[HN Gopher] Faked Beta-Amyloid Data. What Does It Mean?
       ___________________________________________________________________
        
       Faked Beta-Amyloid Data. What Does It Mean?
        
       Author : hprotagonist
       Score  : 195 points
       Date   : 2022-07-25 14:31 UTC (8 hours ago)
        
 (HTM) web link (www.science.org)
 (TXT) w3m dump (www.science.org)
        
       | jmyeet wrote:
       | I'm not in academia but here's what I don't understand.
       | 
       | Generlaly, my understanding was that important results typically
       | get replicated by other institutions and teams. Not necessarily
       | to prove that initial result but to work out the limits of
       | whatever the conclusion was. Imagine you discovered that
       | ibuprofen could reduce the risk of stroke by 30%, for example.
       | You would have other teams that might start playing with the
       | factors and asking different questions like:
       | 
       | - What if we raise or lower the dosage?
       | 
       | - Waht if we mix that with other medications?
       | 
       | In doing so you'd get further confirmation of the original
       | result.
       | 
       | You'd think there'd be some similar studies done of the original
       | result but that doesn't seem to have been the case or this fraud
       | would've been discovered already.
       | 
       | So for anyone who does know about how this works, why didn't this
       | happen?
        
         | photochemsyn wrote:
         | One neglected issue here is the role of government funding
         | agencies and universities in controlling who gets funded. It's
         | common practice for universities to encourage their own
         | researchers to get government positions at funding agencies,
         | where they can help shepherd grants back to their parent
         | institutions, for example. Something like this seems to have
         | gone on with Alzheimer's funding - some people involved with
         | the source lab ended up directing funding at the federal level.
         | 
         | So, if you're a researcher who decides to publish refutation of
         | a fundamental claim by the leading stars in the field, you risk
         | getting on a funding blacklist, and your grant review doesn't
         | get approved. Hence, the safer thing to do is simply ignore the
         | research you suspect to be fraudulent and take your own
         | research in a different direction. There's also the concept
         | that they don't want to discredit the entire field by exposing
         | fraud and thereby risk Congress spiking the funding entirely or
         | something like that.
         | 
         | Incidentally, a lot of the silence on the very plausible notion
         | that Sars-CoV2 escaped from a lab, and that its transmissibiliy
         | and virulence likely were increased in the lab as a consequence
         | of various gain-of-function (well-meaning I suppose) research
         | techniques (serial passage, CRISPR engineering, etc.), appears
         | to be due to similar concerns (i.e. researcher who even discuss
         | the possiblity might run afoul of people like Fauci and cohort
         | who still control virology research funding).
        
         | larkost wrote:
         | Sadly it is the very reasonable assumption that is wrong:
         | important findings often do not get replicated. Usually the
         | setup and execution (even working from great notes) is long and
         | difficult, and often involves something specialized like trans-
         | genetic mice (engineered for experimenting on this specific
         | thing). And the benefits for being the lab that successfully
         | repeats an experiment are approaching 0, and because there are
         | so many thing that could go wrong a failure to replicate is not
         | often a slam-dunk repudiation.
         | 
         | So there is little incentive for people to do this. This should
         | probably be fixed, maybe with some right-of-passage for Post-
         | Docs being assigned to replicate important works, with explicit
         | funding from the NIH (or someone) earmarked for this as a sort
         | of training budget.
        
         | jcranmer wrote:
         | > You'd think there'd be some similar studies done of the
         | original result but that doesn't seem to have been the case or
         | this fraud would've been discovered already.
         | 
         | As Derek Lowe says, this _did_ happen:
         | 
         | > I could be wrong about this, but from this vantage point the
         | original Lesne paper and its numerous follow-ups have largely
         | just given people in the field something to point at when asked
         | about the evidence for amyloid oligomers directly affecting
         | memory. I'm not sure how many groups tried to replicate the
         | findings, although (as just mentioned) when people did it looks
         | like they indeed couldn't find the _56 oligomer. And judging
         | from the number of faked Westerns, that's probably because it
         | doesn't exist in the first place. But my impression is that a
         | lot of labs that were interested in the general idea of beta-
         | amyloid oligomers just took the earlier papers as validation
         | for that interest, and kept on doing their own research into
         | the area without really jumping directly onto the_ 56 story
         | itself. The bewildering nature of the amyloid-oligomer
         | situation in live cells has given everyone plenty of
         | opportunities for that! The expressions in the literature about
         | the failure to find *56 (as in the Selkoe lab's papers) did not
         | de-validate the general idea for anyone - indeed, Selkoe's lab
         | has been working on amyloid oligomers the whole time and
         | continues to do so. Just not Lesne's oligomer.
         | 
         | In other words, the result was tried to be replicated a few
         | times, and no one could replicate it. But the groups working in
         | this space were already pursuing similar paths before this
         | paper, and the results were taken not as a "target this one
         | specific thing and you'll be golden" but rather "here's more
         | evidence that targeting this class of thing is useful in this
         | place."
         | 
         | I'll also point out that by the time you're talking dosage
         | questions, you're generally tackling clinical trials (phase II
         | trials are meant to establish the dosing regime), which is far
         | downstream of work that gets published academically.
        
         | WC3w6pXxgGd wrote:
        
       | jvanderbot wrote:
       | How did we rule out an underlying pathology that triggers toxic
       | buildup of these substances, either as a byproduct or even as a
       | _defense mechanism_ (perhaps to isolate  / destroy neurons that
       | are infected).
       | 
       | It would seem that if cognitive decline were caused by some
       | neurological disease and the body were fighting that, it might
       | cause all kinds of dangerous looking things to happen to neurons.
       | And, if you do dangerous things to neurons, perhaps you _also
       | get_ cognitive decline.
        
         | lazide wrote:
         | It hasn't been ruled out, it just hasn't been able to be
         | identified either.
         | 
         | Some research is ongoing related to viral infection from some
         | common viral species for instance.
         | 
         | The problem is that we have non-destructive and reliable way to
         | image or sample the brain at the resolutions necessary to see
         | what is going on right now.
         | 
         | If you can't see or sense what's happening until it's too late,
         | it's _really_ hard to figure out what is going on.
         | 
         | If doing post-Mortem brain biopsies (most common way) for
         | Alzheimer's patients and the plaques is the equivalent of
         | picking through the wreckage of a lost war, it's pretty hard to
         | figure out who was the enemy and who was collateral damage.
        
           | mitjam wrote:
           | There are some but research into viral origins or other
           | competing ideas seem to be marginalized and underfunded, I
           | don't have first hand insights into it but read about it here
           | https://www.statnews.com/2019/06/25/alzheimers-cabal-
           | thwarte... and elsewhere.
        
           | throwawaymaths wrote:
           | > we have non-destructive
           | 
           | I think you meant to say we _don 't_ have non-destructive?
        
             | lazide wrote:
             | Thank you, yes. I can't edit my comment anymore. :(
        
         | zosima wrote:
         | It hasn't been ruled out, but as Derek Lowe mentions, there is
         | a good amount of genetic evidence that increased cleaving of
         | APP and thus more amyloid-beta leads to earlier, faster and
         | more severe Alzheimer's.
         | 
         | And certain mutations in the amyloid-beta producing APP-
         | cleavage machinery leads to familial dominant Alzheimer's,
         | where the carriers will almost certainly develop early
         | Alzheimer's.
         | 
         | So there is not many ways around APP/amyloid-beta having some
         | role in Alzheimer's pathology.
        
         | throwawaymaths wrote:
         | We didn't rule it out. I worked in an Alzheimer's lab about 15
         | years ago. In our outside voice for Grant committees,
         | publications, etc. We acknowledged the amyloid hypothesis but
         | internally _almost every other group meeting_ the postdocs and
         | grad students disclaimed that we still couldn 't rule out
         | "common factor X". It was also morbid humor we would say "oh
         | maybe the amyloid hypothesis is wrong" whenever something
         | strange would come up. We only about 10% joking. It's nice to
         | see that skepticism has finally bubbled up across the field.
         | 
         | I like to think we were one of the more honest groups in the
         | field -- I have post-publication corrections on my papers, the
         | lab issued an 11-page retraction (with cautions about what not
         | to do experimentally) when it turned out one of our lab's major
         | findings was an artifact [0].
         | 
         | It's worth noting WHY the amyloid hypothesis sticks around,
         | it's because the prion hypothesis is extremely well supported
         | by the data (even though I think pruisner is a shady dude), so
         | it's not a stretch to think that other amyloid diseases work in
         | a similar way [1].
         | 
         | [0] the grad student who pushed through this paper is a huge
         | scientific hero.
         | 
         | [1] there are some subtleties though.
        
           | throwawaymaths wrote:
           | I guess I should post a positive example of what the field
           | (should be/should have been) doing:
           | https://onlinelibrary.wiley.com/doi/full/10.1002/pro.2339
           | 
           | Ms. Murray (aforementioned hero) is doing a startup these
           | days so if you are or know any VCs that talk a good game
           | about funding science then see if they'll throw some money
           | her way.
        
       | pcrh wrote:
       | Here is a lengthy response from more than 20 researchers in the
       | field [0]. In brief, the claims made in the article above are
       | exaggerated. As someone who works in the field, and who is
       | skeptical of the amyloid hypothesis, I agree.
       | 
       | [0] https://www.alzforum.org/news/community-news/sylvain-
       | lesne-w...
        
         | gausswho wrote:
         | Having read it, I don't recognize anything that suggests the
         | Science article is an exaggeration. Perhaps there's something
         | in the comments you're referring to, but if so can you be more
         | specific?
        
           | pcrh wrote:
           | Scientists are often very circumspect in how they phrase
           | things, but this particular phrasing in the main article is
           | notable:
           | 
           | >"This is not a real scientific problem, but it is most
           | unfortunate for general science credibility," Selkoe wrote to
           | Alzforum.
           | 
           | Edit: I should add that the "oligomers" described in the
           | Lesne article have been found by other researchers, see [0]
           | 
           | [0] https://scholar.google.co.uk/scholar?hl=en&as_sdt=0%2C5&q
           | =Ab...
        
             | kamranjon wrote:
             | I read that it might actually be that these specific
             | Oligomers might not be detectable in anything but
             | genetically engineered mice - and detection in humans has
             | not actually been proven outside papers in question, is
             | this true?
        
               | pcrh wrote:
               | It's quite difficult for researchers to gain access to
               | human brains, needless to say, so the number of studies
               | attempting to find specific oligomeric species in human
               | brain are limited.
               | 
               | However (and without attempting an exhaustive search),
               | detection of oligomeric amyloid (if perhaps not the
               | specific species reported by Lesne are reported, e.g.
               | 
               | https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1750-36
               | 39....
        
               | pessimizer wrote:
               | So you're in complete agreement with the article, then?
               | You've said nothing that wasn't mentioned.
        
         | Sniffnoy wrote:
         | In the article above? This is in response to the original
         | article by Charles Piller, not this summary by Derek Lowe.
        
         | jeremyjh wrote:
         | It's so shocking that they don't want their field to be
         | discredited.
        
           | pcrh wrote:
           | Not really. There is plenty of criticism of the amyloid
           | hypothesis within the field, and even specifically of the
           | oligomer variant thereof that Schrag focused on. You can even
           | read that criticism in the link I provided.
           | 
           | Schrag's investigation did not (in my opinion) discover any
           | fraud in the Lesne paper, even if the paper perhaps over-
           | states its case.
           | 
           | The amyloid hypothesis has several very strong strands of
           | evidence in its favor, specifically that it is (currently)
           | the only way to reconcile the indisputable genetic and
           | pathological evidence for mutations in the genes APP and
           | presenilin both producing early-onset Alzheimer's disease.
           | Amyloid is derived from the action of presenilin on APP.
           | 
           | Until an alternate way of reconciling this observation is
           | found, the amyloid hypothesis will always have supporters.
        
       | lazide wrote:
       | Good write up on a very disturbing case of blatant academic
       | fraud.
       | 
       | Some of the methods mentioned that were used to discover it are
       | pretty simple - prior compression artifacts showing borders
       | around sub areas of a large graph, indicating cutting and pasting
       | of elements, etc.
       | 
       | What I don't get, is why the underlying data doesn't get included
       | and any graphs just generated from that? Why have an actual
       | embedded image and that's all good?
        
         | pcrh wrote:
         | Unfortunately, it seems that in this case it is the author of
         | the article published by Science (Schrag) who is remiss and has
         | written a poorly-researched article. See the link I provided
         | elsewhere in this thread.
        
         | searine wrote:
         | This type of data is 'old school' molecular biology.
         | 
         | Creating those blots is a grind. It takes hundreds of hours to
         | set up those experiments and they often don't work, or go
         | wrong, and you have to do it all over again. The people who are
         | good at making these are usually the people who aren't really
         | up to date with the whole 'computers' thing.
         | 
         | Yes, there would a hundred ways to easily verify the provenance
         | of data from an image of a blot all the way to publication.
         | However, this area of research is very slow to incorporate the
         | latest computer tech.
        
           | pmyteh wrote:
           | [Be aware that your comments appear to be default-dead. I've
           | vouched for this one, but you may want to contact dang to ask
           | for your account to be unflagged: I can't see anything
           | objectionable in your post history so it's probably a false-
           | positive].
        
             | searine wrote:
             | Thanks for letting me know. Mods couldn't figure out why
             | either and fixed it.
        
         | sooheon wrote:
         | Western blots are analog -- the captured image _is_ the
         | underlying data.
        
           | gspr wrote:
           | Could one imagine imagining equipment cryptographically
           | signing the images they spit out?
           | 
           | (Sorry if this is a super naive HN-esque comment - the topic
           | is far outside my field, and I don't mean to actually suggest
           | this as a solution, I'm just curious.)
        
             | _Wintermute wrote:
             | That's definitely possible.
             | 
             | These sort of images are typically re-arranged to fit
             | nicely in a figure for publication. It's now more common
             | that any figure that has a western blot within it, you also
             | have to provide the raw unaltered image. Though this wasn't
             | standard practice at the time.
             | 
             | As someone in the field, western blots are terrible for a
             | number of reasons. Even if you get nice bands and you're
             | honest about what you show. The companies that make the
             | antibodies for these commonly sell people duds that will
             | bind to a number of unknown things, and people blindly
             | trust that since the website said it's specific for
             | protein-XYZ, that's what they're measuring.
        
       | tomohawk wrote:
       | This is why censoring people on social media platforms when they
       | disagree with "the experts" is so dangerous.
       | 
       | Science is not about listening to experts. It's about the data,
       | and about falsifiable theories.
        
       | Imnimo wrote:
       | People want to point the finger at structural problems with
       | academia to explain why this wasn't caught earlier. But what
       | about industry? Didn't they have a huge incentive to catch this
       | sort of thing before they spend boatloads of money on clinical
       | trials, and didn't they have some level of immunity to concerns
       | about tenure committees and journal editors? If this was so easy
       | to catch if it weren't for the troubling incentives of academia,
       | why did drug companies still spend billions on it?
        
         | mbreese wrote:
         | Because of the potential upside.
         | 
         | If your potential market is "all aging people", that's a pretty
         | big market. Even better when you realize that as people are
         | older, they have more money, so the market you're targeting
         | tends to have more money to spend on medical expenses.
         | 
         | Now, couple that with a highly competitive landscape where the
         | first to market will capture the vast majority of that market
         | and you can see how some steps might get skipped.
         | 
         | Finally, if we did have random results in clinical trials, if
         | you had 20 companies running a trial, you could expect at one
         | of them to randomly have a positive trial (p <= 0.05). So you
         | could have "promising" results for a small trial that would
         | only fail once you had a larger number of participants.
         | 
         | The market incentives and potential for lost opportunities were
         | probably enough to justify a larger risk for some companies.
        
         | bhk wrote:
         | According to the article, the research in question did not
         | result in any clinical trials.
        
         | throwawaymaths wrote:
         | > why did drug companies still spend billions on it?
         | 
         | Due dill is hard. Why did no one catch ubeam? Why is energous
         | still a thing? Why has no one called out LAZR on their
         | nonsense?
        
         | xiande04 wrote:
         | > why did drug companies still spend billions on it?
         | 
         | Because they made even more off it.
        
           | throwawaymaths wrote:
           | No, they lost money on it. Clinical trials aren't cheap.
        
           | jcranmer wrote:
           | Only one drug has been even provisionally approved--Aduhelm--
           | and that approval is so mired in controversy that everyone is
           | refusing to pay for it, so I doubt its company has made even
           | a million dollars in _revenue_ off of it.
           | 
           | No, Alzheimer's has been a multibillion dollar sinkhole for
           | drug development cash with absolutely nothing to show for it.
        
           | PeterisP wrote:
           | How? They aren't getting revenue until they can sell a drug
           | that has passed clinical trials, and no clinical trials have
           | been successful for Alzheimer's.
        
             | t90z wrote:
        
           | [deleted]
        
       | endominus wrote:
       | Worth rereading; "Time to assume that health research is
       | fraudulent until proven otherwise?" from no less a source than
       | the British Medical Journal [0]. Another example; 5-HTTPLPR
       | studies [1] in psychiatric research (over 450, "proving" the
       | effects of the gene on basically every psychological malady)
       | stretching all the way back to 1996.
       | 
       | [0]: https://blogs.bmj.com/bmj/2021/07/05/time-to-assume-that-
       | hea...
       | 
       | [1]: https://slatestarcodex.com/2019/05/07/5-httlpr-a-pointed-
       | rev...
        
         | gilrain wrote:
         | Unfortunately, this has become a rational precaution.
         | Capitalism has thoroughly undermined humanity's greatest tool.
        
           | MattPalmer1086 wrote:
           | Well, the problem is one of misaligned incentives rather than
           | capitalism per se. From the BMJ article:
           | 
           | "Researchers progress by publishing research, and because the
           | publication system is built on trust and peer review is not
           | designed to detect fraud it is easy to publish fraudulent
           | research. The business model of journals and publishers
           | depends on publishing, preferably lots of studies as cheaply
           | as possible. They have little incentive to check for fraud
           | and a positive disincentive to experience reputational damage
           | --and possibly legal risk--from retracting studies. Funders,
           | universities, and other research institutions similarly have
           | incentives to fund and publish studies and disincentives to
           | make a fuss about fraudulent research they may have funded or
           | had undertaken in their institution--perhaps by one of their
           | star researchers."
           | 
           | Capitalism is certainly the economic context we operate in,
           | but I'd hardly say it is the root cause of most of the above,
           | which could apply equally in other economic funding models.
        
       | scaredginger wrote:
       | When you have problems like this, they must be viewed from a
       | systemic perspective. The truth is that our modern institutions
       | of science are fraught with perverse incentives; people battling
       | for funding, feeling pressure to publish and going to war over a
       | few scarce tenured positions. I don't know how we solve this, but
       | I think reforming academia with some well-placed regulation and
       | an increase in publicly funded research would be a place to
       | start.
        
       | [deleted]
        
       | chaosfox wrote:
       | the silver lining, I hope, is that this will highlight how
       | important independent verification and reproduction of results is
       | in academia, people "know" that but funding for it is still
       | scarce as its always more exciting to try to find something new
       | than to validate a known result.
        
         | Obi_Juan_Kenobi wrote:
         | Replication is far from trivial. It's still worth pursuing, but
         | it's easy to overlook how challenging it can be to successfully
         | execute scientific procedures.
         | 
         | Labs generally specialize, as there's a long learning curve to
         | climb before you can reliably execute even 'bedrock' molecular
         | biology protocols like immunoassays. Small ambiguities in
         | protocol can lead to failure, and there's always simple human
         | error involved that can tank a result. Generally you'll have
         | positive controls available to tell you whether a protocol was
         | successfully executed, but there are cases where that's simply
         | not practical.
         | 
         | In the end, 'failure to replicate' does not necessarily mean
         | there was anything wrong with the original work. Positively
         | concluding that requires a lot of additional work that could
         | explain the discrepancy.
        
         | pca006132 wrote:
         | While independent verification and reproduction is hard, I
         | wonder if there is any requirement for researchers to at least
         | publish their data set for statistical analysis and further
         | research.
         | 
         | Also, I found it interesting that even though computer science
         | research are usually easier to reproduce, a lot of journals and
         | conferences do not mandate artifact evaluation, this is just
         | considered nice to have for submission. If we can have
         | mandatory artifact evaluation, even something not reusable and
         | can just repeat the experiment in the paper, it will be much
         | easier to verify the claims in the papers and compare different
         | approaches.
        
           | mwt wrote:
           | > I wonder if there is any requirement for researchers to at
           | least publish their data set for statistical analysis and
           | further research.
           | 
           | Not generally, though the tide is slowly turning in the right
           | direction. Unfortunately many laws/policies pushing for
           | openness and transparency in research are sidestepped with
           | the classic "data available upon request," a.k.a. "I promise
           | I'll share the Excel files if you email me" (they will not).
        
             | pca006132 wrote:
             | I don't understand why can they use this as an excuse. If
             | they can share the data upon request, why can't they just
             | publish that as well? Is that related to some legal/privacy
             | issue?
        
               | mwt wrote:
               | > Is that related to some legal/privacy issue?
               | 
               | Possibly in some medical or social science fields, I
               | don't know. I know there is not such an issue in
               | chemistry and materials science. There also may be some
               | complications for collaborations with industry, but
               | that's kinda a different situation. For people whose
               | career development is not strongly tied to
               | reproducibility of their work (a.k.a. everybody) it's
               | just another step in the overly complex process of
               | publishing in for-profit journals. Funding agencies
               | generally aren't going to punish people for using this
               | excuse and the watchdogs/groups concerned with
               | reproducibility have no teeth.
               | 
               | Not an excuse, but journals don't make it easy to share
               | files, as hard as that is to believe. Some will only take
               | PDFs for supplemental information and many have garbage
               | UIs, stupidly small file size limits, etc. Just uploading
               | to a repo (or tagged release) on GitHub is common these
               | days because there is much less friction.
        
         | LatteLazy wrote:
         | Isn't that exactly what has NOT happened here? Some combination
         | of:
         | 
         | * People not checking
         | 
         | * People checking and joining the fraud
         | 
         | * People checking, not joining the fraud and then getting their
         | work suppressed.
        
         | mhh__ wrote:
         | Independent verification is why scientific fraud is so
         | dangerous.
         | 
         | On the one hand you'll eventually get caught, but only after
         | potentially millions has been spent on said catching.
        
         | debacle wrote:
         | No one at any point in the funding cycle benefits from asking
         | questions.
         | 
         | In fact, for most of the people in a position to ask the kinds
         | of questions that need to be asked, they risk their entire
         | career when they do so.
         | 
         | The entire industry has issues.
        
       | peter303 wrote:
       | Two reasons why this hypothesis may not be true:
       | 
       | 1) Universal failure of plaque-reduction drug trials.
       | 
       | 2) Numerous post-mortem counter-examples: dementia w/o plaques
       | and plaques without dementia.
        
       | Flankk wrote:
       | Where is the "trust science" crowd when stuff like this goes
       | down. It's strangely quiet in here. Shouldn't they be here
       | telling us how this is a mistake because the editorial and peer
       | review process prevents this? Something about how science brought
       | us all of technology? Oh, that was actually capitalism? Oh great
       | science, where great minds get paid by industry to submit their
       | doctored conclusions to a journal, attached with a small bribe.
        
         | betenoire wrote:
         | Seriously? Science is a process, not a result, and science is
         | literally revealing the fraud here.
        
         | vaidhy wrote:
         | Why not read the original article that actually answers this
         | question? The way we found out about faked data is also through
         | science.
         | 
         | So, is this a feel-good comment to "stick it to the science"
         | when you are on a tech forum? Or did you find this mistake
         | first and feel vindicated that your position is correct?
         | 
         | Just crowing about capitalism means nothing. After all, the
         | incentive to cheat also came from the same capitalism.
        
         | cm42 wrote:
         | We'll have to wait until someone breaks it down into a rhyming
         | Harry Potter reference or something.
        
         | Jaygles wrote:
         | I've never understood "trust science" as "blindly trust
         | scientists". I've always understood it as "trust the scientific
         | process", which is sensible in my opinion, as the process is
         | designed to determine truths.
         | 
         | When people falsify results, what they are doing isn't really a
         | product of the scientific process, they are just committing
         | fraud.
        
           | Flankk wrote:
           | So they're still here, and they're brain dead.
        
           | scarmig wrote:
           | Particularly for heavily politicized topics, "trust the
           | science" usually means something like "trust that the people
           | that the media has designated as scientific authorities
           | always follow the scientific process, understand statistics,
           | and are objective searchers for truth; moreover, don't try to
           | substitute your expertise for theirs."
           | 
           | The scientific community can't simply no-true-scotsman every
           | claim pushed with the banner of Science that turns out to be
           | false or fraud if it wants the true claims to be considered
           | seriously.
        
       | hindsightbias wrote:
       | That the cycle of science works slowly. Slower than to be
       | applicable in your lifespan.
        
       | ta8645 wrote:
       | Just another reminder that scientific consensus should not be
       | blindly accepted with religious fervour.
        
       | lettergram wrote:
       | To quote someone I know in Alzheimer research - "I'm pretty sure
       | it's all fake"
       | 
       | It's funny because more than once I've had conversations off-the-
       | record with people who had the same concerns.
       | 
       | What I think is most troubling is how long it took and how many
       | papers support the claims.
       | 
       | In other words, there are thousands of papers supporting beta-
       | amyloid and/or building off the data / theory. All of that data
       | and everyone conducting that data should be in question. Yes,
       | sometimes you'll see correlations even though the mechanism is
       | not what you'd expect. That said, for 16 years? Lol
       | 
       | No, in reality, this should indicate there is systemic fraud in
       | the industry. I don't think everyone's a fraud, it's as much
       | about what doesn't get published as what does get published. How
       | does this happen? I commented on incentives prior here:
       | https://news.ycombinator.com/reply?id=32213123
       | 
       | I personally don't see how we can advance science with the
       | current credentialing and paper citation == academic success
       | we've seen grow the last 50 years. In many ways, fundamental
       | research has stalled, with applications of research advancing
       | (giving us the illusion of advancing the fundamentals).
       | 
       | To fix this problem, an overhaul is needed. Most importantly, the
       | gate keeping mechanisms should be removed.
        
         | fossuser wrote:
         | These trends have a long history.
         | 
         | Halsted's 'radical mastectomy' was similar. He had an incorrect
         | theory of cancer (centrifugal spiral) that caused a lot of
         | unnecessary harm, but it was not possible for people to push
         | back against it because of his status in the community (iirc
         | pushback eventually came from someone doing research in London
         | where Halsted was less powerful). The emperor of all maladies
         | is a great book about cancer generally which touches on this.
         | 
         | Mendel's peas are another example - breakthrough that went
         | ignored for 40 years because Mendel was a nobody and biologists
         | of the time had their own nonsense theories not backed by real
         | empiricism.
         | 
         | Phlogiston, Elan Vital, etc. - a little different since they
         | weren't even pretending to be empirically true. Just people
         | making stuff up.
         | 
         | Falling into made up tribal nonsense is the default state of
         | humanity - even for scientists, it's hard to think
         | independently to overcome that. At least scientists are
         | supposed to have that as a goal, but focusing on this
         | difficulty and how we're all affected by it does lead to better
         | thinking imo - at least it helps recognize these failures as
         | they're happening more quickly.
        
           | causi wrote:
           | To be fair, there are a lot of exceptions to Mendel's laws
           | and he falsified some of his data so it matched his
           | expectations.
        
           | [deleted]
        
           | qikInNdOutReply wrote:
           | Yes the individual is frail and easily derailed, which is why
           | we have institutions. On whose shoulders the whole process of
           | science rests. So less individual guilt, more answers
           | regarding institutional failures and errors in process
           | design. Obviously, the skinner box built from incentives and
           | punishment, is hacked and useless at best, dangerous at
           | worst.
        
             | fossuser wrote:
             | I think you have it backwards - often it's institutional
             | power that delays disruptive results and an individual that
             | discovers new things despite that.
        
               | qikInNdOutReply wrote:
               | I agree with you that disruption comes from individuals,
               | but the institutions nourish individual types and filter
               | for individuals. Worst of all, some institutions reward
               | the "meta-hack" aka hacking institutions to circumvent
               | the selection pressure (after all its what they
               | themselves often do to thrive) and before you know it its
               | a office full of people who are extremely good at grant
               | hacking and bad at research.
               | 
               | I wonder what would happen, if you would allow for 20 %
               | of the money to be distributed at random.
               | 
               | Like if the grant application fails, you still have a
               | chance for a wildcard.
        
               | naasking wrote:
               | A sortition-like system for grants would help for sure.
               | The problem is, how many proposals are you permitted to
               | submit? If you flood the process you stack the deck for a
               | random win in your favour.
               | 
               | I think random reviews from professionals outside of a
               | field might be possible as well, at least reviewing to
               | what extent the data supports a hypothesis. For instance,
               | say you had a random set of statisticians review the
               | datasets and accompanying hypotheses for 2 or 3 competing
               | theories in biology and cast their votes on what
               | hypothesis seems most plausible given their assessment of
               | the data. They wouldn't be familiar enough with the field
               | to recognize the "leaders" that might be influencing a
               | field politically rather than empirically. Not a perfect
               | system for sure, so maybe someone has a better idea.
        
           | kspacewalk2 wrote:
           | Another good example is the deciphering of Maya script. Yuri
           | Knorozov did it[0], but who was he? Some Soviet nobody, so
           | the field treated him with disdain and upheld the nonsense
           | theories of the leading Mayanist, J. Eric Thompson[1]. Until
           | Thompson died, that is.
           | 
           | [0] https://en.wikipedia.org/wiki/Yuri_Knorozov [1]
           | https://en.wikipedia.org/wiki/J._Eric_S._Thompson
        
             | giraffe_lady wrote:
             | hahaha when I saw the name I thought "this the guy with the
             | cat?" and then clicked through and it is! Why did I know
             | about this guy, but only in the context of the cat?
        
               | Tao3300 wrote:
               | Proof of reincarnation right there. That man came back as
               | Grumpy Cat.
        
           | hinkley wrote:
           | This is one of the primary arguments against immortality as
           | well. If Newton were still alive we'd be arguing about why
           | GPS satellites get clock skew and gravitational lensing.
        
           | dzdt wrote:
           | Mendel faked his data. Its ironic, I think you intended him
           | as an example in the opposite direction. He is an example
           | where he is famous for having the right idea, but modern
           | analysis statistically proves his data were too good to be
           | true.
           | 
           | [1] https://pubmed.ncbi.nlm.nih.gov/27578843/
        
             | GregarianChild wrote:
             | Did he?
             | 
             | From the abstract: _" my analysis could not clearly
             | determine whether the bias was caused by misclassifying
             | ambiguous phenotypes or deliberate falsification of the
             | results."_
        
         | searine wrote:
         | >In other words, there are thousands of papers supporting beta-
         | amyloid and/or building off the data / theory.
         | 
         | It is important to note that the fraud doesn't encompass all of
         | beta-amyloid, but is specific to a subtype called Ab*56.
         | 
         | The plaques are there in autopsy tissue. We can see them. What
         | is causing them is still uncertain.
         | 
         | >No, in reality, this should indicate there is systemic fraud
         | in the industry.
         | 
         | Disagree. This indicates that the field can successfully
         | identify and remove bad/fraudulent lines of inquiry in a
         | relatively short amount of time (a decade).
         | 
         | >A complete overhaul is needed
         | 
         | This is extreme. Fraud happens. Scientific process is designed
         | to root out unverifiable theories, by design. The process is
         | working as intended, why burn it down?
        
           | zzleeper wrote:
           | It's specific to the most important subtype, which single
           | handedly rescued the entire beta-amyloid theory from the
           | waste bin it was headed to in the early 2000s.
           | 
           | Even 5-10 years ago I heard stories of researchers
           | criticizing the "beta-amyloid cabal" for blocking every other
           | avenue for research, as they were the ones in control of the
           | journals (the referees, editors) and grants.
        
           | arbitrage wrote:
           | The process is not working as intended.
           | 
           | 16 years to detect and correct major fraud in the field?
           | That's simply inexcusable, and a sign that things are
           | definitely _not_ working properly.
        
           | mike_hearn wrote:
           | _" the field can successfully identify and remove
           | bad/fraudulent lines of inquiry in a relatively short amount
           | of time"_
           | 
           | It took 16 years and only happened due to a couple of
           | neuroscientists spotting a short selling opportunity, which
           | allowed them to fund an investigation. Phrased differently,
           | the field itself did not find this fraud. Outsiders did, when
           | motivated by non-academic systems.
           | 
           |  _" The process is working as intended, why burn it down?"_
           | 
           | The mis-allocation of hundreds of millions of dollars on the
           | basis of a Photoshop, with the only outcome being that
           | everyone involves says "no comment", is not by any measure
           | the process working as intended.
        
         | sillysaurusx wrote:
         | It's okay to recognize a problem without proposing a solution.
         | I agree that there are alarming levels of fraud. But heading
         | straight to "tear down the journals" seems mistaken.
         | 
         | New progress is rarely made by burning down old structures. New
         | work tends to transcend old work. So the best way to remove the
         | gate keeping mechanisms is to make them irrelevant.
         | 
         | I suspect that a few more generations of tech progress might
         | make that a reality. It seems like a matter of time till some
         | teenage upstart is hacking on their brain the same way I hack
         | on ML, for better or worse. And teenagers tend to notice
         | correlations that the old guard miss.
         | 
         | We're just not there yet. And that's fine. Our options are to
         | work within the confines of existing systems, or build new
         | systems. Removing mechanisms is a bit like removing a dam
         | because it's leaking. The best strategy is probably to fix the
         | leaks.
        
           | lettergram wrote:
           | > But heading straight to "tear down the journals" seems
           | mistaken.
           | 
           | Ultimately, I think journals can be reformed but it'll break
           | their business model.
           | 
           | Effectively, you can publish without reviews. Then have
           | credentialed people anywhere anonymously making comments /
           | challenges. You can also let the public similarly comment.
           | Similar to movie reviews - people in and out of the industry
           | could both review.
           | 
           | On top of that, allocate 25% of grants for replication which
           | could be done in a somewhat public manner and attached to as
           | a report on the paper. Things like that.
           | 
           | That said, Einstein had his work initially rejected. There
           | weren't strong journals at the time as a gate keeper. Just
           | people would publish and publicly debate -- I don't think
           | there's an issue with that now. Particularly, With the
           | internet.
        
             | Beldin wrote:
             | > _Effectively, you can publish without reviews._
             | 
             | Yes, you can. If you want an academic career, you'll also
             | need to publish in prestigious outlets though.
             | 
             | I would love a better model for academia, but I haven't
             | heard a convincing one, let alone that gaining sufficient
             | traction.
        
         | SubiculumCode wrote:
         | that is quite the accusations, verging on slanderous, based on
         | hearsay.
        
         | tptacek wrote:
         | There's somebody _on this thread_ who works in the field of
         | Alzheimers research who says this story is exaggerated.
        
         | rossdavidh wrote:
         | I think this problem is much more severe in cases where a more
         | accurate assessment would be, "we have no idea what is going on
         | or how to stop it, even though we desperately want to". People
         | are more likely to grasp at straws if there is nothing other
         | than straw available.
         | 
         | This does not, of course, mean that it's not still a big
         | problem; far from it.
        
         | matthewdgreen wrote:
         | > I personally don't see how we can advance science with the
         | current credentialing and paper citation == academic success
         | we've seen grow the last 50 years.
         | 
         | As a scientist I would be _thrilled_ to see someone remove
         | these systems. The question then is: what to replace it with
         | that would work better? None of our resources are infinite.
         | 
         | It's even harder when the fundamental problem is _research
         | fraud_.
        
           | hinkley wrote:
           | I'm more worried about, "how do we illustrate the clear need
           | for a change without pouring gasoline directly onto the anti-
           | intellectual bonfires that already exist?"
           | 
           | Every one of these little scandals points us to opportunities
           | to improve, but also is confirmation bias for people who
           | think science is just one system of superstitions amongst a
           | field of viable contenders.
        
             | idontpost wrote:
             | > I'm more worried about, "how do we illustrate the clear
             | need for a change without pouring gasoline directly onto
             | the anti-intellectual bonfires that already exist?"
             | 
             | Asking this question is in and of itself directly pouring
             | gasoline onto the bonfires.
             | 
             | Just work on fixing the damn problems. Trying to PR them is
             | part of the problem.
        
         | pca006132 wrote:
         | Well you don't need to go through the _gate keeping mechanism_
         | , you can just publish a blog. The gate keeping mechanism is
         | like a web of trust that retain only those that are considered
         | valuable in the community, so researchers can have a bounded
         | number of articles to read, at least this is what I think.
        
           | lazide wrote:
           | It's exactly the same problem 'web of trust' has though -
           | incentives for the gate keepers are NOT aligned with accuracy
           | necessarily.
        
             | pca006132 wrote:
             | Yeah, but I think the problem is not really in the web of
             | trust but in the incentive for researchers. If we are still
             | stuck in this publish or perish trend, even if we replace
             | those publishers with journals based on 'open communities',
             | this kind of things will still happen. However, if we
             | abandon the use of such indices (H-index, citation count,
             | whatever), what should we use to evaluate grant
             | applications? Sales pitch like startups asking for VC
             | money?
             | 
             | I don't know, I think the system is problematic but I can't
             | really think of something else that is feasible.
        
         | beanjuice wrote:
         | What do you mean by "the gate keeping mechanisms" should be
         | removed? Do you mean the difficulty of publishing? Or tenure?
         | Or degrees?
        
           | smegsicle wrote:
           | revolutionary ideas will always come from outside, because
           | institutions naturally can only form around what they already
           | assume to be true... but taking that to mean institutions
           | serve no purpose is terribly shortsighted
           | 
           | one thing that does have to go though is the implication that
           | the peer-review process is 'science' and anything outside of
           | it is 'not science', which is just embarrassing
        
           | voakbasda wrote:
           | All of those gate keeping mechanisms have systemic issues and
           | need to be reformed at the very least. "Removed" might be a
           | bit strong, but I definitely see how one could reach that
           | perspective. Regardless, they certainly have lost the
           | credibility to claim any monopolistic authority over the
           | domains they purport to serve.
        
         | not2b wrote:
         | Back when I used to serve on conference review committees I'd
         | talk about the drunk and the lamppost problem: finding the keys
         | in the dark is too hard, so he looks under the lamppost where
         | the light is better (the authors make a simplifying assumption
         | that allows for an elegant approach but the solution is then
         | irrelevant to solving the original problem).
         | 
         | In this case curing Alzheimer's is too hard, but we can make
         | drugs that clear up the plaques that are associated with
         | Alzheimer's and not pay attention to whether doing that
         | actually helps patients: we can document that the plaques are
         | reduced and publish on that basis.
         | 
         | So I suspect that a lot of the research is correct but of no
         | value, because the wrong problem is being "solved".
        
         | fny wrote:
         | One of the big questions I have is what happens if there's no
         | significant financial incentive tied to a therapy. Lithium
         | seems quite promising, for example. However, it's an abundant
         | salt that requires very little research (meager funding
         | opportunities) and can't be patented (non-existent
         | commercialization opportunities.)
        
           | AlotOfReading wrote:
           | You can still IP protect delivery mechanisms and branding.
           | Insulin and tums are examples, respectively. I don't see what
           | the potential for issues here is unless it's an ultra-rare
           | disease where the total market isn't worth the certification
           | costs. That doesn't describe Alzheimer's.
        
         | stuckinhell wrote:
         | I'm not sure how less gatekeeping mechanisms would be helpful ?
         | Wouldn't that just lead to more crap being produced, and
         | informal power structures and cliques forming ?
         | 
         | It sounds like research needs to be held accountable to some
         | kind of standard for accuracy or quality.
        
           | slowmovintarget wrote:
           | Agree.
           | 
           | I don't think we want /r/science moderators determining what
           | is accepted research. But there must be some way to
           | democratize the process short of waiting for the perfect AGI
           | to moderate publications.
        
           | dokein wrote:
           | One issue is that the current gatekeepers (peer reviewers for
           | journals, grant proposal scoring committees, promotion
           | committees, etc.) are often the people most prominent in
           | their field. On one hand this makes sense for obvious reasons
           | (an expert is the most equipped to judge their field), but on
           | the other hand things like the amyloid hypothesis get 'baked-
           | in' because, well, it's pretty hard to ask those same
           | individuals to highly rank a large grant proposal that goes
           | against their own theory.
           | 
           | So I think the answer is gatekeeping needs to be different --
           | not less.
        
           | naasking wrote:
           | It seems plausible that informal power structures may be
           | easier to disrupt with better data than formal power
           | structures.
        
         | 323 wrote:
         | I think one of the fundamental issues is that in science it is
         | absolutely forbidden to accuse someone of fraud. If you do that
         | you will be cancelled to use a modern term.
         | 
         | And no peer reviewer dares question the integrity of the data
         | or researcher, it's taken as gospel.
         | 
         | So while many might know about, nobody dares say a thing.
        
           | sillysaurusx wrote:
           | For what it's worth, this hasn't been my experience in ML.
           | But I've had a limited window into academia.
           | 
           | We were always questioning each other's results. Especially
           | when something seemed too good to be true. "Integrity" can
           | take many forms, and it's surprisingly easy to fool yourself
           | when you're doing work in the field. So the default
           | assumption was that we were all fooling ourselves, not each
           | other, unless proven otherwise.
        
             | PeterisP wrote:
             | ML is a bit different because if the authors provide
             | sufficient data, then any fraud is trivially obvious on
             | replication and if they don't provide sufficient data, then
             | that is a reasonable criticism on its own without having to
             | go into motives.
             | 
             | However, in other areas where you have "real world"
             | experiments, you don't even expect the experiments to
             | replicate - two clinical trials on different sets of
             | patients won't necessarily yield the same results, and
             | different results when repeating a biological experiment
             | does not necessarily imply fraud; we know that in this
             | domain (unlike ML) we sometimes do have unknown confounders
             | that experiments don't control for.
        
             | 323 wrote:
             | But were you accusing others in public of intentional
             | fraudulent activities? Because it's a different thing than
             | "you have bad statistics here" or "wrong assumptions here".
        
               | sillysaurusx wrote:
               | That's true.
        
             | caycep wrote:
             | we have peer review....but peer review is human, and some
             | fields, it's a small world.
             | 
             | I'm not in that particular field of neuroscience (albeit
             | Alzheimer's patients do come in to the clinic...because
             | where else are they going to go?). But when I was in the
             | research world, a big factor was who you knew, and who you
             | could cozy up to, in terms of getting grants, papers
             | published in top journals, etc. Who you ate lunch w/ in big
             | conferences. That being said, fortunately, there was an
             | element of recognition of skill/ability and good work, as
             | well as a decent amount of (sometimes irrelevant)
             | challenge/response and general peacock-ing in terms of the
             | peer review...but it was a reminder that science is above
             | all, a human endeavor and not immune to humanity's sins.
        
           | kensai wrote:
           | You will not be cancelled as long as you can back your claim.
           | Like in everything in this world. The equivalence of
           | cancelling in HN is of course downvoting to oblivion. We have
           | that tool here as well. Controversial opinions are heard as
           | long as they have backing or/and something important to add
           | to the conversation.
        
             | photochemsyn wrote:
             | You can report fraud to the ORI (Office of Research
             | Integrity) and they won't do a thing about it. They won't
             | open an independent audit of any federally-funded academic
             | researcher until after the fraud has been publicly exposed
             | in the media, as this one has been. Even then:
             | 
             | > "The agency's reply, which Schrag shared with Science,
             | noted that complaints deemed credible will go to the
             | Department of Health and Human Services Office of Research
             | Integrity (ORI) for review. That agency could then instruct
             | grantee universities to investigate prior to a final ORI
             | review, a process that can take years and remains
             | confidential absent an official misconduct finding. To
             | Science, NIH said it takes research misconduct seriously,
             | but otherwise declined to comment."
             | 
             | https://www.science.org/content/article/potential-
             | fabricatio...
             | 
             | There is simply no willingness on the part of federal
             | funding agencies to investigate their own grantees after
             | they receive credible evidence of fraud.
        
           | bsder wrote:
           | > So while many might know about, nobody dares say a thing.
           | 
           | Maybe, but it's more likely that compiling solid evidence for
           | fraud is just far too resource intensive and there is no
           | reward for replication-- _especially_ negative replication.
           | 
           | And committing the fraud is far too tempting--you got your
           | needed publication for tenure, and you're mostly safe as long
           | as nobody accidentally makes your paper the cornerstone for
           | something that becomes famous.
           | 
           | As for peers, you can spend your time moving your own ideas
           | forward, or you can take a detour to prove one particular
           | important researcher's ideas wrong. It's pretty clear which
           | is going to be more beneficial to your career.
           | 
           | As the article points out, this was triggered by some short
           | sellers looking to make a buck--not anybody in the field
           | itself.
        
       | joe_the_user wrote:
       | " _First off, I've noticed a lot of takes along the lines of
       | "OMG, because of this fraud we've been wasting our time on
       | Alzheimer's research since 2006". That's not really the case, as
       | I'll explain..._ "
       | 
       | I'm not seeing the explanation. The Amyloid hypothesis was
       | weakening in 2006 and a series of apparently ground-breaking but
       | actually fake results gave new life over a significant period of
       | time. Yes the author says: " _the main inaccuracy in that
       | statement is that we've been actually been wasting our time in
       | Alzheimer's research for even longer than that._ " but the
       | problem is testing a false hypothesis and discarding isn't a
       | waste of time, it's how science should work. Fraud and forgone
       | failures, of course, are how science shouldn't work.
       | 
       | And yes, there's lot of fraud around but I don't see how this
       | isn't especially damaging.
        
       | sudden_dystopia wrote:
       | This sounds just like cholesterol to me. Yes, beta amyloids are
       | correlated with Alzheimer's and cholesterol is correlated to
       | cardiac issues. But correlation is not causation. Why is their
       | seemingly no mainstream discussion that perhaps these
       | correlations are simply the markers of an underlying biological
       | function that has become disregulated and leads to the presence
       | of higher amyloid/cholesterol/etc? When we try to treat cancer,
       | do we focus on the symptoms, or do we try to obliterate the
       | cancer? As far as I can tell, we aren't looking for the "cancer",
       | we are trying to treat symptoms.
        
         | _Wintermute wrote:
         | > Why is their seemingly no mainstream discussion that perhaps
         | these correlations are simply the markers of an underlying
         | biological function that has become disregulated and leads to
         | the presence of higher amyloid
         | 
         | That's a discussion point pretty much every time the amyloid
         | hypothesis is mentioned in the scientific literature.
         | 
         | I'm not sure where you're going to get information about the
         | pathophysiology of Alzheimer's disease, but it doesn't really
         | strike me as a "mainstream" topic where they're going to
         | discuss the finer details or debates.
        
           | throwawaymaths wrote:
           | > That's a discussion point pretty much every time the
           | amyloid hypothesis is mentioned in the scientific literature
           | 
           | I don't feel like that's true. Back when I was a grad student
           | doing this research it was striking to me how _little_ that
           | was in the literature considering how much we said it
           | internally.
        
       | A4ET8a8uTh0 wrote:
       | From the article:
       | 
       | << Now Cassava is a story of their own, and I have frankly been
       | steering clear of it, despite some requests. To me, it's an
       | excellent example of a biotech stock with a passionate (and often
       | flat-out irrational) fan club.
       | 
       | I wonder if this is part of the issue. It is now something of a
       | social club, where allegiance is to the clan. I initially
       | wondered if it is the function of the internet, but the I
       | remembered that various cliques existed way before that. Internet
       | just put a spotlight on it.
       | 
       | The only real question is whether the current club can be
       | reformed.
        
       | VikingCoder wrote:
       | So the University of Minnesota faked Alzheimer's research and
       | injected Linux kernel bugs on purpose? [1]
       | 
       | Not feeling so proud as an alumni today.
       | 
       | [1]: https://news.ycombinator.com/item?id=26887670
        
         | [deleted]
        
       | criddell wrote:
       | Is there a new leading theory?
        
       | temporalparts wrote:
       | Ask HN: What do you think about a law that criminalizes faking
       | and doctoring data for their research? Clearly we need greater
       | punitive consequences for these types of behavior that's becoming
       | an epidemic in research.
        
         | UweSchmidt wrote:
         | That makes it even harder to call out bad science. You hate how
         | your colleague cut corners but do you want to testify against
         | them in court in your free time and have them sent to jail?
         | 
         | I'd go the opposite way and give job security to anyone who is
         | doing solid science to remove some of the weird incentives.
         | There is upside to be amazing and win prizes or get better
         | positions, but there is also space for people to "just"
         | reproduce, or generally do important but non-glamorous stuff.
        
         | arbitrage wrote:
         | Effectively, it's the same reason why the death penalty does
         | not deter crime from happening.
         | 
         | The threat of career-ending shame & humiliation is remote and
         | unlikely. As another poster said much further up-thread, there
         | is more fraud going on that doesn't get detected.
         | 
         | Criminal penalties in this realm are a bit draconian. More
         | punishment & punity is not the answer.
        
       | beanjuice wrote:
       | Pubpeer is an incredible project [0], and unless I am mistaken,
       | you could say that this finding may not have occurred without it.
       | For those that do not know, it is a website (with browser
       | extension) which allows a comment section for academic
       | publication, with anonymous comment, for posting critique and
       | questions about papers. I suggest all of my peers to install the
       | extension, as a pre-warning system for poor quality papers. This
       | paper in question can be found here [1], and it is a good example
       | of what simple image processing techniques can be used to verify,
       | or question claims. It is unfortunate that while things like NMR,
       | XRD, SEM/TEM images, and Western blots are commonly faked, and
       | found out- not all science is based off of verifiable data at the
       | reader's end.
       | 
       | [0] https://pubpeer.com/static/about
       | 
       | [1]
       | https://pubpeer.com/publications/8FF7E6996524B73ACB4A9EF5C0A...
        
       | CommanderData wrote:
       | Wasn't HSV also implicated in Alzheimer's. Seeing most of the
       | world is infected with cold sores I wonder if we should question
       | this research too?
        
       | brighamyoung wrote:
       | It probably means that the Bredesen protocol is the cure for
       | Alzheimers. He has a literally proven track record of success
       | with hundreds of patients.
        
       | stuckinhell wrote:
       | Interesting article. From an non-researchers perspective, I find
       | a couple points extremely disturbing.
       | 
       | - The failure to notice and act on the faked data in the Lesne
       | papers is still a disgrace, and there's plenty of blame to go
       | around among other researchers in the field as well as reviewers
       | and journal editorial staffs.
       | 
       | - Every single Alzheimer's trial has failed.
       | 
       | I strongly suspect there is more fraud, just because of human
       | nature. It looks multiple checkpoints are failing. We also have
       | the replication crisis going on. It's pretty clear at this point
       | incentives are misaligned at every level of the research
       | pipeline.
       | 
       | It's a bad time for this highly public research failure. The
       | general public's faith in experts is dropping, and maybe for good
       | reason. As the economy, and quality of life deteriorates, I think
       | we will see the public demand "results" from experts.
        
         | matthewdgreen wrote:
         | It's also possible that Alzheimer's is an incredibly
         | challenging disease and the tools we have to deal with it are
         | suboptimal. People have a hard time distinguishing failure from
         | malice, unfortunately. It's understandable to want someone to
         | blame.
        
           | stuckinhell wrote:
           | I agree.
           | 
           | However I also think, we are seeing evidence of malice,
           | greed, and maybe desperation in these acts of scientific
           | fraud. Experts need to quickly define what malice in their
           | respective fields means. Then most importantly they need to
           | act on it and restore integrity, discipline, and show
           | results.
           | 
           | Otherwise the general public will define it and act on it
           | themselves.
        
           | naasking wrote:
           | It is a hard disease to study for sure. The hardest part of
           | it is that there's no effective test for it, you just have to
           | check for a somewhat vague constellation of symptoms over a
           | person's entire lifespan.
           | 
           | I think a big part of the obsession with the amyloid plaques
           | hypothesis is that it was the only issue that was consistent
           | among patients that they could actually test for, so rather
           | than continuing the harder work of searching in the dark for
           | something better, researchers latched onto exploring how and
           | why that was associated with Alzheimer's.
           | 
           | And it makes sense in a way, there's obviously _something_
           | going on and figuring out why the plaques are produced should
           | provide _some_ mechanistic insight into what 's going on. And
           | that's true, in the same way that capturing all of the EM
           | emissions from a laptop will provide _some_ insight into what
           | 's going on inside the laptop, but that information will
           | likely only be useful if you already have a good mechanistic
           | model of a laptop's inner workings (people have successfully
           | read data across an air gap this way). I suspect that's what
           | will happen with amyloid plaques as well, ie. plaques will
           | only make sense retrospectively.
        
           | AbrahamParangi wrote:
           | One way for something to be extremely challenging is for it
           | to be impossible
        
         | zubiaur wrote:
         | A lot of systems are based on trust. The checkpoints are
         | sometimes in place not so much as a thorough verification but
         | rather as a signaling mechanism, a vote of confidence.
         | 
         | While I do think that a better aligned system of immediate
         | incentives can ameliorate the symptoms, it's only a patch for
         | moral behavior.
        
       | jtdev wrote:
        
       | renewiltord wrote:
       | Amusing. Second-hand experience[0] with "exciting science areas"
       | led me to this belief already. It's one of those interesting
       | things. For folks outside of science, they think most of this
       | stuff is backed. You can see it in the fact that people will
       | quote "there is evidence that X is Y" using some random study,
       | commonly on HN.
       | 
       | There's a common reaction to this sort of thing where people act
       | like it is some betrayal of a sacred pact, etc. etc. but there is
       | so much fake science out there that it is really hard to believe
       | that there is actually some betrayal and it's not just the
       | reality of the field.
       | 
       | And always there'll be some guy who comes up with a "I've never
       | heard of this and neither has any of the ten guys I talked to
       | about it". Just do the math. At a 10% fake rate (which I would
       | consider extraordinary) there's a 1 in 3 chance that you wouldn't
       | detect it with just independent observations of you and 10
       | friends (and that's assuming you and your friends are independent
       | here, which is very generous). At a 5% fake rate (which is still
       | horrible), there's a 1 in 10 chance that even you and 40 of your
       | friends would not detect it.
       | 
       | The thing with not-so-rare things is that you can fail to detect
       | it through sheer chance.
       | 
       | 0: https://news.ycombinator.com/item?id=25926188
       | 
       | P.S. hn.algolia.com is excellent. I managed to find this comment
       | in a couple of seconds on it.
        
         | bhk wrote:
         | The "I've never heard of this ..." comment can also be
         | explained by the possibility that the person making the comment
         | is one of the fraudsters. This adds 10% to the 1/3 chance in
         | your example. So no matter how high the rate of fraud is, we
         | would expect to hear comments like this.
        
           | renewiltord wrote:
           | I did not think about that, but you are right (with
           | appropriate maths modifications)
        
       | rbanffy wrote:
       | In this age of politically-motivated scientific disinformation,
       | the one thing we don't need is fraudulent science. We need to be
       | able to trust which drugs and vaccines work, anc which don't. We
       | need to be able to trust the predictions about global warning and
       | the societal impact of it so we can chart the optimum path with
       | as little disruption and suffering as we can. In short, we cannot
       | afford not to be rational, not to ground our decisions in hard
       | facts and solid models.
       | 
       | Scientists like Lesne should be detected much earlier in their
       | careers.
        
         | arbitrage wrote:
         | The situation in Academia is similar to child abuse in the
         | Churches. These people often _are_ detected early, and get
         | shuffled around.
         | 
         | A lot of people know about this problem, have for a long time.
         | A lot of people continue to do nothing about it.
        
       | holyknight wrote:
       | I think the main issue is that papers and studies with negative
       | results are almost never published. There should be some
       | procedure in place that ensures that papers will always be
       | published no matter what is the result. This decision shouldn't
       | be in the hands of the researchers and even less so on the
       | investors.
       | 
       | Direct investor oversight over the research is very concerning.
       | With the current method we can only blindly trust that scientist
       | will be willing to sacrifice their career to publish a research
       | that could potentially bury their investor. This makes absolutely
       | no sense and will almost always end in conflict of interest.
       | 
       | I don't know the answer, but the current status quo is deeply
       | flawed and needs to change quickly.
        
       | tomelders wrote:
       | > He was originally hired by two other neuroscientists who also
       | sell biopharma stocks short
       | 
       | I'm blown away by this investment strategy. What a brilliant way
       | to monetise exposing fraud. Get your proof, short the stock,
       | publish your proof, profit!
        
         | 323 wrote:
         | In finance there are a number of hedge funds who do this, like
         | Citron Research which specializes in exposing fraud and short
         | selling it for profit.
        
         | scaredginger wrote:
         | This incentivisation is one of the classical arguments for
         | allowing short sellers in the market
        
         | meepmorp wrote:
         | Doing well by doing good
        
         | pjbk wrote:
         | Unfortunately it's more common than you think... I remember
         | this case in particular from some years ago:
         | 
         | https://www.legalreader.com/st-jude-medical-files-lawsuit-ag...
        
           | JumpCrisscross wrote:
           | > _Unfortunately it 's more common_
           | 
           | Why is calling out fraud unfortunate?
           | 
           | With respect to St. Jude, Muddy Waters was at least partially
           | right [1].
           | 
           | [1] https://www.hipaajournal.com/fda-confirms-muddy-waters-
           | claim...
        
             | DiggyJohnson wrote:
             | Presumably GP is not saying that the calling out of fraud
             | is unfortunate, but that the fraud itself is unfortunate.
        
         | scarmig wrote:
         | This is an improvement over the status quo, which is that fraud
         | exists, hurts patients, and continues to exist.
        
         | Sniffnoy wrote:
         | There are several companies that do this! Hindenburg Research
         | and Muddy Waters Research are two.
        
       | UIUC_06 wrote:
       | Re solutions: now do Project Veritas.
       | 
       | If you're a whistleblower and you're not getting shunned by
       | "respectable" people, you're probably doing something wrong.
        
       | pvg wrote:
       | Recent big threads yesterday and a few days ago with 250+
       | comments each:
       | 
       | https://news.ycombinator.com/item?id=32212719
       | 
       | https://news.ycombinator.com/item?id=32183302
       | 
       | And a danglist with more
       | 
       | https://news.ycombinator.com/item?id=32213973
        
         | dang wrote:
         | Might as well keep it updated I suppose.
         | 
         |  _Two decades of Alzheimer's research was based on deliberate
         | fraud_ - https://news.ycombinator.com/item?id=32212719 - July
         | 2022 (295 comments)
         | 
         |  _Potential fabrication in research threatens the amyloid
         | theory of Alzheimer's_ -
         | https://news.ycombinator.com/item?id=32183302 - July 2022 (236
         | comments)
         | 
         |  _Alzheimer's amyloid hypothesis 'cabal' thwarted progress
         | toward a cure (2019)_ -
         | https://news.ycombinator.com/item?id=31828509 - June 2022 (307
         | comments)
         | 
         |  _How an Alzheimer's 'cabal' thwarted progress toward a cure_ -
         | https://news.ycombinator.com/item?id=21911225 - Dec 2019 (382
         | comments)
         | 
         |  _The amyloid hypothesis on trial_ -
         | https://news.ycombinator.com/item?id=17618027 - July 2018 (43
         | comments)
         | 
         |  _Is the Alzheimer 's "Amyloid Hypothesis" Wrong? (2017)_ -
         | https://news.ycombinator.com/item?id=17444214 - July 2018 (109
         | comments)
        
           | panabee wrote:
           | this isn't a HN comment page, but it contains comments from
           | co-authors, alzheimer's researchers, and most critically the
           | lab lead (professor ashe) who overaw lesne's paper:
           | https://www.alzforum.org/news/community-news/sylvain-
           | lesne-w...
           | 
           | professor ashe declined to comment for the science article
           | but commented here. notably, she claims the journalist
           | conflated two forms of Ab and drew invalid conclusions.
           | 
           | hat tip to @atombender for surfacing this page.
           | 
           | tldr: many scientists believe the fraud is grave and
           | inexcusable but the impact on research is greatly
           | exaggerated. comments on twitter from other researchers seem
           | to echo this sentiment.
        
         | hprotagonist wrote:
         | Not a dupe, per se. Derek Lowe's summaries of current events
         | are themselves valuable and aren't just "hey look, [this
         | thing]!".
        
           | dang wrote:
           | That's a good point. I call this sort of post either a
           | follow-up or a quasidupe, depending on how dupey (?) it is.
           | 
           | The problem is that the HN _discussions_ on a topic cluster
           | tend to be much the same, even if the article itself isn 't.
           | But I've taken the [dupe] stigma off this one now.
        
           | pvg wrote:
           | HN dupes are mostly by value rather than by reference and
           | there's also a kind of topic repetition limit even when the
           | there's more commentary on the topic.
        
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