Regarding the possible gain of function techniques Pfizer mentions in its press release regarding the Jordon Walker allegations https://www.pfizer.com/news/announcements/pfizer-responds-research-claims , in which they claimed their techniques are not gain of function, and are safe, I wrote, in my previous comment: "Pfizer admission that …
Regarding the possible gain of function techniques Pfizer mentions in its press release regarding the Jordon Walker allegations https://www.pfizer.com/news/announcements/pfizer-responds-research-claims , in which they claimed their techniques are not gain of function, and are safe, I wrote, in my previous comment: "Pfizer admission that they create new viruses in the lab, based on genetic data downloaded from sequence repositories".
I wrote that recalling a website item I don't know recall, in which a technique was described which is probably benign. I recall that spike proteins were made in one lab in the USA and sent to another where they were used to create viruses. As best I understand this technique - and I am not a virologist - they would create a virus whose RNA did not contain any instructions for making a spike protein. They would then mix these in a solution with spike proteins which would presumably install themselves on the outside of the virus particle. If so, this technique may involve creating viruses with particular spike protein characteristics which are quite suitable for antibody binding assays or some other research, but which would be safe because the virus's own RNA would not contain instructions for making the spike protein. If such a virus infected a human cell, it would cause the cell to produce only the spikeless viruses, which would not be able to enter and infect other cells. Maybe the document I am thinking of concerned Pfizer, but I can't find it now.
Returning to the press release, the first technique was: " the original SARS-CoV-2 virus has been used to express the spike protein from new variants of concern". In principle this may not be gain of function, since they think they are making viruses which are functional replicas, in some important respects at least, of the real viruses they are researching. However, what if there is an error on their processes, so they create even small quantities of viruses with erroneously copied mRNA, which produce a new variation on the spike protein, or any other aspect of the whole virus? This may not be intended as gain of function, but it could generate novel viruses with infectious potential.
Technique 2 alludes to the possibility of such errors: "a full virus does not contain any known gain of function mutations, such virus may be engineered to enable the assessment of antiviral activity in cells." They are creating novel viruses with full infectious potential and enabling them to infect and so multiply in cell cultures presumably containing human or human-like cells. This could easily lead to novel, infectious, viruses. The fact they do it in a BSL3 lab indicates the dangerous nature of this technique - yet we know that no such lab arrangements are absolutely guaranteed not to allow escape. ("Escape" may mean infecting one of the lab staff - as well as whole viruses somehow getting into the wild.)
The description of technique 3 overlaps somewhat with that of technique 2: "in vitro resistance selection experiments are undertaken in cells incubated with SARS-CoV-2 and nirmatrelvir in our secure Biosafety level 3 (BSL3) laboratory to assess whether the main protease can mutate to yield resistant strains of the virus." While this is not constructing a virus and its RNA by splicing existing segments of mRNA, or creating a genome partly or wholly from codon data in an electronic file, it is still intended to select positively for viral mutations which make the virus less susceptible to the RNA copy fidelity interference mechanism of nirmatrelvir. (These names are a form of torture . . . .) They claim that such trials are required by regulators. Maybe they are, but Pfizer is still deliberately running a process which is intended to prompt the evolution of infectious viruses, with their full RNA, which are resistant to this particular antiviral drug.
Regarding the possible gain of function techniques Pfizer mentions in its press release regarding the Jordon Walker allegations https://www.pfizer.com/news/announcements/pfizer-responds-research-claims , in which they claimed their techniques are not gain of function, and are safe, I wrote, in my previous comment: "Pfizer admission that they create new viruses in the lab, based on genetic data downloaded from sequence repositories".
I wrote that recalling a website item I don't know recall, in which a technique was described which is probably benign. I recall that spike proteins were made in one lab in the USA and sent to another where they were used to create viruses. As best I understand this technique - and I am not a virologist - they would create a virus whose RNA did not contain any instructions for making a spike protein. They would then mix these in a solution with spike proteins which would presumably install themselves on the outside of the virus particle. If so, this technique may involve creating viruses with particular spike protein characteristics which are quite suitable for antibody binding assays or some other research, but which would be safe because the virus's own RNA would not contain instructions for making the spike protein. If such a virus infected a human cell, it would cause the cell to produce only the spikeless viruses, which would not be able to enter and infect other cells. Maybe the document I am thinking of concerned Pfizer, but I can't find it now.
Returning to the press release, the first technique was: " the original SARS-CoV-2 virus has been used to express the spike protein from new variants of concern". In principle this may not be gain of function, since they think they are making viruses which are functional replicas, in some important respects at least, of the real viruses they are researching. However, what if there is an error on their processes, so they create even small quantities of viruses with erroneously copied mRNA, which produce a new variation on the spike protein, or any other aspect of the whole virus? This may not be intended as gain of function, but it could generate novel viruses with infectious potential.
Technique 2 alludes to the possibility of such errors: "a full virus does not contain any known gain of function mutations, such virus may be engineered to enable the assessment of antiviral activity in cells." They are creating novel viruses with full infectious potential and enabling them to infect and so multiply in cell cultures presumably containing human or human-like cells. This could easily lead to novel, infectious, viruses. The fact they do it in a BSL3 lab indicates the dangerous nature of this technique - yet we know that no such lab arrangements are absolutely guaranteed not to allow escape. ("Escape" may mean infecting one of the lab staff - as well as whole viruses somehow getting into the wild.)
The description of technique 3 overlaps somewhat with that of technique 2: "in vitro resistance selection experiments are undertaken in cells incubated with SARS-CoV-2 and nirmatrelvir in our secure Biosafety level 3 (BSL3) laboratory to assess whether the main protease can mutate to yield resistant strains of the virus." While this is not constructing a virus and its RNA by splicing existing segments of mRNA, or creating a genome partly or wholly from codon data in an electronic file, it is still intended to select positively for viral mutations which make the virus less susceptible to the RNA copy fidelity interference mechanism of nirmatrelvir. (These names are a form of torture . . . .) They claim that such trials are required by regulators. Maybe they are, but Pfizer is still deliberately running a process which is intended to prompt the evolution of infectious viruses, with their full RNA, which are resistant to this particular antiviral drug.