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The actual impact of gain-of-function research papers isn't actually what is being critiqued here. That's putting the cart before the horse. What is being criti

The actual impact of gain-of-function research papers isn't actually what is being critiqued here. That's putting the cart before the horse. What is being criticized is that the authors of such papers are pushing their research efforts into this area because they see it as their highest expected value avenue for generating the "impact" they need to secure funding, tenure, etc.

jpeloquin 5y ago
But if the gain-of-function research really is high-impact in the sense that is valuable to society, isn't it a good thing that incentives push scientists to work in this area? It would be an example of careerism "impact" lining up with actual impact; i.e., the system working as intended.
- pdonis 5y ago
  > if the gain-of-function research really is high-impact in the sense that is valuable to society So far its net impact seems to be extremely negative (one pandemic, zero help with any treatments or preventive measures). So by your own argument, we should stop it immediately, right?
  - jpeloquin 5y ago
    I'm not sure whether on the balance gain of function research is a good idea or not. The point of my comment was just that discussing the impact is highly relevant, and isn't "putting the cart before the horse". But I guess I should expand on it. Regarding whether gain of function research is a good idea: Creating synthetic variants (to see if there is gain or loss in function) is very helpful in that it allows well-controlled experiments, which is necessary to establish causation. As I said elsewhere, I don't think the risk is appreciably different whether the lab's collection of dangerous viruses is all-natural or not. That is, if we ban gain of function research we should probably stop studying the unmodified variants also. There have been near-misses with accidental releases of SARS-CoV-1 and Guanarito [0]; no gain of function required. And the 1977 release of H1N1 came from vaccine development. Regarding describing the net impact of gain of function research as one pandemic, zero help: I don't know what would be different if gain of function research had been banned. The underlying methods have been used since at least 1999 on, among other things, MERS and SARS-2003 [0], so they have contributed to the general knowledge base that permitted extremely rapid development of the COVID-19 vaccine. This was a significant help, not zero help. On a technical and scientific level we were very well prepared for COVID-19. Its biology was well-understood almost immediately. Our failures were on the social and organizational levels. Was gain of function research genuinely necessary to achieve that level of preparedness? To answer that one of us would have to sift through the body of work on COVID-19 vaccine development and trialed treatments to see if the people involved used information from mutagenesis or infectious clone technology experiments (the work that is being referred to as "gain of function"). I haven't done that, so I can't give a definitive reply on that point. There is also the matter of side effects from a ban. Creating synthetic variants within the scope of naturally occurring traits seems acceptable given the benefits. But there's no guarantee what a given edit will do in advance. If you ban all genetic engineering that could lead to gain of function then that will severely hamper research, including development of vaccines and antivirals. So overall I guess I favor a restriction on deliberately increasing pathogenicity, virulence, and transmissibility beyond levels that occur in similar natural viruses, but allowing the possibility that this could still happen unintentionally. I also think synthetic variants should be destroyed as soon as their purpose is complete, and facilities where these viruses are studied should have a test/trace/isolate plan in continuous operation. Edit: We also have to keep in mind that COVID-19 wasn't necessarily leaked from a lab, and even it was, it may be a naturally occurring variant. Which would make much of this speculation pointless. [0] https://yurideigin.medium.com/lab-made-cov2-genealogy-through-the-lens-of-gain-of-function-research-f96dd7413748 https://yurideigin.medium.com/lab-made-cov2-genealogy-throug...
    - pdonis 5y ago
      > Creating synthetic variants (to see if there is gain or loss in function) is very helpful in that it allows well-controlled experiments Only if, as I responded to another post of yours elsewhere in this discussion, the experiments consist of infecting humans with different strains and seeing what happens to them. And even then there are a huge number of possible confounders. > There have been near-misses with accidental releases of SARS-CoV-1 and Guanarito [0]; no gain of function required Indeed. The fact that this problem has been around for a while doesn't make it any less of a problem. Plus, those releases had a much smaller impact because those previous viruses were not as well adapted to human infection when they first appeared--a feature that SARS-CoV-2 does not share (see further comments below). > I don't know what would be different if gain of function research had been banned If the lab escape theory is correct, we would not have had this pandemic because the lab would not have done the research in the first place. Seems like a pretty major negative consequence to me. > On a technical and scientific level we were very well prepared for COVID-19. Its biology was well-understood almost immediately. Our failures were on the social and organizational levels. The decision to do gain of function research in the first place, particularly in a lab in China where US officials could not hope to have any useful oversight of safety procedures, was also a social and organizational failure. (So was our failure to get a vaccine widely distributed even though, as you note, we understood the biology of the virus very quickly.) Doesn't make the pandemic any less devastating. > they have contributed to the general knowledge base that permitted extremely rapid development of the COVID-19 vaccine I don't know what knowledge base you're talking about. DNA sequencing technology, and generating mRNA from a given DNA sequence, which is how Pfizer and Moderna were able to produce a COVID-19 vaccine in a matter of hours, were around before any of the research you refer to was done, and that research added nothing new. If you mean knowledge about the spike protein being important, that was known before any gain of function research was done, so I don't see how that research helps. Simple research into "how does this type of virus infect a human cell" would have been enough. > I guess I favor a restriction on deliberately increasing pathogenicity, virulence, and transmissibility beyond levels that occur in similar natural viruses, but allowing the possibility that this could still happen unintentionally. I also think synthetic variants should be destroyed as soon as their purpose is complete, and facilities where these viruses are studied should have a test/trace/isolate plan in continuous operation. While these are nice ideas, the problem is that they would have to be implemented with the same grossly failed institutions that got us into this mess. To me this is similar to an argument I agree with against allowing capital punishment in our society: while I agree in principle that there can be cases where capital punishment is justified, the institutions in our society have shown that they are incapable of exercising the kind of discipline required to make sure that, when a person is sentenced to death, we know to a moral certainty that they are guilty of a crime that merits that punishment. Similarly, while in principle it might be the case that we could gain benefits from dangerous research with viruses, the institutions in our society have shown that they are incapable of exercising the kind of discipline required to do that safely. > COVID-19 wasn't necessarily leaked from a lab, and even it was, it may be a naturally occurring variant The fact that even the earliest samples obtained, in late 2019, were already highly infective to humans, is a huge indicator to me that this virus was not only leaked from a lab, but leaked from a lab that was doing gain of function research, not a naturally occurring variant. As I noted above, previous accidentally released viruses, which were believed to be naturally occurring variants, did not have this property, and, as we can see by comparing the respective outbreaks that followed, it makes a huge difference in the impact.

jpeloquin 5y ago

But if the gain-of-function research really is high-impact in the sense that is valuable to society, isn't it a good thing that incentives push scientists to work in this area? It would be an example of careerism "impact" lining up with actual impact; i.e., the system working as intended.

pdonis 5y ago
> if the gain-of-function research really is high-impact in the sense that is valuable to society So far its net impact seems to be extremely negative (one pandemic, zero help with any treatments or preventive measures). So by your own argument, we should stop it immediately, right?
- jpeloquin 5y ago
  I'm not sure whether on the balance gain of function research is a good idea or not. The point of my comment was just that discussing the impact is highly relevant, and isn't "putting the cart before the horse". But I guess I should expand on it. Regarding whether gain of function research is a good idea: Creating synthetic variants (to see if there is gain or loss in function) is very helpful in that it allows well-controlled experiments, which is necessary to establish causation. As I said elsewhere, I don't think the risk is appreciably different whether the lab's collection of dangerous viruses is all-natural or not. That is, if we ban gain of function research we should probably stop studying the unmodified variants also. There have been near-misses with accidental releases of SARS-CoV-1 and Guanarito [0]; no gain of function required. And the 1977 release of H1N1 came from vaccine development. Regarding describing the net impact of gain of function research as one pandemic, zero help: I don't know what would be different if gain of function research had been banned. The underlying methods have been used since at least 1999 on, among other things, MERS and SARS-2003 [0], so they have contributed to the general knowledge base that permitted extremely rapid development of the COVID-19 vaccine. This was a significant help, not zero help. On a technical and scientific level we were very well prepared for COVID-19. Its biology was well-understood almost immediately. Our failures were on the social and organizational levels. Was gain of function research genuinely necessary to achieve that level of preparedness? To answer that one of us would have to sift through the body of work on COVID-19 vaccine development and trialed treatments to see if the people involved used information from mutagenesis or infectious clone technology experiments (the work that is being referred to as "gain of function"). I haven't done that, so I can't give a definitive reply on that point. There is also the matter of side effects from a ban. Creating synthetic variants within the scope of naturally occurring traits seems acceptable given the benefits. But there's no guarantee what a given edit will do in advance. If you ban all genetic engineering that could lead to gain of function then that will severely hamper research, including development of vaccines and antivirals. So overall I guess I favor a restriction on deliberately increasing pathogenicity, virulence, and transmissibility beyond levels that occur in similar natural viruses, but allowing the possibility that this could still happen unintentionally. I also think synthetic variants should be destroyed as soon as their purpose is complete, and facilities where these viruses are studied should have a test/trace/isolate plan in continuous operation. Edit: We also have to keep in mind that COVID-19 wasn't necessarily leaked from a lab, and even it was, it may be a naturally occurring variant. Which would make much of this speculation pointless. [0] https://yurideigin.medium.com/lab-made-cov2-genealogy-through-the-lens-of-gain-of-function-research-f96dd7413748 https://yurideigin.medium.com/lab-made-cov2-genealogy-throug...
  - pdonis 5y ago
    > Creating synthetic variants (to see if there is gain or loss in function) is very helpful in that it allows well-controlled experiments Only if, as I responded to another post of yours elsewhere in this discussion, the experiments consist of infecting humans with different strains and seeing what happens to them. And even then there are a huge number of possible confounders. > There have been near-misses with accidental releases of SARS-CoV-1 and Guanarito [0]; no gain of function required Indeed. The fact that this problem has been around for a while doesn't make it any less of a problem. Plus, those releases had a much smaller impact because those previous viruses were not as well adapted to human infection when they first appeared--a feature that SARS-CoV-2 does not share (see further comments below). > I don't know what would be different if gain of function research had been banned If the lab escape theory is correct, we would not have had this pandemic because the lab would not have done the research in the first place. Seems like a pretty major negative consequence to me. > On a technical and scientific level we were very well prepared for COVID-19. Its biology was well-understood almost immediately. Our failures were on the social and organizational levels. The decision to do gain of function research in the first place, particularly in a lab in China where US officials could not hope to have any useful oversight of safety procedures, was also a social and organizational failure. (So was our failure to get a vaccine widely distributed even though, as you note, we understood the biology of the virus very quickly.) Doesn't make the pandemic any less devastating. > they have contributed to the general knowledge base that permitted extremely rapid development of the COVID-19 vaccine I don't know what knowledge base you're talking about. DNA sequencing technology, and generating mRNA from a given DNA sequence, which is how Pfizer and Moderna were able to produce a COVID-19 vaccine in a matter of hours, were around before any of the research you refer to was done, and that research added nothing new. If you mean knowledge about the spike protein being important, that was known before any gain of function research was done, so I don't see how that research helps. Simple research into "how does this type of virus infect a human cell" would have been enough. > I guess I favor a restriction on deliberately increasing pathogenicity, virulence, and transmissibility beyond levels that occur in similar natural viruses, but allowing the possibility that this could still happen unintentionally. I also think synthetic variants should be destroyed as soon as their purpose is complete, and facilities where these viruses are studied should have a test/trace/isolate plan in continuous operation. While these are nice ideas, the problem is that they would have to be implemented with the same grossly failed institutions that got us into this mess. To me this is similar to an argument I agree with against allowing capital punishment in our society: while I agree in principle that there can be cases where capital punishment is justified, the institutions in our society have shown that they are incapable of exercising the kind of discipline required to make sure that, when a person is sentenced to death, we know to a moral certainty that they are guilty of a crime that merits that punishment. Similarly, while in principle it might be the case that we could gain benefits from dangerous research with viruses, the institutions in our society have shown that they are incapable of exercising the kind of discipline required to do that safely. > COVID-19 wasn't necessarily leaked from a lab, and even it was, it may be a naturally occurring variant The fact that even the earliest samples obtained, in late 2019, were already highly infective to humans, is a huge indicator to me that this virus was not only leaked from a lab, but leaked from a lab that was doing gain of function research, not a naturally occurring variant. As I noted above, previous accidentally released viruses, which were believed to be naturally occurring variants, did not have this property, and, as we can see by comparing the respective outbreaks that followed, it makes a huge difference in the impact.