[epistasis]

> the very disease mechanism concept underlying the vast majority of research and interventional trials into which countless multiple billions have been poured, is incorrect.

Not "is incorrect," but might be incorrect. And we almost certainly won't know it is correct until we actually have a therapy.

Those pursuing cures could have waited until there was more solid science, but they and their funders took on the risk, knowing full well that the amyloid hypothesis is not proven.

This is not some indictment of science, this is normal risk taking for a problem that hugely affects society.

[smolder]

> Not "is incorrect," but might be incorrect.

That's why the part you quoted is preceded by "the possibility that".

[epistasis]

But the entire framing of the comment is that the amyloid hypothesis is taken as fact and not possibility, when in fact the core research question is whether it is true or not.

It is the best possible explanation so far, but four decades of research have not reached a definitive conclusion.

An open problem is not a problem for science, that's the fundamental focus of science. The problem is people misrepresenting what science is and what it aims to do.

[mft_]

(Late back to this but) It's far more skewed than you're making out. That the a-beta hypothesis is true, is/was the vastly dominant prevailing belief in the field, to the extent that it hasn't been a question that many 'experts' were willing to meaningfully address.

To be clear: for decades, researchers wishing to pursue lines of inquiry contrary to the a-beta hypothesis struggled for traction and funding, and saw their careers struggle as a result[0]. As such, trying to disprove the a-beta hypothesis was not the core research question for many/most, for long time.

[0] https://www.statnews.com/2019/06/25/alzheimers-cabal-thwarte...

[epistasis]

(Edit: forgot to say, thanks for continuing the conversation, it is much appreciated! This comment may come across snippier than I intended, but please know I appreciate your effort here even though my experiences lead me to a different conclusion.) This article is just sensationalization of the standard scientific process. Grants do get awarded by friends and it does appear very much like a cabal. Or things like this:

> A top journal told one that it would not publish her paper because others hadn’t.

Oh the horror, not getting published in a top journal! Turns out that most good science gets published outside the top journals.

This sort of behavior is bad, and has always been part of the process, and may actually be better today than it was a century ago, as the clubs are not nearly so tight as they were back then.

Early in my career I remember reading some of ET Jaynes' (an early Bayesian reasoning guy) discussions of his early career, and how he had to very very carefully choose his topics so that he wouldn't upset the big personalities in physics and thereby have his entire career crushed. It's better these days than it was then!

There will be sour grapes about funding, just as there are when VCs all jump on the hype train for the same idea, but my only scientific exposure to the amyloid hypothesis for the past 20 years has been in terms of it being an unproven hypothesis. Starting down exploratory routes for explanatory hypotheses should have been pursued, and was pursued, and will continue to be pursued, but the question of "how much" is exceptionally difficult to answer.

Perhaps I'm biased from being in Science too long, but I've seen so many sensational Stat News article that never pan out when pushed upon. I wouldn't trust them at all with stuff like this.

[epistasis]

Ok, this is awful, and clearly goes much deeper, and I'm starting to be very convinced of your position:

https://www.science.org/content/article/misconduct-concerns-...