Yes, but it's also the problem that natural evolution would want to solve.
You're starting to convince me to be open to "continuous release" theory, but to really shift toward seeing that as likely I would need to see estimates for the probability of natural appearance of particular variants given what we know about replication fidelity (…
Yes, but it's also the problem that natural evolution would want to solve.
You're starting to convince me to be open to "continuous release" theory, but to really shift toward seeing that as likely I would need to see estimates for the probability of natural appearance of particular variants given what we know about replication fidelity (and possibly taking into account treatments like molnupiravir that dramatically decrease replication fidelity). Assuming that any such probability estimates would have very large error bars (due to complex and not-fully-understood systems), natural appearance probabilities in the range of 1 in 1,000 or lower would be rather convincing, *or* any molecular signatures of additional engineering in VOCs such as were uncovered by the RE site analysis.
RE natural evolution against innate immunity, the only problem (it's not huge, but still) is that it isn't clear what natural evolution would predict about high- vs low-adaptive-immunity environments. Why does the virus "decide" to take on innate immunity in super-saturated areas like Brazil (70% sero+) and India at the same time as kids in England still have a measly 7% sero+ (and to what degree is anything really patched up anyway since the result of the Alpha wave only raises that to 17 https://unglossed.substack.com/i/76838100/the-results).
So it seems like natural evolution is behaving a bit artificially. Of course, there's the question about whether seasonality intrinsically alters clonal competition dynamics and creates windows for high-fitness mutants that don't exist in the middle or residue of a wave regardless of adaptive immune response. So you could say that is why Alpha drops early in the winter wave instead of later. But then you are not really being super-parsimonious at that point, and once again what is up with the retro B.1.1 starting point.
So Hill, et al., aren't really wrong when they say that the only (permissible to publish) origin possible is Immunocompromised Ex Machina.
Yes, but it's also the problem that natural evolution would want to solve.
You're starting to convince me to be open to "continuous release" theory, but to really shift toward seeing that as likely I would need to see estimates for the probability of natural appearance of particular variants given what we know about replication fidelity (and possibly taking into account treatments like molnupiravir that dramatically decrease replication fidelity). Assuming that any such probability estimates would have very large error bars (due to complex and not-fully-understood systems), natural appearance probabilities in the range of 1 in 1,000 or lower would be rather convincing, *or* any molecular signatures of additional engineering in VOCs such as were uncovered by the RE site analysis.
RE natural evolution against innate immunity, the only problem (it's not huge, but still) is that it isn't clear what natural evolution would predict about high- vs low-adaptive-immunity environments. Why does the virus "decide" to take on innate immunity in super-saturated areas like Brazil (70% sero+) and India at the same time as kids in England still have a measly 7% sero+ (and to what degree is anything really patched up anyway since the result of the Alpha wave only raises that to 17 https://unglossed.substack.com/i/76838100/the-results).
So it seems like natural evolution is behaving a bit artificially. Of course, there's the question about whether seasonality intrinsically alters clonal competition dynamics and creates windows for high-fitness mutants that don't exist in the middle or residue of a wave regardless of adaptive immune response. So you could say that is why Alpha drops early in the winter wave instead of later. But then you are not really being super-parsimonious at that point, and once again what is up with the retro B.1.1 starting point.
So Hill, et al., aren't really wrong when they say that the only (permissible to publish) origin possible is Immunocompromised Ex Machina.