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 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'm now about half way through. It's really good.
If anyone wants to know who wrote the article linked before wasting time reading it, there you go.
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 :)
It’s a miracle it works at all
Is that supposed to be an endorsement or a dismissal? The ostensible goals of "rationality" seem like good things, so it sounds like an endorsement, but in the wake of the FTX/SBF fallout they got a bad rap.
The people who know the most are probably busy and (not to be rude) are not necessarily the strongest educators.
Maybe my standard is too low here or I have a different need than you, would make a different accuracy-accessibility tradeoff…
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?
Already have
> 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...
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 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...
...and it really did backfire (in public relations, politics, etc)
now... I don't think they can actually fund 'research-for-their-profit' -- I mean, would you believe "petro is good for earth" research coming from oil companies, even after the 'lead is good or neutral' research?
Not uncritically, but if the research presents a logically consistent hypothesis, and evidence supporting it, then it would be worth following up on with independent groups and if it remains consistent to scrutiny then it should be accepted.
That's how science works.
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://www.scientificamerican.com/article/exxon-knew-about-...
If anything the current consensus on the scientific front lines is that the alarmism is understated, and the real orthodoxy is astroturfed denial of the facts.
The global fossil industry is worth around $11 trillion a year. It supports some of the worst regimes in the world.
Of course they're going to try to FUD away the science, with the usual copy-paste narratives about how it's really scientists and academics who are corrupt.
It's all about money, power, and entitlement. Not about truth or responsibility.
But no amount of PR nonsense, astroturfing, and false accusation is going to make the slightest difference to climate reality.
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.
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.
You didn't ask, but my opinion on it is that we'll probably stabilize on a cleaner energy source and find natural countermeasures when suffering ticks up. Any top down pressure to change things whole cloth seems doomed, no matter how benevolent. We're closed loop creatures.
What better way to find out than to just try it and see if we end up with runaway warming?
Like are we doomed or will it just get a bit warmer before we switch to solar for example.
There are also money issues like with the alzheimer's situation. If climate change is dooming us then we should send more money to climate scientists.
Absolutely, the issues are similar
And if this can upend the business model of some big companies we'll give some "incentives" to some "doubtful" scientists even if their doubts are unfounded (actually very well founded but you get the gist)
Which sucks because such work should be free of pressures and incentives
Couldn't disagree more.
Please spend it on those who might actually fix something. There's plenty of can remove carbon or can undo the effect of X on Y. Let's stop falling back on the bad argument of we must leave nature alone right after arguing we change billion dollar industries because we can.
We shouldn't learn to be custodians watching the planet die because of past mistakes, we should be fixing and improving the planet and improving on nature because we can, must and should, shoulder this reaponsibility.
Please not _yet more modelling_ burning HPC into the ground just for a crappy bar line graph (based on assumptions)...
How do you do this without a process of finding out what works and what doesn't? Isn't that science? Or am I misunderstanding you saying no more modeling to mean we already know everything we might need to know in order to shoulder this planet scale responsibility and just collectively aren't doing anything except making bar charts?
What does your proposal actually look like without science or climate modeling?
There is a yawning abyss of states in between extinction and 'boy sure is a few degrees warmer out here' and none of them are good.
Many organisms would benefit from a warmer climate, just not humans.
We rely on extremely narrow conditions for the fragile supply chains and power structures that keep us on the ragged edge of civilized to continue working. We had an extremely mild contagious disease outbreak, by historic standards, and our economy is still feeling the effects!
Imagine the impacts of something like wildly different rainfall patterns, increased rate of global infectious disease, shifted agricultural zones, changes to Jetstream patterns, large scale crop failures, loss of water supplies, temporary local ecosystem collapses etc. These changes are incredibly fast on the scale of what it takes to reach ecological equilibrium.
These of course mean nothing to biological life, writ large. Life will recover and adapt. To fragile human civilization they mean refugee crisis, resource wars, failed infrastructure, and ten thousand other existentially terrible things.
and a whole fuckin lot that wouldn't, and that may collapse the ecosystem
Depends! If you're a large fossil fuel company, the obvious move might be to spend more money on advertising agencies and scientists who question climate science instead.
However research into what we humans can do to ameliorate it is verboten. For example https://www.scientificamerican.com/article/fertilizing-ocean... was an actual experiment that found a low cost way to both remove lots of CO2, and improve a fishery. But that line of research has been shut down.
Likewise research into the current impact is only allowed if it agrees with what is politically correct. For example many researchers have found that current severe California forest fires are mostly due to poor past policies, that have resulted in very dense forest, with a large fuel overload. But research that stresses the impact of climate change are easier to publish, and this shifts the apparent consensus on the causes of things like the major 2025 fires in the Los Angeles area.
> Not geoengineering
> The project is also unlikely to bury much if any carbon dioxide for one simple reason: metabolism. As other iron fertilization experiments have shown, it is relatively easy to get plankton to bloom, but it is harder for that bloom to sink to the bottom of the ocean, where it takes CO2 with it.
This project is a net carbon emitter by design.
The worst case scenario laid out in that article is that most of the carbon absorbed, was later rereleased. So net zero carbon, not net carbon emitter.
I've seen other reports of that exact experiment that estimated a significant net carbon sink. The actual experiment failed to make measurements that lets us know which actually happened.
Regardless, we've certainly demonstrated that, at least sometimes, there is significant net carbon capture, at low cost. Given the certainty of global damage at present, I believe that this justifies continued experimentation. Even if it means accepting possible risk to local ecosystems. The local ecosystem can generally recover. The planet, not so much.
With any position, you have to distinguish between its thoughtful advocates and its thoughtless ones-every position has both
Any thoughtful “climate change sceptic” is going to say (a) of course the climate is changing-it always has and always will; (b) of course it is implausible than human activity has literally zero impact on that change. But that still doesn’t tell us: (i) the relative scale of anthropogenic versus natural causal factors; (ii) the validity of any specific predictions of future change; (iii) the likely socioeconomic impacts of any future changes that may occur. It is totally possible that a person may affirm (a) and (b) while questioning the “consensus” on (i) and (ii) and (iii)
Personally, I don’t have a strong opinion on the substantive issue - but I wonder about the extent to which mainstream discourse on the topic represents good epistemic hygiene. It is even possible that the sceptics are on the whole more wrong than right, but simultaneously the mainstream response to them is more irrational than rational.
Question a clickbait "we're all gonna die" prediction, and you are immediately branded as a "denier", and no further discourse is possible.
For Climate Change it's a question of opportunity costs. With expected inputs how much will temperature change? What are the effects of that change? How much effort to you put into changing the inputs? How much effort do you put into dealing with the effects?
The biggest difference is that Climate Change is a deeply political question with a bit of science tossed in. Alzheimer's is the mirror opposite - it's a scientific question with politics added to the same degree of most other things.
The idea that they have blocked the treatment of Alzheimer's rather than helping it, is very, very painful. This is perfect for creating cognitive dissonance.
And so, no matter what the evidence, they remain committed to the conclusion.
As a result, the latest Alzheimer's drug to enter stage 3 FDA trials is Trontinemab. (It is currently in stage 3.) It targets the amyloid target.
A relative drop in the bucket is going to, say, the infection hypothesis. This despite the fact that the only intervention that has been shown to reduce the incidence of Alzheimer's, is the shingles vaccine.
The financial motivation for fraud is all on the side of climate-change denial. Literally trillions of dollars of motivation.
Climate-change denial is just like tobacco-cancer denial. It's the same banal "I win, you all lose" mechanism. Enormous resources are available (along with the useful idiots) to propagate falsehoods.
The idea being both to make it easy to get people to agree today (the reductions are tomorrow's problem), and to allow time (and foresight) for industry to adapt to where things are going.
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?
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.
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 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.
Correlation not causation is all the more important in a topic like this; nothing you said suggests amyloid causes alzheimers or just forms because of it.
I mean an amyloid injection is wildly unethical and it’s also not the natural progression of Alzheimer’s. Removing amyloid is a simple matter of investing billions of dollars into drug development. Also how do you tell whether that was actually “causal” if the patients improve after plaque removal.
I mean come on, you have to work the evidence and the experimental tools that we actually have. This kind of epistemic puritanism doesn’t help anyone.
Erm, we kinda did? People who got cadaver-derived human growth hormone from Alzheimer's patients got Alzheimer's.
https://www.nature.com/articles/s41591-023-02729-2
And we just had an actual autopsy confirm a case: https://www.medscape.com/viewarticle/new-evidence-strengthen...
The vaccine prevention connection for example AFAIK is just pure statistics: you get the shingles vaccine, your population level Alzheimer's risk drops but we have no direct evidence of why this should be.
Its entirely possible we later find it has no effect and it's a population level quirk of people who were likely to get a shingles vaccine until that research - conversely the cost of just getting one is incredibly low (hence why I did, in relation to that exact data).
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.
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.
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!).
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.
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.
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.
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.
see also: right wing grift
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.
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".
Why would any competitor sit on a cure for a condition there opponents can only treat when in the short term you'd post amazing next quarter profits, and in the long term you'd financially diminish that competitor in the market place even if we grant the position that you are somehow able to find treatments that aren't cures (others have explained ably why this isn't how it works).
Everything looks like a conspiracy when you don't understand anything.
And cancer isn't one disease. It is hundreds. Many of which have cures.
Diabetes was much harder to understand (and also isn't a single disease). Recent results have demonstrated islet cell transplants in type 1 that don't require life-long immune suppression. That isn't wide-spread yet but it is promising.
An interesting example of an actual cure is ulcers. Most humans who gets ulcers get them because of bacterial infection with H. Pilori. Killing that infection cures the ulcers. That didn't used to be possible because the cause wasn't understood.
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.
can't mark-up snake oil, not in ways to shift the stock price for Fortune 100 tier companies -- too many lawsuits and visibility
Somewhat ironic given the context.
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.
Tautology statement. "We don't know all the details of X" for any X.
Tautology day is today because today is tautology day.
... not by "obviousness"
I can't check every stone for moss. We can't know every detail about anything.
Sorry but good science should be reproducible an given the amount of major retractions around this field I think this starts to become more than a passing question.
Lots of work is built on top of the model which means a lot of money change hands and a lot of honesty hard work was done.
Those who built the bad model should be being asked why a) they were so wrong (bad conclusions are fine) b) their data was so bad (this is not defensible) c) they didn't push for reproducing their work sooner to support the field (more of a daming statement of a field which treats a statistical analysis as a push button tool)...
Derek Lowe's blog is excellent, with 192 posts tagged "Alzheimer's Disease":
https://www.science.org/topic/blog-category/alzheimers-disea...
And, on a more entertaining topic:
https://www.science.org/topic/blog-category/things-i-wont-wo...
"But I have to admit, I'd never thought much about the next analog of hydrogen peroxide. Instead of having two oxygens in there, why not three: HOOOH? Indeed, why not? This is a general principle that can be extended to many other similar situations. Instead of being locked in a self-storage unit with two rabid wolverines, why not three? Instead of having two liters of pyridine poured down your trousers, why not three? And so on - it's a liberating thought. It's true that adding more oxygen-oxygen bonds to a compound will eventually liberate the tiles from your floor and your windows from their frames, but that comes with the territory."
https://www.science.org/content/blog-post/things-i-won-t-wor...
> Recall that this is the compound whose cocrystal with TNT is actually less dangerous than the pure starting material itself, and yeah, I know that sounds like the guy at the pet store packing a starved Komodo dragon into the carrier with your new dog, just to calm him down some.
I'm guessing he just ran out of nasty chemicals. Either that, or he got tired of it and followed his muse elsewhere.
Whether it was fraudulent or just incorrect is a different question. We don’t know all of the details of human biology. We don’t even know what all we don’t know. Most guesses work to some degree to keep pharma alive - otherwise nobody would fund the business.
Edit: Google the in the pipeline blog. This and other have discussed this at length.