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It's not my definition. And I can't tell what experiments you're referring to, so it's not reasonable to comment. But the experiments done at BU had the potent

It's not my definition. And I can't tell what experiments you're referring to, so it's not reasonable to comment. But the experiments done at BU had the potential to produce new viable virus sequences that could display a phenotype that included increased pathogenicity. The researchers had no way of knowing what the results would be in advance. They followed all safety protocols -- that's not being questioned. But their experiments would qualify as GOF experiments under a variety of definitions.

DiogenesKynikos 4y ago
> And I can't tell what experiments you're referring to, so it's not reasonable to comment. Not to be too harsh, but if you don't know about the experiments conducted by Sabin that led to the live attenuated oral polio vaccine, then you don't know enough about virology to comment on the gain-of-function debate. This is the equivalent of wading into a highly technical debate among computer scientists and then saying that you've never heard of the concept of a Turing Machine.
- gus_massa 4y ago
  More details. From https://en.wikipedia.org/wiki/Polio_vaccine#Attenuated_2 https://en.wikipedia.org/wiki/Polio_vaccine#Attenuated_2 > Fifty-seven nucleotide substitutions distinguish the attenuated Sabin 1 strain from its virulent parent (the Mahoney serotype), two nucleotide substitutions attenuate the Sabin 2 strain, and 10 substitutions are involved in attenuating the Sabin 3 strain. > The attenuated poliovirus in the Sabin vaccine replicates very efficiently in the gut, the primary site of infection and replication, but is unable to replicate efficiently within nervous system tissue. [Note that the injectable polio vaccine uses inactivated ("dead") virus, that is safer but not effective to stop contagion.]
  - DiogenesKynikos 4y ago
    The are also efforts to develop a safer live attenuated vaccine, using more modern genetic methods. Sabin developed the original attenuated vaccine in the 1950s-60s, which is basically the stone ages, as far as genetics goes. We now know that the attenuated vaccine reverts to a more dangerous form of polio after it's administered, but that the time it takes to revert is long enough that the vast majority of people develop a robust immune response and don't develop paralysis. The problem is that there is an evolutionary path that the virus can take to revert, and that that path is heavily favored once the virus is actually inside a human gut. However, using modern genetic engineering techniques, it is possible to introduce a set of mutations into the polio virus that make it much more difficult for the virus to revert to a dangerous form. Scientists engineering viruses in a lab could sound scary to laypeople, but it's vital work that might lead to the final eradication of polio.
- possiblydrunk 4y ago
  Well, knowledge of those experiments would be relevant when arguing the merits of GOF research, I'm not. I'm simply saying that Derek Lowe claimed that the uproar over these experiments was overblown because they were not GOF based on a certain narrow definition. The definition itself is not agreed upon by all molecular biologists, virologists and microbiologists. Derek Lowe could have made a variety of arguments around why the experiments were not as dangerous as media reports would have you believe. But he chose to focus on a technical definition of GOF that is hard to defend.
  - DiogenesKynikos 4y ago
    I'm sorry to harp on this, but if you don't know the basics of virology, how do you know whether that technical definition of GOF is hard to defend?
    - possiblydrunk 4y ago
      OK, I'll take the bait ... It's better to attack the argument than to attack the poster. I shouldn't have to defend my credentials to make a comment. I'm not a virologist but I understand how viruses can be mutated and how they replicate. I understand the basics of the BU experiments. Knowledge of a specific set of experiments that were part of developing a specific vaccine does not equate to knowledge of the basics of virology. My point is that claiming the BU experiments on ePPP were not GOF because they didn't produce a more deadly pathogen is a somewhat nonsensical definition (whether NIAID promotes it or not) and an ineffective defense of the work. Derek Lowe can do much better, but he didn't. In the process, he misses addressing the real concerns of critics and fails to understand or acknowledge their fears (which have nothing to do with the precise definition of GOF as used by Derek Lowe).
      - DiogenesKynikos 4y ago
        > Knowledge of a specific set of experiments that were part of developing a specific vaccine does not equate to knowledge of the basics of virology. In this case, it does, because those are some of the most famous experiments in the history of virology. Everyone who learns the basics of virology knows about those experiments. As I said, this is the equivalent of saying one knows the fundamentals of computer science, but not knowing about the Turing Machine. Or imagine someone expressing very strong opinions about programming, but then saying they've never heard of C. I raise this because I'm always shocked in these discussions on HN by how many people who don't seem to know the basics of virology weigh in with such strong opinions. Virology has come under significant attack, and most of it has been very poorly informed. About the experiments themselves, they do not look similar to the experiments that have historically been considered GOF, and which sparked the GOF debate (look up the debate from the 2010s over research into the 1918 pandemic flu strain, if you want to know what the original debate was about). Taking a spike protein from a variant and putting it onto wild-type SARS-CoV-2 is a fairly straightforward way to try to isolate the effect of the changes in the spike protein from other changes in the virus. The Omicron spike is already out there. Omicron is already out there. This isn't adding anything to SARS-CoV-2 that isn't already massively spreading in the real world, and there's no particular reason to think that this experiment will create a more deadly or transmissible virus.
- splistud 4y ago

DiogenesKynikos 4y ago

> And I can't tell what experiments you're referring to, so it's not reasonable to comment. Not to be too harsh, but if you don't know about the experiments conducted by Sabin that led to the live attenuated oral polio vaccine, then you don't know enough about virology to comment on the gain-of-function debate. This is the equivalent of wading into a highly technical debate among computer scientists and then saying that you've never heard of the concept of a Turing Machine.

gus_massa 4y ago
More details. From https://en.wikipedia.org/wiki/Polio_vaccine#Attenuated_2 https://en.wikipedia.org/wiki/Polio_vaccine#Attenuated_2 > Fifty-seven nucleotide substitutions distinguish the attenuated Sabin 1 strain from its virulent parent (the Mahoney serotype), two nucleotide substitutions attenuate the Sabin 2 strain, and 10 substitutions are involved in attenuating the Sabin 3 strain. > The attenuated poliovirus in the Sabin vaccine replicates very efficiently in the gut, the primary site of infection and replication, but is unable to replicate efficiently within nervous system tissue. [Note that the injectable polio vaccine uses inactivated ("dead") virus, that is safer but not effective to stop contagion.]
- DiogenesKynikos 4y ago
  The are also efforts to develop a safer live attenuated vaccine, using more modern genetic methods. Sabin developed the original attenuated vaccine in the 1950s-60s, which is basically the stone ages, as far as genetics goes. We now know that the attenuated vaccine reverts to a more dangerous form of polio after it's administered, but that the time it takes to revert is long enough that the vast majority of people develop a robust immune response and don't develop paralysis. The problem is that there is an evolutionary path that the virus can take to revert, and that that path is heavily favored once the virus is actually inside a human gut. However, using modern genetic engineering techniques, it is possible to introduce a set of mutations into the polio virus that make it much more difficult for the virus to revert to a dangerous form. Scientists engineering viruses in a lab could sound scary to laypeople, but it's vital work that might lead to the final eradication of polio.
possiblydrunk 4y ago
Well, knowledge of those experiments would be relevant when arguing the merits of GOF research, I'm not. I'm simply saying that Derek Lowe claimed that the uproar over these experiments was overblown because they were not GOF based on a certain narrow definition. The definition itself is not agreed upon by all molecular biologists, virologists and microbiologists. Derek Lowe could have made a variety of arguments around why the experiments were not as dangerous as media reports would have you believe. But he chose to focus on a technical definition of GOF that is hard to defend.
- DiogenesKynikos 4y ago
  I'm sorry to harp on this, but if you don't know the basics of virology, how do you know whether that technical definition of GOF is hard to defend?
  - possiblydrunk 4y ago
    OK, I'll take the bait ... It's better to attack the argument than to attack the poster. I shouldn't have to defend my credentials to make a comment. I'm not a virologist but I understand how viruses can be mutated and how they replicate. I understand the basics of the BU experiments. Knowledge of a specific set of experiments that were part of developing a specific vaccine does not equate to knowledge of the basics of virology. My point is that claiming the BU experiments on ePPP were not GOF because they didn't produce a more deadly pathogen is a somewhat nonsensical definition (whether NIAID promotes it or not) and an ineffective defense of the work. Derek Lowe can do much better, but he didn't. In the process, he misses addressing the real concerns of critics and fails to understand or acknowledge their fears (which have nothing to do with the precise definition of GOF as used by Derek Lowe).
    - DiogenesKynikos 4y ago
      > Knowledge of a specific set of experiments that were part of developing a specific vaccine does not equate to knowledge of the basics of virology. In this case, it does, because those are some of the most famous experiments in the history of virology. Everyone who learns the basics of virology knows about those experiments. As I said, this is the equivalent of saying one knows the fundamentals of computer science, but not knowing about the Turing Machine. Or imagine someone expressing very strong opinions about programming, but then saying they've never heard of C. I raise this because I'm always shocked in these discussions on HN by how many people who don't seem to know the basics of virology weigh in with such strong opinions. Virology has come under significant attack, and most of it has been very poorly informed. About the experiments themselves, they do not look similar to the experiments that have historically been considered GOF, and which sparked the GOF debate (look up the debate from the 2010s over research into the 1918 pandemic flu strain, if you want to know what the original debate was about). Taking a spike protein from a variant and putting it onto wild-type SARS-CoV-2 is a fairly straightforward way to try to isolate the effect of the changes in the spike protein from other changes in the virus. The Omicron spike is already out there. Omicron is already out there. This isn't adding anything to SARS-CoV-2 that isn't already massively spreading in the real world, and there's no particular reason to think that this experiment will create a more deadly or transmissible virus.
splistud 4y ago