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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

#241

Post by internet_user »

dccoolgai wrote: post #165
dekhn wrote: post #159

Earlier quoted context omitted.

"""feeding into the narrative that science is just another competitive team sport where people compete with whatever means necessary is downright dangerous.""" This is precisely what modern science is (well, a major subset). The competition for grant funding and attention space is extremely intense. I agree there was no "alzheimer's cabal" but it's not uncommon in science for the prevailing mainstream position to (in…

Interesting... Are there any current issues you can think of in academia where disagreeing with the prevailing opinion can make one a pariah... Even, perhaps, assigned an epithet like "denier"? I think whenever this happens in academia/science, it is incredibly dangerous. Proper science invites and celebrates denial - seeks to deconstruct it and understand it to be more certain of the truth. The mere presence of any…

Literally anything that contradicts your bosses position.

a.n.y.t.h.i.n.g

I've watched very experienced, top school trained MDs freeze up and begin to stutter, as they've just realized they said something their lab chief does not like.

Coincidentally, that chief writes treatment guidelines and consults the FDA, and is probably one of the most powerful physicians in the profession.

Medicine is a very hierarchical top-down command structure type of field.

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

#242

Post by greglindahl »

quantified wrote: post #237
knzhou wrote: post #232

Whenever you hear about science being a "cabal", you have to remember that there's a huge survivorship bias. At any moment in science, there are a few dominant hypotheses, which seem to work pretty well, and hundreds of alternative hypotheses, with only vague evidence in favor of them. The vast majority of alternative hypotheses turn out to be completely wrong, and the researchers pushing them are forgotten. The few…

Recall the saying that science proceeds one funeral at a time. I believe it was coined as part of describing the shift to acceptance of plate tectonics.

That's the worst case. It doesn't always proceed that slowly.

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

#243

Post by internet_user »

JimBrimble35 wrote: post #219

"“Once a field commits to a particular hypothesis, the research resources — funding, experimental models, and training — all get in line,” she wrote in a 2018 analysis. That brings backers of the dominant idea accolades, awards, lucrative consulting deals, and well-paid academic appointments. Admitting doubt, let alone error, would be not only be a blow to the ego but also a threat to livelihood." Is this not extreme…

How is that controversial? That's just people for you.

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

#244

Post by internet_user »

wavepruner wrote: post #226
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…

"I suspect this dynamic is not limited to Alzheimer’s research." Agreed, I think it is a universal problem in science. I have an illness that has been curable for decades now, but this cure is treated with hostility by the medical establishment. I look forward to the day when the cabal of my illness collapses. Hopefully then I will be able to talk about what happened without people getting angry.

Lyme? You were able to clear long-term post-lyme with i.v. abx?

I am interested to hear what you have to say.

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

#245

Post by internet_user »

derefr wrote: post #179
leftyted wrote: post #155

Earlier quoted context omitted.

> In this day and age, feeding into the narrative that science is just another competitive team sport where people compete with whatever means necessary is downright dangerous. I think that narrative is correct. We can't fix the problem if we don't discuss it. The whole "I believe in science" thing (which you seem to be pushing) is really quite silly. Funding is a political game and the people who are best at politic…

You’re talking about scientific academia, not science. Much of science occurs outside of academia. Military and industrial scientific R&D, corporations’ basic-research labs, independents, etc. It’s only in scientific academia that these “strictly adhere to the popular scientific paradigm in order to get published” worries exist.

Where do you think military R&D occurs?

They fund universities like anyone else. Yes, there is some internal research, but even in fields like math, where NSA probably does a lot of internal reseach, you still have classified top-secret research performed in public universities.

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

#246

Post by internet_user »

shakil wrote: post #216
dccoolgai wrote: post #165

Earlier quoted context omitted.

Interesting... Are there any current issues you can think of in academia where disagreeing with the prevailing opinion can make one a pariah... Even, perhaps, assigned an epithet like "denier"? I think whenever this happens in academia/science, it is incredibly dangerous. Proper science invites and celebrates denial - seeks to deconstruct it and understand it to be more certain of the truth. The mere presence of any…

Dr Atkins invited the wrath of the medical community because he pushed for a low carb, high fat diet at a time when the medical consensus was that fats are the root of all evil. They eventually took his license for some unrelated issue but the driving force was the fact he went against the medical establishment and ridiculed low-fat but high-carb diets

I thought his license was only pulled temporarily and was reinstated?

Did he end up permanently losing it?

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

#247

Post by halfjoking »

g42gregory wrote: post #47

An honest question: How does this compare to the group-think in the climate change/global warming research? Are we similarly rejecting funding to any research that does not fit into the common consensus? The fact that we call some people "climate change deniers" tells me that we have an unhealthy dynamics going on there. Will it take 30 years to get to the same point?

In 30 years we'll all be dead.

Since the IPCC is worried about being too "alarmist" and other external pressures no one is investigating the plausible scenarios where CO2 increases exponentially in the next 20 years. The amount of potential feedbacks that could cause rapid climate change are alarming.[1] If anything group-think is making it so we're not taking enough action.

[1] http://arctic-news.blogspot.com/p/feedbacks.html

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

#248

Post by zosima »

memling wrote: post #211
zosima wrote: post #143

Earlier quoted context omitted.

FDA usually puts some quite strict limits on the amount of p-hacking and general shenanigans they allow in clinical trials. But there's no approval yet, and no data to look at, so it's too early to judge. Anyway, usually Alzheimer trials are a jumble of noise. The cognitive measurements are imperfect and patients are improving and deteriorating randomly, taking a very different disease course than you'd expect from t…

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 significant drop. ADAS-COG on the other hand is more sensitive, especially in early disease [2]. It would be plausible then that patients in an early dementia stage treated with a higher dose, respond, while patients in a later disease stage can not be treated using Aducanumab. (Maybe it even has a paradoxical detrimental effect in late-stage dementia, who knows?)

I would hope that they dig down in the data and find an objectively identifiable subpopulation where there appears to be significant effect, and rerun a phase III trial on that subgroup. Even if they only can treat a subset of Alzheimer patients, that's a very significant breakthrough.

[1] https://www.bgs.org.uk/sites/default/files/content/attachmen...

[2] https://www.ncbi.nlm.nih.gov/pubmed/12079572

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

#249

Post by mirimir »

snowwrestler wrote: post #201
leftyted wrote: post #155

Earlier quoted context omitted.

> In this day and age, feeding into the narrative that science is just another competitive team sport where people compete with whatever means necessary is downright dangerous. I think that narrative is correct. We can't fix the problem if we don't discuss it. The whole "I believe in science" thing (which you seem to be pushing) is really quite silly. Funding is a political game and the people who are best at politic…

Scientific funding is a political game only to the extent that the politics are not contradicted by evidence. For example, no matter how good you are at scientific politics, you're not going to get the NSF to give you $1 billion to test whether the Earth is flat, or if gravity is actually caused by little fairies pushing us all down toward the ground. Why? Because, at least for public scientific funding, it is bad po…

> gravity is actually caused by little fairies pushing us all down toward the ground.

That's not entirely distinguishable from gravitons in quantum gravity. Or, for that matter, photons.

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

#250

Post by narag »

quantified wrote: post #237
knzhou wrote: post #232

Whenever you hear about science being a "cabal", you have to remember that there's a huge survivorship bias. At any moment in science, there are a few dominant hypotheses, which seem to work pretty well, and hundreds of alternative hypotheses, with only vague evidence in favor of them. The vast majority of alternative hypotheses turn out to be completely wrong, and the researchers pushing them are forgotten. The few…

Recall the saying that science proceeds one funeral at a time. I believe it was coined as part of describing the shift to acceptance of plate tectonics.

... the shift to acceptance of plate tectonics

Of all things. My favourite odd anecdote of the year.

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