6 ms·

Many people falsely assume that anything leaked from a lab was made in a lab.

by base3 5y ago

ctrlp 5y ago
That's not why people think the virus was made in a lab. The reason people think it was man-made have to do with strangely well-adapted protein sequences found on the virus with no known natural ancestors. Virus evolution requires hosts and time. The nearest common ancestor to this virus is not a good candidate for SARS-COV2 and there are no known intermediate ancestors in the thousands of animals tested.
- ikt 5y ago
  > The reason people think it was man-made have to do with strangely well-adapted protein sequences found on the virus with no known natural ancestors. I was under the impression it was a natural sequence, I read about it way back in the beginning: https://www.labmate-online.com/news/laboratory-products/3/breaking-news/is-covid-19-man-made-or-natural/51980 https://www.labmate-online.com/news/laboratory-products/3/br... They found that the spike protein, a receptor-binding domain (RBD) that hooks onto host cells, had evolved to target ACE2, an enzyme founded on the outer surface of human cells that helps to regulate blood pressure. The team say the COVID-19 spike protein is so efficient at binding to human cells that it could only be a result of natural selection, not artificial engineering. Another tell-tale sign of natural origins is the molecular structure of COVID-19, which is substantially different from other known viruses. Rather than mimicking other viruses known to cause severe illness in humans, COVID-19 more closely resembles strains of coronavirus found in bats and pangolins. "These two features of the virus, the mutations in the RBD portion of the spike protein and its distinct backbone, rules out laboratory manipulation as a potential origin for SARS-CoV-2" says Andersen.
  - sterlind 5y ago
    I don't understand that argument. Wouldn't serial passage through human lung cells produce efficient bindings? Is that sort of artificial selection not what they meant by "laboratory manipulation?" If they mean it's not the product of genetic engineering then sure, but leaving out the possibility of serial passage is misleading at best.
    - sgt101 5y ago
      The rapid evolution (gain) between the wild virus and Alpha and then Delta and now Delta+ indicates to me that if there was a gain of function experiment in the evolution of this virus then it was stopped far too early! Also it seems tuned to infect Mustelidae - like the Mink in Belgium and Holland, and Ferret Badgers. The thing about that is that why would that be if you were passaging it through mice? Mustelidae are going to be a pretty difficult lab target in comparison to mice (they bite, they're big, they take a season to mature). The fact that Ferret Badgers were sold for meat in the Wuhan market is pretty interesting in this context (although none of the animals tested had Cov19).
      - loceng 5y ago
        COVID-19 could be the base discovered that they saw in lab experiments gaining function, evolving rapidly, and so an ideal candidate as the base starting point - where now there's the four variants - and who knows how many more variants may escape with the mRNA vaccine most effective only for the original strain and arguably exponentially less effective against the evolving variants.
      - taneq 5y ago
        I don’t know if it counts as “rapid” given the infected population and time scale involved. Getting from the original COVID-19 to Delta+ in a lab would take a long time compared to in the millions of infected humans ‘in the wild’.
        sudosysgen 5y ago
        It's a single nucleotide mutation. I don't see how the dozens of nucleotides from before would have been easy but the last nucleotide would be impossible.
      - Amezarak 5y ago
        Ferrets are commonly used in serial passaging and gain of function research. https://nymag.com/intelligencer/article/coronavirus-lab-escape-theory.html https://nymag.com/intelligencer/article/coronavirus-lab-esca... > In 2011, a tall, confident Dutch scientist, Ron Fouchier, using grant money from Fauci’s group at NIH, created a mutant form of highly pathogenic avian influenza, H5N1, and passaged it ten times through ferrets in order to prove that he could “force” (his word) this potentially fatal disease to infect mammals, including humans, “via aerosols or respiratory droplets.” https://www.salon.com/2020/11/29/covid-19-mutations-spread-mink-ferrets-gain-of-function-biowarfare/ https://www.salon.com/2020/11/29/covid-19-mutations-spread-m... > Because ferrets are the animals most like humans in terms of how their immune systems respond to influenza, scientists have experimented with them to make existing viruses more deadly, a biowarfare concept known as "gain of function" research.
  - wk_end 5y ago
    That article is reporting on the letter by Andersen et al [1] that Nicolas Wade addresses in his article in the Bulletin of the Atomic Scientists [2] that was published a few weeks back, right around the time the lab hypothesis started gaining steam; it's still probably the strongest case that's been made for it. I think it dispatches the Andersen letter quite handily, but YMMV: > A second statement that had enormous influence in shaping public attitudes was a letter (in other words an opinion piece, not a scientific article) published on 17 March 2020 in the journal Nature Medicine. Its authors were a group of virologists led by Kristian G. Andersen of the Scripps Research Institute. “Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus,” the five virologists declared in the second paragraph of their letter. > [...] True, some older methods of cutting and pasting viral genomes retain tell-tale signs of manipulation. But newer methods, called “no-see-um” or “seamless” approaches, leave no defining marks. Nor do other methods for manipulating viruses such as serial passage, the repeated transfer of viruses from one culture of cells to another. If a virus has been manipulated, whether with a seamless method or by serial passage, there is no way of knowing that this is the case. Andersen and his colleagues were assuring their readers of something they could not know. > [...] The two reasons the authors give for supposing manipulation to be improbable are decidedly inconclusive. > First, they say that the spike protein of SARS2 binds very well to its target, the human ACE2 receptor, but does so in a different way from that which physical calculations suggest would be the best fit. Therefore the virus must have arisen by natural selection, not manipulation. > If this argument seems hard to grasp, it’s because it’s so strained. The authors’ basic assumption, not spelt out, is that anyone trying to make a bat virus bind to human cells could do so in only one way. First they would calculate the strongest possible fit between the human ACE2 receptor and the spike protein with which the virus latches onto it. They would then design the spike protein accordingly (by selecting the right string of amino acid units that compose it). Since the SARS2 spike protein is not of this calculated best design, the Andersen paper says, therefore it can’t have been manipulated. > But this ignores the way that virologists do in fact get spike proteins to bind to chosen targets, which is not by calculation but by splicing in spike protein genes from other viruses or by serial passage. With serial passage, each time the virus’s progeny are transferred to new cell cultures or animals, the more successful are selected until one emerges that makes a really tight bind to human cells. Natural selection has done all the heavy lifting. The Andersen paper’s speculation about designing a viral spike protein through calculation has no bearing on whether or not the virus was manipulated by one of the other two methods. > The authors’ second argument against manipulation is even more contrived. Although most living things use DNA as their hereditary material, a number of viruses use RNA, DNA’s close chemical cousin. But RNA is difficult to manipulate, so researchers working on coronaviruses, which are RNA-based, will first convert the RNA genome to DNA. They manipulate the DNA version, whether by adding or altering genes, and then arrange for the manipulated DNA genome to be converted back into infectious RNA. > Only a certain number of these DNA backbones have been described in the scientific literature. Anyone manipulating the SARS2 virus “would probably” have used one of these known backbones, the Andersen group writes, and since SARS2 is not derived from any of them, therefore it was not manipulated. But the argument is conspicuously inconclusive. DNA backbones are quite easy to make, so it’s obviously possible that SARS2 was manipulated using an unpublished DNA backbone. > And that’s it. These are the two arguments made by the Andersen group in support of their declaration that the SARS2 virus was clearly not manipulated. And this conclusion, grounded in nothing but two inconclusive speculations, convinced the world’s press that SARS2 could not have escaped from a lab. [1] https://www.nature.com/articles/s41591-020-0820-9 https://www.nature.com/articles/s41591-020-0820-9 [2] https://thebulletin.org/2021/05/the-origin-of-covid-did-people-or-nature-open-pandoras-box-at-wuhan/ https://thebulletin.org/2021/05/the-origin-of-covid-did-peop...
  - T-A 5y ago
    The fact that the virus emerged already well adapted to human cells is a primary reason to suspect something's off. How could it be so well adapted right after making the jump to humans? And why have no closely related precursors been found in the wild? A hypothesis which addresses both questions is that the virus evolved in humanized mice. That would also explain why it doesn't look genetically engineered; it wasn't, the mice were.
    - sudosysgen 5y ago
      Because it wasn't. It evolved to become this way. But on the path to this evolution it was not anything of note and no one would notice it.
      - T-A 5y ago
        Nobody noticed the precursors to SARS and MERS either, until those emerged in humans. But once they did, the precursors were quickly found in civets and camels, respectively. A reminder: https://www.technologyreview.com/2021/03/26/1021263/bat-covid-coronavirus-cause-origin-wuhan/ https://www.technologyreview.com/2021/03/26/1021263/bat-covi...
        sudosysgen 5y ago
        It took half a decade for SARS. It wasn't immediate by any stretch of the imagination.
        T-A 5y ago
        > It took half a decade for SARS. It wasn't immediate by any stretch of the imagination. It took less than a year from outbreak to publication: https://science.sciencemag.org/content/302/5643/276 https://science.sciencemag.org/content/302/5643/276
  - ctrlp 5y ago
    Fauci emails reveal that Kristian Anderson originally raised concerns that it was a lab leak based on analysis of the virus before he was brought to heel by Peter Daszak. His later water-carrying for his GoF comrades was, I hope, the low point of his career.
- injinj 5y ago
  If SARS-COV2 has the ability to evolve really quickly, we have little chance to defeat it with vaccines and natural immunity. Cross fingers for lab-made virus.
himinlomax 5y ago
Gain Of Function
bloak 5y ago
There's also the possibility that the leak was from people or activities associated with the lab but not from inside the lab. For example, they hire some local people to go and fetch some more bats from the bat caves in another province. Those people drive to the other province in their white van, go into the caves, inhale lots of guana, grab some bats, drive back to the Wuhan lab, hand over the bats, then drive into central Wuhan to get a coffee and see if there are any good offers at the wet market. (OK, they probably wouldn't actually be infectious straight afterwards, but they're local people so they might visit the market next week, too.)

Many people falsely assume that anything leaked from a lab was made in a lab.

by base3 5y ago

Many people falsely assume that anything leaked from a lab was made in a lab.

That's not why people think the virus was made in a lab. The reason people think it was man-made have to do with strangely well-adapted protein sequences found on the virus with no known natural ancestors. Virus evolution requires hosts and time. The nearest common ancestor to this virus is not a good candidate for SARS-COV2 and there are no known intermediate ancestors in the thousands of animals tested.

ikt 5y ago
> The reason people think it was man-made have to do with strangely well-adapted protein sequences found on the virus with no known natural ancestors. I was under the impression it was a natural sequence, I read about it way back in the beginning: https://www.labmate-online.com/news/laboratory-products/3/breaking-news/is-covid-19-man-made-or-natural/51980 https://www.labmate-online.com/news/laboratory-products/3/br... They found that the spike protein, a receptor-binding domain (RBD) that hooks onto host cells, had evolved to target ACE2, an enzyme founded on the outer surface of human cells that helps to regulate blood pressure. The team say the COVID-19 spike protein is so efficient at binding to human cells that it could only be a result of natural selection, not artificial engineering. Another tell-tale sign of natural origins is the molecular structure of COVID-19, which is substantially different from other known viruses. Rather than mimicking other viruses known to cause severe illness in humans, COVID-19 more closely resembles strains of coronavirus found in bats and pangolins. "These two features of the virus, the mutations in the RBD portion of the spike protein and its distinct backbone, rules out laboratory manipulation as a potential origin for SARS-CoV-2" says Andersen.
- sterlind 5y ago
  I don't understand that argument. Wouldn't serial passage through human lung cells produce efficient bindings? Is that sort of artificial selection not what they meant by "laboratory manipulation?" If they mean it's not the product of genetic engineering then sure, but leaving out the possibility of serial passage is misleading at best.
  - sgt101 5y ago
    The rapid evolution (gain) between the wild virus and Alpha and then Delta and now Delta+ indicates to me that if there was a gain of function experiment in the evolution of this virus then it was stopped far too early! Also it seems tuned to infect Mustelidae - like the Mink in Belgium and Holland, and Ferret Badgers. The thing about that is that why would that be if you were passaging it through mice? Mustelidae are going to be a pretty difficult lab target in comparison to mice (they bite, they're big, they take a season to mature). The fact that Ferret Badgers were sold for meat in the Wuhan market is pretty interesting in this context (although none of the animals tested had Cov19).
    - loceng 5y ago
      COVID-19 could be the base discovered that they saw in lab experiments gaining function, evolving rapidly, and so an ideal candidate as the base starting point - where now there's the four variants - and who knows how many more variants may escape with the mRNA vaccine most effective only for the original strain and arguably exponentially less effective against the evolving variants.
    - taneq 5y ago
      I don’t know if it counts as “rapid” given the infected population and time scale involved. Getting from the original COVID-19 to Delta+ in a lab would take a long time compared to in the millions of infected humans ‘in the wild’.
      - sudosysgen 5y ago
        It's a single nucleotide mutation. I don't see how the dozens of nucleotides from before would have been easy but the last nucleotide would be impossible.
    - Amezarak 5y ago
      Ferrets are commonly used in serial passaging and gain of function research. https://nymag.com/intelligencer/article/coronavirus-lab-escape-theory.html https://nymag.com/intelligencer/article/coronavirus-lab-esca... > In 2011, a tall, confident Dutch scientist, Ron Fouchier, using grant money from Fauci’s group at NIH, created a mutant form of highly pathogenic avian influenza, H5N1, and passaged it ten times through ferrets in order to prove that he could “force” (his word) this potentially fatal disease to infect mammals, including humans, “via aerosols or respiratory droplets.” https://www.salon.com/2020/11/29/covid-19-mutations-spread-mink-ferrets-gain-of-function-biowarfare/ https://www.salon.com/2020/11/29/covid-19-mutations-spread-m... > Because ferrets are the animals most like humans in terms of how their immune systems respond to influenza, scientists have experimented with them to make existing viruses more deadly, a biowarfare concept known as "gain of function" research.
- wk_end 5y ago
  That article is reporting on the letter by Andersen et al [1] that Nicolas Wade addresses in his article in the Bulletin of the Atomic Scientists [2] that was published a few weeks back, right around the time the lab hypothesis started gaining steam; it's still probably the strongest case that's been made for it. I think it dispatches the Andersen letter quite handily, but YMMV: > A second statement that had enormous influence in shaping public attitudes was a letter (in other words an opinion piece, not a scientific article) published on 17 March 2020 in the journal Nature Medicine. Its authors were a group of virologists led by Kristian G. Andersen of the Scripps Research Institute. “Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus,” the five virologists declared in the second paragraph of their letter. > [...] True, some older methods of cutting and pasting viral genomes retain tell-tale signs of manipulation. But newer methods, called “no-see-um” or “seamless” approaches, leave no defining marks. Nor do other methods for manipulating viruses such as serial passage, the repeated transfer of viruses from one culture of cells to another. If a virus has been manipulated, whether with a seamless method or by serial passage, there is no way of knowing that this is the case. Andersen and his colleagues were assuring their readers of something they could not know. > [...] The two reasons the authors give for supposing manipulation to be improbable are decidedly inconclusive. > First, they say that the spike protein of SARS2 binds very well to its target, the human ACE2 receptor, but does so in a different way from that which physical calculations suggest would be the best fit. Therefore the virus must have arisen by natural selection, not manipulation. > If this argument seems hard to grasp, it’s because it’s so strained. The authors’ basic assumption, not spelt out, is that anyone trying to make a bat virus bind to human cells could do so in only one way. First they would calculate the strongest possible fit between the human ACE2 receptor and the spike protein with which the virus latches onto it. They would then design the spike protein accordingly (by selecting the right string of amino acid units that compose it). Since the SARS2 spike protein is not of this calculated best design, the Andersen paper says, therefore it can’t have been manipulated. > But this ignores the way that virologists do in fact get spike proteins to bind to chosen targets, which is not by calculation but by splicing in spike protein genes from other viruses or by serial passage. With serial passage, each time the virus’s progeny are transferred to new cell cultures or animals, the more successful are selected until one emerges that makes a really tight bind to human cells. Natural selection has done all the heavy lifting. The Andersen paper’s speculation about designing a viral spike protein through calculation has no bearing on whether or not the virus was manipulated by one of the other two methods. > The authors’ second argument against manipulation is even more contrived. Although most living things use DNA as their hereditary material, a number of viruses use RNA, DNA’s close chemical cousin. But RNA is difficult to manipulate, so researchers working on coronaviruses, which are RNA-based, will first convert the RNA genome to DNA. They manipulate the DNA version, whether by adding or altering genes, and then arrange for the manipulated DNA genome to be converted back into infectious RNA. > Only a certain number of these DNA backbones have been described in the scientific literature. Anyone manipulating the SARS2 virus “would probably” have used one of these known backbones, the Andersen group writes, and since SARS2 is not derived from any of them, therefore it was not manipulated. But the argument is conspicuously inconclusive. DNA backbones are quite easy to make, so it’s obviously possible that SARS2 was manipulated using an unpublished DNA backbone. > And that’s it. These are the two arguments made by the Andersen group in support of their declaration that the SARS2 virus was clearly not manipulated. And this conclusion, grounded in nothing but two inconclusive speculations, convinced the world’s press that SARS2 could not have escaped from a lab. [1] https://www.nature.com/articles/s41591-020-0820-9 https://www.nature.com/articles/s41591-020-0820-9 [2] https://thebulletin.org/2021/05/the-origin-of-covid-did-people-or-nature-open-pandoras-box-at-wuhan/ https://thebulletin.org/2021/05/the-origin-of-covid-did-peop...
- T-A 5y ago
  The fact that the virus emerged already well adapted to human cells is a primary reason to suspect something's off. How could it be so well adapted right after making the jump to humans? And why have no closely related precursors been found in the wild? A hypothesis which addresses both questions is that the virus evolved in humanized mice. That would also explain why it doesn't look genetically engineered; it wasn't, the mice were.
  - sudosysgen 5y ago
    Because it wasn't. It evolved to become this way. But on the path to this evolution it was not anything of note and no one would notice it.
    - T-A 5y ago
      Nobody noticed the precursors to SARS and MERS either, until those emerged in humans. But once they did, the precursors were quickly found in civets and camels, respectively. A reminder: https://www.technologyreview.com/2021/03/26/1021263/bat-covid-coronavirus-cause-origin-wuhan/ https://www.technologyreview.com/2021/03/26/1021263/bat-covi...
      - sudosysgen 5y ago
        It took half a decade for SARS. It wasn't immediate by any stretch of the imagination.
        T-A 5y ago
        > It took half a decade for SARS. It wasn't immediate by any stretch of the imagination. It took less than a year from outbreak to publication: https://science.sciencemag.org/content/302/5643/276 https://science.sciencemag.org/content/302/5643/276
- ctrlp 5y ago
  Fauci emails reveal that Kristian Anderson originally raised concerns that it was a lab leak based on analysis of the virus before he was brought to heel by Peter Daszak. His later water-carrying for his GoF comrades was, I hope, the low point of his career.
injinj 5y ago
If SARS-COV2 has the ability to evolve really quickly, we have little chance to defeat it with vaccines and natural immunity. Cross fingers for lab-made virus.

himinlomax 5y ago

Gain Of Function

bloak 5y ago

There's also the possibility that the leak was from people or activities associated with the lab but not from inside the lab. For example, they hire some local people to go and fetch some more bats from the bat caves in another province. Those people drive to the other province in their white van, go into the caves, inhale lots of guana, grab some bats, drive back to the Wuhan lab, hand over the bats, then drive into central Wuhan to get a coffee and see if there are any good offers at the wet market. (OK, they probably wouldn't actually be infectious straight afterwards, but they're local people so they might visit the market next week, too.)