Faked Beta-Amyloid Data. What Does It Mean?
science.org
science.org
https://news.ycombinator.com/item?id=32212719
https://news.ycombinator.com/item?id=32183302
And a danglist with more
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.
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)
professor ashe declined to comment for the science article but commented here. notably, she claims the journalist conflated two forms of Aβ 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.
[0] https://pubpeer.com/static/about
[1] https://pubpeer.com/publications/8FF7E6996524B73ACB4A9EF5C0A...
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.
Compare to the recent similar scandal on "self-reported data" for US News college rankings. [https://hn.algolia.com/?dateRange=all&page=0&prefix=false&qu...]
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
It sounds like research needs to be held accountable to some kind of standard for accuracy or quality.
So I think the answer is gatekeeping needs to be different -- not less.
An experiment by the NIPS conference in 2014 found that ~60% of submissions are in the "gray middle" - not obviously great or obviously crap.
In more detail: they split the PC in two, and had 10% of papers (166) reviewed by both halves. Each half had to accept ~37 papers. The halves disagreed on 21 accepted papers [1].
So yeah, if your submission is sciencey, it's the flip of a coin whether peer review will accept it.
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.
I don't know, I think the system is problematic but I can't really think of something else that is feasible.
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.
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.
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.
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.
> "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.
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.
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?
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.
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.
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.
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.
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.
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.
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.
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.
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.
[0] https://en.wikipedia.org/wiki/Yuri_Knorozov [1] https://en.wikipedia.org/wiki/J._Eric_S._Thompson
From the abstract: "my analysis could not clearly determine whether the bias was caused by misclassifying ambiguous phenotypes or deliberate falsification of the results."
I've read that the guy we now credit as discovering oxygen, was actually trying to (and died believing he did) create 'de-phlogistoned' air, and because there was no phlogistons in it, things burned really well in it as it sucked the phlogistons out of the burning matter even faster than normal air.
The key difference is that for 'negative oxygen' to be a thing it would need negative mass as oxidised (or de-phlogistoned) materials gained weight.
Just looked it up on Wikpedia, in case I was repeating urban legends:
> During his lifetime, Priestley's considerable scientific reputation rested on his invention of carbonated water, his writings on electricity, and his discovery of several "airs" (gases), the most famous[7] being what Priestley dubbed "dephlogisticated air" (oxygen). Priestley's determination to defend phlogiston theory and to reject what would become the chemical revolution eventually left him isolated within the scientific community.
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.
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.
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.
This does not, of course, mean that it's not still a big problem; far from it.
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".
If you're old enough, imagine how we (USA-centric) would mock flawed research coming out of the Soviet Union.
Well, here we are. And unfortunately there are plenty of signs of decline once it dawns on you that's what's happening.
I'm not sure what to do.
Correlation is not causation
- The failure to notice and act on the faked data in the Lesné 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.
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.
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.
While I do think that a better aligned system of immediate incentives can ameliorate the symptoms, it's only a patch for moral behavior.
Because they made even more off it.
No, Alzheimer's has been a multibillion dollar sinkhole for drug development cash with absolutely nothing to show for 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?
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.
> Did the 56 Work Lead to Clinical Trials?
> [snip] And the answer is that no, I have been unable to find a clinical trial that specifically targeted the AB56 oligomer itself
It was industry (well short traders) that led to this being uncovered:
> He was originally hired by two other neuroscientists who also sell biopharma stocks short - my kind of people, to be honest - to investigate published research related to Cassava Sciences and their drug Simufilam, and that work led him deeper into the amyloid literature.
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.
It's in there:
> 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.
So labs wanted to work on this for their own reasons, not because of this result.
> Did the 56 Work Lead to Clinical Trials? > That’s a question that many have been asking since this scandal broke a few days ago. And the answer is that no, I have been unable to find a clinical trial that specifically targeted the AB56 oligomer itself
So there weren't even any wasted clinical trials.
Basically his point is that maybe this drew some extra researchers into that area, but it was a worthwhile area anyway. The fact that nothing worked isn't particularly relevant because nothing has worked for Alzheimer's anyway.
[0] https://www.alzforum.org/news/community-news/sylvain-lesne-w...
Schrag's investigation did not (in my opinion) discover any fraud in the Lesné 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.
>“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=Aβ...
However (and without attempting an exhaustive search), detection of oligomeric amyloid (if perhaps not the specific species reported by Lesné are reported, e.g.
https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1750-3639....
With a little extra searching, I found this article below which does appear to replicate detection of a potential 56 kDa form of Aβ in human tissue by western blot of SDS-PAGE gels, as shown in the Lesné paper (Figure 1), though they express concern that its true concentrations may be very low and may be artefacts.
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1582-4934...
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.
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?
(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.)
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.
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.
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?
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).
As Derek Lowe says, this did happen:
> I could be wrong about this, but from this vantage point the original Lesné 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 Lesné’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.
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.
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!
https://www.legalreader.com/st-jude-medical-files-lawsuit-ag...
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...
On the one hand you'll eventually get caught, but only after potentially millions has been spent on said catching.
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.
* People not checking
* People checking and joining the fraud
* People checking, not joining the fraud and then getting their work suppressed.
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.
“Here, I did this magic trick, but I’m unable to tell you sufficient detail for how it works!”
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.
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).
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.
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.
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.
I think you meant to say we don't have non-destructive?
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.
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.
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.
One hot area of research is currently focused on herpesviruses such as HSV1. Here [1] is a paper summarizing some of that research.
The thing about viruses is that they are weird things with unexpected behaviours. For example, we are still learning about Epstein-Barr (EBV, which is another type of herpesvirus); only this year did researchers come to suspect that EBV could be responsible for MS.
If you're a whistleblower and you're not getting shunned by "respectable" people, you're probably doing something wrong.
[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...
"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.
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.
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.
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.
Science is not about listening to experts. It's about the data, and about falsifiable theories.
<< 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.
1) Universal failure of plaque-reduction drug trials.
2) Numerous post-mortem counter-examples: dementia w/o plaques and plaques without dementia.
When people falsify results, what they are doing isn't really a product of the scientific process, they are just committing fraud.
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.
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.
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.
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.
Scientists like Lesné should be detected much earlier in their careers.
A lot of people know about this problem, have for a long time. A lot of people continue to do nothing about it.
Not feeling so proud as an alumni today.