28 ms·

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

• anigbrowl 7y ago
  I have the impression when we read stories like this that it's not that the leading researchers in the field are hostile to other ideas, as such, but that they are not very well versed in economics and thus think that scarce research funding should flow their way because giving any to other possibly-wrong approaches would be wasteful, and likewise abandoning or discounting the predominant theory would be a terrible mistake because of all the money that has already gone into it (a sunk cost fallacy). Over and over we see that expertise in one field - even a very rigorous scientific one - doesn't immunize one from fallacious thinking in other contexts.
  • dba7dba 7y ago
    think that scarce research funding should flow their way because giving any to other possibly-wrong approaches would be wasteful I heard someone recently tell me how using science to form views on topics (social/psychology/etc) is dangerous, because science is really about funding. AND large donors/entities who can fund science often pick science research projects that sound cool and sexy. They may not be pushing any agenda but do lean toward funding trendy ideas. So really, science is often biased because of who hold the checkbooks. That really made me think.
    • WalterBright 7y ago
      Science is funded: 1. by desire for profit 2. by desire for political gain 3. by charitable impulses by people with money to spare Each has its problems and advantages. Best if we allow all three.
      • birdyrooster 7y ago
        Does creating weapons of mass destruction count for profit, political gain, both or something else?
        • saagarjha 7y ago
          Both, probably.
        • WalterBright 7y ago
          Generally speaking, government funded research is allocated for political gain. For example, defense R+D projects are famously (infamously?) allocated to the districts of Congressmen whose votes are needed.
      • smt88 7y ago
        Which of these categories does the National Science Foundation fall under?
        • garmaine 7y ago
          #2, as it is funded by politicians.
          • smt88 7y ago
            Politicians don't make decisions about which researchers get grants and which don't.
            • garmaine 7y ago
              They make decisions about what money is available in the first place, and appoint the leaders of the organization that runs the grant selection process.
              • smt88 7y ago
                No one is campaigning on NSF research. The director is appointed, but most of the staff are career workers who aren't replaced when the President or Senate change.
    • marmaduke 7y ago
      One can be wary of big money projects while trusting the larger trends, critical reasoning and method itself.
    • prox 7y ago
      I also wonder if it is a victim of the just-one-more-try problem you see in big code projects: you get funded for a year or more and the lead researcher honestly thinks he is - almost there - if only for that one more try. This means all resources are diverted, and only really late in the game you have to admit you were wrong, which gets harder and harder to do.
    • garmaine 7y ago
      What definition of “science” is this?
      • SiempreViernes 7y ago
        Reads like "science = titles of approved funding applications". One would hope people don't form opinions based on that (outside of how the funding system work).
    • bsder 7y ago
      > AND large donors/entities who can fund science often pick science research projects that sound cool and sexy. They may not be pushing any agenda but do lean toward funding trendy ideas. As well as those who do the science. You want tenure, you better not be too far off the beaten path. The biggest "scandal" at this level was the "cellular immunology" folks who based entire edifices around "recognition of non-self". And then DNA sequencing came along and completely smashed that. However, those professors were still tenured.
  • smt88 7y ago
    > sunk cost fallacy ...doesn't really make sense here. Let's say it takes 20 years and 5+ institutions to fully explore a single avenue of research. If you're 15 years into that research and you think there is a chance that you'll reach a breakthrough in 5 years, you're much more inclined to want your (and the other 4+ institutions) to pursue it for 5 more years rather than starting over. That's not sunk-cost fallacy. It's more like "a bird in the hand is worth two in the bush" or perhaps confirmation bias (the inertia the scientists felt to discard their conclusions about the causes and treatment pathways for Alz).
    • WhompingWindows 7y ago
      "If you're 15 years into that research and you think there is a chance that you'll reach a breakthrough in 5 years, you're much more inclined to want...to pursue it for 5 more years rather than starting over." How is that not sunk-cost fallacy?
      • smt88 7y ago
        An example of what I'm describing is: Decision A: 5 years (after 15 already spent) = 75% chance of success Decision B: 20 years (after 0 already spent) = 10% chance of success In that scenario, Decision A (sticking with your current research) is more rational as long as your estimate of your chance of success is accurate. We know from the article that this is not true -- their estimates were wrong. The sunk-cost fallacy would apply for something like: Decision A: 20 years (after 15 already spent) = 10% chance of success Decision B: 20 years (after 0 already spent) = 10% chance of success Since both A and B have the same cost and same likelihood of success, you should not consider the time you've already spent. Most humans would, though.
        • davinic 7y ago
          I would say that this is an example of the planning fallacy.
• ping_pong 7y ago
  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 later, and it has to do with how things get funded which is unfortunately leading society the wrong way.
  • Galanwe 7y ago
    > “ The same thing happened for decades where low fat diets were supposed to help for heart disease but that has only recently been reversed” Oh did not know that. Do you have reference material?
    • redis_mlc 7y ago
      A shill scientist was paid to promote high sugar, low fat diet a few decades ago by the sugar lobby. Just like every other food paper quoted in the press.
    • catoc 7y ago
      Read this: https://thebigfatsurprise.com/ https://thebigfatsurprise.com/ The website initially may look like yet another diet approach, but this is actually a serious publication. And a good read.
      • jonplackett 7y ago
        I spoke to someone about this the other day and they claimed it was now the dairy and meat industry campaigning in response to get their fatty foods re-accepted. Is there any truth to this? Or anyone heard anything about this?
        • catoc 7y ago
          I actually did read the book. It is really well researched. It certainly did not come across like that when the book was first published.
• rooundio 7y ago
  Unfortunately true for most scientific communities and the reason why the current academic system is badly broken and talented young minds decide to quit academia before even submitting a dissertation.
  • smt88 7y ago
    Talented young minds are mostly quitting because of terrible pay, inexperienced/cruel supervisors, long hours, gambling on tenure, and opportunities in private industry. The groupthink and publishing pressure are also problems, but they're very secondary to hellish career conditions.
    • rooundio 7y ago
      The reasons you raise are very true (I have been there), but most of them are mere symptoms of something deeper. I believe the root causes are exactly the kind of social dynamics discussed in the article. Terrible pay / other opportunities: Even at Ass. Prof. level pay is not so terrible. Sure, you won't get rich, but for most in academia that never has been a goal and would not matter. Long Hours: That also mostly would not be a problem, as long as you would be able to do what you truly like. Cruel supervisors: Here it's getting interesting. Why do you think that is? My hypothesis is that people become cruel if they don't like what they do. They basically become grumpy old men at the age of 40, because they always have to fight. Fight for money, fight against reviewers, fight internal department politics. Supervisors become cruel because they secretly hate their jobs, or better: the jobs the system makes them do. Gambling on Tenure: If you have the "right" supervisor in the "right" field (read: a good networker in the current hype topic) your chances are actually not that bad. But as soon as you do something that is either currently not on the radar of the community, or you do something that is even controversial, you get yourself into a fight - which as a young researcher you will lose. In academia you can only make it, if you are well connected and the community carries you there. Group think again. After years in the system I believe it all boils down to that: social dynamics and group think.
  • elfexec 7y ago
    Academia was always broken. Despite the current undeserved reputation as academia being open to debate and new ideas, the opposite has always been true. Academia has its sordid history of dogmaticism and hero-worshipping. And progress in knowledge usually advanced in spite of academia rather than because of it. Go read about the battles between Newton and Hooke or even Newton and Leibniz. The doctor who first suggested washing hand to cut down on infections in the 1800s was ridiculed and mocked by surgeons. Scientists who brought up germ theory were mocked as quacks by doctors and scientists who rigidly adhered to the miasma theory as gospel. Of course white supremacy was accepted "scientific fact" for a very long time by academia and anyone who thought otherwise would have been viewed similarly to a flat earther today. You could argue that white supremacy would still be "scientific fact" were it not for ww2. My personal favorite is Georg Cantor who was mercilessly attacked by his fellow academics within math and even without for his theories on infinite numbers. "The objections to Cantor's work were occasionally fierce: Leopold Kronecker's public opposition and personal attacks included describing Cantor as a "scientific charlatan", a "renegade" and a "corrupter of youth".[8] Kronecker objected to Cantor's proofs that the algebraic numbers are countable, and that the transcendental numbers are uncountable, results now included in a standard mathematics curriculum. Writing decades after Cantor's death, Wittgenstein lamented that mathematics is "ridden through and through with the pernicious idioms of set theory", which he dismissed as "utter nonsense" that is "laughable" and "wrong".[9][context needed] Cantor's recurring bouts of depression from 1884 to the end of his life have been blamed on the hostile attitude of many of his contemporaries,[10] though some have explained these episodes as probable manifestations of a bipolar disorder" https://en.wikipedia.org/wiki/Georg_Cantor https://en.wikipedia.org/wiki/Georg_Cantor "charlatan", "renegade", "corrupter of youth". Isn't it interesting how academics attack each other like religious people attack each other? The odd thing about some of the attacks on Cantor is that it came after his death and after he had PROVEN his countable and uncountable infinites. The history of academia is as nasty and vicious as any other institution. And its gatekeepers and heroes as petty and pathetic as any you'd find anywhere else.
• lenguyen 7y ago
  Great
  • lenguyen 7y ago
    Hello
• tempsy 7y ago
  Hasn’t Alzheimer’s been referred to as diabetes type III? It’s inflammation of the brain, and eating a low inflammation diet (low carb, no sugar, fasting) is the best thing one can do to drastically reduce getting it.
  • creato 7y ago
    > It’s inflammation of the brain, and eating a low inflammation diet (low carb, no sugar, fasting) is the best thing one can do to drastically reduce getting it. Do you have a source? If you state something like this with such authority/in a "matter of fact" way (and is something that seems likely to be controversial), you really should have a source.
    • abgfm 7y ago
      Here u go: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769828/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769828/
  • PunksATawnyFill 7y ago
    I thought that it was also strongly associated with gum disease: https://www.alzheimers.net/alzheimers-and-gingivitis-disease-linked-to-gum-disease https://www.alzheimers.net/alzheimers-and-gingivitis-disease...
    • ncmncm 7y ago
      Yes, which drove suspicion of a bacterial link. It could be quite complex -- bacteria helping herpes, or herpes helping bacteria into the brain, and the brain responding to one or the other or both with inflammation and plaques. And maybe something else involved, like inadequate or excess dietary intake of something like sugar, or trans fats, or PCBs, or glyphosate. We need to explore many, many possibilities.
      • frogger23123 7y ago
        Gum disease is linked to carbohydrates, which aligns with the "type 3 diabetes" hypothesis. (carbs feed bacterial overgrowth)
• ncmncm 7y ago
  > those alternatives are now being explored in both basic research and clinical trials. Some of those alternatives are being explored. Those of everybody driven out of the field are not. Is there any work on the bacterial observations?
• bransonf 7y ago
  I only learned of the flaws in the amyloid hypothesis a few weeks ago. The single most influential thing I read was this. [0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207354/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207354/
  • twic 7y ago
    I studied Alzheimer's a bit during my degree, so in 2002 or so, and it seemed pretty clear that the amyloid hypothesis was wrong even then. I had no idea it was still the dominant paradigm.
• allovernow 7y ago
  >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 in academia might bias climate science too? Except as another commenter pointed out, it doesn't take a shadowy cabal. Just a strong trend that individuals can believe in for ethical or moral reasons. Even when it becomes dogmatic.
  • BorisVSchmid 7y ago
    I can imagine that a dominant hypothesis could play a role in the predictions of future trajectories of climate on earth, but not so much for things like measuring past temperature / sea level rise. To twist the analogy back to Alzheimer - all these scientists still agreed on the patient-level diagnosis of Alzheimer.
  • baq 7y ago
    Anyone can put some co2 and a thermometer in a sealed container. A second one without additional ghgs, too. Alzheimer’s probably more difficult to understand and you have to trust somebody.
    • allovernow 7y ago
      I really, really think you're oversimplifying climate science.
      • baq 7y ago
        that's how it started over a hundred years ago, it's harder to start seeing progress on treating Alzheimer's.
      • ben_w 7y ago
        Sure, but in the same way that Newton’s laws of motion are an oversimplification of rocket science while still being enough to tell you that it works.
• praptak 7y ago
  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".
  • OneGuy123 7y ago
    You are missing the point. The point is this: we do not have a cure for this dieases now. Therefore, we do not know where to look at all. Therefore the best approach is to look at everything possible, since we obviously have no idea where to look. If we knew where to look, we would have atleast a partial cure. But no cure works now, none.
    • twic 7y ago
      > The point is this: we do not have a cure for this dieases now. > Therefore, we do not know where to look at all. This doesn't follow.
    • gus_massa 7y ago
      There are too many possible alternatives that may lead to a cure. What about homeopathic cures? I think it is snake oil, but some people think it is useful. If you try everything possible, you should try it. But it would be a big waste of money and allocation of patients and medical doctors. And also, there are many homeopathic recipes, so which one(s) should you try? What about radiation? A huge amount of radiation may help or may he harmful. I think it's harmful, but at least it can cause a real effect. Should we include that in the list of everything possible? Antibiotics? I don't think it would work, but it solved stomach ulcers after year of traying other treatments. Which antibiotic? Exercise? There are some studies from time to time, but I think most of them have the causation link backwards. I think we should make less studies in this field, but nobody asked me. I can add more and more alternatives. Some are ridicules, like nuns prayers, some may be legit like CRISP9. There are more possibilities than the current level of funding and patients available for clinical studies, so someone has to choose the more promising alternatives and hope they made the correct guess.
    • 7y ago
• sillysaurusx 7y ago
  The truth has a habit of shining through if you are encouraged to keep asking questions and follow up on them. The point is that people are actively discouraged from asking questions and following up on them. People lose their careers and livelihoods for asking the wrong sorts of questions. Truth is no barrier to social backlash. In fact, questions that might be true tend to be the ones that get people the most heated. https://twitter.com/a_centrism/status/1211170458902487042 https://twitter.com/a_centrism/status/1211170458902487042 (I have no stance either way regarding that account, but it's an interesting phenomenon that someone has to basically shroud themselves in anonymity to present certain flavors of scientific research.)
  • igorkraw 7y ago
    On the specific topic of IQ and scientific racism, the "centrist" position of "just asking questions" has been a cloak for agendas and not caring about the truth for a while now. Exhibit A: https://mobile.twitter.com/Simon_Whitten/status/1173319663322841088 https://mobile.twitter.com/Simon_Whitten/status/117331966332... Exhibit B, what happens when you actually dig into the science behind the most well known peddler of the IQ is real and important, therefore racism is actually not a problem meme https://m.youtube.com/watch?v=UBc7qBS1Ujo https://m.youtube.com/watch?v=UBc7qBS1Ujo Note that I'm not saying there aren't good faith inquiries to be had, but it is really hard to have these with racist agendas being pushed whole claiming "neutral" questions. A few observations that I would like people to keep in mind when looking at these fields: - the people who complain about being "silenced" continue to find funding, public platforms to push their research and in some cases, tenure - the "hard questions not being raised" seem to cluster around the question of differences between "races" and less around whether the concept of race actually makes sense in humans (AFAIK geneticists generally think no), whether these differences might be socially constructed (yes, that's possible. If there are systemic social biases against groups with genetic genes the impacts of these will be 100% explained by the presence of these genes in data, but 0% genetically determined as in biologically determined). And often they are then raised to dismiss concerns about the systematic problems which might have caused the measured problems - scientific racism and shoddy science in this field has a long history, and people carry their misconceptions around. Famous examples are "objective" written IQ tests given to barely literal test subjects, or asking trigonometry questions, Both of which test the schooling of the subjects more than the IQ In an inherently political field of science, denying the political nature and implications of questions being raised and the manner in which they are raised and trying ot claim "objectiveness" is in and of itself a political tactic.
• raincom 7y ago
  It is a well known phenomenon if you have studied the history and philosophy of sciences. Dominant paradigm(research program) writes off any anomalies their core hypothesis faces. They will explain away these anomalies with subsidiary hypotheses. Grants will be denied; tenures are denied; etc--all are common to anyone participating in a research program(paradigm) that competes with the dominant one.
• g42gregory 7y ago
  An honest question: How does this compare to the group-think in the climate change/global warming research? Are we similarly rejecting funding to any research that does not fit into the common consensus? The fact that we call some people "climate change deniers" tells me that we have an unhealthy dynamics going on there. Will it take 30 years to get to the same point?
  • buzzkillington 7y ago
    The same way that it compares to the group think that asbestos causes mesothelioma.
  • ivalm 7y ago
    > The fact that we call some people "climate change deniers" tells me that we have an unhealthy dynamics going on there 1. Climate change is observable, it doesnt rely on a theory, just measurements. Nonetheless there are a bunch of people trying to discredit what is essentially a very well established observation. 2. Genesis of climate change (ie is it anthropogenic) is not a direct observable, but looking at concentrations of CO2/other gasses and where it comes from it is not too hard to convince yourself of humans as root cause. Again, a lot of people deny human-driven climate change despite all evidence pointing one way. 3. Perhaps the most uncertain are climate model predictions. I agree that this where something might be overlooked, or maybe not. At any rate, "climate change deniers" by and large object to (1) and (2), and those people really have no credibility. If someone accepts anthropogenic climate change but proposes a new model that fits observation-- more power to them!
    • zorked 7y ago
      The biggest red flag is that "climate change deniers" aren't a fringe group of meteorologists, but a group of politically-inclined people who also denounce "cultural Marxism" and other crank theories. I assume that actual expert skeptics are given a lot more respect but also get far less exposure than deniers.
      • ivalm 7y ago
• ekianjo 7y ago
  > there is not even a disease-slowing treatment. True-ish, but Aricept is generally seen and used as a disease-slowing treatment (even if the data is inconclusive, it is perceived this way by physicians). > In patients with Alzheimer's Dementia participating in clinical trials, administration of single daily doses of 5 mg or 10 mg of ARICEPT produced steady-state inhibition of acetylcholinesterase activity (measured in erythrocyte membranes) of 63.6% and 77.3%, respectively when measured post dose. The inhibition of acetylcholinesterase (AChE) in red blood cells by donepezil hydrochloride has been shown to correlate to changes in ADAS-cog, a sensitive scale that examines selected aspects of cognition. The potential for donepezil hydrochloride to alter the course of the underlying neuropathology has not been studied. Thus ARICEPT cannot be considered to have any effect on the progress of the disease. > Efficacy of treatment of Alzheimer's Dementia with ARICEPT has been investigated in four placebo-controlled trials, 2 trials of 6-month duration and 2 trials of 1-year duration. > In the 6 months clinical trial, an analysis was done at the conclusion of donepezil treatment using a combination of three efficacy criteria: the ADAS-Cog (a measure of cognitive performance), the Clinician Interview Based Impression of Change with Caregiver Input (a measure of global function) and the Activities of Daily Living Subscale of the Clinical Dementia Rating Scale (a measure of capabilities in community affairs, home and hobbies and personal care). - % Response - Intent to Treat Population n=365, Evaluable Population n=352 - Placebo Group 10%, 10%, - ARICEPT tablets 5-mg Group, 18% (sig), 18% (sig) - ARICEPT tablets 10-mg Group, 21% (sig), 22% (sig) Aricept does not seem to have much efficacy overall, but it makes a lot of money for the lack of alternatives. (https://www.medicines.org.uk/emc/product/3776/smpc https://www.medicines.org.uk/emc/product/3776/smpc)
  • omgwtfbyobbq 7y ago
    I'm guessing the perception that it slowed Alzheimer's is because some patients were misdiagnosed. Aricept can help with falls in Parkinson's patients with balance problems, and in my experience seems to help with arousal. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3013493/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3013493/ Accurately diagnosing the elderly is difficult. My grandmother was diagnosed with Alzheimer's 15-20 years ago, which was likely inaccurate. At this point it looks like she probably has Dopa-Responsive Dystonia and may also have some form of Vascular Dementia, some sort of CSF disorder, and possibly some other problem that hasn't been diagnosed.
• Gatsky 7y ago
  Indeed. Nothing will save you if you have the wrong idea.
• TrackerFF 7y ago
  Is Alzheimer's on the rise, or are are simply more people getting diagnosed with it due to increased life expectancy? A quick google search yields avg. age of diagnosis to be 80 years; 50 years ago life expectancy in the western world was 70 years, so a bunch of people would've probably passed from Heart Diseases and stroke back then, before getting to the point of dementia. So it's pretty reasonable to assume that more research went towards things like heart diseases, etc. the past 50 years, than towards dementia and the likes. But now, as we see a steady decline in those things (or at least them being the leading cause of death), we see more longevity-related diseases, like cancer and dementia. What I'm trying to get at here is: Yes, maybe there have been ruling forces in academia and research that have stopped alternative theories, but wouldn't a simpler explanation be that there have simply been more pressing issues up until now, and we're now seeing a rise in things like dementia, due to having deal with those previous problems. We have dementia in one side of our family, even though most have gotten it in their late 70s / early 80s, so I obviously hope they come up with something - which I have no doubt will happen, the next decades.
• zosima 7y ago
  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's disease, noted amyloid-beta plaques as a key pathological finding. Amyloid-beta plaques are a characteristic of the disease, and a proper Alzheimer diagnosis requires the presence of amyloid-beta plaques. Many variants of early-onset Alzheimer are caused by mutations either directly in APP (the precursor to amyloid-beta) or genes intimately involved with APP-processing (e.g. PSEN1 and PSEN2). These mutations often cause extreme levels of amyloid-beta and amyloid plaques. Raised levels of amyloid-beta and amyloid plaques is a necessary condition for Alzheimer's disease, both early- and late-onset. But it's clearly not a sufficient criteria: many people have brains full of plaques and amyloid-beta, but little or no cognitive decline. So the problem with Alzheimer's research is not so much the understanding that amyloid-beta is a significant part of the story, but rather focusing on it as the only part of the story and the only conceivable solution. [1] https://edition.cnn.com/2019/10/22/health/biogen-alzheimers-drug-fda/index.html https://edition.cnn.com/2019/10/22/health/biogen-alzheimers-...
  • amluto 7y ago
    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.
    • zosima 7y ago
      FDA usually puts some quite strict limits on the amount of p-hacking and general shenanigans they allow in clinical trials. But there's no approval yet, and no data to look at, so it's too early to judge. Anyway, usually Alzheimer trials are a jumble of noise. The cognitive measurements are imperfect and patients are improving and deteriorating randomly, taking a very different disease course than you'd expect from textbooks. Finding a signal in the data, even for a working drug can be quite hard. I could just as well believe that Biogen ended the trial hastily because all competitors had failed and they didn't do a thorough analysis.
• svara 7y ago
  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) was first described: In 1911, Alois Alzheimer found plaques in his dementia patient's brain. [0] These plaques are what researchers would focus on for more than the next 100 years. Much later, the protein giving rise to the plaques (APP) was discovered and there seemed to be good evidence for a causal role: Mice with mutated APP developed AD. Quoting the article: """ By the mid-1990s, a now-defunct San Francisco biotechnology company, Athena Neurosciences, created the first genetically engineered mice with a mutated, amyloid-producing human gene. The animals’ brains filled with amyloid plaques, and their memories were destroyed. The mice were hailed as a “model for testing therapeutic [Alzheimer’s] drugs” """ So we should really take this story as a cautionary tale. There was, however, no conspiracy or "cabal". These were simply people who were convinced they were on the right track. In a way, they were, since hereditary Alzheimer's is caused by APP mutations, it just turns out that this isn't as important as other ways of developing the disease. [0] https://en.wikipedia.org/wiki/Auguste_Deter https://en.wikipedia.org/wiki/Auguste_Deter
  • michaelbarton 7y ago
    > 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 research.
    • dmix 7y ago
      If you watched the NBA the top 5% of players/top 5 teams get 90% of the media attention. The rest who are still doing good and interesting things fight for the last 10% of the crumbs and are forever complaining they are being excluded despite performance and other factors. It happens in a lot of places. And to be honest it’s what most of the people want and while places like r/nba are more neutral and give respect where it is due, ESPN knows the casual 12yr old knows Lebron James and Steph Curry and they recruit “talent” to only talk about them, not just what is going well for the sport as a whole. It’s a difficult balance that is really up to the power players and the quality of leadership to get right. With science though you’d hope far more meritocracy than big names, but sadly I believe this is a human and non-expert efficiency thing (as most people are not really experts). Some people might blame capitalism of the bio firms but they are just the sum of their people who run and fund them too.
• jaggednad 7y ago
  The article talks of journals rejecting papers because the author had already been rejected by other journals or because the author’s prior papers were in less-prestigious journals. This method of selecting papers is the perfect recipe for groupthink. The names of the authors should be removed while a paper is being reviewed—the reviewers shouldn’t know who wrote it so that they’ll be forced to evaluate the paper on its intrinsic merits rather than the reputation of its author. That might not solve this beta amyloid orthodoxy problem, but it’d help at least
  • btrettel 7y ago
    > they’ll be forced to evaluate the paper on its intrinsic merits rather than the reputation of its author Similarly, many academics won't evaluate published papers on their own merits and instead focus heavily on proxies like publication venue. Conference papers are unfairly viewed with suspicion compared against journal articles (in my field at least), and certain venues are viewed as superior in general to the point where some "don't count". These academics instead outsource the evaluation to a few reviewers, who often don't know what they're doing. Peer review does not appear to be as reliable as it is treated. I view peer review as closer to a lottery. And the "best" journals still frequently publish nonsense. It tends to be more pretentious nonsense in my field, though. I don't care too much about signaling the quality of my work and instead would rather publish in more specialized journals and conferences where I can reach the people I want to reach and get better feedback. I recall at a presentation on getting a faculty job someone said that they won't count any publications in journals with names they don't recognize. Both quality specialized journals and bad journals are included in that set. Add on top of that the common view that conference papers also "don't count" and I think the incentives here are bad.
  • greglindahl 7y ago
    Ask people who work in any field that does have blind review, and they'll tell you that it isn't actually blind... you can make good guesses on the author list by examining the description of previous work, the reference list, the style of the writing, etc etc.
    • 7y ago
• LifeLiverTransp 7y ago
  Maybe there should be a auto-anti-dogmatic percentage in all research funded.
• richk449 7y ago
  It is easy in retrospect to see that going all in on the amyloid hypothesis was a mistake. But that is always true once a hypothesis has been proven false (or at least not completely true). Is it possible to look at this as a very large “fail fast” experiment? Given the limited funding, would it really have been better to spread it over many hypotheses, rather than pick the most likely, and test a minimal viable solution?
  • vidarh 7y ago
    It may well be that the right strategy sometimes is to pour most funding into the most promising candidate, but the question is how large a proportion of the funding that ought to be vs. how much is left over to fund at least initial inquiries into alternatives. Even more so how soon you should rebalance funding if further progress isn't achieved with respect to your biggest bet.
  • WhompingWindows 7y ago
    I collaborate with an expert in Alzheimer's Disease. She stated to me that the Amyloid hypothesis was so strong for so long because it is "like the garbage left over in a stadium after a big event...you see concrete evidence something happened, it's obvious this garbage is bad and should be cleaned up, but the garbage itself did not cause the event."
  • ppseafield 7y ago
    It's hard to see this as a fail fast experiment when: > In more than two dozen interviews, scientists whose ideas fell outside the dogma recounted how, for decades, believers in the dominant hypothesis suppressed research on alternative ideas: They influenced what studies got published in top journals, which scientists got funded, who got tenure, and who got speaking slots at reputation-buffing scientific conferences. It's one thing to go all-in on a hypothesis, but another to undermine other folks' hypotheses directly. Especially when your hypothesis has not produced any results for decades.
• WhompingWindows 7y ago
  I presented my research on Delirium, dementia, and frailty at an Alzheimer's conference last year. There was no evidence of an Alzheimer's amyloid "cabal" in that room. Around 90% of the work being done had to do with early diagnosis: since this is a chronic, long-term disease, like diabetes or heart disease, most of the research and talks were about how to diagnose and treat EARLY, before the neurological damage has been inflicted. In my opinion, there will probably be no silver bullet for Alzheimers, though we may develop long-term treatments which slow the rate and severity of the disease in those pre-disposed or in the early stages of AD.
• JackFr 7y ago
  Plate tectonics. Literally ridiculed and dismissed as pseudoscience. Now we consider it manifestly obvious.
• cockatiel_day 7y ago
  This article is 100% true. My first job out of college 10 years ago was in a lab focused on Alzheimer’s research. Our Principle Investigator made an art of writing grant applications for studies that would appear to be in line with mainstream theory, but were really intended to test theories he actually thought were worth testing, presented in results as an “interesting” aside. He believed the amyloid theory had been conclusively disproven. He explained to me that people like him work for decades, quasi-retire into positions accepting grant applications, and have a conscious or unconscious agenda to preserve or validate their life’s work. His money quote was “science is like the Catholic Church, a lot of nice sentiments but full of people”. I don’t have any evidence or examples, but I suspect this dynamic is not limited to Alzheimer’s research. Another anchor to research not mentioned in the article is how much sponsoring universities take from research labs. To put a university endorsement on our research, which is needed to be credible, the university took half (half!) our grant money.
  • wavepruner 7y ago
    "I suspect this dynamic is not limited to Alzheimer’s research." Agreed, I think it is a universal problem in science. I have an illness that has been curable for decades now, but this cure is treated with hostility by the medical establishment. I look forward to the day when the cabal of my illness collapses. Hopefully then I will be able to talk about what happened without people getting angry.
    • keeganpoppen 7y ago
      looks like that day isn't today, given the downvotes xD in fairness, i think people have a hard time taking claims like this seriously without a little more information, due to its superficial similarity to those of a "crackpot". (but while the _precision_ is pretty poor on the correctness of "crackpot" theories, the _recall_ is pretty much 100%) arguably > 100%, to be a bit tongue-in-cheek
      • roenxi 7y ago
        Even more information wouldn't really help. 'Crackpot' is something of a shorthand for an idea that disagrees with consensus research position. The only tool an average person has to determine an idea as truth or fiction is whether it lines up with the current professed norms; so for a technical forum like HN ideas that disagree with the standard research position can only be ignored due to lack of evidence.
• JimBrimble35 7y ago
  "“Once a field commits to a particular hypothesis, the research resources — funding, experimental models, and training — all get in line,” she wrote in a 2018 analysis. That brings backers of the dominant idea accolades, awards, lucrative consulting deals, and well-paid academic appointments. Admitting doubt, let alone error, would be not only be a blow to the ego but also a threat to livelihood." Is this not extremely controversial? It was always my belief that "not creating a cure for X disease keeps the money flowing" was the calling card of tinfoil hat wearing conspiracy nuts. This statement, and the following paragraphs seem to suggest this is somewhat commonplace
  • internet_user 7y ago
    How is that controversial? That's just people for you.
• m3kw9 7y ago
  Is like to hear some pro Amyloid researchers chime in on this.
• m3kw9 7y ago
  The article says it has nothing to do with evil or anything but it all comes back down to money, incentives and sustaining egos.
• goodcanadian 7y ago
  "A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die, and a new generation grows up that is familiar with it." -Max Planck Or, as it is more commonly put: Science advances one funeral at a time.
  • mirimir 7y ago
    Right. Also Thomas Kuhn's The Structure of Scientific Revolutions (1962).
  • lincolnq 7y ago
    Is there an age at which you favor forcing scientists into retirement?
    • NotSammyHagar 7y ago
      It's not forced retirement that is needed, it's constant replenishing of leaders and decision makers to let new ideas have a chance. So things can't advance, sometimes, until the people who are invested in the old ways stop blocking the new ways.
  • quantified 7y ago
    Just made the same observation, then scrolled down to see yours.
• knzhou 7y ago
  Whenever you hear about science being a "cabal", you have to remember that there's a huge survivorship bias. At any moment in science, there are a few dominant hypotheses, which seem to work pretty well, and hundreds of alternative hypotheses, with only vague evidence in favor of them. The vast majority of alternative hypotheses turn out to be completely wrong, and the researchers pushing them are forgotten. The few that turn out to be right get funding and recognition, exactly as many of the researchers mentioned in this article are getting now. In fact, most criticisms of dominant paradigms in science you read are not from outsiders, but from career scientists who are leading the charge towards the next dominant paradigm. I say this just to point out that understanding the world is not as simple as believing contrarians. At any moment in time, almost all contrarians are completely wrong. Almost all paradigm shifts didn't work. Almost all anomalies faded away.
  • quantified 7y ago
    Recall the saying that science proceeds one funeral at a time. I believe it was coined as part of describing the shift to acceptance of plate tectonics.
    • greglindahl 7y ago
      That's the worst case. It doesn't always proceed that slowly.
      • caycep 7y ago
        The professional science/medicine funding system (i.e. NIH money) can be characterized by "cabal" depending on how you look at at it. If by "cabal" they mean any organized profesional vetting system. I suppose there is a trade off between vetting good funding ideas from the bad, vs. the risk of "suppressing" original views aside from the "dogma". Did some alternative views get squashed by not receiving R or K grants? maybe. I would bet some of them might have been true original ideas that needed money to get good preliminary data. But many of them probably did not pan out. A lengthy way of saying I agree w/ the OP of the thread...
    • 7y ago
• colin_fraizer 7y ago
  Great article. Now do “climate change”!
• kd0amg 7y ago
  if alternative ideas received little funding support, it was because NIH’s Alzheimer’s budget was woefully insufficient ($425 million in 2012, $2.4 billion in 2019) low NIH funding for Alzheimer’s from the 1980s through the 2000s is to blame for alternative ideas languishing This seems like a hollow excuse. AFAIK, NIH doesn't have a mandate to put a certain amount of funding towards one line of inquiry before funding another.
  • aidenn0 7y ago
    > This seems like a hollow excuse. AFAIK, NIH doesn't have a mandate to put a certain amount of funding towards one line of inquiry before funding another. Rather NIH can't fund projects for the 10 most likely ideas, so it funds projects for the 1 or 2 most likely ideas.
• cpr 7y ago
  Isn't this exactly the same in other areas such a cancer research?
• rosybox 7y ago
  We don't seem to understand much about any of diseases that affect the brain or nervous system. MS, Parkinson's, ALS, Huntington's disease, alzheimers, not even essential tremors or BFS. All these futurists thinking longer lives are just around the corner when in reality we don't jack shit about shit. Something goes wrong with your nerves or brain, you're likely fucked and there's little anyone can do to help you.
• lenguyen 7y ago
  Hello
• alpineidyll3 7y ago
  Perhaps the most pernicious example of a common dysfunction of the grant system and entrenchment of power in old faculty. We hired a friend of mine exclusively to study amyloid beta spectroscopy. He was aware that it probably didn't explain the pathology, but how else would he get a job?
• LatteLazy 7y ago
  >Several who tried to start companies to develop Alzheimer’s cures were told again and again by venture capital firms and major biopharma companies that they would back only an amyloid approach. I wonder if that's because their internal advice was from "cabal members" or if they didn't like the fundamental science or some other reason? Maybe the economics of (well understood) beta amyloid ideas worked better economically than new ideas (I guess it's a big, unhedgable gamble to invest in something that might be a cure, but won't be on the market for 20 years). The whole point of venture capital is to fund things that "mainstream" has rejected but rejected without good reason. That does make me wonder a bit how good the science behind other ideas was.
• blargmaster33 7y ago
  This is exactly what you would expect from government research.
• djeyeteheget 7y ago
  Ffsfgxdbdydhdh
• D-Coder 7y ago
  The author of the article, Sharon Begley, is a very good science writer. I've seen her writing elsewhere too.
• gardenfelder 7y ago
  I am reading the book "An Epidemic of Absence" by Moises Velasquez-Manoff, which articulates a basis for everything being covered in this HN thread. While I wish the author made better use of citations and footnotes, the narrative seems compelling.