A vaccine brought to clinical trials has already overcome many more hurdles than this has.
I’m not sure what your level of background knowledge is, but I heard that the Moderna vaccine was designed in two days. Clearly they did not do any significant in vitro or in vivo testing in that timespan. Maybe they did some in-vitro before human trials, I don’t know; that would support an argument against using “vaccine brought to clinical trials” as a reference class.
But the deeper point which this is trying to operationalize is “vaccine design just isn’t that hard”, in the sense that we don’t need to test many designs to find one which works. People basically-know-how-to-design-vaccines, maybe not to quite the same extent as people basically-know-how-to-design-bridges, but to enough of an extent that experimental verification just isn’t necessary in order to get a >50% chance that the design works, especially for relatively-mechanical designs like mRNA or peptides.
Under this view, the reasons we don’t see nearly-every vaccine trial succeed are (1) commercial vaccines are harder than lab (especially if you want no boosters, easy logistics, etc), and (2) diseases which are harder-than-average will naturally end up with disproportionately many trials, and (3) out-of-date companies take time to die off.
The in vitro testing had already been done before those two days; they had the basic structure of the vaccine known, so once they had a virus sample they could fill in the blank (the spike protein of this particular virus rather than another in its ‘family’) with high confidence that it would work. One of the two days, IIUC, was spent synthesizing a sample vaccine and running some very-short-term tests.
This, again, has only simulation to support that it’s hitting the correct target at all. There is no indication that any of that has been done, by the authors or anyone else; IIUC there is not a clear path for doing short-term tests for this type of vaccine.
Also, it’s not my background knowledge that you should be comparing to, it’s Sarah’s. And I literally believe there is no one in the world who can be more trusted to reason clearly, well-informedly, correctly, and with humility and arrogance in their respective correct places than Sarah Constantin. Evaluating biomedical research has been her job for many years, with some gaps, and she’s really good at rationality, Aumann-level good. The bare fact that Sarah C thinks this is very unlikely to work is conclusive on its own.
How does the “vaccine design just isn’t that hard” align with these points?
a) Average time to develop a vaccine for a new virus is many years
b) There is still no HIV vaccine after 35 years of well-funded research
c) Until a few months ago, there were no approved coronavirus vaccines for humans
I’m prepared to accept that “bureaucracy” is the main cause for the delays in standard big company vaccine development and approval.
But if it’s easy to develop vaccines, why has there been no coronavirus vaccine previously? Why is there still no vaccine for SARS 1 or MERS or the common cold? Why was this Radvac idea or something similar not rolled out pre-Covid? (or was it? maybe nasal vaccines are easier?)
Anyway, I’m just stuck on the logical conflict between “it’s easy to develop a coronavirus vaccine” and “we’ve never had one (approved) before.” Any thoughts?
First, I expect a disproportionate number of vaccine trials are for “unusually difficult” viruses, like HIV. After all, if it’s an “easy” virus to make a vaccine for, then the first or second trial should work. It’s only the “hard” viruses which require a large number of trials.
But if it’s easy to develop vaccines, why has there been no coronavirus vaccine previously? Why is there still no vaccine for SARS 1 or MERS or the common cold? Why was this Radvac idea or something similar not rolled out pre-Covid?
I expect this is still mainly a result of regulatory hurdles. Clinical trials are slow and expensive, so there has to be a pretty big pot of gold at the end of the rainbow to make it happen. Also, companies tend to do what they already know how to do, so newer methods like mRNA or peptide vaccines usually require a big shock (like COVID) in order to see rapid adoption.
I’m not sure what your level of background knowledge is, but I heard that the Moderna vaccine was designed in two days. Clearly they did not do any significant in vitro or in vivo testing in that timespan. Maybe they did some in-vitro before human trials, I don’t know; that would support an argument against using “vaccine brought to clinical trials” as a reference class.
But the deeper point which this is trying to operationalize is “vaccine design just isn’t that hard”, in the sense that we don’t need to test many designs to find one which works. People basically-know-how-to-design-vaccines, maybe not to quite the same extent as people basically-know-how-to-design-bridges, but to enough of an extent that experimental verification just isn’t necessary in order to get a >50% chance that the design works, especially for relatively-mechanical designs like mRNA or peptides.
Under this view, the reasons we don’t see nearly-every vaccine trial succeed are (1) commercial vaccines are harder than lab (especially if you want no boosters, easy logistics, etc), and (2) diseases which are harder-than-average will naturally end up with disproportionately many trials, and (3) out-of-date companies take time to die off.
The in vitro testing had already been done before those two days; they had the basic structure of the vaccine known, so once they had a virus sample they could fill in the blank (the spike protein of this particular virus rather than another in its ‘family’) with high confidence that it would work. One of the two days, IIUC, was spent synthesizing a sample vaccine and running some very-short-term tests.
This, again, has only simulation to support that it’s hitting the correct target at all. There is no indication that any of that has been done, by the authors or anyone else; IIUC there is not a clear path for doing short-term tests for this type of vaccine.
Also, it’s not my background knowledge that you should be comparing to, it’s Sarah’s. And I literally believe there is no one in the world who can be more trusted to reason clearly, well-informedly, correctly, and with humility and arrogance in their respective correct places than Sarah Constantin. Evaluating biomedical research has been her job for many years, with some gaps, and she’s really good at rationality, Aumann-level good. The bare fact that Sarah C thinks this is very unlikely to work is conclusive on its own.
How does the “vaccine design just isn’t that hard” align with these points?
a) Average time to develop a vaccine for a new virus is many years
b) There is still no HIV vaccine after 35 years of well-funded research
c) Until a few months ago, there were no approved coronavirus vaccines for humans
I’m prepared to accept that “bureaucracy” is the main cause for the delays in standard big company vaccine development and approval.
But if it’s easy to develop vaccines, why has there been no coronavirus vaccine previously? Why is there still no vaccine for SARS 1 or MERS or the common cold? Why was this Radvac idea or something similar not rolled out pre-Covid? (or was it? maybe nasal vaccines are easier?)
Anyway, I’m just stuck on the logical conflict between “it’s easy to develop a coronavirus vaccine” and “we’ve never had one (approved) before.” Any thoughts?
Good questions.
First, I expect a disproportionate number of vaccine trials are for “unusually difficult” viruses, like HIV. After all, if it’s an “easy” virus to make a vaccine for, then the first or second trial should work. It’s only the “hard” viruses which require a large number of trials.
I expect this is still mainly a result of regulatory hurdles. Clinical trials are slow and expensive, so there has to be a pretty big pot of gold at the end of the rainbow to make it happen. Also, companies tend to do what they already know how to do, so newer methods like mRNA or peptide vaccines usually require a big shock (like COVID) in order to see rapid adoption.