7 ms·

One problem in these kinds of investigations is that nobody involved really wants the truth to be known. The lab isn't going to let anyone poke around and see w

by manv1 4y ago

One problem in these kinds of investigations is that nobody involved really wants the truth to be known. The lab isn't going to let anyone poke around and see what it was doing until the CPP falls. And even then records have probably been wiped already. The problem is that there really isn't any evidence. SARS-COV-2 has never been detected in any Chinese land animals associated with the market. We know that birds can transmit it, but it needs to come from somewhere. There's no reservoir of the stuff found in the wild...unlike viruses like Ebola, Marburg, MERS, etc. There were two variants in the market...but given the speed at which SARS-COV-2 variants have mutated in humans, well, how likely is it that the market was the source? SARS-COV-2 went through millions of humans before the first variant popped out. Is it reasonable to assume that some progenitor virus went though millions of iterations to become SARS-COV-2 in the market, then did it again and again? But however unlikely, this is where we are today. Was it just bad luck that some virus entered an immuno-compromised animal at the market and mutated...twice?

oasisbob 4y ago
> There were two variants in the market... No, there were two distinct lineages in the market. That's different than variants. The lineages are important because although the differences between the sequences are small, they are distinct, and there are no known transitional haplotypes. > given the speed at which SARS-COV-2 variants have mutated in humans, well, how likely is it that the market was the source? See Pekar et al: https://zenodo.org/record/6342616 https://zenodo.org/record/6342616 They deal with this question directly.
Consultant32452 4y ago
In Dr. Birx's recently released book she claims to have known it came from a lab origin from the start, based on evolutionary reasoning. As she describes: A virus takes years to learn/evolve the ability to infect humans, and does so poorly at the start. But covid was extremely effective at infecting humans "right out of the box." In a lab environment the virus is repeatedly exposed to human cells and gets better at infecting human cells with each iteration. Evolutionary biologist Heather Heying similarly reasoned the origin of the virus through an understanding of evolution. Covid doesn't appear to transmit outside. If covid evolved naturally, it would be capable of spreading outside, where animals live. Instead, it appeared to evolve to spread in lab-like air conditioned conditions only.
- lamontcg 4y ago
  > In a lab environment the virus is repeatedly exposed to human cells and gets better at infecting human cells with each iteration. That is just replicating what nature does when it hops from individual to individual. Nature has billions of animals to do serial passage through. And we still don't know that the species jump happened in the market, and I'm somewhat skeptical of the claims of this author. I tend to think it was circulating in rural Hubei, probably coinfecting domestic animals and people, getting better and better at infecting people until the market event happened which was where it found a densely packed human population where it spread with R0 significantly greater than 1 and took off. There's no evidence of that though because when the grandparents of farmers in rural villages die of pneumonia nobody bothers collecting samples because that's normal. And we only noticed it when it started to efficiently infect human beings because that is when the pandemic started. The initial poor cryptic spread between humans and animals before that wouldn't have been detected because poor spreading couldn't cause the pandemic to start. And we know that its possible for the virus to jump backwards and forwards between humans and minks, so the idea that an intermediate animal reservoir would have been infected with this virus and would have repeatedly attempted to jump to farm workers until it finally got good at spreading in humans is not that far fetched at all. Then the intermediate animal host becomes a massive bioreactor in close contact with humans, giving it many opportunities to roll the dice until it finds a combination that unlocks its pandemic potential, and then the first time it was transported into a dense human population it takes off. There could be a hundred other viruses in animals in China all knocking on the door, occasionally infecting humans and not being good at it all right now, happening every day in China. This one was very good at infecting humans, along with being very good at infecting all kinds of other animals (mink, deer, dogs, cats, etc) because in order to cause a pandemic it had to be good at that, if it was bad at that it wouldn't have happened. It is like the anthropic principle--the virus seems incredibly lucky, because it had to be.
  - Consultant32452 4y ago
    It would actually be extremely unlikely for a virus that is "medium good at spreading to humans" to stay in an isolated location, especially one that spreads asymptomatically.
tripletao 4y ago
Note that the zoonotic path of Ebola into humans isn't well-understood. There was pretty good evidence of the path for SARS-1 though, and very good evidence for MERS. For SARS-CoV-2, there's still nothing, despite the recent emergence and considerably greater effort searching. The "two lineages" argument has been grossly distorted by Worobey and the media. They're just two single-nucleotide polymorphisms apart, so they could easily have arisen in a single human-to-human transmission. SARS-CoV-2 averages something around a third of an SNP per human-to-human transmission, so ~10% of such transmissions differ by two SNPs. If a missing link does exist, then it's just a single mutation away from either strain. So there's no reason to consider the "two lineages" too significant in any direction, unless you believe sampling in humans has been perfectly good. That belief seems unreasonable to me, especially since belief in a natural zoonotic origin requires us to believe sampling in animals has been perfectly bad. https://mobile.twitter.com/jbloom_lab/status/1534630607220711425 https://mobile.twitter.com/jbloom_lab/status/153463060722071...
- oasisbob 4y ago
  > They're just two single-nucleotide polymorphisms apart The problem with that argument, is that it doesn't explain the polytomies and is misleading, as you accuse Worobey of being. "Just a few SNPs" is disingenuous and glosses over the usefulness of this evidence that almost everyone agrees on - eg, that it's highly unlikely that lineage B evolved from lineage A. (Even Jesse Bloom agrees on this.) It may take a bit to find consensus on the dual-zoonosis theory and related phylogenetics, but the eagerness with which people dismiss this issue drives me nuts. https://twitter.com/jepekar/status/1499840349807656960 https://twitter.com/jepekar/status/1499840349807656960
  - tripletao 4y ago
    You're correct that it's highly unlikely that B evolved from A, but why do you think that's significant? We know the spread of SARS-CoV-2 is highly stochastic, with most lineages dying out and a few exploding, and we know the IFR in humans is small enough that considerable cryptic spread is possible before enough people die to raise the alarm. So why do you take the two lineages as conclusive evidence of two zoonotic events (as Worobey has repeatedly claimed in the media, even though his papers are more cautious)? Given the above, I don't see how we can exclude that the two lineages evolved in early human cryptic spread, before we started sampling enough to draw a perfect phylogenetic tree.
lamontcg 4y ago
> SARS-COV-2 has never been detected in any Chinese land animals associated with the market. They acted very quickly to sterilize the market which eliminated the evidence. In SARS-1 the market associated with that was allowed to operate until investigators were able to take samples from the animals there and find the related virus. As a containment measure this was probably the right reflex to have, as an investigative measure this was highly counterproductive. If, however, you are one of the people who blame China for not acting fast enough to contain the spread then you can't criticize them for this. > There's no reservoir of the stuff found in the wild...unlike viruses like Ebola, Marburg, MERS, etc. MERS just happened to be very easy since we sampled the camels and they were positive and sitting right there with lots of human contact. In the case of SARS-1 the actual progenitor virus was only found 10 years later in bats in Yunnan. With Ebola the species that harbors the virus has actually yet to be determined, decades later. Marburg was first discovered in 1967 and was only isolated from Egyptian fruit bats in 2009, 42 years later. I think you're vastly underestimating how hard it is to track down animal reservoirs, and with the reservoir of Ebola still being unknown 46 years after it was discovered kind of undermines your entire point. We also now have the BANAL viruses found in bats in Laos which are getting closer and closer to a match to SARS-CoV-2, which is actually good progress after only 2-3 years (it would actually be highly suspicious if someone found the 99% homologous bat progenitor of SARS-CoV-2 after only a few years of looking, that would suggest that China knew where it was all along -- actual science that isn't on the TV or movies is quite difficult and usually a lengthy needle-in-a-haystack process as all of these examples show).
- tripletao 4y ago
  > In the case of SARS-1 the actual progenitor virus was only found 10 years later in bats in Yunnan. Why do you keep saying this? As you know, the closest animal viruses to SARS-1 were found in civet cats and raccoon dogs, within about a year of its emergence in humans. The bat viruses that Dr. Shi later discovered are scientifically important, because most of SARS-1's genome probably evolved in bats. They provide no new insight as to how the virus came to infect humans, though.
  - lamontcg 4y ago

by manv1 4y ago

oasisbob 4y ago

> There were two variants in the market... No, there were two distinct lineages in the market. That's different than variants. The lineages are important because although the differences between the sequences are small, they are distinct, and there are no known transitional haplotypes. > given the speed at which SARS-COV-2 variants have mutated in humans, well, how likely is it that the market was the source? See Pekar et al: https://zenodo.org/record/6342616 https://zenodo.org/record/6342616 They deal with this question directly.

Consultant32452 4y ago

In Dr. Birx's recently released book she claims to have known it came from a lab origin from the start, based on evolutionary reasoning. As she describes: A virus takes years to learn/evolve the ability to infect humans, and does so poorly at the start. But covid was extremely effective at infecting humans "right out of the box." In a lab environment the virus is repeatedly exposed to human cells and gets better at infecting human cells with each iteration. Evolutionary biologist Heather Heying similarly reasoned the origin of the virus through an understanding of evolution. Covid doesn't appear to transmit outside. If covid evolved naturally, it would be capable of spreading outside, where animals live. Instead, it appeared to evolve to spread in lab-like air conditioned conditions only.

lamontcg 4y ago
> In a lab environment the virus is repeatedly exposed to human cells and gets better at infecting human cells with each iteration. That is just replicating what nature does when it hops from individual to individual. Nature has billions of animals to do serial passage through. And we still don't know that the species jump happened in the market, and I'm somewhat skeptical of the claims of this author. I tend to think it was circulating in rural Hubei, probably coinfecting domestic animals and people, getting better and better at infecting people until the market event happened which was where it found a densely packed human population where it spread with R0 significantly greater than 1 and took off. There's no evidence of that though because when the grandparents of farmers in rural villages die of pneumonia nobody bothers collecting samples because that's normal. And we only noticed it when it started to efficiently infect human beings because that is when the pandemic started. The initial poor cryptic spread between humans and animals before that wouldn't have been detected because poor spreading couldn't cause the pandemic to start. And we know that its possible for the virus to jump backwards and forwards between humans and minks, so the idea that an intermediate animal reservoir would have been infected with this virus and would have repeatedly attempted to jump to farm workers until it finally got good at spreading in humans is not that far fetched at all. Then the intermediate animal host becomes a massive bioreactor in close contact with humans, giving it many opportunities to roll the dice until it finds a combination that unlocks its pandemic potential, and then the first time it was transported into a dense human population it takes off. There could be a hundred other viruses in animals in China all knocking on the door, occasionally infecting humans and not being good at it all right now, happening every day in China. This one was very good at infecting humans, along with being very good at infecting all kinds of other animals (mink, deer, dogs, cats, etc) because in order to cause a pandemic it had to be good at that, if it was bad at that it wouldn't have happened. It is like the anthropic principle--the virus seems incredibly lucky, because it had to be.
- Consultant32452 4y ago
  It would actually be extremely unlikely for a virus that is "medium good at spreading to humans" to stay in an isolated location, especially one that spreads asymptomatically.

tripletao 4y ago

Note that the zoonotic path of Ebola into humans isn't well-understood. There was pretty good evidence of the path for SARS-1 though, and very good evidence for MERS. For SARS-CoV-2, there's still nothing, despite the recent emergence and considerably greater effort searching. The "two lineages" argument has been grossly distorted by Worobey and the media. They're just two single-nucleotide polymorphisms apart, so they could easily have arisen in a single human-to-human transmission. SARS-CoV-2 averages something around a third of an SNP per human-to-human transmission, so ~10% of such transmissions differ by two SNPs. If a missing link does exist, then it's just a single mutation away from either strain. So there's no reason to consider the "two lineages" too significant in any direction, unless you believe sampling in humans has been perfectly good. That belief seems unreasonable to me, especially since belief in a natural zoonotic origin requires us to believe sampling in animals has been perfectly bad. https://mobile.twitter.com/jbloom_lab/status/1534630607220711425 https://mobile.twitter.com/jbloom_lab/status/153463060722071...

oasisbob 4y ago
> They're just two single-nucleotide polymorphisms apart The problem with that argument, is that it doesn't explain the polytomies and is misleading, as you accuse Worobey of being. "Just a few SNPs" is disingenuous and glosses over the usefulness of this evidence that almost everyone agrees on - eg, that it's highly unlikely that lineage B evolved from lineage A. (Even Jesse Bloom agrees on this.) It may take a bit to find consensus on the dual-zoonosis theory and related phylogenetics, but the eagerness with which people dismiss this issue drives me nuts. https://twitter.com/jepekar/status/1499840349807656960 https://twitter.com/jepekar/status/1499840349807656960
- tripletao 4y ago
  You're correct that it's highly unlikely that B evolved from A, but why do you think that's significant? We know the spread of SARS-CoV-2 is highly stochastic, with most lineages dying out and a few exploding, and we know the IFR in humans is small enough that considerable cryptic spread is possible before enough people die to raise the alarm. So why do you take the two lineages as conclusive evidence of two zoonotic events (as Worobey has repeatedly claimed in the media, even though his papers are more cautious)? Given the above, I don't see how we can exclude that the two lineages evolved in early human cryptic spread, before we started sampling enough to draw a perfect phylogenetic tree.

lamontcg 4y ago

> SARS-COV-2 has never been detected in any Chinese land animals associated with the market. They acted very quickly to sterilize the market which eliminated the evidence. In SARS-1 the market associated with that was allowed to operate until investigators were able to take samples from the animals there and find the related virus. As a containment measure this was probably the right reflex to have, as an investigative measure this was highly counterproductive. If, however, you are one of the people who blame China for not acting fast enough to contain the spread then you can't criticize them for this. > There's no reservoir of the stuff found in the wild...unlike viruses like Ebola, Marburg, MERS, etc. MERS just happened to be very easy since we sampled the camels and they were positive and sitting right there with lots of human contact. In the case of SARS-1 the actual progenitor virus was only found 10 years later in bats in Yunnan. With Ebola the species that harbors the virus has actually yet to be determined, decades later. Marburg was first discovered in 1967 and was only isolated from Egyptian fruit bats in 2009, 42 years later. I think you're vastly underestimating how hard it is to track down animal reservoirs, and with the reservoir of Ebola still being unknown 46 years after it was discovered kind of undermines your entire point. We also now have the BANAL viruses found in bats in Laos which are getting closer and closer to a match to SARS-CoV-2, which is actually good progress after only 2-3 years (it would actually be highly suspicious if someone found the 99% homologous bat progenitor of SARS-CoV-2 after only a few years of looking, that would suggest that China knew where it was all along -- actual science that isn't on the TV or movies is quite difficult and usually a lengthy needle-in-a-haystack process as all of these examples show).

tripletao 4y ago
> In the case of SARS-1 the actual progenitor virus was only found 10 years later in bats in Yunnan. Why do you keep saying this? As you know, the closest animal viruses to SARS-1 were found in civet cats and raccoon dogs, within about a year of its emergence in humans. The bat viruses that Dr. Shi later discovered are scientifically important, because most of SARS-1's genome probably evolved in bats. They provide no new insight as to how the virus came to infect humans, though.
- lamontcg 4y ago