I thought despite the fraud, it's still the best model we have[1]? The fact there was fraud doesn't mean the model is immediately incorrect. At best, it means its foundations are shakier than we thought, but it's not a slam dunk repudiation.
[1] https://www.astralcodexten.com/p/in-defense-of-the-amyloid-h...
The problem us "consensus science". You could get funding to research beta amyloids, but not to research any competing hypotheses.
It's much like climate science today: any dissent at all, even just questioning the predictions of catastrophe, immediately brands you as a heretic.
I'm not sure I understand this. We've added hundreds of gigatons of carbon to the atmosphere. There's no mystery here, it's basic physics and chemistry that this will change things, and it's accepted that we don't know exactly _how_ things will change. The alternative: "adding gigatons of carbon to the atmosphere will _not_ change anything" is simply non-sensical. It goes against the basic rules of physics and causality. I'm happy to be proved wrong here, I just legitimately can't see how an alternative position makes any sense.
Edit: I see you specifically pointed out "predictions of catastrophe", which if that is true (and not just the position of radicals on Twitter) is indeed unfortunate.
I think this is not a great example, as there’s a huge group of people that, in fact, does not agree with the consensus and would happily fund research that (tries to) prove otherwise.
I fully agree with your point, though, just not the example.
“When we began our study, we felt that skeptics had raised legitimate issues, and we didn’t know what we’d find. Our results turned out to be close to those published by prior groups. We think that means that those groups had truly been very careful in their work, despite their inability to convince some skeptics of that.”
https://www.nas.org/blogs/article/after_climate_research_phy...
If you haven’t read up on both, it’s hard to appreciate how unlike climate science is from the beta amyloid theory. The latter has some evidence but there were always alternate theories by serious researchers because it involved multiple systems which scientists were still working to understand and basic questions around causation and correlation had significant debate.
In contrast, climate scientists reached consensus about climate change four decades ago and by now have established many separate lines of evidence which all support what has been the consensus position. More importantly, since the 1970s they have been making predictions which were subsequently upheld by measured data from multiple sources. The ongoing research is in fine-tuning predictions, estimating efficacy of proposed interventions, etc. but nobody is seriously questioning the basic idea.
Almost all of the people you hear dismissing climate change are funded by a handful of companies like Exxon, whose own internal research showing climate change was a significant threat produced a chart in 1982 which has proven accurate:
https://skepticalscience.com/pics/Exxonpredictions.png
https://insideclimatenews.org/news/16092015/exxons-own-resea...
The few examples of research driven from the skeptic PoV (eg: urban heat skewing, etc) have landed on the side of the AGW consensus.
https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/trc...
Nonsense. It is actually quite unlike climate science, where the consensus of catastrophe and the evidence for it are both overwhelming. Dissenters are listened to only to the extent they can provide overwhelming evidence to the contrary, which they so far cannot.
If anyone wants to know who wrote the article linked before wasting time reading it, there you go.
I, also a non-expert, spent six months studying what the experts are doing, concluded that they actually seem to know what they’re talking about, and shared my understanding of that with other non-experts.
If you’re going to dismiss me for saying the experts are right, since I’m not an expert, then shouldn’t you dismiss those who spent far less time than I to learn about the subject, who are saying the experts are wrong?
wrt. original post - quickly googled, and that for example https://www.news-medical.net/health/What-are-Amyloid-Plaques... - pretty short and seems to be clear that amyloids do have some correlation while may or may be not the cause.
"Amyloid plaques form one of the two defining features of Alzheimer’s disease, the other being neurofibrillary tangles"
Interesting that the latter is inside the neurons while the former is outside - speaking of complexity. The article also describes that activating microglia back helps with amyloid plaques while this
https://pubmed.ncbi.nlm.nih.gov/33010092/#:~:text=The%20stud...
"The neurofibrillary tangles (NFT) and amyloid-ß plaques (AP) that comprise Alzheimer's disease (AD) neuropathology are associated with neurodegeneration and microglial activation. "
Human body reminds a large monolith codebase - fixing one thing breaks some other :). Claude Code, Human Body CRISPR edition, can't come soon enough...
It’s a miracle it works at all
The current findings seem consistent with "both plaques and tangles are significant components of the pathology" and "our interventions are typically late and the accumulated neurological damage is already extreme by the time clinical symptoms show".
Attacking the plaques wasn't completely worthless - findings show that this often slows disease progression, especially in early cases. There are pre-symptomatic trials ongoing that may clear the air on whether "intervention is late" is the main culprit in treatment underperformance.
> I thought despite the fraud, it's still the best model we have[1]?
It is observed that one of the features of neurodegenerative diseases is decline in glucose metabolism. Supplementing energy availability (e.g. ketones [1], creatine [2]) does improve symptoms in patients with wide variety of CNS diseases, including Alzheimer's, senile dementia, epilepsy, and migraines.
The ATN model you have linked might as well be just ONE OF possible pathways to glucose uptake inhibition, which could be the causal pathology of the symptoms.
So no, it is very much not necessarily the best model we have. Inhibiting any pathway towards a disease is always a good thing, but the characteristics of "best" models are broad applicability and we have a serious contender.
[1]: https://link.springer.com/article/10.1016/j.nurt.2008.05.004 [2]: https://alz-journals.onlinelibrary.wiley.com/doi/full/10.100...
And probably the more important question. How badly is the machine that does science broken? If we don’t focus here and fix it, there will be further decades without progress, all while wasting further billions.
Somewhat ironic given the context.
What happened is we got the tools to start studying viral associations with other diseases and ... whooops ... suddenly there are associations. The shingles and RSV vaccines seem to affect dementia while others like influenza don't.
Now people can ask questions about why those particular vaccines affect dementia while others don't. And suddenly we have falsifiable tests.
Now we can subject all hypotheses (including Amyloid) to stronger scrutiny.
The hypothesis didn't come from nowhere.
To contrast, look at how much trouble medicine has had treating brain tumors. It has taken a long time to get effective treatments for various reasons. And Alzheimer's is way less direct in cause/effect.
Do you want think carefully about how this can possibly suggest this is a causal link?
> People with mutations that caused amyloid got Alzheimer's earlier than others.
People with mutations in those genes got a particular type of inherited alzheimers early, this says nothing about the cause of general Alzheimers.
And it's also not a good idea to suppose that you are dealing with unrelated effects without good reason. Mutations->more amyloid->earlier symptoms should be considered indicative of the disease pathway until sufficient evidence counteracts that, by Occam's razor.
This is completely analogous to claiming that people with mutations in BRCA (which causes a lot of early breast cancers) says nothing about general "cancer".
That's simply flat-out wrong. Genetic mutations like BRCA affect certain subsystems and many of those subsystems are common and relevant to many different cancers outside of breast cancer or breast cancers that appear later. Lots and lots of cancer research proceeded by studying the common systems that BRCA affects. Sure, those subsystems aren't involved in every cancer, but they're involved in a solid chunk of them.
And, even better, when you find one that isn't affected by one of those subsystems that BRCA touches, that's an interesting result, too. Now you can look at what the differences are, figure out what the new subsystems are and categorize your cancer more specifically which makes successful treatment more likely.
There is absolutely no reason to believe that Alzheimer's is any different on that front.
That sort of question is what the response from user @bsder above helpfully tries to answer. That mode would invite more productive discussion, not more defensive annoyance.
Rules on HN say “Be kind. Don't be snarky. Converse curiously; don't cross-examine. Edit out swipes.” but it is hard.
All I can suggest is: be patient and try to be positive
And before someone says, "well theres nuance to it," "in hindsight its easy," "biology is complex," my answers are, no no and no. Debate me. Ill bring receipts.
as general of a label as it may be?
To be clearer, Pharma is chasing a nice long treatment plan, that will require expensive drugs till the end. Pharma does not heal - this is not good for business. So there are criteria around what they are searching for.
This is a trope regurgitated by people who don't know any better. It would imply that pharma are deliberately avoiding research directions that would generate cures, or (even worse) discovering cures and putting them in a dark secret safe somewhere.
The reality is that drug development is serendipitous and really hard, and any company seeing even a sniff of a drug that works will throw everything behind making that drug a success. During the early stages of investigation of a promising new agent, the animal data can't predict much, and certainly can't predict whether something is "curative" - this would only be seen during human trials, after which hiding that benefit would be close to impossible. It's just not how it works.
There are plenty of examples of actual (rather than functional) cures being developed and marketed:
1) Previously-untreated DLBCL (a type of blood cancer) can be cured. CHOP chemotherapy cured ~35-40% of cases. The addition of rituximab boosted that to 60-65%. There then followed a long string of failed phase III studies (probably billions spent, cumulatively) trying to beat rituximab + CHOP, and finally in recent years there has been some success. So: multiple attempts across multiple pharma companies, trying to improve on an already impressive cure rate... not much evidence of an anti-cure conspiracy.
2) Hepatitis C - cures were discovered and marketed from ~2014 onwards; now ~95% of cases can be cured with a treatment lasting only a couple of months. So: multiple treatments, from multiple pharma companies, which offer a hugely effective cure for a pretty unpleasant disease.
From the human perspective, researchers are people, and they do have their incentives. Making a breakthrough, of any kind, is important for them - even if for their career (but many do genuinely care and want to help humanity as a whole).
From marketing and sales perspective, look at what happen to pharma companies capitalization when Ozempic appeared: a relatively small Elly Lily suddenly got bigger then Merck, Novartis, Roche or Johnson & Johnson. You can hardly call it a long treatment plan with expensive drugs "till the end".
Really, there is a lot of bad things going on in healthcare and pharma industry, but the conspiracy theory "they don't want to invent efficient drugs" really makes no sense when you dig deeper.
An example of “good” pharma would be Hepatitis C. We can now cure that. Although, pharma is charging the lifetime equivalent in order to do that (a treatment can run over $100k and insurance balks at covering it)
So pharma will absolutely develop a cure if they can. They however will still charge you as if you had to take a dose for the rest of your life.
Well yes, Ozempic doesn't solve the habits of a bad diet.
The weight rebound is surely due in little part to removal of hunger suppression as in "hormone rebound", but if you resume eating 5000+ kcal/day because you don't have something that keeps you from doing it, you'll end up in the same situation as before. Ozempic was never meant and is not going to fix your diet. That's a psychological and environmental problem.
Not really. Note that it's not taking ozempic for life vs taking nothing for life, but actually taking ozempic for life vs taking ozempic and 5 different medications for life when obesity related illnesses bite you in the ass. So generally ozempic still is "good" pharma (and the plot twist is that almost every pharma is good pharma!).
Lots of treatments start expensive and then come down in cost as competitors step in.
> From the human perspective, researchers are people, and they do have their incentives. Making a breakthrough, of any kind, is important for them - even if for their career (but many do genuinely care and want to help humanity as a whole).
Researchers are people, but they are paid and directed. They can't go off and do what they like. The corporation directs them, and they are paid for their efforts. Researchers (and all working people) aren't doing what is right - they are doing what they are paid to do.
All the financial upside for pharmaceuticals is in prolonged treatments. It is a 'long sickness' industry. This is perhaps too bitter a pill to swallow for most, so this is where marketing and education come in with the sugar.
For cancer in particular, pharmas don't (and mostly can't) just target a drug to chronically treat some cancer over the long term but not cure it. Instead they pick some target that's believed to contribute to development (/ metastasis / treatment resistance / whatever) in whatever cancer, and make a drug to interfere with it or to target an immune response to cells that make it. If it's stable, nontoxic, and looks potentially effective enough they'll take it to clinical trials. During clinical trials they'll find out whether it does nothing, gives you a few extra months, or has a chance at curing the disease. Usually the answer is that it does nothing or almost nothing, or isn't worth the side effects, and then the company wasted its time and money. Drugs with a chance to cure common types of cancer can be enormous successes -- see eg Herceptin.
Cancers are difficult diseases and it's rare to find something that reliably cures them. But drug companies aren't pulling their punches. Like they would never say "oh this drug clears breast cancer too reliably, we should make it less effective so that people will be more likely to die but also might take it for longer".
Chicken pox, polio, hepatitis C, dracunculiasis, yaws, malaria (on the way of it), tuberculosis, syphilis, everything that can be killed with antibiotics, rubella...
Halcyon days.
Type I diabetes - no, but this is a condition in which the body attacks the part of itself that makes insulin. So by the time it happens, it's too late. Sadly, we're generally bad at understanding and preventing autoimmune diseases, but this needs more basic research, not drugs.
Type II diabetes - essentially a lifestyle condition. May be functionally cured in some/many cases with strict lifestyle interventions. Ironically, GLP-1s may help move some people towards a functional cure.
Cancer - yes, where possible. The open secret is that the best way to fight cancer is to not get it in the first place, or failing that to catch it very early, but these are issues of lifestyle and public health policy - both of which we're currently very bad at optimising, as a species.
> All the financial upside for pharmaceuticals is in prolonged treatments.
Except for the examples to the contrary.
Improving standard of care for 100 is less risky/more profitable because you have more shots at an expensive process with a high failure rate. And it is a lower bar to improve patient care than to permanently fix a medical mystery. But there is another factor. Focusing on treatment/management over cure most likely maximizes the positive impact on patients within the the constraints you work under.
There have been at least three new major treatments for a chronic thing I have that received FDA approval over my lifetime. Those treatments have had a massive impact on my quality of life, ability to have a career, etc. I don't believe that happens for me if we allocate to cures.
The point I am making is that you are a/ not getting cured, and b/ paying a lot of money. The reason for this, is this is best strategy for maximising profits. Its really the exact same model as your local heroin/crack dealer.
Please set me straight if those conditions differ in your case.
Profits are what pharma companies want.
The consumer is mostly labouring under the illusion that companies want the best for you. They are not your mum. They want what's best for them. And, most people would do the same - no one is gifting anyone health.
All I'm saying is let's drop the illusions and fantasy and call a spade a spade.
Again, if your choice is improving quality of care for 100 conditions or trying to moonshot your way to curing one disease, more patients benefit from the former even if pharma also profits more.