How an Alzheimer’s ‘cabal’ thwarted progress toward a cure • Hacker News Board

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

#131

Post by tempsy » Mon, Dec 30, 2019, 1:36 PM UTC

scottlocklin wrote: post #124

frogger23123 wrote: post #98

Earlier quoted context omitted.

Gum disease is linked to carbohydrates, which aligns with the "type 3 diabetes" hypothesis. (carbs feed bacterial overgrowth)

Gum disease is also linked to being old, just like Alzheimers disease, heart disease, baldness, wrinkly faces, diabetic disease and lots of other things. Sermon: people are really, really shit at linear regression.

The logic that chronic illness can’t be prevented and is either genetic or inevitable is so problematic.

Like everyone is going to get old and if I think getting old means I will inevitably get gum disease which could cause Alzheimer’s then why bother flossing or caring about preventative oral health?

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

#132

Post by Psyladine » Mon, Dec 30, 2019, 1:38 PM UTC

michaelbarton wrote: post #108

svara wrote: post #100

A super interesting article, but the title is pure clickbait. 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. Reality is much more nuanced, and the article actually does a good job of detailing that. In some sense this all started from the very beginning, from when Alzheimer's disease (AD) wa…

> science is just another competitive team sport where people compete with whatever means necessary 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 res…

Michael Crichton said as much and the community turned on him.

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

#133

Post by Dumblydorr » Mon, Dec 30, 2019, 1:42 PM UTC

ping_pong wrote: post #3

This is another example of group-think in scientific research. The same thing happened for decades where low fat diets were supposed to help for heart disease but that has only recently been reversed after decades of indoctrination. This happens all throughout scientific research, where science is supposed to be immune to this, but it's obviously not. So many things we take as gospel, only to be reversed decades late…

That's a fairly different example, as there has been a lot more low quality, industry funded science in nutrition than in Alzheimers. Sad as it is, those who profited from sugar sales funded a lot of garbage work into low fat diets.

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

#134

Post by oblio » Mon, Dec 30, 2019, 1:45 PM UTC

allovernow wrote: post #31

>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 Not quite in topic, but Is it really such a stretch to acknowledge that the same forces i…

> Not quite in topic, but Is it really such a stretch to acknowledge that the same forces in academia might bias climate science too?

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 :-)

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

#135

Post by datastoat » Mon, Dec 30, 2019, 1:47 PM UTC

svara wrote: post #100

A super interesting article, but the title is pure clickbait. 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. Reality is much more nuanced, and the article actually does a good job of detailing that. In some sense this all started from the very beginning, from when Alzheimer's disease (AD) wa…

What the linked article says:

> 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!

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

#136

Post by amluto » Mon, Dec 30, 2019, 1:58 PM UTC

zosima wrote: post #93

The article is not quite updated. Biogen did end their phase 3 trial of the amyloid-beta antibody Aducanumab early, citing lack of efficacy. A closer look at the numbers however appeared to reveal that they shouldn't have. And Biogen is now filing Aducanumab for approval by FDA. [1] All in all, there is no question that amyloid-beta is a key part of Alzheimer. Already Alois Alzheimer, when first describing Alzheimer'…

Nothing says p-hacking like a drug company canceling a trial and then, a few months later, re-analyzing the data and magically finding a benefit.

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

#137

Post by nextos » Mon, Dec 30, 2019, 2:09 PM UTC

dnautics wrote: post #115

svara wrote: post #100

A super interesting article, but the title is pure clickbait. 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. Reality is much more nuanced, and the article actually does a good job of detailing that. In some sense this all started from the very beginning, from when Alzheimer's disease (AD) wa…

I think the evidence goes deeper than that. Humans with downs syndrome, which duplicates the APP gene, evince symptoms of Alzheimer's as they reach their 40s.

Genetics is important, but lots of current research in biology reduces everything to genetics. Paradoxically, when twin studies have shown environmental factors typically make an equally important contribution towards disease onset.

For example, consider type 1 diabetes (T1D). Lots of research tries to understand genetic risk factors. Despite this being so difficult to translate into treatment, as its many small effects past the top 3 genes, and twin studies show 50% is contribution from the environment.

So very recently, someone said OK the immune system is a classifier that takes sets of little protein chunks in a tissue microenvironment and decides whether its seeing self or something foreign and acts accordingly. Then, your own microbiome has to do something to avoid immune immune responses, as the immune system is only pre-trained using your own DNA. Then, let's assume your microbiome has to mimic (copy) some of your DNA to signal self to the immune system.

And it turns out it is true [1]. Lots of bacteria mimic insulin. And when those bacteria end up being classified as non-self, you also destroy your pancreatic beta cells, which produce insulin.

There's good evidence for lots of other diseases. For example, multiple sclerosis [2]. The first paper cites other diseases, including Alzheimer's that look like mis-classification induced by dysbiosis in the microbiome or an infection.

[1] https://www.biorxiv.org/content/10.1101/2019.12.18.881433v1

[2] https://stm.sciencemag.org/content/10/462/eaat4301

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

#138

Post by ethbro » Mon, Dec 30, 2019, 2:10 PM UTC

michaelbarton wrote: post #126

Certhas wrote: post #112

Earlier quoted context omitted.

I completely agree with your second sentence, but also with the OPs statement that there is no conspiracy to suppress correct results. There is intense competition to be right. There is intense competition for funds, so being perceived to be promising is hugely important. But at the end of the day I haven't really ever seen any explicit attempts to suppress uncomfortable results.

I agree, that's fair. I don't think it's an explicit conspiracy. However there are some practices that do end up suppressing results. One particular example is that lack of publication of negative results because there is no incentive for doing so. You can imagine a scenario where similar experiments are repeated over and over again in different laboratories because no one writes up the negative result. After all wha…

It's a good idea: have a fully-open repository where negative results can be documented. With the ability to tag on if a negative result is replicated.

Then gradually re-enculture review boards to expect any given author to have a substantial number of results published to said repository, if they're actively performing research.

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

#139

Post by SolaceQuantum » Mon, Dec 30, 2019, 2:21 PM UTC

Psyladine wrote: post #132

michaelbarton wrote: post #108

Earlier quoted context omitted.

> science is just another competitive team sport where people compete with whatever means necessary 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 res…

Michael Crichton said as much and the community turned on him.

I tried to find more information and I'm struggling to find information that Michael Crichton said this exact thing and that turned the scientific community against him. I did find that he was a global warming skeptic and also believed in astral projection and auras and the like, both of which garnered scientific backlash. Could you help me clarify?

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

#140

Post by partyboat1586 » Mon, Dec 30, 2019, 2:22 PM UTC

praptak wrote: post #32

The major and established beliefs in science usually have some fringe competition/opposition. You can only tell in hindsight whether it's "a cabal stifling valid criticism" or "scientists refusing to waste time on distractions".

It's all a matter of degree. Exploitation vs exploration in search theory.

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.