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

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.

It's a sunken cost fallacy at this point, people have build entire careers on the beta-amyloid stuff and they will NEVER accept an alternative because it would make them irrelevant. These same people hold a lot of power in the field.

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 beta launched).

this is depressing, means I have to second-guess if I have found a cause to spend energy on

That’s a great quote. Pretty much any activity that humans are involved in are at risk for this type of behavior. Egos get involved and objectivity goes out the window.

You are responding to an article that very much puts it into question. You should read the article, it's not long. But it'll give some quotes:

“The amyloid hypothesis has been one of the most tragic stories [in] disease research,” said neurobiologist Rachael Neve of Massachusetts General Hospital.

And

Making it worse is that the empirical support for the amyloid hypothesis has always been shaky.

  But in 2019, evidence pointed the finger elsewhere: at
  Porphyromonas gingivalis, a type of bacteria involved 
  in gum disease. Research ... suggests that beta-amyloid
  is a symptom, not a cause of the condition. Instead, it
  may be the toxins released by P. gingivalis, called
  gingipains, that result in the brain damage that brings 
  on the disease.

(I posted the story earlier today [2], but it didn't end up on the front page.)

[1] https://www.newscientist.com/article/mg24432613-800-im-testi...

[2] https://news.ycombinator.com/item?id=21917192

The point is this: we do not have a cure for this dieases now.

Therefore, we do not know where to look at all.

Therefore the best approach is to look at everything possible, since we obviously have no idea where to look.

If we knew where to look, we would have atleast a partial cure.

But no cure works now, none.

1. A spinning top weighs less if it spins one way than if it spins the other

2. A "fifth force," IIRC it was linked to baryons

3. The climate is warming, not (as people thought) cooling

4. Superconductivity can be achieved at high (liquid Ln2) temperatures

5. Fusion can be achieved at low (room) temperatures ("cold fusion").

6. Homeopathic properties of water

7. Faster-than-light travel of neutrinos

In each case there was a rush for confirmation- tons of excitement in the field, etc. Some were confirmed; some debunked; some remain controversial. I read somewhere that Google is working on cold fusion?

How many failed clinical trials for amyloid reducing drugs does it take to see a significant possibility that we might need to explore other ideas?

People will happily invest other people's money in trials that will likely fail if it's the leading academic theory since they can shift the blame (lack of skin in the game). Academics will have built careers on amyloid research and so will destroy opposition, subconsciously controlled by their egos looking to protect themselves.

The incentives are not aligned to use the best exploitation, exploration ratio that might be used in the ideal case but instead heavily weighted towards exploitation ignoring negative results from clinical trials for extended periods of time.

Just one data point, but in my experience in academia that was almost exactly how I found it. The exception that it wasn't a team sport because there's only space for one first author.

My feeling is that the recognition and 'impactfulness' tied to being successful in academia are antagonistic to conducting unbiased research.

No one thought the weapons of mass destruction were fake and lied and said they were real.

The conspiracy was "These were simply people who were convinced they were on the right track." so did not allow competing theories.

Exactly the same with the VW emissions issue.

This is exactly how conspiracies and cabals work. They are emergent behaviour.

> In a sea of amyloid-focused grants, there are tiny islands of research on oxidative stress, neuroinflammation, and, especially, a protein called tau.

The Wikipedia article you cite:

> On examining her brain, he found senile plaques and neurofibrillary tangles [which are made of tau protein -- https://en.wikipedia.org/wiki/Neurofibrillary_tangle]

What you actually wrote:

> In 1911, Alois Alzheimer found plaques in his dementia patient's brain. These plaques are what researchers would focus on for more than the next 100 years.

You omitted the tangles and played up the plaques. It looks like you're part of the cabal!

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 politics tend to be the worst at research (and vice-versa). I think this is exacerbated by the fact that a lot of scientists are hangers-on, i.e. not capable of doing original research. These scientists are terrified of people who can do original research since it makes them look bad (and feel bad, it's actually depressing to think about all the people out there who are way smarter than me).

You can imagine funding schemes that attempt to account for these issues. "For every dollar of funding for interpretation A, earmark 25 cents for alternative interpretations". View science as a market, something beyond our powers to predict, then diversify your investments.

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 (intentionally or otherwise) suppress alternative opinions ("extraordinary ideas require extraordinary evidence" is often used to maintain the status quo).

One of the important issues is when an idea ends up dominating funding. If you have a legitimate alternative hypothesis but can't get the funding to run the experiments to provide that extraordinary evidence, you'll fail to convince people. The people who get the most funding are the ones who are the most competitive, not the smartest, or the rightest.

It is perfectly natural to fund science that seems like a good idea at the time, and not fund ideas that seem less plausible than the prevailing explanation, and while it does suck that it takes a while to overturn the idea that the idea is good, representing our 20/20 hindsight as some irredeemable inertia with conspiracist overtones is a big problem.

https://www.sciencemag.org/news/2019/11/colombian-woman-s-ge...

Better = more accurate and neutral, using representative language from the article.

>Reality is much more nuanced, and the article actually does a good job of detailing that.

It's bad to sow too much mistrust in science, sure, but it certainly feels like society right now is way too far in the opposite direction right now, with people blindly believing any headline following the phrase "a new study says..." or "scientists say...". A lot of scientific fields are very competitive for funding right now, there is immense pressure to twist every result into a "win" while equally important null results ("we tried X and surprisingly it did not worked") are basically treated as worthless.

People shouldn't blindly mistrust science, but blind trust is just as dangerous, the system right now is far from perfect. I believe most researchers still ultimately want to solve mysteries in nature and improve life, but they're also human beings who ultimately want to be able to keep working and provide for themselves and their families, these two motivations are not always perfectly aligned.

I heard someone recently tell me how using science to form views on topics (social/psychology/etc) is dangerous, because science is really about funding. AND large donors/entities who can fund science often pick science research projects that sound cool and sexy. They may not be pushing any agenda but do lean toward funding trendy ideas.

So really, science is often biased because of who hold the checkbooks. That really made me think.

...doesn't really make sense here.

Let's say it takes 20 years and 5+ institutions to fully explore a single avenue of research.

If you're 15 years into that research and you think there is a chance that you'll reach a breakthrough in 5 years, you're much more inclined to want your (and the other 4+ institutions) to pursue it for 5 more years rather than starting over.

That's not sunk-cost fallacy. It's more like "a bird in the hand is worth two in the bush" or perhaps confirmation bias (the inertia the scientists felt to discard their conclusions about the causes and treatment pathways for Alz).

The groupthink and publishing pressure are also problems, but they're very secondary to hellish career conditions.

Go read about the battles between Newton and Hooke or even Newton and Leibniz.

The doctor who first suggested washing hand to cut down on infections in the 1800s was ridiculed and mocked by surgeons.

Scientists who brought up germ theory were mocked as quacks by doctors and scientists who rigidly adhered to the miasma theory as gospel.

Of course white supremacy was accepted "scientific fact" for a very long time by academia and anyone who thought otherwise would have been viewed similarly to a flat earther today. You could argue that white supremacy would still be "scientific fact" were it not for ww2.

My personal favorite is Georg Cantor who was mercilessly attacked by his fellow academics within math and even without for his theories on infinite numbers.

"The objections to Cantor's work were occasionally fierce: Leopold Kronecker's public opposition and personal attacks included describing Cantor as a "scientific charlatan", a "renegade" and a "corrupter of youth".[8] Kronecker objected to Cantor's proofs that the algebraic numbers are countable, and that the transcendental numbers are uncountable, results now included in a standard mathematics curriculum. Writing decades after Cantor's death, Wittgenstein lamented that mathematics is "ridden through and through with the pernicious idioms of set theory", which he dismissed as "utter nonsense" that is "laughable" and "wrong".[9][context needed] Cantor's recurring bouts of depression from 1884 to the end of his life have been blamed on the hostile attitude of many of his contemporaries,[10] though some have explained these episodes as probable manifestations of a bipolar disorder"

https://en.wikipedia.org/wiki/Georg_Cantor

"charlatan", "renegade", "corrupter of youth". Isn't it interesting how academics attack each other like religious people attack each other? The odd thing about some of the attacks on Cantor is that it came after his death and after he had PROVEN his countable and uncountable infinites.

The history of academia is as nasty and vicious as any other institution. And its gatekeepers and heroes as petty and pathetic as any you'd find anywhere else.

I felt the author did a decent job trying to explain this themselves, but the title is pretty misleading in my opinion.

Some of the ones that are right eventually get funding, as long as their proponents stick around long enough and produce enough results to convince someone to fund them. On the time scale this article talks about, I'd expect a quite a few people who had ideas worth looking into gave up and went off to do something else instead.

Similarly, many academics won't evaluate published papers on their own merits and instead focus heavily on proxies like publication venue. Conference papers are unfairly viewed with suspicion compared against journal articles (in my field at least), and certain venues are viewed as superior in general to the point where some "don't count".

These academics instead outsource the evaluation to a few reviewers, who often don't know what they're doing. Peer review does not appear to be as reliable as it is treated. I view peer review as closer to a lottery. And the "best" journals still frequently publish nonsense. It tends to be more pretentious nonsense in my field, though.

I don't care too much about signaling the quality of my work and instead would rather publish in more specialized journals and conferences where I can reach the people I want to reach and get better feedback. I recall at a presentation on getting a faculty job someone said that they won't count any publications in journals with names they don't recognize. Both quality specialized journals and bad journals are included in that set. Add on top of that the common view that conference papers also "don't count" and I think the incentives here are bad.

Oh did not know that. Do you have reference material?

And science is not supposed to be immune to this, the culture of science is supposed to uncover things like this/errors like this as part of a process. The truth has a habit of shining through if you are encouraged to keep asking questions and follow up on them.

And again, not saying the system is perfect or that calling things out is enough. But too often comments like this get turned anti-science or "we can't improve anything, slow decay is inevitable" cynicism (or FUD if you want to be less charitable)

The situation isn't even close, low-fat diets are an example of how science is distorted by evil and money without a care for the lives of millions.

I wish it was exclusive, but it just isn't. There's ego, prestige, institutions, social arrangement, capital structures... The practice of science is the cleanest practice we've found but its quest for truth hasn't fully escaped the influence of these things.

There may be a way to structure the finances, work, and collaboration to escape these things through some new kind of institutional approach, but it's just not there yet.

Compare science to its predecessors, such as witchcraft and magic (ex: a medicinal herb would have been called magic for centuries). Look at zoology's predecessor, bestiary studies, wherein sea monsters, unicorns, and a giraffe were considered in the same class of anecdotal creatures. Psychology works far better than its predecessors as well, astrology and exorcisms.

Science is a far better approach then these things but there's still work left to do. We're not at the end of history but instead are tasked with moving it forward.

"A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die and a new generation grows up that is familiar with it. . . . An important scientific innovation rarely makes its way by gradually winning over and converting its opponents: it rarely happens that Saul becomes Paul. What does happen is that its opponents gradually die out, and that the growing generation is familiarized with the ideas from the beginning: another instance of the fact that the future lies with the youth."

https://en.wikipedia.org/wiki/Planck%27s_principle

Do you have a source?

If you state something like this with such authority/in a "matter of fact" way (and is something that seems likely to be controversial), you really should have a source.

If it does turn out that inflammation is the cause, then things like fasting will also help.

Also Thomas Kuhn's The Structure of Scientific Revolutions (1962).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3013493/

Accurately diagnosing the elderly is difficult. My grandmother was diagnosed with Alzheimer's 15-20 years ago, which was likely inaccurate. At this point it looks like she probably has Dopa-Responsive Dystonia and may also have some form of Vascular Dementia, some sort of CSF disorder, and possibly some other problem that hasn't been diagnosed.

Rather NIH can't fund projects for the 10 most likely ideas, so it funds projects for the 1 or 2 most likely ideas.

Even more so how soon you should rebalance funding if further progress isn't achieved with respect to your biggest bet.

> In more than two dozen interviews, scientists whose ideas fell outside the dogma recounted how, for decades, believers in the dominant hypothesis suppressed research on alternative ideas: They influenced what studies got published in top journals, which scientists got funded, who got tenure, and who got speaking slots at reputation-buffing scientific conferences.

It's one thing to go all-in on a hypothesis, but another to undermine other folks' hypotheses directly. Especially when your hypothesis has not produced any results for decades.

To twist the analogy back to Alzheimer - all these scientists still agreed on the patient-level diagnosis of Alzheimer.

Can you detect any evidence of any forces attempting to bias climate science? Perhaps you mean energy companies?

Banning plastic straws, planting trees, etc. are popular yet entirely ineffective measures. Actually effective measures like rolling out nuclear power are unpopular and yet most climate scientists agree that we're likely boned without it.

I urge everyone to look at tools like [1] to get an idea of what it takes to deal with climate change.

[1] https://en-roads.climateinteractive.org/scenario.html?v=2.7....

So yeah, science isn't perfect and we have seen cases in the past where group think has held back progress and discovery. But we have also seen plenty of examples of corporations and trade groups bending and influencing the scientific narrative to their benefit (see the low-fat discussion in this thread). And in the case of climate change, the most monetarily interested party is literally the wealthiest industry in the history of the world. So I think it is safe to say that the current consensus is facing plenty of scrutiny.

[1] https://blogs.scientificamerican.com/observations/scientists...

Sure, but bear in mind that in the case of the amyloid plaque hypothesis, there wasn't really any bad science going on. It's not as if false results were being published (after all the drugs kept failing in trials); the problem is simply that too many resources were focused on research based on a hypothesis that didn't pan out.

Unfortunately, if there was something similar happening with climate change that would still mean that all the published results are correct and climate change is real, but maybe too much effort is being spent on solutions that aren't realistic (e.g. carbon capture).

What's the downside to "believing" in climate science, though? Let's say it's all a hoax. The way I see it, the worst thing is funds are diverted for things that don't help us that much.

But what's the real down side to climate science for the general population? I don't think anyone wants to inhale exhaust gases, have coal power plants in their neighborhood, plastics pollute almost everything they touch and they do it long term...

The way I see it, if climate science is correct, everybody wins. If it's not correct, we'll be mildly inconvenienced for 20 years, until it's debunked for good.

To me the huge uproar about climate science kind of proves that it's just hated by a hornets' nest of very powerful people, most likely because they're about to lose a lot of money or gasp have to work harder to make that money :-)

Note that I'm not saying there aren't good faith inquiries to be had, but it is really hard to have these with racist agendas being pushed whole claiming "neutral" questions.

A few observations that I would like people to keep in mind when looking at these fields:

- the people who complain about being "silenced" continue to find funding, public platforms to push their research and in some cases, tenure

- the "hard questions not being raised" seem to cluster around the question of differences between "races" and less around whether the concept of race actually makes sense in humans (AFAIK geneticists generally think no), whether these differences might be socially constructed (yes, that's possible. If there are systemic social biases against groups with genetic genes the impacts of these will be 100% explained by the presence of these genes in data, but 0% genetically determined as in biologically determined). And often they are then raised to dismiss concerns about the systematic problems which might have caused the measured problems

- scientific racism and shoddy science in this field has a long history, and people carry their misconceptions around. Famous examples are "objective" written IQ tests given to barely literal test subjects, or asking trigonometry questions, Both of which test the schooling of the subjects more than the IQ

In an inherently political field of science, denying the political nature and implications of questions being raised and the manner in which they are raised and trying ot claim "objectiveness" is in and of itself a political tactic.

It's the clearest example where a simple disclaimer like "I'm not racist but" is no more adequate than handling plutonium with kitchen gloves. It needs to be kept in an extremely safety-orientated environment, not splashed all over the internet.

https://news.ycombinator.com/newsguidelines.html

We detached this subthread from https://news.ycombinator.com/item?id=21911548 and marked it off-topic.

1. Climate change is observable, it doesnt rely on a theory, just measurements. Nonetheless there are a bunch of people trying to discredit what is essentially a very well established observation.

2. Genesis of climate change (ie is it anthropogenic) is not a direct observable, but looking at concentrations of CO2/other gasses and where it comes from it is not too hard to convince yourself of humans as root cause. Again, a lot of people deny human-driven climate change despite all evidence pointing one way.

3. Perhaps the most uncertain are climate model predictions. I agree that this where something might be overlooked, or maybe not.

At any rate, "climate change deniers" by and large object to (1) and (2), and those people really have no credibility. If someone accepts anthropogenic climate change but proposes a new model that fits observation-- more power to them!

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