8 ms·

https://www.sciencedirect.com/science/article/pii/S1873506120304165 https://www.sciencedirect.com/science/article/pii/S187350612... Here is a paper that states

by ximeng 5y ago

https://www.sciencedirect.com/science/article/pii/S1873506120304165 https://www.sciencedirect.com/science/article/pii/S187350612... Here is a paper that states that the furin cleavage site appears naturally in a number of viruses. I looked into these lab origin theories for the furin cleavage site last year. The problem with it being a laboratory insertion was that although performing an insertion is relatively easy once you know what to insert, generally it’s beyond current science to independently create mutations for a specific purpose. It’s a bit beyond me as a non-biologist but my feeling based on the literature was that the lab origin was unlikely. However it is pushed in certain circles partly for ideological reasons, based on evidence that is plausible at first glance but with a lot more digging not entirely convincing evidence. However, there didn’t really seem to be much neutral expert analysis of the evidence.

trevelyan 5y ago
> generally it’s beyond current science to independently create mutations for a specific purpose. No it isn't. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810786/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810786/
- ximeng 5y ago
  Quite a long article, but skimming it it looks like that experiment involves applying naturally occurring mutations to an existing virus?
  - pclmulqdq 5y ago
    Yes. Gain of function research involves putting evolutionary pressure on an organism to give it certain traits that can be found in the wild, but the resulting virus is anything but natural. I think a lot of people dismiss the lab leak hypothesis based on the idea that a lab-created virus must have an engineered genome rather than an evolved one.
Pepe1vo 5y ago
From the OP, it appears that scientists knew exactly where to insert a furin cleavage site: >“Since 1992 the virology community has known that the one sure way to make a virus deadlier is to give it a furin cleavage site at the S1/S2 junction in the laboratory,” writes Steven Quay, a biotech entrepreneur interested in the origins of SARS2.
- ximeng 5y ago
  The problem is knowing how to put in the furin cleavage site, and generally if it's done in the lab it's done by copying a particular sequence from an existing virus as scientists can't predict how to do it themselves (without copying) with current state of knowledge.
- matzab 5y ago
  That's such a mischaracterisation, I don't even know where to start. That Quay-guy obviously searched for "furin" on pubmed, found some papers (that don't even say that - and most definitely not for any coronaviruses) and thought it fit his thesis. If only viruses and infections were that simple!
  - pas 5y ago
    Could you still start somewhere and explain it a bit please? Thank you very much!
  - nyolfen 5y ago
    he left out the most damning part: > “At least 11 gain-of-function experiments, adding a furin site to make a virus more infective, are published in the open literature, including [by] Dr. Zhengli Shi, head of coronavirus research at the Wuhan Institute of Virology.”
reuben_scratton 5y ago
The furin cleavage site in SARS-Cov-2 does not appear in any other SARS-related beta coronavirus (sarbecovirus).
- sradman 5y ago
  From 2014, Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein [1]: > Such furin-mediated activation is unusual in that it occurs in part during virus entry. Our findings may explain the polytropic nature, pathogenicity, and life cycle of this zoonotic coronavirus. MERS-CoV uses furin cleavage of S1/S2 but it does not bind to ACE2 like SARS-CoV-2. [1] https://www.pnas.org/content/111/42/15214 https://www.pnas.org/content/111/42/15214
zby 5y ago
The natural origin hypothesis is also pushed for ideological reasons - at this level of meta analysis we are at a stalemate. The article was good at revealing that there is not just ideology - but also material interests involved and that the two prestigious letters that were so categorical in dismissing the lab escape hypothesis were quite a bit tainted by conflicts of interests.
- ximeng 5y ago
  I believe the lab origin theory is flawed based on the scientific reasoning, not the meta analysis. I agree that the meta analysis is inconclusive as it is not emphasising the science enough. The feeling I get is China doesn't really want to talk about it because it encourages ideologically motivated people to attack China, and serious scientists are mostly not convinced that this is a lab escape and so don't feel the need to discuss it. At the same time, China risks looking guilty because they are defensive and try to control the information. All this leaves this kind of article with a seemingly plausible scientific and ideological basis that is difficult for laymen and even scientific journalists to evaluate due to the complexity of the science involved, and not many scientists interested in spelling out why the reasoning might be flawed. You also see in the quote from the article: “Yes, but your wording makes this sound unlikely — viruses are specialists at unusual events,” is the riposte of David L. Robertson, a virologist at the University of Glasgow who regards lab escape as a conspiracy theory.
  - prox 5y ago
    The article is great at spelling a few things out, personally I feel enticed by it in some form. It is the job of other scientists to dispel any wrong or inaccurate information. Usually the more interesting questions are of the kind of what -isn’t- being said, of what information isn’t being related or investigated.
    - ximeng 5y ago
      I agree it's enticing. I tend to agree with the scientist quoted that it's a conspiracy theory, but if it is then it's a really good one, and this article is well written. If I'm right the reason it's not being analysed or investigated is that from a scientific perspective it's just not an interesting question, rather than for a deeper ideological reason as suggested in this article. I drew the conclusion that this furin cleavage site theory wasn't actually convincing after a few days of wading through scientific literature, but as a non-expert I was pretty disappointed that there wasn't more accessible analysis of well-written arguments as presented in the article that would put it into a more objective perspective. It would have been great if that scientist they quote would have provided a more detailed rebuttal. The problem is it actually isn't the job of scientists to dispel wrong or inaccurate information for the most part. They do detailed esoteric studies and write them up for specialists. It's nobody's job to rebut bad arguments, and that's the problem.
roenxi 5y ago
> generally it’s beyond current science to independently create mutations for a specific purpose. Labs are the places where people go to push the boundaries. If we go with lab-leak, it is extremely possible that they had figured something new out. They were doing something novel in there, because they were paid money to do novel things.
- TheOtherHobbes 5y ago
  If we're going to play at paranoia and assume the virus was engineered, it doesn't necessarily follow that the release was an accidental leak. It would be trivially easy for a hostile power to covertly release a pathogen in another country. It would also be trivially easy to engineer simultaneous release in multiple locations. It would be less easy but not impossible to take an existing pathogen during a pandemic, engineer a variant, and release it in another country. There would always be ambiguity and uncertainty about the source, because there are no telltale markers that unambiguously define an origin, or even whether a pathogen is natural or man-made. I am not suggesting any of this happened. But I am pointing out that biowarfare has some unexpected covert possibilities. While Covid may or may not be an example - insufficient data - any defensive strategy should consider the possibility that some other pathogen might be seeded deliberately.
  - arisAlexis 5y ago
    We are not playing paranoia. And you have a valid point that in this scenario it's not crystal clear that it was accidental.
- misja111 5y ago
  It's true that labs were pushing boundaries, the Wuhan lab as well. But every time they succeeded in doing something novel, they were celebrating it in the media. If they really had been able to reach this major technological breakthrough, one would expect that they would have made this one public as well. I would say that it's more likely that this was a natural mutation that got its chance to survive natural selection because of the lasting and intense contact with human researchers in the Wuhan lab. There are some media sources that show that researches didn't take too many precautions with avoiding this contact. E.g. there are pictures of researchers without wearing gloves and one that's even showing bites from bats.
CuriouslyC 5y ago
Introducing mutations with purpose is beyond us, but inserting a variety of mutations randomly in areas of the proteins known to be impactful in various processes, then observing the behavior of the mutants in vivo is not. We do high throughput mutant screening all the time.
rainbowzootsuit 5y ago
Maybe this URL makes it seem more legit than it is, but the linked article below has a "2.5" version of events that proposed that samples taken from a group with who'd been infected by a coronavirus from bats may have been released accidentally. In other words that the lab was the point of release, but that they didn't construct or alter the virus as it already had adapted to humans in an earlier time. I've done some separate reading that this is a legitimate way that viruses can adapt to a new species, but I don't have any background to evaluate the argument much beyond face value. Some of the adjacent comments shed some doubt there as it sounds like bats aren't a plausible source because of the spike protein genetics. https://www.independentsciencenews.org/commentaries/a-proposed-origin-for-sars-cov-2-and-the-covid-19-pandemic/ https://www.independentsciencenews.org/commentaries/a-propos...
hkmaxpro 5y ago
The Wu and Zhao paper [0] you cited is based on this paper [1] by Zhou et al, whose conclusions were questioned by this preprint [2]. In fact, the paper [3] cited in the top comment has the following response to the Wu and Zhao paper you cited: > The recent acquisition of the FCS by SARS-CoV-2 via a natural insert was proposed by Wu and Zhao (2021) on the basis of the existence of FCS in other, more distant Betacoronaviruses with different loop positions to SARS-CoV-2 and the existence of a partial natural insert in the same region in RmYN02 (Zhou et al. 2020a). The reliability of the conclusions of Zhou et al. (2020a) has been questioned by Deigin and Segreto (2020), who particularly challenge the claim that RmYN02 has an insertion around the site of the FCS insertion in SARS-CoV-2 and instead point to a two amino acid deletion in RmYN02 at that locus. Therefore, RmYN02 should not be used as evidence of the natural origin of SARS-CoV-2′s FCS until its claimed insertion is properly validated. Disclaimer: I’m no biologist/virologist. [0] https://www.sciencedirect.com/science/article/pii/S1873506120304165 https://www.sciencedirect.com/science/article/pii/S187350612... [1] https://doi.org/10.1016/j.cub.2020.05.023 https://doi.org/10.1016/j.cub.2020.05.023 [2] https://arxiv.org/abs/2012.00627 https://arxiv.org/abs/2012.00627 [3] https://link.springer.com/article/10.1007/s10311-021-01211-0 https://link.springer.com/article/10.1007/s10311-021-01211-0

by ximeng 5y ago

trevelyan 5y ago

> generally it’s beyond current science to independently create mutations for a specific purpose. No it isn't. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810786/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810786/

ximeng 5y ago
Quite a long article, but skimming it it looks like that experiment involves applying naturally occurring mutations to an existing virus?
- pclmulqdq 5y ago
  Yes. Gain of function research involves putting evolutionary pressure on an organism to give it certain traits that can be found in the wild, but the resulting virus is anything but natural. I think a lot of people dismiss the lab leak hypothesis based on the idea that a lab-created virus must have an engineered genome rather than an evolved one.

Pepe1vo 5y ago

From the OP, it appears that scientists knew exactly where to insert a furin cleavage site: >“Since 1992 the virology community has known that the one sure way to make a virus deadlier is to give it a furin cleavage site at the S1/S2 junction in the laboratory,” writes Steven Quay, a biotech entrepreneur interested in the origins of SARS2.

ximeng 5y ago
The problem is knowing how to put in the furin cleavage site, and generally if it's done in the lab it's done by copying a particular sequence from an existing virus as scientists can't predict how to do it themselves (without copying) with current state of knowledge.
matzab 5y ago
That's such a mischaracterisation, I don't even know where to start. That Quay-guy obviously searched for "furin" on pubmed, found some papers (that don't even say that - and most definitely not for any coronaviruses) and thought it fit his thesis. If only viruses and infections were that simple!
- pas 5y ago
  Could you still start somewhere and explain it a bit please? Thank you very much!
- nyolfen 5y ago
  he left out the most damning part: > “At least 11 gain-of-function experiments, adding a furin site to make a virus more infective, are published in the open literature, including [by] Dr. Zhengli Shi, head of coronavirus research at the Wuhan Institute of Virology.”

reuben_scratton 5y ago

The furin cleavage site in SARS-Cov-2 does not appear in any other SARS-related beta coronavirus (sarbecovirus).

sradman 5y ago
From 2014, Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein [1]: > Such furin-mediated activation is unusual in that it occurs in part during virus entry. Our findings may explain the polytropic nature, pathogenicity, and life cycle of this zoonotic coronavirus. MERS-CoV uses furin cleavage of S1/S2 but it does not bind to ACE2 like SARS-CoV-2. [1] https://www.pnas.org/content/111/42/15214 https://www.pnas.org/content/111/42/15214

zby 5y ago

The natural origin hypothesis is also pushed for ideological reasons - at this level of meta analysis we are at a stalemate. The article was good at revealing that there is not just ideology - but also material interests involved and that the two prestigious letters that were so categorical in dismissing the lab escape hypothesis were quite a bit tainted by conflicts of interests.

ximeng 5y ago
I believe the lab origin theory is flawed based on the scientific reasoning, not the meta analysis. I agree that the meta analysis is inconclusive as it is not emphasising the science enough. The feeling I get is China doesn't really want to talk about it because it encourages ideologically motivated people to attack China, and serious scientists are mostly not convinced that this is a lab escape and so don't feel the need to discuss it. At the same time, China risks looking guilty because they are defensive and try to control the information. All this leaves this kind of article with a seemingly plausible scientific and ideological basis that is difficult for laymen and even scientific journalists to evaluate due to the complexity of the science involved, and not many scientists interested in spelling out why the reasoning might be flawed. You also see in the quote from the article: “Yes, but your wording makes this sound unlikely — viruses are specialists at unusual events,” is the riposte of David L. Robertson, a virologist at the University of Glasgow who regards lab escape as a conspiracy theory.
- prox 5y ago
  The article is great at spelling a few things out, personally I feel enticed by it in some form. It is the job of other scientists to dispel any wrong or inaccurate information. Usually the more interesting questions are of the kind of what -isn’t- being said, of what information isn’t being related or investigated.
  - ximeng 5y ago
    I agree it's enticing. I tend to agree with the scientist quoted that it's a conspiracy theory, but if it is then it's a really good one, and this article is well written. If I'm right the reason it's not being analysed or investigated is that from a scientific perspective it's just not an interesting question, rather than for a deeper ideological reason as suggested in this article. I drew the conclusion that this furin cleavage site theory wasn't actually convincing after a few days of wading through scientific literature, but as a non-expert I was pretty disappointed that there wasn't more accessible analysis of well-written arguments as presented in the article that would put it into a more objective perspective. It would have been great if that scientist they quote would have provided a more detailed rebuttal. The problem is it actually isn't the job of scientists to dispel wrong or inaccurate information for the most part. They do detailed esoteric studies and write them up for specialists. It's nobody's job to rebut bad arguments, and that's the problem.

roenxi 5y ago

> generally it’s beyond current science to independently create mutations for a specific purpose. Labs are the places where people go to push the boundaries. If we go with lab-leak, it is extremely possible that they had figured something new out. They were doing something novel in there, because they were paid money to do novel things.

TheOtherHobbes 5y ago
If we're going to play at paranoia and assume the virus was engineered, it doesn't necessarily follow that the release was an accidental leak. It would be trivially easy for a hostile power to covertly release a pathogen in another country. It would also be trivially easy to engineer simultaneous release in multiple locations. It would be less easy but not impossible to take an existing pathogen during a pandemic, engineer a variant, and release it in another country. There would always be ambiguity and uncertainty about the source, because there are no telltale markers that unambiguously define an origin, or even whether a pathogen is natural or man-made. I am not suggesting any of this happened. But I am pointing out that biowarfare has some unexpected covert possibilities. While Covid may or may not be an example - insufficient data - any defensive strategy should consider the possibility that some other pathogen might be seeded deliberately.
- arisAlexis 5y ago
  We are not playing paranoia. And you have a valid point that in this scenario it's not crystal clear that it was accidental.
misja111 5y ago
It's true that labs were pushing boundaries, the Wuhan lab as well. But every time they succeeded in doing something novel, they were celebrating it in the media. If they really had been able to reach this major technological breakthrough, one would expect that they would have made this one public as well. I would say that it's more likely that this was a natural mutation that got its chance to survive natural selection because of the lasting and intense contact with human researchers in the Wuhan lab. There are some media sources that show that researches didn't take too many precautions with avoiding this contact. E.g. there are pictures of researchers without wearing gloves and one that's even showing bites from bats.

CuriouslyC 5y ago

Introducing mutations with purpose is beyond us, but inserting a variety of mutations randomly in areas of the proteins known to be impactful in various processes, then observing the behavior of the mutants in vivo is not. We do high throughput mutant screening all the time.

rainbowzootsuit 5y ago

Maybe this URL makes it seem more legit than it is, but the linked article below has a "2.5" version of events that proposed that samples taken from a group with who'd been infected by a coronavirus from bats may have been released accidentally. In other words that the lab was the point of release, but that they didn't construct or alter the virus as it already had adapted to humans in an earlier time. I've done some separate reading that this is a legitimate way that viruses can adapt to a new species, but I don't have any background to evaluate the argument much beyond face value. Some of the adjacent comments shed some doubt there as it sounds like bats aren't a plausible source because of the spike protein genetics. https://www.independentsciencenews.org/commentaries/a-proposed-origin-for-sars-cov-2-and-the-covid-19-pandemic/ https://www.independentsciencenews.org/commentaries/a-propos...

hkmaxpro 5y ago

The Wu and Zhao paper [0] you cited is based on this paper [1] by Zhou et al, whose conclusions were questioned by this preprint [2]. In fact, the paper [3] cited in the top comment has the following response to the Wu and Zhao paper you cited: > The recent acquisition of the FCS by SARS-CoV-2 via a natural insert was proposed by Wu and Zhao (2021) on the basis of the existence of FCS in other, more distant Betacoronaviruses with different loop positions to SARS-CoV-2 and the existence of a partial natural insert in the same region in RmYN02 (Zhou et al. 2020a). The reliability of the conclusions of Zhou et al. (2020a) has been questioned by Deigin and Segreto (2020), who particularly challenge the claim that RmYN02 has an insertion around the site of the FCS insertion in SARS-CoV-2 and instead point to a two amino acid deletion in RmYN02 at that locus. Therefore, RmYN02 should not be used as evidence of the natural origin of SARS-CoV-2′s FCS until its claimed insertion is properly validated. Disclaimer: I’m no biologist/virologist. [0] https://www.sciencedirect.com/science/article/pii/S1873506120304165 https://www.sciencedirect.com/science/article/pii/S187350612... [1] https://doi.org/10.1016/j.cub.2020.05.023 https://doi.org/10.1016/j.cub.2020.05.023 [2] https://arxiv.org/abs/2012.00627 https://arxiv.org/abs/2012.00627 [3] https://link.springer.com/article/10.1007/s10311-021-01211-0 https://link.springer.com/article/10.1007/s10311-021-01211-0