[HN Gopher] Potential fabrication in research threatens the amyl...
___________________________________________________________________
Potential fabrication in research threatens the amyloid theory of
Alzheimer's
Author : panabee
Score : 550 points
Date : 2022-07-21 18:54 UTC (1 days ago)
(HTM) web link (www.science.org)
(TXT) w3m dump (www.science.org)
| tmaly wrote:
| Yes, that is a lot of grant money to waste, but I think the
| biggest loss here is 16 years of research in the wrong direction.
| [deleted]
| nabla9 wrote:
| Intentionally diverting resources and skewing research from one
| of the most biggest growing epidemics of our time seems seems
| like huge crime against humanity that has not been criminalized
| yet.
| [deleted]
| legulere wrote:
| Alzheimer isn't a growing epidemic. The incidence is going
| down.
| nabla9 wrote:
| On a global scale, Alzheimer's is growing epidemic.
|
| The age adjusted mortality is declining in some countries,
| but when boomer generations age, the number of cases
| increases.
| Dylan16807 wrote:
| Enough to compensate for population growth?
| johndhi wrote:
| hehe, ironically diverting resources and skewing research and
| overall making worse the biggest PANDEMIC of our time isn't a
| crime at all :)
| dang wrote:
| " _Eschew flamebait. Avoid unrelated controversies and
| generic tangents._ "
|
| https://news.ycombinator.com/newsguidelines.html
| upwardbound wrote:
| Agree. The perpetrator should go to prison for some sort of
| criminal fraud or racketeering or whatever a prosecutor can
| apply. This is serious crime.
| mike_hearn wrote:
| Unfortunately it's probably not serious crime. It would
| have been in the private sector, see Theranos, but not in
| academia. The USA is rather unusual in having the ORI, but
| it's toothless and does only a handful of announced
| sanctions per year. There aren't the laws on the books, nor
| prosecutors and investigative forces in governments
| dedicated to pursuing scientific fraud.
|
| So I'm afraid to say that assuming the allegations are
| true, they will probably get away with it. It's absolutely
| standard when these sorts of things are discovered that
| everyone sweeps it under the rug as vigorously as possible.
|
| Fixing it would be difficult. There are a huge variety of
| ways to produce fraudulent science. Even coming up with a
| law that captures half of them is fiendishly hard, and how
| to do enforcement in a timely manner? In this case
| capitalism came to the rescue because the investigation was
| funded by short sellers, so this has to be one of the best
| arguments for short selling around. But by the time there's
| a publicly listed company whose share price is dominated by
| research suspected to be fraudulent it's way too late.
|
| There's probably also a fear of looking too closely.
| There's a culture of coverups in science that I've seen
| first hand. It's deeply unpleasant and breeds the suspicion
| that they do it so blatantly because it's become a way of
| life, because they know there won't be any consequences
| even if they're called out on it. If you start going after
| image tampering, well, it's only a tiny next step to say
| that if your paper reports a mean that's statistically
| impossible given the data set then that's also fraud. But
| then you'd have to investigate and mount prosecutions for a
| significant fraction of all psychology researchers. And
| then you're going to have to make it a crime to not share
| data on request as otherwise incriminating data is always
| going to be inconveniently lost. And then you're up to 90%+
| of researchers facing action. Draining this swamp would be
| very hard.
| Ekaros wrote:
| Also anyone who used the results without sufficient due
| diligence should be barred from working as researcher or
| receiving grant money. They are not quilt free either.
| dash2 wrote:
| Steady on now. Scientists rely on each other, they're not
| supposed to be fraud investigators.
| schnitzelstoat wrote:
| What is due diligence though?
|
| Are they supposed to do a forensic analysis of every
| paper they cite? It's sad if it's arrived to this point.
|
| Reproducing the original result can be prohibitively
| expensive and difficult in many fields (ideally, this
| wouldn't be a concern - but generally, research groups
| aren't rolling in cash and resources, plus you need to be
| fast not to get scooped for the next paper and lose
| future grant money)
| SturgeonsLaw wrote:
| Given the replication crisis, more questions should be
| asked. Everyone knows a disturbingly large number of
| papers are on shaky foundations, but nobody is good at
| picking which ones
| kyaghmour wrote:
| Patential link with diabetes:
| https://www.health.harvard.edu/blog/whats-the-relationship-b...
| pedalpete wrote:
| "Potential"
|
| I work in the neurotech/sleeptech space, and specifically in
| stimulation of slow-wave oscillations.
|
| These SWOs decrease as we age, which is linked to the build-up
| of amyloid plaque, and increased insulin resistance. They
| aren't necessarily linked to each other, but rather to the
| decreased capabilities in the brain, from what I understand.
| Taniwha wrote:
| I love how the researchers are shorting the stock - they're not
| insiders because the data is public available for anyone (with
| the requisite very domain specific knowledge) to see.
|
| There a whole lot of the sorts of investor who are normally
| shorting stuff who must feel that this is somehow insider
| information
| f38zf5vdt wrote:
| There are so many correlations of vascular injury with dementia
| that it seems obvious that the fibrils would not be causative but
| rather correlated to dementia. I personally believe that dementia
| is related to or caused by repeated small vascular injuries that
| eventually cause degradation of the brain. That is, transient
| ischemic attacks that are completely subclinical aside from the
| injury that is visible after autopsy.
| fithisux wrote:
| Covid jabs are the next frontier in fabrication.
| icermann wrote:
| I think many of us has heard about the Xerox copying machine
| changing digits on copies, using a "visually similar enough"
| replacement algorithm.
| https://www.theverge.com/2013/8/6/4594482/xerox-copiers-rand...
|
| I wonder if you could get the same unexpected result when copying
| images of Western blots?
|
| It's probably not the case here but it could be devastating for a
| researcher to be accused of fabricating data by using an affected
| copier/image editor/file format.
| appleflaxen wrote:
| No. The xerox machine had a digital analysis phase with a
| feedback loop between the image being recorded and the output
| being printed.
|
| A western blot is a direct measurement.
|
| It's like asking whether the xerox example might explain why
| the splatter pattern is identical in sections of two putatively
| different Jackson Pollock paintings.
| ThePhysicist wrote:
| Reminds me of that famous paper about Majorana fermions [1] that
| got retacted because they edited a figure (I'd say with malice)
| to support their sensationalist claim. In the unedited image the
| claimed effect is all but gone. The publication of the paper led
| to a flurry of research funding and a partnership with Microsoft
| (who were keen on using Majorana fermions for topological quantum
| computing).
|
| 1: https://physicsworld.com/a/retraction-of-nature-paper-
| puts-m...
| snapetom wrote:
| Holy hell. Someone please correct me, but the beta-amyloid camp
| has been under attack, establishment researchers still keep going
| despite weak evidence, and now the best drug they have might have
| fabricated data???
| resoluteteeth wrote:
| Nope. It wasn't evidence for a drug that was fabricated, it was
| a 2006 study published in Nature that convinced everyone to
| believe the amyloid hypothesis.
| JPLeRouzic wrote:
| > * it was a 2006 study published in Nature that convinced
| everyone to believe the amyloid hypothesis.*
|
| The amyloid hypothesis is one century old.
| dekhn wrote:
| No, it's not. It was introduced in the 90's. "The amyloid
| hypothesis was first proposed in 1991 by John Hardy and
| David Allsop." You're probably thinkinng of the person who
| "discovered" Alzheimer's disease (Alois Alzheimer).
| jamiek88 wrote:
| Oh my god if true, and it looks to be true this is huge.
|
| The amyloid beta (Ab) hypothesis has always been fishy but this
| paper is basically the bedrock of the current investigational
| trajectory.
|
| The Ab hypothesis was almost dead in 2006 when this method was
| invented and results posted and it sent shockwaves through the
| research world. Since then spending on Ab research by NIH has
| gone from $0 to $290 million all it seems based on a lie cited
| over 2000 times in further papers.
|
| The article is pretty convincing as is the independent
| verification that not only concurred but found _additional
| evidence_.
|
| Sylvain Lesne has some 'splainin to do.
| phkahler wrote:
| >> it seems based on a lie cited over 2000 times in further
| papers.
|
| Since papers tend to get published only if they have positive
| results, what does it mean for thousands of publications all
| citing a fraudulent paper? This seems really strange. If the
| first 1000 failed to produce results and were partially based
| on that original paper it should cast significant doubt on it,
| but again failures are rarely published.
|
| What does this mean then?
| derbOac wrote:
| To me this is one of the most damning things about this: all
| the people citing these papers and probably burying negative
| results. Yes, fraud is unacceptable, but what about all the
| people using it to further their careers?
|
| These types of cases tend to focus on the fraud, but then
| everyone eventually walks away and then there's no larger
| discussion of how this was enabled by the field to have such
| a hold.
|
| I don't buy the idea that it's all so quixotic and involves
| so many variables to get right that who knows what's causing
| a lack of replication. I've heard whispers like this about
| other big effects in other fields. People know what's going
| on, and often it's right there in published results but
| ignored.
| api wrote:
| Citation doesn't mean dependency. It just means the paper was
| mentioned. What it does mean is that each and everyone of
| those papers must be re-examined with extra scrutiny to see
| if they hold up without the cited paper.
| BoorishBears wrote:
| That's why it was described as a "bedrock".
|
| A lot of papers that came after were producing results in the
| framework it established.
|
| Because of the nature of a disease like Alzheimer's not many
| studies can easily measure the final effectiveness of their
| addition to the space on patients.
| civilized wrote:
| If the results are fraudulent, why didn't anyone notice in the
| past 16 years that they failed to replicate?
| mtlmtlmtlmtl wrote:
| If this is true, it is beyond fraud. These are crimes against
| humanity.
|
| My paternal grandfather got diagnosed at around 70, and my
| father is 62 now, definitely getting more forgetful but normal
| for 60+... Still, I worry about him regularly. My father is a
| clinical psychologist, he's helped people all his life.
|
| These news make me so angry I can hardly see straight. I
| genuinely hope this sociopath waste of skin gets Alzheimers
| himself, and has to relive every moment of his disgusting
| crimes as his brain slowly turns to mush and he forgets every
| person he ever loved(if he is even capable of love...)
| Balgair wrote:
| You may want to express you feelings to Dr Lense' personally.
| It may help with your grief and make a positive change. His
| contact information and that of his lab can be found here:
| https://med.umn.edu/bio/department-of-
| neuroscience/sylvain-l... and here:
| https://lesnelab.org/people/
| mtlmtlmtlmtl wrote:
| I appreciate the sentiment, but as good as it felt to blow
| off some steam in this thread this morning, I'm not the
| type of person who sends deathwishes to people's work
| email...
| Balgair wrote:
| Understandable. My condolences to you and your family on
| having to go through the hell you have had to.
|
| When a bit calmer, I would still encourage you to reach
| out and find constructive ways of dealing with the grief.
|
| That may commonly be to write letters/email to those that
| have affected you. It seems that Dr. Lense's work has had
| that affect on you and it may be helpful to you to write
| to him. Academics don't interact much with the public and
| having someone write to them does help focus their work
| and right wrongs. You may come to new understandings of
| the Dr.'s efforts and of your own self.
|
| Again, best of luck and I hope you find peace and
| guidance.
| calf wrote:
| This is weirdly confrontational, my therapist would not
| recommend writing an email to a professor who wronged me
| even on some abstract level. That's not how a
| psychologist counsellor would suggest confronting one's
| grief.
| macinjosh wrote:
| FTA:
|
| ""So much in our field is not reproducible, so it's a huge
| advantage to understand when data streams might not be reliable,"
| Schrag says."
|
| I am just a lowly engineer, but this alarms me. Why is anything
| that has not been reproduced considered valid science by anyone?
| Why aren't our standards higher?
|
| If you can't reproduce an experimental result, it is useless
| information is it not? At least an experiment that can be
| reproduced yet fails to prove a hypothesis can teach you
| something. An experiment that cannot be reproduced yields no
| useful information. In fact, it can even mislead!
|
| I just don't understand the motivations at play. These are
| obviously intelligent people who know that you can't fake
| reality, so why do they publish fraudulent papers? Just for
| short-term gain? Do they become blinded by belief in their
| hypothesis?
| niemandhier wrote:
| Biological systems are so complex that reproducing results is
| extremely hard even if the authors publish their method in
| detail, simply because they might not know why it works for
| them.
|
| This is hard to understand for software people, since code
| tends to behave reproducible as a default.
|
| Basically the only way to reproduce a difficult finding is to
| learn the procedure at the original lab.
|
| An example: A friend of mine could not reproduce his own
| findings in another lab. Turned out the precise type of the
| lamp build into the setup mattered.
|
| Another example: I could not reproduce a finding the was
| something I wanted to build upon. Turned out the precise method
| to dissolve one of the chemicals in the buffer as the problem.
| It was even hinted in the paper, but who would describe in
| detail what he means by " vigorously stirred" ?
| ncmncm wrote:
| This is why almost all results from running rats in mazes are
| spurious.
|
| There was an early, very good paper identifying all the
| details needed to make a valid maze experiment. Nobody cites
| it, so nobody reads it or acts on its results.
| summm wrote:
| Do you happen to have a link to said paper?
| ncmncm wrote:
| Sorry, read about it 30 years ago.
| ALittleLight wrote:
| Biological systems being complicated and unintuitive is an
| excellent explanation for slow or no progress. It's entirely
| orthogonal to the question of why published results are not
| reproducible, misleading, or wrong. If some problem is super
| hard that explains why I can't answer it, it doesn't explain
| why I continually publish fake answers.
|
| My understanding of the situation is that academics and
| scientists work in a weird bureaucracy, there is an incentive
| to publish, academics are very bad at detecting fraud and
| worse at punishing it and statistical manipulation is easy
| and endemic. These things explain why there's so much
| academic research that can't be reproduced and why some
| academic fields are basically the modern equivalent of
| astrology.
| niemandhier wrote:
| You only notice the cases where you try to reproduce
| things, and time being limited ,you only reproduce obscure
| results.
|
| As a comparison: I did a bunch of math too and in some
| cases just accepted the proofs I build on.
|
| Same for programming: I neither audited lapac not GCC.
|
| For the engineering crowd software dependencies are a
| probably a good comparison. If they come from a credible
| source you trust them and build on top of them.
|
| Nobody blames companies for not auditing the kernel if
| there is a security problem in it, but everybody screams:
| "You should have verified the result", if some paper is
| redracted.
| ncmncm wrote:
| They are blinded by assuming good faith and competence.
|
| Most scientists consider most of their colleagues more or less
| incompetent, and even where they accept experimental results,
| often reject the experimenter's interpretation of the result,
| often correctly. Scientists advise us to ignore the abstract,
| ignore the interpretation, ignore the conclusion, and trust
| only the data, at most. But we mostly don't get to do that for
| fields not our own.
|
| High prestige is detrimental in that it short-circuits this
| skepticism. This happens not only in Alzheimer Syndrome work.
| It put psychology research in the grip of behaviorism,
| statistics in the grip of non-causality, political science in
| the grip of dialectics.
| sfrautschy wrote:
| This is ridiculous. Dozens if not hundreds researchers have
| confirmed the high MW oligomers correlated with pathogenesis. I
| have. To say that he found this or everything relied on this
| theory is absurd. We've know this since the early 90's when Lesne
| was in high school or earlier (e.g Cotman's work at UC IRVINE and
| Christian Pike now at USC , my work etc.) . this is way before
| Lesne even considered a career. I can't stand this ridiculous
| media that make this out a scandal and create false
| disinformation that the entire hypothesis is based on this.
| WhitneyLand wrote:
| _"The immediate, obvious damage is wasted NIH funding and wasted
| thinking in the field because people are using these results as a
| starting point for their own experiments," says Stanford
| University neuroscientist Thomas Sudhof, a Nobel laureate and
| expert on Alzheimer's and related conditions."_
|
| I guess he's the Nobel prize winner, but I would've thought the
| immediate and obvious damage was unnecessarily delayed research
| progress while people are dying.
|
| Over a decade? Who knows what the overall impact was.
| a-dub wrote:
| forensic image analysis is cool and all, but i think maybe
| instead of:
|
| "A neuroscience image sleuth finds signs of fabrication in scores
| of Alzheimer's articles, threatening a reigning theory of the
| disease."
|
| it would be better to see:
|
| "A neuroscientist conducts an irrefutably strong study that
| upends 16 years of theory on the disease process behind
| Alzheimer's."
|
| i don't care if someone cheated, i care that their results are
| discredited by scientific processes, not forensic review.
| appleflaxen wrote:
| The scientific process is the systematic identification of what
| is true.
|
| Wikipedia: "the scientific method involves careful observation,
| applying rigorous skepticism about what is observed, given that
| cognitive assumptions can distort how one interprets the
| observation."
|
| So identifying fraud _is_ the scientific process.
| a-dub wrote:
| sure. but i think i'd rather see biologists debunk prevailing
| theories in biology by doing biology while in the process
| getting better at biology rather than dabbling in forensic
| image analysis. (although, who knows, maybe said dabbling
| could lead to some new meaningful insights down the line)
|
| i guess the bigger point is that the act of topical inquiry
| should have inbuilt mechanisms for discarding ideas and
| approaches that turn out to be dead ends, without having to
| rely on them actually being fraudulent (they can be, and
| often are, completely legitimate, yet also completely wrong).
|
| we shouldn't be discovering bad ideas in science by fraud
| detection, we should be discovering them by mainstream
| scientific process.
| axg11 wrote:
| The most powerful results in science are continually reproduced
| by being built upon to uncover further new knowledge. I'm no
| expert in the toxic oligomer hypothesis or Ab hypothesis, but it
| appears that these paths have led to very little new knowledge.
| ramraj07 wrote:
| Still half a billion dollars of NIH money went into this sub
| field.
|
| The article points to how the main accused got an R01 approved
| AFTER this misconduct started to come out, and the guy awarding
| it was one of the coauthors of the first fabricated papers.
| api wrote:
| It reminds me of the eating cholesterol hypothesis for artery
| blockage and heart disease. Most artery blockages are made of
| cholesterol therefore eating cholesterol must be the culprit.
| Simple, straightforward, and now apparently wrong. The
| cholesterol buildup is a symptom of something else.
|
| Seems likely with Alzheimers that the amyloid buildup is a
| symptom not a cause.
| sfrautschy wrote:
| This is ridiculous. Dozens if not hundreds researchers have
| confirmed the high MW oligomers correlated with pathogenesis. I
| have. To say that he found this or everything relied on this
| theory is absurd. We've know this since the early 90's when Lesne
| was in high school or earlier (e.g Glabe and Cotman's work at UC
| IRVINE and Christian Pike now at USC , my work etc.) . this is
| way before Lesne even considered a career. It used to be called
| "micelles' or soluble abeta. Also the post doc supervisor
| repeated the data and found the same thing so she took him at his
| word. I can't stand this ridiculous media that make this out a
| scandal and create false disinformation that the entire
| hypothesis is based on this.
| dmatech wrote:
| And this is why I'm increasingly suspicious of "consensus" in the
| scientific establishment. With careers, egos, reputations, and
| grant money at stake, it's tempting to use one's power to
| entrench this consensus.
|
| Scientific consensus has value, but science also requires that
| people be open to having their pet theories be validated through
| replication.
| rmatt2000 wrote:
| This is why I grit my teeth whenever I hear a politician say
| something like "the science is settled". Anyone who understands
| the scientific method knows to say "the science is settled,
| except if <some specific thing> happens".
| c3534l wrote:
| Its fair to be skeptical and to use your critical thinking
| abilities, but I worry that people go "oh, this generally
| credible source isn't perfectly reliable, I guess I'll go
| listening to crackpots and charlatans." Almost as bad is when
| you become convinced you have the answers, despite not being
| remotely qualified to speak on the subject. This is how you get
| flat earthers and 5G conspiracy theorists.
| jrumbut wrote:
| I've begun to tune out societal criticism that doesn't come
| from someone with a better idea, who isn't willing to stand
| in one place and defend a proposal.
|
| The experience of saying how you would do it better and
| getting it torn to shreds really brings you back down to
| earth.
| telchior wrote:
| What does consensus mean, exactly? It doesn't sound like Ab-56
| had full buy-in; the article mentions people complaining about
| an "amyloid mafia" and half of all funding still going to
| alternate research, so clearly there were a lot of people who
| weren't part of whatever the "consensus" was.
|
| What's really interesting to me is that such vast sums can be
| spent, a number of people apparently did not like the Ab*56
| hypothesis and had substantial reason to oppose it or try to
| find holes in it with substantial rewards for doing so, yet the
| ones to find problems were some dudes (without any funding at
| all) just poking around.
| epgui wrote:
| I'm a scientist, and I don't think things so easily become
| consensus. In order to get to consensus, a model needs to have
| been tested from many different angles. It's never enough to
| get to statistical significance, things either get replicated
| or, more often, triangulated.
|
| Consensus is an extremely time-consuming thing to build, and
| it's extremely important to be aware of when there exists a
| consensus, where there isn't one, and what the consensus is.
|
| It isn't an appeal to authority fallacy, it's a form of
| deferral to expertise, and it's one of the most important
| heuristics we have.
| ramraj07 wrote:
| Absolutely not true. I've seen things become consensus
| because of one single questionable image in one paper from a
| "trusted" lab.
|
| In my alma matter field the question was whether her2
| receptor recycles (has implication of all breast cancer
| antibody therapies that target her2) and a paper from a
| Genentech lab had ONE FIGURE (where different data points
| from different experiments) as proof. An entire sub field
| including projects in my own lab were spawned assuming this.
|
| Whenever I point out this flaw in lab meetings I'd be shut
| down by my professors as "they know the authors they trust
| them".
| epgui wrote:
| I think I'm going to continue disagreeing with you on this
| point, but I will point out that our difference of opinion
| is a semantic one.
|
| To say that everyone "believes in" a model could mean that
| everyone accepts it as plausible (and thus worthy of
| further exploration), or it could mean that everyone is
| justifiably certain that it maps properly to a real
| phenomenon.
|
| I never say that something is "consensus" in the first
| case: IMO, the term should be reserved for the latter case,
| or appropriately qualified.
|
| In any case, the situation you describe appears to lack
| meaningful triangulation. [1]
|
| [1] https://www.nature.com/articles/d41586-018-01023-3
| hcknwscommenter wrote:
| There is also the fact that anti-her2 is now know to be a
| very effective cancer treatment.
| JPLeRouzic wrote:
| This guy might well have cheated but how could he be responsible
| for the huge mess which is the amyloid-b research (and amyloid-b
| lobby as told by Statnews [0])?
|
| Sylvain Lesne, has no Wikipedia page. He seems to publish roughly
| a paper per year while some famous scientists publish one every
| month. He is not at the origin of the amyloid-b hypothesis which
| is more than 100 years old.
|
| Even more there are thousand papers published about Ab*56 and
| Alzheimer's disease. How could this guy responsible for this
| mess?
|
| And if what he published was wrong, why this was discovered only
| 18 later if thousands scientists are working in the field?
|
| My understanding is that there is a need to find a scapegoat for
| the amyloid-b and pointing to an obscure guy is in the interest
| of many big fish.
|
| [0] https://www.statnews.com/2019/05/21/alzheimers-disease-
| amylo...
| spfzero wrote:
| The OA points out it was, or was one of, the most cited papers
| in subsequent AB research. They make the argument that it has
| mislead many other researchers and cause a waste of many
| millions in funding. He's not an obscure guy in the field of AB
| research.
| xigency wrote:
| So the observations it made were pivotal to expanding
| research, but none of the following studies discovered
| counter-evidence? It seems like something is missing here.
| dralley wrote:
| That's precisely why it should have been caught earlier.
| jibe wrote:
| _Even more there are thousand papers published about Ab_ 56 and
| Alzheimer's disease. How could this guy responsible for this
| mess?*
|
| Because he started it?
|
| https://www.nature.com/articles/nature04533
|
| But it is ultimately in indictment of everyone who went along
| unskeptically, collecting grant money.
| JPLeRouzic wrote:
| > _Because he started it?_
|
| This paper is from 1988:
|
| https://pubmed.ncbi.nlm.nih.gov/2893291/
| AlexandrB wrote:
| I think AB and AB*56 are related but different. The article
| is about AB*56.
| fabian2k wrote:
| As far as I understand this is not about the Ab hypothesis
| itself, but the toxic oligomer hypothesis.
| dang wrote:
| Related:
|
| _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)
| smm11 wrote:
| Compare who has it, to who doesn't have it.
|
| My un-scientific version of this is that if you have a large bowl
| of ice cream for desert every night for 55 years, you may develop
| Alzheimer's Disease.
| onionisafruit wrote:
| I've never heard this before. The people I have lost to
| Alzheimer's were very healthy up to the point where the disease
| started manifesting.
| ChrisMarshallNY wrote:
| I remember the story about the addiction "study" ("Porter Jick")
| that was used as the basis for declaring OxyContin "non-
| addictive." It was dramatized (but fairly accurately) in
| _Dopesick_.
|
| It was a letter to the editor, by a doctor, describing a small
| study on hospitalized patients, and was seized upon by Purdue, as
| the basis for their entire sales pitch.
|
| When there's money to be made, people can look the other way,
| quite easily.
| schnitzelstoat wrote:
| "It is difficult to get a man to understand something when his
| salary depends upon his not understanding it." - Upton Sinclair
| Gatsky wrote:
| > She and others in the lab often ran experiments and produced
| Western blots, Larson says, but in their papers together, Lesne
| prepared all the images for publication.
|
| This is a well known thing scientific fraudsters do, "touche
| finale". Any scientist knows preparing figures for publication is
| tedious, no PI in their right mind would routinely do that.
| kazinator wrote:
| These dots don't connect for me very well in this article:
|
| > _In 2006, Schrag's first publication examined how feeding a
| high-cholesterol diet to rabbits seemed to increase Ab plaques
| and iron deposits in one part of their brains. Not long
| afterward, when he was an M.D.-Ph.D. student at Loma Linda
| University, another research group found support for a link
| between Alzheimer's and iron metabolism._
|
| Yet, fast forward to December 2021 or early 2022:
|
| > _Three of the papers listed Lesne, whom Schrag had never heard
| of, as first or senior author._
|
| If Schrag was doing research in the same area, at around the time
| Lesne's results started to dominate, propelling his career, it's
| odd that Lesne's existence somehow eluded Schrag for 16 years.
|
| Did Schrag switch to something else at around that time and never
| give it a second thought for a decade and a half?
| Nelkins wrote:
| I think we are going to find out that diet plays an enormous role
| in all sorts of metabolic diseases in the coming years.
| Specifically as it pertains to Alzheimer's, increasingly strong
| evidence is coming out that your risk can be reduced by avoiding
| excess carbs/glucose, and also by avoiding oxidized foods (in the
| typical Western diet, usually polyunsaturated fats that have been
| sitting in a bottle).
|
| Presentations like these are very compelling:
|
| https://www.youtube.com/watch?v=O36CNNdgDGQ
|
| https://www.youtube.com/watch?v=-tiGIIGOQS0
| ken47 wrote:
| Within its statistical boundaries, the scientific method is
| absolutely trustworthy. Humans though? Not so much.
| mekoka wrote:
| Reminiscent of this equally upsetting article a couple of years
| ago https://news.ycombinator.com/item?id=21911225
| de6u99er wrote:
| >Journals are often uninterested in negative results, and
| researchers can be reluctant to contradict a famous investigator.
| 1-6 wrote:
| How does this finding affect companies that have created
| therapeutics related to Beta Amyloid such as Eli Lilly or Biogen?
| rmatt2000 wrote:
| I wonder if the Univ. of Minnesota is has any potential
| liability here?
| onionisafruit wrote:
| What makes me the most angry about this is the huge difference
| between what the scientist personally gained from this fraud and
| the cost of believing in these results for that past 16 years.
| Maybe he is a bit richer because of this, but it comes at the
| cost of hundreds of millions of dollars being spent on research
| that is destined to be fruitless.
|
| In the time since he published, I lost my father after investing
| hope that a trial that is supposed to prevent amyloid plaques and
| now my mother-in-law is slipping further into dementia.
| upwardbound wrote:
| 1,000% agree. I hope he is brought to justice and sees time
| behind bars.
| nextos wrote:
| As an insider, I am tempted to say research in most diseases is
| driven by lots of fraudulent and oversold results.
|
| Maybe not direct image manipulation as in this case with
| Alzheimer's, but certainly there is always a lot of
| monopolistic rich-gets-richer behavior.
|
| Nearly all professors at top universities I have met develop
| intimate relationships with funders and journals, which they
| use to steer the field in their preferred direction. As the
| posted article says "You can cheat to get a paper. You can
| cheat to get a degree. You can cheat to get a grant. You can't
| cheat to cure a disease."
|
| I have been asked directly to misrepresent results on several
| occasions. In the most recent one, a professor who has received
| all prizes and accolades in his field threatened me and others
| when we refused to misrepresent research results. I could
| afford to do this, but my workmates who have families to
| support were on the brink of giving up to the bully.
| maegul wrote:
| It's also important I feel to stress that this behaviour
| exists at multiple levels of magnitude. A professor may not
| be bending journals and whole fields to their will, but can
| expect and pressure consistently positive results from their
| lab, to the point of being actively reckless with the truth
| and blind to the flaws in their theories.
|
| Just getting caught up in the practice of self-promotion and
| the trumpeting of one's "novel and impactful" ideas while
| managing a lab from the top without having done actual
| frontline research work in some time can take you pretty far
| from scientific integrity IMO.
|
| With no culture of being proud of reporting negative or
| contradictory results, I'd say "excessive scientific zeal" is
| an easy and common trap. Even a slightly forceful lab-leader
| or PI can end up swaying a group of people into some grey
| dishonest zone of scientific practice.
| klipt wrote:
| This is why science needs to formally pre register
| hypotheses. "People tested this ten times and it worked
| once" is infinitely more useful info than "someone
| published a paper because this works! But we have no idea
| how many people tried exactly the same thing and got a
| negative result".
| emmelaich wrote:
| Can you tell us what level of fraudulence is present in
| research for other mysterious diseases? Such as MS or Crohn's
| or ..
| [deleted]
| vba616 wrote:
| If people were faking research suggesting a cure for MS or
| Crohn's, then there would be (alleged) cures to discuss,
| no?
| emmelaich wrote:
| There are quite a few treatments and theories of cause.
| No need for alleged full cure.
| mike_hearn wrote:
| Cancer, unfortunately:
|
| https://www.nature.com/articles/d41586-022-02002-5
|
| _" Exclusive: investigators found plagiarism and data
| falsification in work from prominent cancer lab"_ (July 20,
| 2022)
| dayvid wrote:
| I know two people personally who dropped out of PhD programs
| due to fraud in their departments. I never asked them too
| much about it, but I'm imagining it's related to not wanting
| to lose potential funding or waste years of research to a
| wrong conclusion.
| elihu wrote:
| I could imagine that they might also not want to invest the
| effort and time needed to complete a degree that would be
| of little value if it became public knowledge that the
| department issuing the degree had a problem with fraud.
| CoastalCoder wrote:
| > I have been asked directly to misrepresent results on
| several occasions. In the most recent one, a professor who
| has received all prizes and accolades in his field threatened
| me and others when we refused to misrepresent research
| results.
|
| I wonder if intentional research fraud should carry legal
| consequences.
| cjmb wrote:
| as severe as anything the SEC can bring to bear, imo
| hcknwscommenter wrote:
| It does carry severe legal consequences. If you defraud a
| federal agency into funding your research (which almost
| always accompanies any fraud in basic scientific research)
| you are committing a federal crime and you can go to jail.
| [deleted]
| prox wrote:
| We need a glassdoor-ish site for these kind of underhand
| dealings and fraud.
|
| Also, make a paper/proof trail and get it to
| court/media/government.
| nextos wrote:
| A Glassdoor-like site would be a great idea.
|
| Kind of related, https://forbetterscience.com reports lots
| of research frauds.
| papandada wrote:
| Also, Retraction Watch
| buitreVirtual wrote:
| Just don't post from New Zealand on that site
| onionisafruit wrote:
| Thank you for making a stand on this. My doctor has a "No
| Free Lunch" sign in his office saying he won't talk to
| pharmaceutical reps. Maybe the research side needs a similar
| pledge to avoid being corrupted by funding. I don't know what
| it would be though.
| Fomite wrote:
| The problem is rarely corruption by funding in the way
| you're thinking - Merck going "Hey, can you take another
| look at those numbers?"
|
| The problem is the pressure to _get_ funding by being
| productive. Negative results are wildly harder to get
| funded. Less productive labs are at a disadvantage for
| grants. Which means, like any metric upon which people 's
| salaries rest, people are tempted to game it.
| ghastmaster wrote:
| > NIH spent about $1.6 billion on projects that mention
| amyloids in this fiscal year, about half its overall
| Alzheimer's funding
|
| The funding for one year from this one agency amounting
| to 1.6 billion dollars is a stunning.
|
| If what you say is true, promoters of the validity of the
| NIH should be a push for statutory changes that mandate
| NIH commit a percentage of the overall budget to
| confirming significant past research.
| jmcgough wrote:
| I think part of the challenge is no one wants to throw
| their hands up in the air and abandon amyloid after so
| many years and dollars spent on it. Instead, they say
| "well we just weren't doing an early enough
| intervention", which is how Aducanumab was forced through
| with weak evidence of effectiveness.
|
| The big question is what do we do now? There's Tau, but
| that hasn't been a slam dunk either.
| chevman wrote:
| This is code that the price of entry at a minimum is an
| even more expensive dinner ;)
| throwaway81523 wrote:
| Timeless ;-).
| https://www.gocomics.com/doonesbury/1986/08/10
| [deleted]
| axg11 wrote:
| Fraud and fabrication of results are abhorrent, but this is too
| simplistic a take. These fraudulent results didn't single-
| handedly spawn 16 years of fruitless research. Instead blame
| the incentives that create a system where nobody validates a
| result for 16 years.
|
| If academic science were in a healthy state, novel results
| would be validated 100s of times. The current system is setup
| such that only novel results are rewarded. There is no reward
| for validation. During my PhD I was actively discouraged from
| performing experiments/studies that weren't "new". Everything
| ultimately comes back to the funding model. Scientists are only
| funded for groundbreaking work, measured by the number of
| publications. In turn, journals will only accept previously
| unpublished work.
| upwardbound wrote:
| The fraudster's refusal to confess for 16 years as they saw
| the field go astray and elderly people suffer is a crime
| against the health of so many people. If I were a prosecutor
| I would try to get them for fraud, criminal negligence, or
| even manslaughter. If I were a vigilante, I would have some
| strong "words" with this perpetrator who caused so many
| elderly people to suffer. I hope they are brought to justice
| within their lifetime while they are still alive to be
| punished.
| pawsforthought wrote:
| Hold on a second. In no way did this person "cause" people
| to contract Alzheimer's. Let's remember that all of
| medicine is an intervention. There's nothing to say that
| research going in a different direction would have lessened
| the suffering of people with the disease.
|
| I'm not saying this person is faultless, but scapegoating
| is hardly a sound response to what is clearly a systemic
| issue of misaligned incentives.
| elliekelly wrote:
| What (if any) recourse is there against those who have falsified
| scientific data? It almost feels like fraud on the {scientific
| research} market. Billions of dollars and, perhaps even worse,
| countless human hours, have been wasted in reliance ob completely
| fabricated information. For what? An ego boost? Citations? I
| don't work in science so I truly don't understand the motive(s)
| on the other side of the equation.
| derbOac wrote:
| This is so typical of contemporary academics, at least in
| biomedicine, I don't know where to start. For me, this is
| exemplary of a lot of what I see in the field, that happens
| every day, to larger or smaller degrees. It's not the
| exception.
|
| There's so many elements to this story that echo things I've
| encountered, and read about in studies of trends. For every
| case of outright fraud like this might be, there's dozens of
| "soft fraud" (read: "questionable research practices") that get
| the benefit of the doubt or are never brought to light. No one
| has discussed this here yet, but part of the story is that the
| program officer on one of the accused' recent grants was a
| coauthor with him on this very research -- consistent with
| trends discussed in the literature (of the largest predictor of
| grant receipt being coauthoring papers with grant review panel
| members or officers). So there's this fraud, potentially
| involving someone who then goes on to help decide who gets
| research dollars.
|
| Your reaction is something I've wrestled with a lot. Many times
| there are no consequences really. People talk about lost
| reputation or something, but in cases of soft fraud nothing
| really happens. It just all kind of evaporates into a fog of
| scientific dispute between parties. In cases of blatant, legal
| fraud, someone can be fired or lose a position, but that
| requires significant evidence.
|
| For what? Yes, ego, citations, money, titles, accolades as a
| "rising star" or a "genius" or whatever it is.
|
| The saddest thing to me really, aside from all those harmed by
| bogus treatments, or forgoing real treatments, is all the
| researchers with legitimate ideas, who go against trend, who
| are pushed out because doing the hard work isn't glitzy and has
| lots of dead ends. You end up in this system where the buzz is
| what matters, and riding waves of self-perpetuating hype is
| what gets you to the top. Appropriate skepticism and careful
| thought, meanwhile, costs you because that takes time and risk.
| MattGaiser wrote:
| Presumably the same incentives as everywhere else. Money.
| hackerlight wrote:
| Personal gain, whether that's money or status, at the expense
| of other people.
| dormento wrote:
| And people who might've benefited from an actual, more reliable
| treatment who might have been developed, had the scientist
| refocused to other hypotheses.
|
| This is infuriating.
| fabian2k wrote:
| When I started reading the article I thought the title was a bit
| click-baity for Science. But then I noticed that the theory it
| refers to was not the amyloid hypothesis itself, but the toxic
| oligomer hypothesis that emerged later. That theory is pretty
| much the main potential explanation on why every single drug
| targeting Ab failed that still keeps Ab fibrils relevant. It's a
| very convenient theory because it keeps the main original
| observations about the fibrils relevant while explaining why
| therapies that target them don't work.
|
| One part that is really important that is mentioned in the middle
| of the article is that these systems are very difficult to
| handle, and it's almost impossible to make many of them nicely
| reproducible. Fibril and oligomer formation depends a lot on the
| environment and reacts to tiny differences.
|
| I find this kind of fraud deeply frustrating, there is so much
| wasted effort in the wake of faked high-profile results.
| galangalalgol wrote:
| What are the other hypothesis that would have been explored in
| the absence of the toxic oligamer papers?
| chmod600 wrote:
| "very difficult to handle, and it's almost impossible to make
| many of them nicely reproducible"
|
| Those same qualities that make a study hard to reproduce should
| also create skepticism that the first study was done properly.
| szundi wrote:
| If they wrote this in the article then bad interpretations
| are coming from readers.
|
| It makes sense to publish this, maybe someone else can make
| it stable and reproduce.
| fabian2k wrote:
| It's more insidious than that. In a field where the core
| subject is difficult to handle it is nothing unusual if a
| different lab cannot recreate known experiments on their
| first try. This doesn't mean anything is wrong with the
| original research, it might just mean that the second lab
| didn't control all the variables.
|
| The part that is difficult and annoying is that the variables
| are not necessarily known, it takes a lot of time and
| experiments to actually nail down those. And even then for
| some sensitive stuff every detail can matter, like the exact
| type of tube you did the experiment in or the vendor, batch
| and age of every chemical you used. Very often you can
| control this enough to have consistent results for a set of
| experiments, but that kind of stuff is really hard to control
| across different labs.
| LudwigNagasena wrote:
| But is there a reason to privilege the first study results
| over others? Sounds like a case of the baby duck syndrome.
| mxwsn wrote:
| The social default is in some fields where work is hard
| to reproduce is they still get into good journals and are
| believed up front. Usually this is fine. A lot of work
| that is hard to reproduce, but are relatively important
| or open up many research directions, do eventually get
| reproduced, though it might take a year or more. And
| usually the first party does their best to try to help
| reproduce the results.
| vlovich123 wrote:
| I wonder what it would look like if you're not allowed to
| cite papers in the field unless there's been 5
| independent labs that have managed to reproduce the
| result and all the labs that reproduce get to share in
| the credit (eg if there's a Nobel prize). Would that
| change the incentive structure and create better
| outcomes? Science isn't science until you have a
| repeatable process in place where observations match
| outcomes and the underlying theory. Someone proposing a
| bold new theory without the ability to test it usually
| gets significant credit even if posthumously for being a
| bold visionary which seems to have been sufficient
| throughout time as a motivator for the really
| foundational scientific victories.
| toxik wrote:
| The effort required to reproduce a result, especially an
| exotic one, is often prohibitive. The reward for
| successful reproduction is near zero, and if you fail,
| it's often absolutely zero - you are not going to be able
| to contest a result by a failure. The original authors
| can simply say that your reproduction was flawed, if they
| need to answer at all.
|
| A journal that requires five confirmations to cite a work
| is a journal that will fast have zero submissions.
|
| The main reason people attempt reproduction is to
| continue that line of research, and that often starts
| with reproduction plus a slight tweak. This is why you
| find a lot of papers like this. This is also how
| irreproducible results become sort of known about but not
| challenged in many fields.
| ebiester wrote:
| So what does the incentive structure look like? Do you
| get tenure for running a lab that replicates? Are your
| postdocs in line for tenure track positions? How is it
| funded: do you put the secondary replications into the
| original grant? What happens if you can't find X number
| of labs to run the test?
|
| It's an interesting idea, but it all comes down to how
| the incentive structures happen.
| elcritch wrote:
| Presuming the original lab didn't also intentionally leave
| out important details to make it harder for others to
| replicate their research quickly. Why list all the details
| needed to replicate your research and possibly let other
| labs catch up and take your next grant? Much better to add
| a veneer of listing details but leave out a few of the
| really important ones.
| WalterGR wrote:
| > Presuming the original lab didn't also intentionally
| leave out important details to make it harder for others
| to replicate their research quickly.
|
| Is this common?
| vkazanov wrote:
| Well, half of DS and CS papers are like this: shallow
| descriptions, no public data, no code. And things are
| MUCH easier with computers!
|
| Extrapolation to a more complex field tells me that it's
| a norm there.
| ImPostingOnHN wrote:
| how can extrapolation tell you anything if you don't know
| whether the extrapolation is appropriate, much less true?
| vkazanov wrote:
| Yup. Never read a non-CS paper in my life. This is why I
| used this word - extrapolation.
|
| I am pointing out certain shady incentives in our field
| that might apply in another scientific field as well.
| obscur wrote:
| I heard from a chemistry researcher that it is also
| common in that field to give vague descriptions of
| synthesis procedures in order to allow authors to churn
| out more papers.
| Ekaros wrote:
| From reading online it feels that most important thing is
| to be first. And prevent anyone else even from
| potentially moving forward on your topic. The actual
| scientific progress is secondary.
| shusaku wrote:
| To me this is why the emphasis on "reproducibility" is
| misguided. You might end up failing because you lack the
| technical capability. Conversely, you might "succeed" by
| making a mistake. We should be focusing on coming up with
| new ways to test the same hypothesis.
| ImPostingOnHN wrote:
| that is what multiple reproductions are for
|
| indeed, the initial experiment is not immune to such
| concerns, and might itself have succeeded by making a
| mistake or failed because it lacked the technical
| capability
| vlovich123 wrote:
| The null hypothesis tells us that if we can reproduce
| repeatedly and reliably then we can actually use even
| relatively small number of reproductions to raise the net
| significance of the result (which also diminishes the
| ability for fraud to work as it requires a larger
| conspiracy instead of people just accepting people at
| their word).
|
| If you think reproductions have failed then it's on you
| to try to have a cogent explanation for why if you're
| personally motivated by a belief that the experiment is
| actually valid.
|
| The particle physics folks also have a different approach
| these days where they blind the ability to see results
| and do multiple cross checks of each other's results to
| validate the data (because the underlying experiment is
| so expensive to run). That can also work in theory
| although hard to say what the success rate of that
| approach is just yet.
| spoonjim wrote:
| I worked for a pharmaceutical company that tried to open a
| second factory producing more of the same thing that it was
| already successfully making and it never worked. They built
| the entire factory, it didn't work, they spent years and
| millions of dollars trying to debug it, it simply never
| worked out. They ended up just essentially running the US
| factory at three shifts to meet the increased demand. To this
| day I don't think anyone knows why the European production
| line never worked. Things can fail to reproduce without
| fraud.
| vaylian wrote:
| Very fascinating. Were you at least able to pinpoint a part
| of the production process that produced different results,
| or was the difference only visible once the final product
| was "assembled"?
| spoonjim wrote:
| I was not closely involved with the project. They
| essentially built the first one to "spec" like "use this
| kind of steel in the tanks" and the remediation process
| was essentially tearing those out one by one and "use the
| steel that we used in the first tank."
| Aqwis wrote:
| Sounds like a process similar to how you would debug a
| difficult bug in a big and/or complicated codebase -
| through trying to isolate the code causing the bug,
| comparing the buggy code with code that's known to work,
| replacing other parts of the code with dummy code/mocks
| etc. And sometimes a bug seems impossible to solve
| regardless of how much developer time you throw at it,
| and you just have to ship the product with the bug (seems
| to be especially common in the game dev business).
| buscoquadnary wrote:
| It turns out applying those might not even be enough.
|
| https://slatestarcodex.com/2014/04/28/the-control-group-
| is-o...
| panabee wrote:
| as a non-scientist outsider, a few questions if you don't mind:
|
| 1. is it common for a non-reproduced experiment to gain
| prominence as a leading hypothesis and spur related research?
|
| 2. if so, why? if not, why did this hypothesis take hold?
|
| 3. how can we make science more reproducible?
|
| reproducibility is held as a tenet of science, but this
| example, assuming it is true, would violate the principle.
| elihu wrote:
| The standard of truth in science is reproducibility. But
| publication usually happens before results have been
| independently reproduced. Papers are peer reviewed, but
| generally peer reviewers are just ensuring that the results
| are sufficiently interesting to warrant publication and there
| aren't any obvious methodology mistakes.
|
| For the purpose of funding, publication in important journals
| or conference proceedings is the important thing. And the
| public generally tends to treat publication as the standard
| of truth. But publication kind of works on the honor system
| and is susceptible to fabricated results.
|
| Maybe there should be more funding towards reproducing (or
| not) important results?
| londons_explore wrote:
| Trust, but don't verify, because verification is expensive
| and unrewarding both financially and career-wise
| marsven_422 wrote:
| ethbr0 wrote:
| 1. Yes. Science has a snowball effect as a result of
| committee-driven grant decisions. Research in a hot current
| topic attracts more grant funding more reliably.
|
| 2. It does because some fields of science are intrinsically
| long-duration, highly sensitive to variables, or only
| testable at scales that exceed our experimental capability.
| That's just a consequence of physics and natural laws of
| reality. E.g. nutrition, chemical toxicity, economics, high
| energy physics.
|
| 3. We can cheat and find proxies or more tenable micro-
| systems to experiment on. But often those have their own
| problems (e.g. rodent models) or aren't feasible.
|
| Reproducibility is a _goal_ of science. It 's not always an
| achievable goal.
|
| When it's not, we do the best we can, as with drug testing
| pipelines.
| panabee wrote:
| thanks for this response.
|
| given the prevalence of non-reproducibility, what other
| fields do you believe have suspect leading hypotheses?
| mike_hearn wrote:
| Here's a couple:
|
| 1. Twitter bot / misinformation research. A surprisingly
| large field in which papers are almost never replicable
| because they don't supply the actual tweets, but only
| opaque IDs and classifications. Trying to cross-check
| them is futile because by the time you tried months later
| many of the accounts have been suspended. They could
| easily supply the contents of the tweets they scraped
| along with account metadata, but don't. The few times I
| did deeper checks of these papers I always found some
| accounts that were identified as bots but weren't
| suspended, and on manual inspection were very obviously
| human. This field also has the problem of being
| increasingly based on ML pseudo-science.
|
| 2. Germ theory! It can't explain several aspects of the
| epidemiology of respiratory diseases. It's probably not
| wrong but is certainly incomplete. As we saw with COVID,
| models based on simple germ theory always make wrong
| predictions, but this problem pre-dates COVID. It was
| known for a long time that standard germ theory fails to
| explain the behavior of influenza, for example, why it's
| seasonal, why waves peak and enter decline before
| everyone is infected, why variants disappear totally
| instead of coexisting, why flu season seems to start
| everywhere in season almost simultaneously, why there
| have been outbreaks of respiratory viruses in totally
| isolated environments like arctic bases, and so on.
|
| The issues here are deeper than reproducibility though.
| Even if bot papers were reproducible they would still be
| wrong because their methodologies are invalid and cannot
| support the stated conclusions. It's important not to get
| too focused on mere replication.
| Blahah wrote:
| In general, anything that's at the bleeding edge of
| theoretical understanding and intersects with commercial
| interest or draws social/media hype has a relatively low
| probability of standing the test of time. Whether that's
| replicability, applicability, or just validity.
|
| The most exciting hypotheses tend to go one of two ways.
| They are rapidly supported with independent evidence, by
| being applied or replicated. Or they draw a lot of
| attention and money which helps them persist in spite of,
| or in the absence of, evidence.
|
| Charlatans, purveyors of snake oil, and (most often)
| people who for whatever reason don't want to be seen to
| be wrong - they exist in every walk of life. Science is
| the same. The incentives in the system strongly select
| for these people in the 'leading hypotheses' space.
| Quekid5 wrote:
| Not the person you replied to, but...
|
| _Everything_ is extremely hype-driven -- it turns out
| that "cannot confirm X" isn't very compelling for
| journals, etc. etc. or even the news cycle. Journals,
| etc. thrive on exciting new findings... and that tends to
| lessen the critical looks.
|
| Of course, there are lots of other things to this
| problem: Very narrow fields where people absolutely know
| who their "anonymous" paper reviewers will be, and so
| _must_ include even extremely tangential references to
| those reviewers ' papers, etc. etc.
|
| Usually the sciences self-correct eventually[0], but
| that's only because there is such a thing as objectively
| verifiable facts and overwhelming statistics in science.
|
| [0] Unfortunately often as slowly as "one funeral at a
| time" (Max Planck, I think).
| ta988 wrote:
| One of the issues is that by chance the models used have an
| unexpected behavior that seems to confirm the initial
| hypothesis is sound.
|
| And this is not rare. Sometimes it is fraudulent, people know
| things are faulty but continue anyway. In other cases it
| could be by ignorance of the existence of the phenomenon
| behind the faulty behavior or simply because that phenomenon
| has not been discovered yet.
| narrator wrote:
| Methylene Blue is in phase 3 trials with Taurx[1] The patented
| version will be slightly tweaked version of the century old drug
| so they can make some money on it. Still, it would be one for the
| ages that an out of patent cheap drug makes decades and billions
| of research obsolete. They say it clears tau, but it probably
| works some other way like being an antimicrobial that can cross
| the blood brain barrier.
|
| A doctor I know takes Kordon methylene blue which is pennies a
| dose.
|
| [1]https://taurx.com/the-science/clinical-trials
| pengaru wrote:
| > A Phase 3 clinical trial of LMTM (TauRx0237 or LMT-X), a
| derivative of methylene blue, failed to show any benefit
| against cognitive or functional decline in people with mild to
| moderate Alzheimer's disease. Disease progression for both the
| drug and the placebo were practically identical.
|
| https://en.wikipedia.org/wiki/Methylene_blue#Alzheimer's
| narrator wrote:
| The cite for that was from 2016. The latest study has yet to
| publish results.
|
| https://clinicaltrials.gov/ct2/show/NCT03446001?term=TRX0237
| pengaru wrote:
| You act as if the cited article was simply about an honest
| presentation of negative results. When in fact it
| illustrates a similar kind of dishonesty and manipulation
| as TFA being discussed in this thread.
|
| I don't see why we should have any amount of optimism in
| this direction based on the evidence in front of us.
|
| Do you hold stock in TauRx or its affiliates?
|
| https://www.alzforum.org/news/conference-coverage/first-
| phas...
| dav_Oz wrote:
| One needs a theory of mechanism to develop an intervention i.e.
| "new drug". The simpler the better.
|
| But given the tremendous complexities involved in biological
| systems one has to be very careful with the data. Quite frankly
| most in the field are not sufficiently trained or aren't rigorous
| enough in dealing with uncertainties and I wouldn't blame them
| it's mind-boggling and paralysing.
|
| This of course can be exploited given the incentives stated above
| combined with the public's unawareness of e.g. statistical
| significance vs clinical significance etc., with the myriad
| _mathematically correct_ ways of presenting data, and a
| handwaving attitude about reproducibility, this really opens up
| the floodgates for someone in a lab to become "creative", an
| entrepreneur. Which of course should be highly discouraged in the
| context of scientific research and in order to relieve some
| pressure _the community_ once in a while condemn the most daring
| of examples without imhv looking too deep into the entrenched
| mechanisms enabling this.
|
| A PhD student (biomedicine) once jokingly told me about the old
| HeLa contamination "problem"[0] in labs experimenting with cells.
| I must have reacted shocked as he laughingly added: Well, that
| was quite a long time ago, the problems now, only compounded.
|
| So, in order to get the full picture it is "healthy" to zoom out
| and look at the other side of the spectrum i.e. longitudinal
| studies (with its own sets of limitations). One impressive one
| relating to Alzheimer's is the famous nun study[1].
|
| [0]https://en.m.wikipedia.org/wiki/HeLa#Contamination
|
| [1]https://en.m.wikipedia.org/wiki/Nun_Study
| ta8645 wrote:
| There is so much of this, through many fields of science today.
| Incentives that corrupt and undermine the scientific method. And
| yet, many people will deny that there is justification in
| skepticism of say, relatively new mRNA vaccines.
|
| Yes, it's good that science usually deals with such problems in
| the long run, but how is the average person supposed to trust
| that the latest scientific assurance, isn't 15 years away from
| being retracted like in this example?
| JulianMorrison wrote:
| A big part of the problem is things moving so fast that a lot
| of stuff doesn't _have_ a long run. Covid and its vaccines
| being an example. In the end the reason to trust them was a mix
| of "if not this, then what?" and "it doesn't seem to be
| killing people".
| fabian2k wrote:
| We have a lot of really good evidence that the vaccines are
| preventing a lot of deaths.
| ncmncm wrote:
| It has been unfortunately necessary to downplay cases of
| debilitation and, even, death apparently traceable to
| vaccination. If vaccination saves the lives of a hundred
| times as many people as it harms, in the "trolley" sense,
| that should be good enough, but in popular imagination it
| is not.
|
| Rational treatment might enable identifying individuals
| particularly at risk and not vaccinating those, but that
| option is closed to us. Instead, a random, suspicious
| fraction of the population pays particular attention to
| negative outcomes and avoids vaccination, to its detriment,
| and most of those at risk for problems get vaccinated
| anyway.
| ta8645 wrote:
| > It has been unfortunately necessary to downplay cases
| of debilitation
|
| I don't think it was necessary at all, and instead is
| very counterproductive. Many people know they're not
| being dealt with honestly by the government and media,
| resulting in more distrust and resistance to vaccination,
| than there otherwise would be.
| ncmncm wrote:
| The number of deaths would objectively be larger if
| people had access to accurate numbers, because even more
| would avoid vaccination and then die of the infection
| vaccinated against.
|
| It is a tragic calculus. "Trolley Problems" are very far
| from theoretical in public health management. We are
| forced by distrust to sub-optimal choices that themselves
| promote distrust. Managing risk of a better population
| would be easier, but you battle pandemic in the
| population you have, not the population you want.
| jtbayly wrote:
| You state confidently that deaths would be higher, but
| you gave no evidence for that. I believe you are wrong.
| The lies confirm to all that we should not trust you.
| Assuming you have any ability to recommend things that
| will actually save lives, in the long term proving
| yourself a liar will only lead to fewer people believing
| you and taking your advice.
|
| So tell the truth, build trust, and let people decide for
| themselves. That will save lives in the long run.
| Dylan16807 wrote:
| Downplaying isn't lying, and categorizing people into
| those that tell the truth and those that don't tell the
| truth is a stupid way of assessing anything important.
| jtbayly wrote:
| Lying about the risks is lying, regardless of what ends
| you think will justify the means.
|
| But even if you disagree, let's talk about your claim
| that categorizing into two groups is stupid. Think from
| the citizen's perspective of the CDC. The question is,
| "Do I trust them enough to take health advice from them?"
| If they have lied to you too many times about things that
| are important enough, the answer is no way. I never
| implied all that this lying group said was lies.
| Obviously one lie wipes out thousands of truths. Trust is
| gone. Listening stops.
| Dylan16807 wrote:
| If you decide to do your own research, you need to do the
| damn research. Just not listening is a terrible idea.
|
| And all sources are flawed!
| zeven7 wrote:
| This is exactly why a large portion of the population is
| not wrong to doubt the official narrative.
|
| Science shouldn't even be engaged in trying to save as
| many lives as possible. Science should only be concerned
| with discovering and disseminating the truth as it is.
| ncmncm wrote:
| Public health should not be confused with science. They
| are separate activities.
| ncmncm wrote:
| Excuse me, where did I lie? I have no role in collecting
| or reporting on adverse reactions. I don't even know for
| sure that adverse reaction numbers are as large as I
| suspect.
|
| I do empathize with the people trying to minimize deaths
| from a raging pandemic in an atmosphere of politically-
| motivated disinformation that is actively contemptuous
| toward public safety. People with your attitude make
| their work that much harder, and cost more unnecessary
| deaths.
| jtbayly wrote:
| Sorry. You spoke in the first person plural "we" so I
| just addressed my comment back to a generic "you." I
| never meant to say anyone in particular (let alone you)
| was a liar.
|
| However, you were advocating for not giving people
| accurate numbers. Whoever is in charge of that decision
| should _not_ lie. They should give accurate numbers.
| ncmncm wrote:
| What they should do if the goal is to minimize public
| mortality is not obvious.
|
| What they should do as a matter of abstract merit, or of
| public perception of benignity, are two wholly different,
| generally easier and less vexing questions.
| pawsforthought wrote:
| Perhaps public health officials need to pay more
| attention to the _iterated trolley problem_. Difficult,
| for sure, when dealing with the pandemic in front of you,
| and not the next one that comes, but our encroachment on
| animal viral reservoirs and insistence on conducting
| hazardous gain-of-function research all but guarantees
| the next one will come sooner or later.
| upwardbound wrote:
| Could someone in this thread please cite the alluded to
| cases of disability or death caused by one of the COVID
| vaccines? It would be helpful if people can be specific.
| I'd like to understand (1) whether this really happened
| or is a myth (2) which vaccine and (3) what's the
| biological mechanism of damage.
| pawsforthought wrote:
| I can't do as you ask, except to say that vaccine
| skeptics will point to any and every health problem in a
| vaccine recipient they know as having been _caused_ by
| the vaccine. (I've found that) it's very difficult to
| counter that anecdata.
| fithisux wrote:
| We have excellent evidence that the amyloid hypothesis is
| valid. Otherwise you get no grant (enter the clothing
| shop).
|
| This is sarcasm of course.
| theduder99 wrote:
| ncmncm wrote:
| We cannot be confident that "science usually" overcomes faulty
| models. The best we can say is that science has often been seen
| to succeed at this, in well publicized cases. Many less visible
| fields might never overcome their biases. Usually a field
| cannot correct course until a whole generation trained on a
| false premise dies or retires.
|
| Economics is a field that has been particularly resistant to
| correction, but is far from alone. Geology and statistics are
| recovering from a similar handicap.
|
| As Max Planck is often quoted, "Science advances one funeral at
| a time." Often vindication is finally delivered only after all
| the opponents are dead, and the ultimate victor has retired
| from a career blighted by them. Probably much more often people
| are driven out of the field and never vindicated.
|
| Lynn Conway was driven out of computer architecture (where she
| invented out-of-order execution in the '60s, thus long delaying
| that advance) before finding success many years later in VLSI
| chip design methods.
| lightup wrote:
| At the U of MN? Say it ain't so. My proud alma mater. Hacking
| linux kernel. Round up. Someone should start a list of what tax
| dollars pay for.
| ta988 wrote:
| I worked in a lab doing research based on that amyloid hypothesis
| (working on other projects). The only thing that got out of it
| were molecules that were really good at messing up the assays
| used but had 0 biological effect in vivo. So in the end the lab
| optimized the protein and cell assays to make them were more
| sensitive to artifacts. This wasn't made on purpose, just a
| combination of human and institutional factors that combined as a
| perfect storm. Several dozens of academic papers were published
| on that... That's what happens when you have isolated labs in a
| university that doesn't favor and nurture collaborations but
| focuses instead on political and economical aspects. Now all the
| people that took the wrong decisions have either retired or got
| fancy positions elsewhere.
| jajag wrote:
| > Ashe declined via email to be interviewed or to answer written
| questions posed by Science ... But she wrote, "I still have faith
| in Ab*56,"
|
| Richard Dawkins won't be impressed.
| LeonB wrote:
| I felt like the author's choice to quote that specific part of
| whatever she wrote was a pretty harsh choice. As a reader you
| see that and jump to the exact conclusions you're alluding to
| here.
| Archelaos wrote:
| The article mentions that the main reason for suspecting that
| results were fabricated is that many images from the researcher's
| papers seem to have been manipulated. As someone who is not
| particularly familiar with AI but occasionally picks up on it
| here on HN, I am now wondering how difficult or easy it is these
| days to take a manipulated image of a western blot and feed it to
| an AI tool trained on unmanipulated western blots to create a
| deepfake that is then virtually indistinguishable from a true
| one. -- Can perhaps anyone here familiar with deepfake technology
| provide an assessment?
| chmod600 wrote:
| Proposal: if a paper isn't reproduced in ten years after
| publication, then it gets automatically retracted (which can be
| reversed as soon as it is reproduced). Any papers that cite the
| retracted study (in a way that the conclusions depend on it)
| would also get retracted. That would be powerful incentive for
| all the researchers who cite the study to try and reproduce it so
| their papers don't get retracted.
|
| You could still search these retracted studies when doing
| research, of course. You just can't cite them.
| anakaine wrote:
| The same issues exist. The next dodgy scientist on the hamster
| wheel looking to get a name for themselves will claim
| reproducibility and then publish a follow up in the spirit of
| publish or perish. You could further entrench the issue with
| this approach, unfortunately.
| lamontcg wrote:
| Better solution might be for the government to just fund
| reproducibility studies, and even departments of
| reproducibility. Take the profit motive out of it, find good
| scientists who are painstaking but maybe not innovative and
| fund them to reproduce major results. The scientists would
| never get the credit for major breakthroughs, but could
| occasionally be wrecking balls that called research like this
| into question. With consistent and reliable funding from the
| government their reward could be stability of employment
| rather than innovative fame (of course these days some
| partisan politics would probably gut it, which is why we
| can't have nice things).
| chmod600 wrote:
| I'm open to that idea but not sure how it would play out.
| It could go wrong in a few ways.
|
| One potential problem is that it could become "the"
| authority on reproducing results. If they repro something
| and another scientist can't, or vice versa, would the other
| scientist get ignored?
|
| Another problem is that it could take away the independence
| of science. The government might start saying what is good
| science and what isn't.
| lamontcg wrote:
| They can only publish their results, though, they can't
| force people to accept them.
|
| Any other institution, anywhere else in the world, is
| free to publish results which disagree.
|
| Scientists should then have the necessary tools to figure
| out which one is likely to be correct, and try an
| independent third or fourth time.
|
| It would be expected that sometimes there would be a
| failure to replicate which was a mistake in how it was
| replicated, that shouldn't be seen as being a failure of
| the goal of replication, and the original authors should
| be incentivized to reach out and discuss the issues with
| the methods.
| c3534l wrote:
| How about the threshold for publishability is that two
| independent groups come up with the same conclusion? So you
| have to partner with another team somewhere else in the world
| in order to get published, and then you get joint credit.
| chmod600 wrote:
| I think there's a powerful incentive to be first, which
| drives people to research in the face of so much doubt.
| Trying to convince one lab that the idea is worth funding is
| hard enough. Two labs is just unrealistic.
|
| My idea hacks around the problem by not diminishing that huge
| incentive to be first. Even if your paper is retracted due to
| lack of repro study, you were still the first, and if it does
| repro you are back to full credit.
|
| I just add an extra incentive to get people who cite the
| study to verify that its reproducible. And at the same time,
| give the original author more incentive to include lots of
| details in their papers so it's more likely to be reproduced,
| and lock in their fame.
| dmatech wrote:
| We just need to cement the notion that no theory is truly
| proven or beyond attempts to disprove it through replication.
| Attempts to discourage replication should be a red flag.
| Fomite wrote:
| The amount of money for an NIH R01 non-modular budget hasn't
| changed since 1999. Which means due to inflation, the average
| "gold standard" grant budget covers half as much as it used to,
| roughly.
|
| Wherein are you going to fund mandatory replication studies -
| some of which are massive cohort studies, so you're going to
| need a whole new population cohort - let alone the...citation
| police...to review every citation not just for its existence,
| but for its _content_.
| abeppu wrote:
| Is there a level of collaboration among so many people that at
| least data can be re-used without being "reproduced"? I.e. the
| field as a whole has put enough work into an apparatus or
| infrastructure that we can regard the initial observation to
| have been trustworthy? We shouldn't have to build a second LHC
| before we believe any claims from the first one, right?
| chmod600 wrote:
| Hypothesis comes before data collection in the scientific
| method.
|
| You can share equipment, but if you share data, then it's the
| same experiment not a new one reproducing the first.
|
| Sharing data would not only miss fraud, it would miss
| experimental errors (e.g. spilled beer in the petri dish),
| p-hacking, etc.
| mtlmtlmtlmtl wrote:
| Actually the LHC does have two detectors with completely
| independent research teams, often doing the same experiment.
| MattGaiser wrote:
| What percentage of research is ever replicated? Are there a lot
| of scientists doing replication studies?
| swatcoder wrote:
| All that does it create an industry for replication labs, and
| then a market where these labs compete to develop the most
| "guaranteed" replications for the least cost, and then a whole
| lot of replications which check the box but actually rely on
| strained interpretations, questionable modifications to
| process, uncaught fraud, etc.
|
| That sounds worse than what we have since it just eviscerates
| the significance of what replication means in the first place.
| smt88 wrote:
| This would work. For-profit replication labs could be part of
| it, but the market would have to be regulated such that:
|
| - any university receiving public funding must participate in
| mandatory replication
|
| - some % of any grant would be reserved for replication
|
| - replication labs would be licensed/accredited, subject to
| government inspections
|
| - labs would not be able to choose who replicates their work
|
| - replication labs would be rewarded for the work, not for
| the outcome
| sebastialonso wrote:
| It's almost like the free market is not the silver bullet
| algorithm many seems to think it is.
| hackerlight wrote:
| Free market? It's government funding doled out by
| centralized committees that drove this.
|
| It was actually the incentives created by the free market
| that finally unravelled this whole thing, as per the
| article.
| sooheon wrote:
| What part about the described system is free or a market?
| axg11 wrote:
| This is a powerful idea. Most problems in science are
| incentives problems. Sadly there's little or no incentive for
| journals to adopt this policy.
| cjmb wrote:
| I agree.
|
| Correcting the many incentive problems in modern American
| science would need a hypothetical body with significant
| funding leverage over journals & scientists to exert
| executive action. Sadly there is no such centralized funding
| body, so the problem must be unsolvable.
| hcknwscommenter wrote:
| Something doesn't quite make sense here. It seems there is good
| evidence that certain figures in Lesne's papers are fraudulent.
| Certainly that is a huge red flag and it is likely that some (or
| all) of the findings are wrong. But that doesn't mean that the
| paper's ultimate conclusions are necessarily incorrect. I mean,
| thousands of papers go on to report on Ab56, do they all just
| assume that Lesne's findings are true without further
| investigation? That seems highly unlikely. What's notable is that
| the entire article here never once refutes the most important
| finding of the original Lesne paper (Ab56 can produce alzheimer's
| like symptoms in rats).
| appleflaxen wrote:
| > What's notable is that the entire article here never once
| refutes the most important finding of the original Lesne paper
| (Ab56 can produce alzheimer's like symptoms in rats).
|
| You refute a paper by showing that part of it is incorrect. The
| research sleuths have provided incredibly strong evidence that
| the very _existence_ of Ab56 is demonstrated (in the paper) by
| a sham line on the western blot.
|
| It's like somebody has demonstrated that a photo of a "ghost"
| is actually a double-exposed film, and you are stating "What's
| notable is that the entire article here never once refutes the
| most important finding of the original photo (that ghosts can
| haunt the waffle house)."
| bluenose69 wrote:
| A new wrinkle in all of this is the current practice of promoting
| research to the public. Many (most? practically all?)
| universities employ nontechnical people whose jobs it is to
| identify newsworthy research results that can be dumbed-down and
| puffed-up in press releases.
|
| Granting agencies do the same thing, either directly via
| newsletters and press releases, or indirectly, by encouraging
| research teams to hire public-relations people.
|
| Members of the public cannot be expected to be able to read, let
| alone understand, the dizzying array of specialized articles that
| are published on any given topic. Heck, this is a real challenge
| even for scientists looking at work that is slightly outside
| their domain of expertise. Some form of overview is necessary,
| but press releases, usually biased and ill-informed, are just not
| the way forward.
|
| But will press releases go away? No chance. This is how students
| get attracted to universities, and it's how alumni get encouraged
| to donate for that oh-so-important sports complex.
| cleandreams wrote:
| Just to note the human cost, my father died of Alzheimers. It's
| not impossible this fraud prevented lives from being restored and
| even saved.
| mkl95 wrote:
| Is there any relevant (non-fabricated) research about the causes
| of fabrication in research? Is it just money or is there
| something else?
| nomel wrote:
| If it's anything like the data fabrication I've seen in
| industry, it's lack of ethics, laziness, mixed with
| deadlines/constraints beyond the individuals control, with a
| dash of arrogance that the conclusion is still correct,
| regardless, and it'll be fine.
|
| I've also seen very qualified people have a massive holes in
| their perception, making them somehow unaware that they're
| generating garbage, and even defending the garbage when it's
| pointed out.
| upsidesinclude wrote:
| This is what makes statements like "trust the science" so
| sickening. Science isn't religion and it isn't always honest
| ncmncm wrote:
| The science is only more reliable than non-science, not
| reliable in any absolute sense. And scientists are as fond of
| superstition as anybody.
|
| Masks were described as useless for countering COVID
| transmission because of what turned out to be superstition
| around "airborne transmission", itself finally traced to a
| result that properly only applied to tuberculosis.
|
| Belief in ivermectin efficacy was a similarly widespread
| superstition among mostly non-scientists.
|
| We have generally had much better results from science. Science
| was finally obliged to abandon its "airborne transmission"
| model by people who knew better publicizing correct
| information. But most ivermectin fans still cling to it.
| throwawaylinux wrote:
| > The science is only more reliable than non-science, not
| reliable in any absolute sense.
|
| What "the" science?
|
| The scientific method is proven to be a very good way to make
| predictions about the world based on observations. The body
| of scientific work built up is immeasurably valuable and
| incredibly good at predicting things.
|
| Some random corporation or politician or person claiming to
| have The Science on their side, and that anybody who
| disagrees or questions them is a heretic and an unbeliever?
| That's not reliable and it's not science.
| ncmncm wrote:
| "The science" as a body of received knowledge refined from
| the rough consensus of a moment among working scientists is
| something distinct from the practice of actually doing
| science. The latter mostly interests those doing it, and
| mostly frustrates everybody else with its apparent wishy-
| washy attitude toward questions of public policy.
| upsidesinclude wrote:
| "Superstition" does a disservice to the fact that _many_
| scientists internationally were reporting on efficacy with
| ivermectin. Meanwhile the information coming from
| "reputable" sources in the world have proven to be less than
| accurate if not complete misrepresentation
|
| Edit:
|
| There is no such thing as 'the science'. There is science.
| Which is testing and questioning to determine facts. Anything
| more must be "trust in the science of..." some actual thing.
| And that actual thing is not public policy. We have
| sufficient evidence that the CDC and NIH are interested in
| appeasing their corporate sponsors and otherwise believe
| themselves to be beyond reproach
| m348e912 wrote:
| You have to think that this type of news does add ammo for
| climate science deniers, covid vaccine skeptics, and
| ivermectin/hcq proponents to make the case consensus science
| != absolute science. Regardless, I do think most people agree
| that all science should have the opportunity to be subjected
| to earnest and thoughtful scrutiny, and it shouldn't be a
| career ending endeavor to do so.
| rtsil wrote:
| One problem the amount of press and hype that these type of
| research receive in the mass media (same thing for the
| "cancer cure breakthrough"), likely promoted by researchers
| and labs looking for funding, and which generally amount to
| nothing. The general public may forget about a specific
| claim, but they don't forget the number of false or
| misleading headlines they've read over the years.
|
| Add to that a blatant case of forgery like this on a high
| priority subject, and you have the recipe for antivaxx, covid
| denialism and overall decline of the trust in science.
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