> There’s been a long-running Internet movement to cast the beta-amyloid and beta-amyloid/tau hypotheses as an evil plot by scientist
No one was twirling their mustache trying to make people suffer. Someone had a lab, and prestige and control over funding and the best way to keep it all was by being dishonest. That negatively affected progress in the field. You can call it "evil" if you want, but more objectively it was unaligned incentives. The corruption was covered in mainstream news, it's not a conspiracy theory. Since the scandal got out, the speed of progress has improved significantly.
It was a concerted and intentional effort to fake data and falsify research into a pervasive deadly disease, specifically in order to hoard funds going to research they knew was, if not a dead end, at least not nearly as promising as they were claiming, preventing those funds from going to other research groups that might actually make progress, essentially stealing donations from a charity, and using their power and clout to attack the reputations of anyone who challenged them. They directly and knowingly added some X years to how long it will take to cure this disease, with X being at least 2 and possibly as much as 10. When Alzheimer's is finally cured, add up all the people who suffered and died from it in the X years before that point, and this research team is directly and knowingly responsible for all of that suffering. Yes, I think I will call it absolutely fucking evil.
Yes, I share some of your concerns about groupthink and research cliques. The best and balanced critique is Karl Herrup’s book at MIT Press: “How Not To Study a Disease”.
Your comment is over the top with respect to NIH-funded researchers doing Alzheimer’s research. The emotion would be entirely appropriate if directed at RJ Reynolds Inc. and other cigarette companies or Purdue Pharma. Those are evil companies that many governments have tolerated killing for profit—Purdue Pharma and the OxyContin disaster alone about 500,000 Americans over 20 years; and US tobacco companies contribute to about as many excess deaths per year.
The systematic image manipulation by a postdoctoral fellow, Dr. Sylvain Lesné, was egregious and worthy of jail time but he was a truly exceptional case and polluted 20 or more papers that did distract the entire field. You can read all about it here.
PMID: 35862524
Piller C. Blots on a field? Science. 2022 377:358-363.
doi: 10.1126/science.add9993
Again, I urge you to read this article and stop promoting conspiracy nonsense. I take this very personally because my mom has this disease, and people who clearly don't understand what they're talking about fuming about conspiracies really doesn't help anyone, and probably hurts them immeasurably. https://www.astralcodexten.com/p/in-defense-of-the-amyloid-h...
I can't guess what point you're trying to make with a long article that acknowledges the fraud in the beginning, and then rehashes the initial reasons for looking into the amyloid hypothesis. No one is claiming it was stupid to look into the amyloid hypothesis. They are complaining that it hasn't been the most promising theory in quite a long time, and it was fraudulently held as the most promising. Other theories, arguably more promising, are listed throughout your article.
There is a testable prediction in your article. Unfortunately, I don't think the mechanism is quite restricted enough. TFA says that repairing the BBB helps amyloid plaque clearance. Would the author of your blog post claim that as a win, or admit that the plaques are downstream of the problem, and that BBB integrity is closer to the root cause of the disease process?
Unfortunately, I don't think the mechanism is quite restricted enough. TFA says that repairing the BBB helps amyloid plaque clearance. Would the author of your blog post claim that as a win, or admit that the plaques are downstream of the problem, and that BBB integrity is closer to the root cause of the disease process?
The author of that blog post, for whom I am in an excellent position to speak, would point to the "sole intended mechanism" clause in the testable prediction. That is, if the therapeutic's developers do not claim any other intended pathway for clinical benefit from improved BBB integrity other than amyloid−β clearance, then it would count. If not, then it would not count, even if it's plausible or even likely that that's the main pathway by which the benefits are accruing.
However, because this is early preclinical research, it's not likely to reach a late-stage clinical trial within the 12-year window of the author's prediction. Furthermore, in every year there are about a dozen of these preclinical studies that go viral for some reason or other, often having little correlation with how promising the science is. I haven't had a chance to look into this one in detail, so this isn't a negative comment about it, but the base rate of this stuff panning out is low, even if it's good research.
The author of that article would also point out that the concept of "the root cause" isn't terribly well-defined, but that strong evidence points to amyloid pathology as the common entrypoint in all cases of Alzheimer's disease, even if multiple upstream factors (some possibly relating to the BBB) can feed into that, depending on the specific case. Similarly, calorie surplus causes obesity in nearly all cases, but the specific cause of calorie surplus may vary from person to person.
I can't guess what point you're trying to make with a long article that acknowledges the fraud in the beginning, and then rehashes the initial reasons for looking into the amyloid hypothesis. No one is claiming it was stupid to look into the amyloid hypothesis. They are complaining that it hasn't been the most promising theory in quite a long time, and it was fraudulently held as the most promising. Other theories, arguably more promising, are listed throughout your article.
A correction: the article does discuss other hypotheses, in pointing out that they can't account for crucial evidence, whereas there isn't any major evidence the amyloid hypothesis seems to have trouble accounting for, and it thus remains very strong.
> No one was twirling their mustache trying to make people suffer. Someone had a lab, and prestige and control over funding and the best way to keep it all was by being dishonest.
The second sentence and the first sentence are merely literal and figurative descriptions of the same activity.
Also, for this to be true, it has to mean lab workers knew about progress but fucked over their own family with Alzheimers. And it has to mean every single one of them did this.
*Edit* Actually there's another way to interpret what you wrote. My mistake. I imagined a scenario where someone knew of progress and was dishonest by hiding it, but you might've been alluding to someone knowing an avenue wasn't fruitful but was dishonest by making it seem more fruitful.
I think the latter is easier to hide than the former since it doesn't require directly fucking over your family, merely very indirectly by siphoning off a fraction of total funds to be flushed down the toilet.
The latter is what happened, for upwards of ten years. And it wasn't a small fraction of the funding -- almost no funding was allocated to any research not looking at amyloid plaques, because the intellectual giants' (falsified) research was showing that that was by far the most promising avenue to explore.
Again, there were a couple of instances of fraud in one sub-branch of a sub-branch of a field ages ago, and The Internet has decided to turn it into a conspiracy theory.
On the off chance that you're actually a decent, honest person, I urge you to actually go learn about this theory that you're promoting. Go out and actually figure out the truth, because if it turns out that you're wrong about the impact and intentions, you're helping to harm a lot of people.
No one was twirling their mustache trying to make people suffer. Someone had a lab, and prestige and control over funding and the best way to keep it all was by being dishonest. That negatively affected progress in the field. You can call it "evil" if you want, but more objectively it was unaligned incentives. The corruption was covered in mainstream news, it's not a conspiracy theory. Since the scandal got out, the speed of progress has improved significantly.