[pessimizer]

> Who will read nine paragraphs that I think are necessary context for all of this?

They are very interesting, but I'd have to be convinced that they were necessary context. Because the question that I think is important is whether this was true and widespread:

> I think there are a lot of people who feel like they were locked out of funding opportunities because of the focus on amyloid-beta. Maybe this is true, I don’t know.

And you don't know. I don't know either.

We can't say that anything would be farther along if these frauds had not happened, because that is a counterfactual. We can just guess that if we spend resources in areas that didn't have as much fraud surrounding them, we would be more likely to be farther along. Any argument otherwise is an argument that the direction and funding of research doesn't ever really matter.

I don't think any avenue of research should be abandoned if anybody still sees any possible value in it. But I know that funding decisions heavily influenced by fraudulent research are not going to be better made than decisions not influenced by fraud; and that if we were making decisions based on fraud over a long period of time, it is safe to assume that there was a loss. If we want to be less likely to repeat this loss, we probably need to change how we evaluate where to allocate funding.

[bartathe]

Thank you for your comment. I am not saying the field was not stalled because of these frauds, I am saying I do not think it was significantly stalled. I think fraud is an easy scapegoat for broader issues, especially when the case that people keep referring to is whether a single amyloid beta oligomer species is involved. There are some very esteemed researchers who do not believe oligomers are physiologically relevant or discrete enough to be analyzed at all. I am trying to point out the ways that "amyloid hypothesis" actually refers to many distinct things to try to prevent very non-specific reactions like another comment that replied to me had, where we decide to throw out amyloid research entirely for chronic inflammation, etc.

If we want less fraud, we need less incentives for fraud. What do you think the easiest route to take is when funding in a field that already attracts some nutso people is cut every year? That so little fraud happens is a testament to the integrity of most scientists. I grew up part of an ascetic religious sect. The personality types of many scientists in the field are that of the hermits I knew as a child. You probably cannot totally get rid of fraud, some people cannot really seem to produce anything themselves, they exist, they will find some way to survive (often better than those who are not this way). You can keep rates of fraud low, but if you think it is more prevalent than it is, you risk developing a social autoimmune disease. Remember that means-testing has its own costs, too.

[thereticent]

It's also my field. One clarification I would make is, I think, foundational. The amyloid research that was famously falsified was not the mainstream "amyloid hypothesis" research. It was a very niche subset, as GP described.

As for people feeling shut out of funding: people feel a lot of things all the time, but I've never seen a good idea be repeatedly denied funding because it wasn't amyloid-primary. Unfortunately, it's usually a lack of rigor, lack of pertinence, lack of preliminary data demonstrating plausibility and feasibility, or some combination. Not always--there are big money and prestige politics going on all the time, but that has nothing to do with amyloid.

To add another nearly useless data point, my lab and those I collaborate with focus on amyloid as well as tau, alpha-synuclein, TDP-43, microvascular changes, and inflammatory contributions. Metabolomics, proteomics, and transcriptomics are other big systems biological approaches. Not to mention social determinants of health, which are also massive.

All that said, I'll read the book, but the "daring journalist finds a crew of whistleblowers" framing strokes me as either ignorant or disingenuous. Off-putting either way, as we face major cuts to public funding of health science, which has overall been an extremely generative and sustainable model for improving national and world health.

[daveguy]

> I think there are a lot of people who feel like they were locked out of funding opportunities because of the focus on amyloid-beta. Maybe this is true, I don’t know.

...

You completely excluded the last sentence of the quote by the GP. That sentence at least partially addresses your concern:

> The lab I’m in has worked on tau for decades.

The lab the GP is working in has been, for decades, funded and working to study ameloid tau -- one of the very alternative hypotheses that are under study. Most of the entire post was about all the other hypotheses that are active and regularly funded.

No one is omniscient, no one can know exactly the right set of funding to get the optimal scientific outcome with the least amount of money. That omniscience isn't going to happen no matter how awesome AI is.

The best course for medical breakthroughs is to fund multiple hypotheses at once which is exactly what NIH does. The more funding to allow research into various hypotheses the better. Whatever it is doge is doing straight shutting shit down is the incompetent fools course plotted by megalomaniacal and ignorant billionaires.