5 ms·

They had a biological model. They had multiple drugs that were showed activity against that model, and effectiveness in humans. Problem was, the model was wro

by jleyank 6mo ago

They had a biological model. They had multiple drugs that were showed activity against that model, and effectiveness in humans. Problem was, the model was wrong. Pharma’s burned billions chasing this as it’s possibly the biggest market imaginable. 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.

gruez 6mo ago
> Problem was, the model was wrong. 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-hypothesis https://www.astralcodexten.com/p/in-defense-of-the-amyloid-h...
- mnode 6mo ago
  Many in the research community realised the model was wrong a long time ago. This is a great read about the reasons why: 'How not to study a disease: the story of Alzheimer’s.' by Karl Herrup.
  - ACCount37 6mo ago
    Wrong or incomplete? 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.
  - sien 6mo ago
    Thanks for recommending this book. I'm now about half way through. It's really good.
- Drupon 6mo ago
  >I am David Schneider-Joseph, an engineer formerly with SpaceX and Google, now working in AI safety. Alzheimer’s isn’t my field If anyone wants to know who wrote the article linked before wasting time reading it, there you go.
  - trhway 6mo ago
    there is even easier way to estimate the chances of time wasting - it is a "rationalist" website, an "effective altruism"-like version of rationality. wrt. original post - quickly googled, and that for example https://www.news-medical.net/health/What-are-Amyloid-Plaques.aspx 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%20study%20found%20that:%20*%20**Ramified%20microglia,contribute%20to%20focal%20neurodegeneration%20characteristic%20of%20PPA%2DAD. 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...
    - ifwinterco 6mo ago
      Huge codebase with years of fixes, features and hacks added on top and nothing ever refactored. It’s a miracle it works at all
      - generic92034 6mo ago
        It is worse. The code changes are mostly random, only surviving the tests of fitness nature is applying (on various levels though; immediately catastrophic changes on level of cell biology are sorted out). And at least the high-level tests are also random and unreliable.
- friendzis 6mo ago
  It's a classic example of "correlation does not imply causation". It was indeed observed that some patients with neurodegenerative conditions do indeed have amyloid plaques. It was further observed that patients with known Alzheimer's do not necessarily have amyloid plaques and patients without it do have plaques. The existence of amyloid plaques itself or the level, apparently, correlates extremely poorly, if at all, with the existence, onset or severity of the disease. Drugs attacking amyloid plaques might work, but they don't reverse the disease and do very little to slow progression. That's all scientific observations. > 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 https://link.springer.com/article/10.1016/j.nurt.2008.05.004 [2]: https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/trc2.70101 https://alz-journals.onlinelibrary.wiley.com/doi/full/10.100...
- bradley13 6mo ago
  Pretty clearly not. It would seem that beta amyloids correlate with Alzheimer's, but do not cause it. 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.
  - enraged_camel 6mo ago
    >> It's much like climate science today: any dissent at all, even just questioning the predictions of catastrophe, immediately brands you as a heretic. 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.
  - stingraycharles 6mo ago
    > 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.
    - defrost 6mo ago
      Over the past decades the group that are not happy with the AGW consensus in the hard earth sciences crowd have principally funded FUD via think tanks, ala the pro-tobacco lobby back in the day, rather than research. The few examples of research driven from the skeptic PoV (eg: urban heat skewing, etc) have landed on the side of the AGW consensus.
      - TheOtherHobbes 6mo ago
        And when they funded research, it confirmed the known science. https://www.scientificamerican.com/article/exxon-knew-about-climate-change-almost-40-years-ago/ 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.
- caycep 6mo ago
  the model is wrong, but the amyloid is still sitting there, staring at you, asking you what are you going to do about it?
bsder 6mo ago
The Amyloid hypothesis persisted for so long because we didn't have any obvious counterarguments since it is so hard to do studies on the brain. Which also means that it's not a bad hypothesis. 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.
- ramraj07 6mo ago
  There were no cointerarguments? There was a very simple counterargument: where was the causal data? If none exist why should I counter argue when you hadn't proven it to begin with.
  - bsder 6mo ago
    There is a LOT of causal data. Autopsies of brains of Alzheimer's patients were rife with amyloid. People with mutations that caused amyloid got Alzheimer's earlier than others. 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.
    - ramraj07 6mo ago
      > Autopsies of brains of Alzheimer's patients were rife with amyloid 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.
      - stackghost 6mo ago
ramraj07 6mo ago
[flagged]
- UberFly 6mo ago
  The peer review process was repeatedly cheated by self-serving fraud. The medical field requires honest results and reporting. Why are you defending the fraud?
  - t-3 6mo ago
    Science is no longer a hobby for the idle rich, it's an occupation. Peer review cannot function in a hostile environment governed by self interest (results == resume). Science practice needs to adapt to modern conditions rather than to pretend the idealized system that worked for an exclusive and elite group would work for a competetive worldwide industry.
    - uecker 6mo ago
      This is exaggerating and generalizing too much. Science still works extremely well in general.
- DANmode 6mo ago
  For replying to me, can you skip to the part where you explicitly call out what you believe the cause may be, as general of a label as it may be?
verisimi 6mo ago
> Pharma’s burned billions chasing this as it’s possibly the biggest market imaginable. 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.
- dvfjsdhgfv 6mo ago
  I think you are wrong, for several reasons. 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.
  - Closi 6mo ago
    Plus even if it does involve expensive drugs and long term treatment, that would be a huge step towards cheap drugs and short term treatment. Lots of treatments start expensive and then come down in cost as competitors step in.
    - jleyank 6mo ago
      Patents run out also.
  - SomaticPirate 6mo ago
    I agree with you but Ozempic is a bad example here. Part of the reason it is so valuable is that patients usually must take it for the rest of their lives. Its actually the perfect example of “evil” pharma since patients slmost akways regain the weight if they stop taking it. This leads to dependence or people searching for grey market sources. 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.
moffkalast 6mo ago
> We don’t even know what all we don’t know. Somewhat ironic given the context.
SwtCyber 6mo ago
A wrong model is not the same thing as fraud, and biology is full of plausible models that later turn out to be incomplete or misleading
- yxhuvud 6mo ago
  While true, there are a bunch of very influential results in Alz science that turned out to be fraud.
next_xibalba 6mo ago
> Whether it was fraudulent or just incorrect is a different question. 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.
deepsun 6mo ago
> We don’t know all of the details of human biology. Tautology statement. "We don't know all the details of X" for any X.
- jvanderbot 6mo ago
  That is not a tautology. But you're right it's trivially true.
  - deepsun 6mo ago
    > In logic and mathematics, it is a statement that is true in every possible interpretation or situation.
    - jvanderbot 6mo ago
      ... by definition 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.
rob_c 6mo ago
> Whether it was fraudulent or just incorrect is a different question. 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)...
dtgriscom 6mo ago
> Edit: Google the in the pipeline blog. This and other have discussed this at length. Derek Lowe's blog is excellent, with 192 posts tagged "Alzheimer's Disease": https://www.science.org/topic/blog-category/alzheimers-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-work-with https://www.science.org/topic/blog-category/things-i-wont-wo...
- frereubu 6mo ago
  I miss Derek Lowe's "Thing I Won't Work With" series. I know there have always been large gaps between those posts, but it's been seven years since the last one so I guess they might be over. An excerpt from a favourite of mine: "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-work-peroxide-peroxides https://www.science.org/content/blog-post/things-i-won-t-wor...
  - dtgriscom 6mo ago
    Yeah; they had a wonderful earthiness to their language; both highly technical and highly vivid. Like this comment on hexanitroisowurtzitane: > 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.

by jleyank 6mo ago

gruez 6mo ago

> Problem was, the model was wrong. 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-hypothesis https://www.astralcodexten.com/p/in-defense-of-the-amyloid-h...

mnode 6mo ago
Many in the research community realised the model was wrong a long time ago. This is a great read about the reasons why: 'How not to study a disease: the story of Alzheimer’s.' by Karl Herrup.
- ACCount37 6mo ago
  Wrong or incomplete? 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.
- sien 6mo ago
  Thanks for recommending this book. I'm now about half way through. It's really good.
Drupon 6mo ago
>I am David Schneider-Joseph, an engineer formerly with SpaceX and Google, now working in AI safety. Alzheimer’s isn’t my field If anyone wants to know who wrote the article linked before wasting time reading it, there you go.
- trhway 6mo ago
  there is even easier way to estimate the chances of time wasting - it is a "rationalist" website, an "effective altruism"-like version of rationality. wrt. original post - quickly googled, and that for example https://www.news-medical.net/health/What-are-Amyloid-Plaques.aspx 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%20study%20found%20that:%20*%20**Ramified%20microglia,contribute%20to%20focal%20neurodegeneration%20characteristic%20of%20PPA%2DAD. 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...
  - ifwinterco 6mo ago
    Huge codebase with years of fixes, features and hacks added on top and nothing ever refactored. It’s a miracle it works at all
    - generic92034 6mo ago
      It is worse. The code changes are mostly random, only surviving the tests of fitness nature is applying (on various levels though; immediately catastrophic changes on level of cell biology are sorted out). And at least the high-level tests are also random and unreliable.
friendzis 6mo ago
It's a classic example of "correlation does not imply causation". It was indeed observed that some patients with neurodegenerative conditions do indeed have amyloid plaques. It was further observed that patients with known Alzheimer's do not necessarily have amyloid plaques and patients without it do have plaques. The existence of amyloid plaques itself or the level, apparently, correlates extremely poorly, if at all, with the existence, onset or severity of the disease. Drugs attacking amyloid plaques might work, but they don't reverse the disease and do very little to slow progression. That's all scientific observations. > 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 https://link.springer.com/article/10.1016/j.nurt.2008.05.004 [2]: https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/trc2.70101 https://alz-journals.onlinelibrary.wiley.com/doi/full/10.100...
bradley13 6mo ago
Pretty clearly not. It would seem that beta amyloids correlate with Alzheimer's, but do not cause it. 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.
- enraged_camel 6mo ago
  >> It's much like climate science today: any dissent at all, even just questioning the predictions of catastrophe, immediately brands you as a heretic. 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.
- stingraycharles 6mo ago
  > 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.
  - defrost 6mo ago
    Over the past decades the group that are not happy with the AGW consensus in the hard earth sciences crowd have principally funded FUD via think tanks, ala the pro-tobacco lobby back in the day, rather than research. The few examples of research driven from the skeptic PoV (eg: urban heat skewing, etc) have landed on the side of the AGW consensus.
    - TheOtherHobbes 6mo ago
      And when they funded research, it confirmed the known science. https://www.scientificamerican.com/article/exxon-knew-about-climate-change-almost-40-years-ago/ 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.
caycep 6mo ago
the model is wrong, but the amyloid is still sitting there, staring at you, asking you what are you going to do about it?

bsder 6mo ago

The Amyloid hypothesis persisted for so long because we didn't have any obvious counterarguments since it is so hard to do studies on the brain. Which also means that it's not a bad hypothesis. 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.

ramraj07 6mo ago
There were no cointerarguments? There was a very simple counterargument: where was the causal data? If none exist why should I counter argue when you hadn't proven it to begin with.
- bsder 6mo ago
  There is a LOT of causal data. Autopsies of brains of Alzheimer's patients were rife with amyloid. People with mutations that caused amyloid got Alzheimer's earlier than others. 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.
  - ramraj07 6mo ago
    > Autopsies of brains of Alzheimer's patients were rife with amyloid 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.
    - stackghost 6mo ago

ramraj07 6mo ago

[flagged]

UberFly 6mo ago
The peer review process was repeatedly cheated by self-serving fraud. The medical field requires honest results and reporting. Why are you defending the fraud?
- t-3 6mo ago
  Science is no longer a hobby for the idle rich, it's an occupation. Peer review cannot function in a hostile environment governed by self interest (results == resume). Science practice needs to adapt to modern conditions rather than to pretend the idealized system that worked for an exclusive and elite group would work for a competetive worldwide industry.
  - uecker 6mo ago
    This is exaggerating and generalizing too much. Science still works extremely well in general.
DANmode 6mo ago
For replying to me, can you skip to the part where you explicitly call out what you believe the cause may be, as general of a label as it may be?

verisimi 6mo ago

> Pharma’s burned billions chasing this as it’s possibly the biggest market imaginable. 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.

dvfjsdhgfv 6mo ago
I think you are wrong, for several reasons. 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.
- Closi 6mo ago
  Plus even if it does involve expensive drugs and long term treatment, that would be a huge step towards cheap drugs and short term treatment. Lots of treatments start expensive and then come down in cost as competitors step in.
  - jleyank 6mo ago
    Patents run out also.
- SomaticPirate 6mo ago
  I agree with you but Ozempic is a bad example here. Part of the reason it is so valuable is that patients usually must take it for the rest of their lives. Its actually the perfect example of “evil” pharma since patients slmost akways regain the weight if they stop taking it. This leads to dependence or people searching for grey market sources. 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.

moffkalast 6mo ago

> We don’t even know what all we don’t know. Somewhat ironic given the context.

SwtCyber 6mo ago

A wrong model is not the same thing as fraud, and biology is full of plausible models that later turn out to be incomplete or misleading

yxhuvud 6mo ago
While true, there are a bunch of very influential results in Alz science that turned out to be fraud.

next_xibalba 6mo ago

> Whether it was fraudulent or just incorrect is a different question. 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.

deepsun 6mo ago

> We don’t know all of the details of human biology. Tautology statement. "We don't know all the details of X" for any X.

jvanderbot 6mo ago
That is not a tautology. But you're right it's trivially true.
- deepsun 6mo ago
  > In logic and mathematics, it is a statement that is true in every possible interpretation or situation.
  - jvanderbot 6mo ago
    ... by definition 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.

rob_c 6mo ago

> Whether it was fraudulent or just incorrect is a different question. 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)...

dtgriscom 6mo ago

> Edit: Google the in the pipeline blog. This and other have discussed this at length. Derek Lowe's blog is excellent, with 192 posts tagged "Alzheimer's Disease": https://www.science.org/topic/blog-category/alzheimers-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-work-with https://www.science.org/topic/blog-category/things-i-wont-wo...

frereubu 6mo ago
I miss Derek Lowe's "Thing I Won't Work With" series. I know there have always been large gaps between those posts, but it's been seven years since the last one so I guess they might be over. An excerpt from a favourite of mine: "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-work-peroxide-peroxides https://www.science.org/content/blog-post/things-i-won-t-wor...
- dtgriscom 6mo ago
  Yeah; they had a wonderful earthiness to their language; both highly technical and highly vivid. Like this comment on hexanitroisowurtzitane: > 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.