuhan recombinant, but not humans.

lamontcg 4y ago

You didn't read carefully what I wrote. The T-cell epitopes in all strains of SARS-CoV-2 are not subject to immune escape and there are thousands of them. Even the neutralizing antibodies to Wu-Hu-1 spike will cross react with omicron still. Nobody at this point is immune naive to this combination. And the most recent pandemic strain of SARS-CoV-2 was Omicron. If this Omicron spike containing virus escaped into the wild then it will encounter a human race with substantial neutralizing antibody activity to this exact spike protein sequence. And there isn't any "but maybe by splicing them together it literally changes everything, you can't possibly prove that isn't true" argument. This isn't science fiction. Inside the cell all of these proteins are diced up into small hexamers and displayed on MHC and it doesn't matter what the combination of the spike and the backbone are, the T-cell epitopes are going to be the same. Omicron spike will have Omicron antibody epitopes and Omicron T-cell epitopes, doen't matter what backbone you splice it onto. If you want to create a new pandemic, particularly one with "millions of potential deaths" you need to change this virus sufficiently that it is no longer identified as SARS-CoV-2 by our T-cells and you don't get that just by combining two different variants.

tripletao 4y ago
If that's your argument, then what do you even need the XD strain for? You could simply assert that because natural omicron has spread widely, any lab chimera with the omicron spike must be safe. That seems remarkably cavalier though, considering that (a) natural omicron continues to spread, and kill people every day; and (b) while China's reported case counts are probably inaccurate, they probably do still have a large population that's completely omicron-naive.
- lamontcg 4y ago
  I clearly didn't need the XD strain, I thought that would be read as supplementary. I routinely forget that no matter how clear your argument sounds to you that someone on the Internet will always misunderstand it (and pick apart a detail that has no central relevance).
  - tripletao 4y ago
    Except that natural omicron continues to kill people now? So it's empirically true that at least one backbone (i.e., the natural omicron backbone) plus the omicron spike remains able to cause significant sickness and death, despite the immunity we've built up, even outside China. So what's your argument that the risk from a different backbone is "zero"?
    - lamontcg 4y ago
      Yet more misunderstanding. First of all they used BA.1 and that spike is nearly extinct and isn't causing much sickness and death, it has been out-competed by BA.5. BA.1 is literally "last years news" and BA.5 is immune evasive against BA.1. Any BA.1 spike is going to be recognized by the same neutralizing antibodies which has suppressed BA.1 circulation in the larger population. And I should have written something like the additional risk over the existing circulating pandemic strains is zero. It could cause infections and deaths, but just like XD it would be outcompeted quickly by BA.5 and wouldn't go anywhere, and the infected people would run exactly the same risk as they would have against the existing global pandemic. There is no way you get from this lab experiment to "COVID-22", it is still all the same virus, same pandemic, and a variant of the virus which will be substantially less fit against population immunity than BA.5 or whatever new variant winds up circulating this winter.
      - tripletao 4y ago
        So you're acknowledging now that the lab chimera might infect some people if it escaped, but you're saying that's okay because those people would otherwise have gotten infected with a natural variant anyways? But if the IFR for the lab chimera is higher than the IFR for natural omicron (which it was, at least in their mice), then those people are paying a higher price in mortality for the same immunity--that's the gain of function of concern. And really, is there anything in biology that we know with sufficient confidence to risk millions of lives in exchange for no immediate practical benefit? Like I guess whoever did the 1977 flu vaccine trials also assumed that if their virus escaped, it would get outcompeted by the existing natural viruses; but we know what happened there.
alchemist1e9 4y ago
You and Derek Lowe are at best apologists who due to your myopic perspective can’t see the obvious risks that many of us outsiders can imagine. At worst you’re part of a group for which “it is difficult to get a man to understand something, when his salary depends on his not understanding it”
- lamontcg 4y ago
  If I wind up rotting in hell with Derek Lowe that'll be pretty good company, I think I'll take that.
benibela 4y ago
>Nobody at this point is immune naive to this combination. My mother did not get vaccinated and she probably was not infected
- lamontcg 4y ago
  She's got less to fear from this lab experiment (based on variants that are existing or nearly existing) than from the ongoing natural pandemic.

Izkata 4y ago

> As far as I know, the latter was extinct in the wild by the time the former emerged. Omicron isn't a descendant of Delta. It has an odd lineage that couldn't be explained and (unless new info has come up since I last looked) it was likely a descendant of either Wuhan or Alpha that mutated hidden from most of the world - one of the theories was that Wuhan/Alpha jumped to rats, then back to humans after becoming Omicron.

tripletao 4y ago
I agree, but I don't think that's relevant? So I think my terminology was unclear. By "omicron/delta" I meant a recombinant of the omicron spike with the delta backbone, the one that apparently happened naturally and Derek Lowe describes as the XD strain. By "omicron/Wuhan" I meant a recombinant of the omicron spike with the Wuhan backbone, which these researchers created in their lab (and I don't believe had any opportunity to occur naturally, since the two lineages never existed simultaneously).
- Izkata 4y ago
  > since the two lineages never existed simultaneously Some version of it would likely have existed in the rat-origin theory of Omicron as an intermediate stage, is what I meant.
  - tripletao 4y ago
    Ah, got it now. Then I guess the rats (or other cryptic hosts in which omicron evolved) might have been exposed to the omicron/Wuhan recombinant, but not humans.