[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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