>> the evidence for it was obviously good enough to convince a large number of people to spend a decade or more on it
> This doesnt mean much to me. If thats where the funding is then people will link their research to it. If NIH is about "aging" this year then you change your grant to use "aged rats", or somehow link your study to "climate change" or whatever.
I don't mean doing research with grant money, I mean that hundreds of people at half a dozen or more companies spent billions of dollars of private funding and at least a decade of their lives to develop drugs based on the amyloid hypothesis. That means that the evidence was good enough, or the evidence for any alternatives bad enough, to speculate on. Drug development is always speculative, but it's not crazy or irrational. And it's not a lack of quantitative thought, either; it's speculation.
But my purpose here wasn't to defend the evidence (as you seem to want me to do), it was merely to point out that for all this time "the" amyloid hypothesis (again, it's a family of hypotheses because each drug has a different intended mechanism of action and is therefore a different testable hypothesis) has been the only workable theory of how the disease works. Thus someone used the word "unthinkable", which you objected to. He clearly didn't mean it literally, since people have actually thought about alternatives, so it must have been hyperbole. Since he probably agrees with you that the evidence is weak in absolute terms, I don't see why you would object to the hyperbole. I pointed it out because your question (which was "What made it so previously unthinkable?") indicated that you were taking the word literally.
>'"the" amyloid hypothesis (again, it's a family of hypotheses because each drug has a different intended mechanism of action and is therefore a different testable hypothesis) has been the only workable theory of how the disease works.'
Afaict, there was nothing especially workable about it vs eg the "cholinergic hypothesis". In fact the only drugs that are said to help were devised based on that hypothesis.[1] So something else is going on here.
> This doesnt mean much to me. If thats where the funding is then people will link their research to it. If NIH is about "aging" this year then you change your grant to use "aged rats", or somehow link your study to "climate change" or whatever.
I don't mean doing research with grant money, I mean that hundreds of people at half a dozen or more companies spent billions of dollars of private funding and at least a decade of their lives to develop drugs based on the amyloid hypothesis. That means that the evidence was good enough, or the evidence for any alternatives bad enough, to speculate on. Drug development is always speculative, but it's not crazy or irrational. And it's not a lack of quantitative thought, either; it's speculation.
But my purpose here wasn't to defend the evidence (as you seem to want me to do), it was merely to point out that for all this time "the" amyloid hypothesis (again, it's a family of hypotheses because each drug has a different intended mechanism of action and is therefore a different testable hypothesis) has been the only workable theory of how the disease works. Thus someone used the word "unthinkable", which you objected to. He clearly didn't mean it literally, since people have actually thought about alternatives, so it must have been hyperbole. Since he probably agrees with you that the evidence is weak in absolute terms, I don't see why you would object to the hyperbole. I pointed it out because your question (which was "What made it so previously unthinkable?") indicated that you were taking the word literally.