I wish ppl would pour their energy into helping ppl with long covid instead of complaining about gain of function. Like, help me gain my function back🫤😂I went from 70.3 mile triathlon training to the ER for EKG’s and no one is talking about that. 7 million Americans are suffering and you are stuck on gof?
"What would it take, they wondered, to turn the bird flu into a human flu? They decided to give it a try, and they announced their plans to the world. Then, just a few months later, they published results (in the journal Nature), showing that they had succeeded, using a bird flu called H7N9."
But your statement is wrong, for many reasons, as clearly shown by even a cursory reading of the paper you are linking to:
1. The primary experiment performed was testing two human isolates for transmissability in ferrets. These are natural viruses that have already infected humans. This is not gain of function.
2. Three mutations (N123D and N149D and M523I) were then tested in these isolates, and in all three cases, phenotypes either were unchanged or had a negative impact on stability. Therefore, these experiments were losses of function, not gain.
3. Therefore it is flatly incorrect to say as you have that "they had succeeded", because in this work, the virus is never altered to become more transmissable, stable, or more pathogenic, only less so.
4. To quote: "Fortunately, additional changes required to, for example, further tune receptor preference, lower the pH for HA fusion, and increase HA stability, may be needed for the A(H7N9) viruses to transmit efficiently in mammals18,20"
5. You ask "Why did they do this?". The scientists tell us this, but you do not appear to approach this question with any seriousness or intellectual honesty. The actual answer was: because these experiments can tell us which mutations to track in new clinical cases, and can inform when a virus might be on the verge of spillover.
Next, You attempt to connect the end of NIH's moratorium on Gain of Function to research at the Wuhan Institute of Virology and the origins of COVID-19. But this is flatly straight out wrong for so many reasons that it is actually rather hard to count them all:
1. The NIH's moratorium only applied to viruses already known to be human pathogens, like SARS-CoV, that infected humans. It did not apply to work on SARS-related bat coronaviruses, and it was not supposed to. That's why Shi Zheng-Li's lab was doing plenty of work on bat coronavirus genetics during the moratorium itself: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006698
2. Scientific research on the genetics of bat sarbecoviruses has been ongoing in China since the SARS epidemic in 2003 which greatly impacted that country. The NIH moratorium from 2014-2017 has nothing to do with it.
3. There is no NIH grant or project that directly funded work that could have contributed to the emergence of COVID-19 at the Wuhan Institute of Virology. The grants that Dr. Shi's group received are all public, as as their progress reports now, and none of the work proposed isolating and performing gain of function genetic experiments in novel sarbecoviruses, only experiments using existing viral backbones. You can, as others have done, argue that the lab pursued other unknown projects at the same time using other funding sources, but the fact is, their grants and progress reports do not describe an avenue of research that could have ever led to the emergence of SARS-CoV-2.
4. There is an enormous amount of evidence that Dr. Shi's group did not have a progenitor virus to COVID-19, let alone one that they performed genetics on and that spilled into the human population. The lab members tested negative for SARS-CoV-2 antibodies in 2020. The lab members went to international conferences in December 2019. International researchers were working with the lab at the time in 2020, and saw no evidence of any laboratory incidents. The lab shared their sarbecovirus viral sequences in 2018 and again in 2019, before there was any reason to hide a particular virus, and they did not have SARS-CoV-2.
5. There is also an enormous amount of scientific evidence that SARS-CoV-2 emerged in the human population via the wildlife trade, as SARS-CoV-1 did. please see the scientific papers on the topic.
My ask for you, and for anyone concerned about the risks of gain of function research is this: if it is important, it is important enough to not make up a fairy tale about the origin of the pandemic. It is important enough to not lie or mislead people about. It is important enough to be honest about the reality that SARS-CoV-2 was a pandemic started by a natural zoonosis. If you cannot treat the subject with enough importance to be academically honest about these things, then I don't really see why I should trust your opinion on the topic as a whole.
If the negative risks from Gain of Function experiments are indeed important, then the topic is also worth our close attention, careful research, and scientific and intellectual honesty. You have clearly afforded none of these in your contributions on the topic, which appear cursory and lazy, as the post above. Therefore it is hard to believe that you yourself take the issue particularly seriously.
I agree, as do almost all virologists and scientists, that we should not unnecessarily create infectious viruses in the lab that would be expected to be more infectious or transmissible. But evaluating experiments on this requires expertise and careful consideration of the context, not laziness.
just one response to this very long set of comments. You claim that there is “an enormous amount of scientific evidence that SARS-CoV-2 emerged in the human population via the wildlife trade” and you cite several papers. I read those papers - and wrote a column about them while they were still in preprint form. They are very sloppy, biased, poorly-done papers. They’d never have been published in normal times, but at the height of the pandemic, journals were eager to push out studies that made controversial claims. They didn’t find a single case of an animal-borne virus, so all we’re left with is evidence that humans carrying SARS-CoV-2 were in that large marketplace in Wuhan. The Chinese investigators didn’t look anywhere else - or if they did, they never published what they found. All the evidence is entirely consistent with a lab leak, in which one or more scientists at WIV got infected and then traveled around the city. We’ll probably never know for sure, because China destroyed all the samples from WIV.
Steven -- In June 2021, you wrote: "Even more curious is that WIV was actively doing research on coronaviruses in bats, including the bats that carry a strain of SARS-CoV-2 [RaTG13] that is the closest known relative to the Covid-19 virus itself."
This became entirely irrelevant to COVID-19 origins in September 2021 when it turned out more closely related viruses were found elsewhere, hundred of kilometers from where WIV had ever sampled.
You also wrote: "We need to know if any viruses in WIV are similar to the Covid-19 virus" but you did not mention that in May 2021, the eight viruses sampled at the same place as RaTG13 that had been the focus of lab leak theories were sequenced and described and found to be irrelevant to COVID-19 origins.
You also wrote: "We know that WIV was conducting gain-of-function experiments, and we know that its work included coronaviruses."
Previous WIV gain-of-function experiments proposed as being relevant to COVID-19 origins at the time -- swapping spike proteins into different backbones -- were also found to be irrelevant to COVID-19 origins in September 2021. Furthermore, the DEFUSE proposal and its drafts reveal several experimental approaches of interest to Zhengli Shi and her collaborators, some of them being possible gain-of-function experiments. None of them are gain-of-function experiments that plausibly explain anything about SARS-CoV-2.
These are three pieces of evidence that you previously cited as supporting lab leak. All are now known to be irrelevant to SARS-CoV-2 origins. So, when you say that "all the evidence is entirely consistent with a lab leak," are you referring to evidence that remains today? Have you correspondingly updated how likely you think a lab leak origin is to account for nearly all of your previous supporting evidence collapsing?
I’d venture to say that both these issues are important. Nevertheless, I worry more that, with all the universal cuts in research, we risk losing ground on finding ways to treat long Covid, not to mention on the increasingly overlapping findings with other virally-caused illnesses such as Lyme, ME/CFS, and Lupus. It is heart-wrenching to hear what you have suffered and continue to suffer, and there are millions out here, including a beloved family member, who are grappling with similar circumstances and need help. I get a bitter feeling when I think about how the economic cost of neglecting this is perhaps the only currency politicians seem to care about.
I wish ppl would pour their energy into helping ppl with long covid instead of complaining about gain of function. Like, help me gain my function back🫤😂I went from 70.3 mile triathlon training to the ER for EKG’s and no one is talking about that. 7 million Americans are suffering and you are stuck on gof?
Steven, you wrote:
"What would it take, they wondered, to turn the bird flu into a human flu? They decided to give it a try, and they announced their plans to the world. Then, just a few months later, they published results (in the journal Nature), showing that they had succeeded, using a bird flu called H7N9."
But your statement is wrong, for many reasons, as clearly shown by even a cursory reading of the paper you are linking to:
https://www.nature.com/articles/nature12476#Abs3
1. The primary experiment performed was testing two human isolates for transmissability in ferrets. These are natural viruses that have already infected humans. This is not gain of function.
2. Three mutations (N123D and N149D and M523I) were then tested in these isolates, and in all three cases, phenotypes either were unchanged or had a negative impact on stability. Therefore, these experiments were losses of function, not gain.
3. Therefore it is flatly incorrect to say as you have that "they had succeeded", because in this work, the virus is never altered to become more transmissable, stable, or more pathogenic, only less so.
4. To quote: "Fortunately, additional changes required to, for example, further tune receptor preference, lower the pH for HA fusion, and increase HA stability, may be needed for the A(H7N9) viruses to transmit efficiently in mammals18,20"
5. You ask "Why did they do this?". The scientists tell us this, but you do not appear to approach this question with any seriousness or intellectual honesty. The actual answer was: because these experiments can tell us which mutations to track in new clinical cases, and can inform when a virus might be on the verge of spillover.
Next, You attempt to connect the end of NIH's moratorium on Gain of Function to research at the Wuhan Institute of Virology and the origins of COVID-19. But this is flatly straight out wrong for so many reasons that it is actually rather hard to count them all:
1. The NIH's moratorium only applied to viruses already known to be human pathogens, like SARS-CoV, that infected humans. It did not apply to work on SARS-related bat coronaviruses, and it was not supposed to. That's why Shi Zheng-Li's lab was doing plenty of work on bat coronavirus genetics during the moratorium itself: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006698
2. Scientific research on the genetics of bat sarbecoviruses has been ongoing in China since the SARS epidemic in 2003 which greatly impacted that country. The NIH moratorium from 2014-2017 has nothing to do with it.
3. There is no NIH grant or project that directly funded work that could have contributed to the emergence of COVID-19 at the Wuhan Institute of Virology. The grants that Dr. Shi's group received are all public, as as their progress reports now, and none of the work proposed isolating and performing gain of function genetic experiments in novel sarbecoviruses, only experiments using existing viral backbones. You can, as others have done, argue that the lab pursued other unknown projects at the same time using other funding sources, but the fact is, their grants and progress reports do not describe an avenue of research that could have ever led to the emergence of SARS-CoV-2.
4. There is an enormous amount of evidence that Dr. Shi's group did not have a progenitor virus to COVID-19, let alone one that they performed genetics on and that spilled into the human population. The lab members tested negative for SARS-CoV-2 antibodies in 2020. The lab members went to international conferences in December 2019. International researchers were working with the lab at the time in 2020, and saw no evidence of any laboratory incidents. The lab shared their sarbecovirus viral sequences in 2018 and again in 2019, before there was any reason to hide a particular virus, and they did not have SARS-CoV-2.
5. There is also an enormous amount of scientific evidence that SARS-CoV-2 emerged in the human population via the wildlife trade, as SARS-CoV-1 did. please see the scientific papers on the topic.
https://www.cell.com/cell/fulltext/S0092-8674(24)00901-2
https://www.science.org/doi/10.1126/science.abp8337
https://www.science.org/doi/10.1126/science.abp8715
https://www.cell.com/cell/fulltext/S0092-8674(21)00991-0
https://www.biorxiv.org/content/10.1101/2025.04.05.647275v1
My ask for you, and for anyone concerned about the risks of gain of function research is this: if it is important, it is important enough to not make up a fairy tale about the origin of the pandemic. It is important enough to not lie or mislead people about. It is important enough to be honest about the reality that SARS-CoV-2 was a pandemic started by a natural zoonosis. If you cannot treat the subject with enough importance to be academically honest about these things, then I don't really see why I should trust your opinion on the topic as a whole.
If the negative risks from Gain of Function experiments are indeed important, then the topic is also worth our close attention, careful research, and scientific and intellectual honesty. You have clearly afforded none of these in your contributions on the topic, which appear cursory and lazy, as the post above. Therefore it is hard to believe that you yourself take the issue particularly seriously.
I agree, as do almost all virologists and scientists, that we should not unnecessarily create infectious viruses in the lab that would be expected to be more infectious or transmissible. But evaluating experiments on this requires expertise and careful consideration of the context, not laziness.
just one response to this very long set of comments. You claim that there is “an enormous amount of scientific evidence that SARS-CoV-2 emerged in the human population via the wildlife trade” and you cite several papers. I read those papers - and wrote a column about them while they were still in preprint form. They are very sloppy, biased, poorly-done papers. They’d never have been published in normal times, but at the height of the pandemic, journals were eager to push out studies that made controversial claims. They didn’t find a single case of an animal-borne virus, so all we’re left with is evidence that humans carrying SARS-CoV-2 were in that large marketplace in Wuhan. The Chinese investigators didn’t look anywhere else - or if they did, they never published what they found. All the evidence is entirely consistent with a lab leak, in which one or more scientists at WIV got infected and then traveled around the city. We’ll probably never know for sure, because China destroyed all the samples from WIV.
Steven -- In June 2021, you wrote: "Even more curious is that WIV was actively doing research on coronaviruses in bats, including the bats that carry a strain of SARS-CoV-2 [RaTG13] that is the closest known relative to the Covid-19 virus itself."
This became entirely irrelevant to COVID-19 origins in September 2021 when it turned out more closely related viruses were found elsewhere, hundred of kilometers from where WIV had ever sampled.
You also wrote: "We need to know if any viruses in WIV are similar to the Covid-19 virus" but you did not mention that in May 2021, the eight viruses sampled at the same place as RaTG13 that had been the focus of lab leak theories were sequenced and described and found to be irrelevant to COVID-19 origins.
You also wrote: "We know that WIV was conducting gain-of-function experiments, and we know that its work included coronaviruses."
Previous WIV gain-of-function experiments proposed as being relevant to COVID-19 origins at the time -- swapping spike proteins into different backbones -- were also found to be irrelevant to COVID-19 origins in September 2021. Furthermore, the DEFUSE proposal and its drafts reveal several experimental approaches of interest to Zhengli Shi and her collaborators, some of them being possible gain-of-function experiments. None of them are gain-of-function experiments that plausibly explain anything about SARS-CoV-2.
These are three pieces of evidence that you previously cited as supporting lab leak. All are now known to be irrelevant to SARS-CoV-2 origins. So, when you say that "all the evidence is entirely consistent with a lab leak," are you referring to evidence that remains today? Have you correspondingly updated how likely you think a lab leak origin is to account for nearly all of your previous supporting evidence collapsing?
I’d venture to say that both these issues are important. Nevertheless, I worry more that, with all the universal cuts in research, we risk losing ground on finding ways to treat long Covid, not to mention on the increasingly overlapping findings with other virally-caused illnesses such as Lyme, ME/CFS, and Lupus. It is heart-wrenching to hear what you have suffered and continue to suffer, and there are millions out here, including a beloved family member, who are grappling with similar circumstances and need help. I get a bitter feeling when I think about how the economic cost of neglecting this is perhaps the only currency politicians seem to care about.
COVID was not caused by GoF.