First, base rates are critical. Looking at potential drugs overall, the rate of approvals due to safety alone—i.e. “Investigational New Drugs” to phase-II efficacy trials, is very low. Phase 1 trials are typically 80-100 people, and most don’t manage to make it past that stage. It would take much stronger evidence than I have seen to think that this vaccine is going to be outside of the norm.
Second, even if the process as done was safe, I can’t imagine that greater than 99% of people manage to do this without screwing up in some serious way. That’s less true of the LW crowd, but I don’t think people are aware of how dumb the mistakes that get made are, or how much quality control matters, and how difficult it is with trying to enforce it for DIY projects.
Lastly, I’m well within the consensus for almost all the rest of the questions—I think it probably works in most cases, and I think it will have side effects in far fewer than 50% of cases.
(But another place I’m a bit outside the consensus is that I think it’s unlikely to trigger standard antibody tests, since standard antibody tests are looking for antibodies against a specific part of the virus, and I’m unsure, reading the “Antibodies and B-cell immune response” section of the white paper, that standard tests would detect the elicited types of NABs.)
As someone considering taking it, I’d be interested in whether you have models of particular side effects or severities that might happen and why? Do you just have vague “accidents and harmful unknown unknowns aren’t that unlikely here”?
I have not currently read the paper or looked into anything very hard. But one question I’d have is “given the ingredients you’re working with, is there are particularly obvious way to mix these on purpose that’d result in something harmful happening?”
Mostly vague “accidents and harmful unknown unknowns aren’t that unlikely here”—because we have data on baseline success at “not have harmful side effects,” and it is low. We also know that lots of important side effects are unusual, so the expected loss can be high even after a number of “successes,” and this is doubly true because no-one is actually tracking side effects. We don’t know much about efficacy either, but again, on base rates it is somewhat low. (Base rates for mRNA are less clear, and may be far higher—but these sequences are unfiltered, so I’m not sure even those bse rates would apply.)
Finally, getting the adjuvants to work is typically tricky for vaccines, and I’d be very concerned about making them useless, or inducing reactions to something other than the virus. But if you want to know about intentional misuse, it’s relatively low. I would wonder about peanut protein to induce you to develop a new allergy because you primed your immune system to react to a new substance, but you’d need someone more expert than I.
Overall, I’d be really happy taking bets that in 20 years, looking back with (hopefully) much greater understanding of mRNA vaccines, a majority of immunologists would respond to hearing details about this idea with a solid “that’s idiotic, what the hell were those idiots thinking?” (If anyone wants to arrange details of this bet, let me know—it sounds like a great way to diversify and boost my expected retirement returns.)
@Davidmanheim you’re a pretty big outlier here, and this is also the kind of question where I’d trust your judgement a fair bit:
So curious if you wanted to elaborate a bit on your model?
First, base rates are critical. Looking at potential drugs overall, the rate of approvals due to safety alone—i.e. “Investigational New Drugs” to phase-II efficacy trials, is very low. Phase 1 trials are typically 80-100 people, and most don’t manage to make it past that stage. It would take much stronger evidence than I have seen to think that this vaccine is going to be outside of the norm.
Second, even if the process as done was safe, I can’t imagine that greater than 99% of people manage to do this without screwing up in some serious way. That’s less true of the LW crowd, but I don’t think people are aware of how dumb the mistakes that get made are, or how much quality control matters, and how difficult it is with trying to enforce it for DIY projects.
Lastly, I’m well within the consensus for almost all the rest of the questions—I think it probably works in most cases, and I think it will have side effects in far fewer than 50% of cases.
(But another place I’m a bit outside the consensus is that I think it’s unlikely to trigger standard antibody tests, since standard antibody tests are looking for antibodies against a specific part of the virus, and I’m unsure, reading the “Antibodies and B-cell immune response” section of the white paper, that standard tests would detect the elicited types of NABs.)
As someone considering taking it, I’d be interested in whether you have models of particular side effects or severities that might happen and why? Do you just have vague “accidents and harmful unknown unknowns aren’t that unlikely here”?
I have not currently read the paper or looked into anything very hard. But one question I’d have is “given the ingredients you’re working with, is there are particularly obvious way to mix these on purpose that’d result in something harmful happening?”
Mostly vague “accidents and harmful unknown unknowns aren’t that unlikely here”—because we have data on baseline success at “not have harmful side effects,” and it is low. We also know that lots of important side effects are unusual, so the expected loss can be high even after a number of “successes,” and this is doubly true because no-one is actually tracking side effects. We don’t know much about efficacy either, but again, on base rates it is somewhat low. (Base rates for mRNA are less clear, and may be far higher—but these sequences are unfiltered, so I’m not sure even those bse rates would apply.)
Finally, getting the adjuvants to work is typically tricky for vaccines, and I’d be very concerned about making them useless, or inducing reactions to something other than the virus. But if you want to know about intentional misuse, it’s relatively low. I would wonder about peanut protein to induce you to develop a new allergy because you primed your immune system to react to a new substance, but you’d need someone more expert than I.
Overall, I’d be really happy taking bets that in 20 years, looking back with (hopefully) much greater understanding of mRNA vaccines, a majority of immunologists would respond to hearing details about this idea with a solid “that’s idiotic, what the hell were those idiots thinking?” (If anyone wants to arrange details of this bet, let me know—it sounds like a great way to diversify and boost my expected retirement returns.)