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How an Alzheimer’s ‘cabal’ thwarted progress toward a cure

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Re: How an Alzheimer’s ‘cabal’ thwarted progress toward a cure

#301

Post by wtallis »

roenxi wrote: post #281
keeganpoppen wrote: post #233

Earlier quoted context omitted.

looks like that day isn't today, given the downvotes xD in fairness, i think people have a hard time taking claims like this seriously without a little more information, due to its superficial similarity to those of a "crackpot". (but while the _precision_ is pretty poor on the correctness of "crackpot" theories, the _recall_ is pretty much 100% ) arguably > 100%, to be a bit tongue-in-cheek

Even more information wouldn't really help. 'Crackpot' is something of a shorthand for an idea that disagrees with consensus research position. The only tool an average person has to determine an idea as truth or fiction is whether it lines up with the current professed norms; so for a technical forum like HN ideas that disagree with the standard research position can only be ignored due to lack of evidence.

> The only tool an average person has to determine an idea as truth or fiction is whether it lines up with the current professed norms; so for a technical forum like HN ideas that disagree with the standard research position can only be ignored due to lack of evidence.

The manner in which someone presents their ideas is a decent secondary indicator. Common red flags include being evasive about what disease they're referring to, being unable to demonstrate where the mainstream theory fails, being unable to point to any good experimental evidence that even hints that the crackpot theory may be an equal or better explanation, not being able to anticipate and have a good answer for the most obvious questions raised by the crackpot theory.

Re: How an Alzheimer’s ‘cabal’ thwarted progress toward a cure

#302

Post by wtallis »

hitekker wrote: post #299
wavepruner wrote: post #285

Earlier quoted context omitted.

Thanks for the summary. (edit: although I do not think CFS is an appropriate diagnosis as it doesn't even come close to describing all the symptoms.) I led with the details on a different account. My karma was destroyed and afaict my posting privileges were revoked for posting too frequently with explanations. I don't think you understand the huge amount of anger that some people have towards people like me saying me…

Thank you for the context, but I wouldn't defend yourself in this thread: you already have one person narrating your posting history, and another cursing at you (in seeming rage) for not oversharing. Who would have thought that, on HN of all places, a request for privacy would be interpreted as a license for abuse?

When you claim to have superior knowledge than the medical establishment and allege that there's a "cabal" in opposition to your miracle cure, you cannot expect to be taken seriously while withholding information. That's a very clear "put up or shut up" situation.

Re: How an Alzheimer’s ‘cabal’ thwarted progress toward a cure

#303

Post by dhimmel »

barmstrong wrote: post #298
cockatiel_day wrote: post #187

This article is 100% true. My first job out of college 10 years ago was in a lab focused on Alzheimer’s research. Our Principle Investigator made an art of writing grant applications for studies that would appear to be in line with mainstream theory, but were really intended to test theories he actually thought were worth testing, presented in results as an “interesting” aside. He believed the amyloid theory had been…

Sorry to hear that this was the case! I wrote about how scientific research is broken earlier this year, and what you're describing is one of the most pernicious. https://medium.com/@barmstrong/ideas-on-how-to-improve-scien... https://www.researchhub.com/about is a project I'm helping get off the ground which hopefully can help this problem, by eventually replacing the traditional journals. Still early days (just bet…

At some level, any system for evaluating research will have to rely on peer assessment. And some amount of groupthink is inevitable with peer assessment.

But the ResearchHub model of open collaborative assessment could have provided more incentives and visibility for research that deviated from the beta amyloid hypothesis.

It sounds like gatekeepers were a large problem here... i.e. peer reviewers for journals or grants that were insistent on beta amyloid. Disentangling dissemination from assessment (as preprints are doing) will help bring contrary findings to the light.

We also need to make all assessment public. Rather than basing the validity of a study on a few anonymous unpublished reviews, let anyone provide feedback and increase the sample size and diversity of assessment. Finally, add some incentives for contrarians who advance unpopular hypotheses that time proves correct.

Anyways, lot's of thoughts, but I agree a radical shift in how scientists communicate could help get to the root of the hivemind described in the article and by @cockatiel_day.

Re: How an Alzheimer’s ‘cabal’ thwarted progress toward a cure

#304

Post by mirimir »

hitekker wrote: post #292
mirimir wrote: post #235

Earlier quoted context omitted.

How about "The beta-amyloid paradigm thwarted progress toward an Alzheimer’s cure"?

I disagree. The article articulates a political problem, not an error in reasoning. These few scientists did not just choose a stable approach that later turned out to be wrong: they doubled-down, tripled-down on a shakey guess for decades and suppressed voices to the contrary. The seemingly credentialed, respected, and authoritative experts of Alzheimer's sabotaged the science around a hot-button problem for their o…

That's why I suggested "paradigm". Because that includes all the political stuff. Not just a widely accepted hypothesis.

Re: How an Alzheimer’s ‘cabal’ thwarted progress toward a cure

#305

Post by darkerside »

nextos wrote: post #291
el_cujo wrote: post #283

Earlier quoted context omitted.

This has been my experience more-or-less as well. Any graduate student that does anything even alzheimer's adjacent at the school I used to work at absolutely had to have a certain two researchers on their dissertation committee and they would 100% not let you progress without throwing a bone to beta-amyloid in your proposal (along with heavily pushing you to pander to some of their personal pet theories). It's a sun…

It's the same with autoimmunity. Some researchers are obsessed with genetics. But it's mostly about self misclassification due to infections and dysbiosis. Luckily, some top journals have started accepting this, but it's still an uphill battle against the establishment: * Type 1 diabetes: https://www.biorxiv.org/content/10.1101/2019.12.18.881433v1 * Multiple sclerosis: https://stm.sciencemag.org/content/10/462/eaat43…

Are you saying many diseases we believe to be autoimmune may be caused by infections?

Re: How an Alzheimer’s ‘cabal’ thwarted progress toward a cure

#306

Post by darkerside »

roenxi wrote: post #281
keeganpoppen wrote: post #233

Earlier quoted context omitted.

looks like that day isn't today, given the downvotes xD in fairness, i think people have a hard time taking claims like this seriously without a little more information, due to its superficial similarity to those of a "crackpot". (but while the _precision_ is pretty poor on the correctness of "crackpot" theories, the _recall_ is pretty much 100% ) arguably > 100%, to be a bit tongue-in-cheek

Even more information wouldn't really help. 'Crackpot' is something of a shorthand for an idea that disagrees with consensus research position. The only tool an average person has to determine an idea as truth or fiction is whether it lines up with the current professed norms; so for a technical forum like HN ideas that disagree with the standard research position can only be ignored due to lack of evidence.

Hard disagree. Science is great, but logic is greater.

Re: How an Alzheimer’s ‘cabal’ thwarted progress toward a cure

#308

Post by Dylan16807 »

zosima wrote: post #248
memling wrote: post #211

Earlier quoted context omitted.

Derek Lowe's comments on the reboot were understandably a bit skeptical: > [W]hile the new larger EMERGE data do look like there’s a dose-responsive effect in the primary measurement (the CDR-SB scale) and three secondary dementia scores, the ENGAGE data actually show worse than placebo for CDR-SB at the higher dose (see slide 19 in Biogen’s presentation). They’re also worse than placebo in the MMSE scoring, but both…

Different dementia rating scales may give different results because the study is underpowered for the effect, and/or Aducanumab is only effective in a subset of patients. There is something to suggest that the latter is the case. The MMSE score usually becomes low relatively late in dementia. The questions are easily solvable for most non-affected people [1] and the cognitive impairment must be quite severe for a sig…

> Different dementia rating scales may give different results because the study is underpowered for the effect, and/or Aducanumab is only effective in a subset of patients.

Though if a couple thousand people is underpowered for the effect, that's not a great sign for the drug.

Re: How an Alzheimer’s ‘cabal’ thwarted progress toward a cure

#309

Post by temac »

dnautics wrote: post #197
temac wrote: post #127

Earlier quoted context omitted.

Your source for the belief tha Iraq had WMD is an article explaining they had yellowcake? Even a youtuber made some and processed it (and this was completely legal)

Yes? That was, after all, concretely the claim made by the administration before the invasion (recall the joke by Dave Chappelle about yellow cake) There's also plenty of evidence that Iraq had (known, small) stockpiles of chemical weapons, too (last I checked those were classed as WMD), which are widely accepted to be a likely cause of gulf war syndrome and a contributing factor to congenital disease in some parts o…

If you are thinking about the fear of contraband imports of yellowcake, well none of that has ever been found and its highly unlikely to have existed. The removed yellowcake had been stockpiled prior to the first Gulf War, and was declared to the International Atomic Energy Agency and under IAEA safeguards.

Of course at one old point Iraq had WMD programs. But you were completely misrepresenting the situation by stating for the later period that "The funny thing about that conspiracy is that the WMD were real. Hussein had them, and and its true that he didn't give them up". Even the very article you linked stated clearly: "There was no evidence of any yellowcake dating from after 1991, the official said." As for the small amount of chemical weapons or precursors, they also have not been interpreted afterwhile has having any significance regarding the willingness to comply.

Re: How an Alzheimer’s ‘cabal’ thwarted progress toward a cure

#310

Post by nextos »

darkerside wrote: post #305
nextos wrote: post #291

Earlier quoted context omitted.

It's the same with autoimmunity. Some researchers are obsessed with genetics. But it's mostly about self misclassification due to infections and dysbiosis. Luckily, some top journals have started accepting this, but it's still an uphill battle against the establishment: * Type 1 diabetes: https://www.biorxiv.org/content/10.1101/2019.12.18.881433v1 * Multiple sclerosis: https://stm.sciencemag.org/content/10/462/eaat43…

Are you saying many diseases we believe to be autoimmune may be caused by infections?

Yes. Or dysbiosis, i.e. your own commensal bacteria, fungi and phages going out of control in different ways. The consequence of this in both cases is that your immune system mis-classifies some of your own tissues as non-self and attacks them (autoimmunity). See introduction in:

https://www.biorxiv.org/content/10.1101/2019.12.18.881433v1

The reason is that both pathogens and your own microbiome mimic your tissue components. Especially proteins. They want to avoid being recognized as non-self, either to infect you or to keep their symbiotic relationship.

Hence, in some scenarios it's hard for the immune system to classify a virus or a commensal as foreign and the mimicked tissue in your own body as self at the same time.

The first reference in my previous post explains it well. Viral mimicry is quite old and well established in the literature both as an infection strategy and as a cause of autoimmunity [1-3]. But microbiome (commensal) mimicry is surprisingly unexplored, except for a few recent studies. Some are those I referred to in my previous post.

Note in many ways tumors are also an immune problem. They should have been caught by the immune system. There is growing evidence that this is also related to mimicry and dysbiosis.

[1] https://link.springer.com/chapter/10.1007/978-3-642-74594-2_...

[2] https://www.nejm.org/doi/full/10.1056/NEJM199912303412707

[3] https://science.sciencemag.org/content/279/5355/1344

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