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Comment by atombender | Hacker News Reader

I recommend reading the comments on AlzForum [1]. From the discussions, it sounds like this fraud is significant in terms of Dr. Sylvain Lesné's work, but that the news has been vastly blown out of proportion.

These comments are written by real Alzheimer's researchers. They all disagree with the notion that Lesné's papers have been important to the field, and therefore undermine the idea that this has any bearing on "two decades of Alzheimer's research". (Karen Ashe, co-author of the main paper referenced here, also stops by the thread.)

[1] https://www.alzforum.org/news/community-news/sylvain-lesne-w...

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I agree, the discussion here is reassuring. This may just be a case of a fraudulent paper piggybacking on an otherwise credible research program focusing on amyloid oligomers - not the plaques which recent failed therapies have targeted, and which many of these researchers knew were poor targets for decades before the FDA debacle over aducanumab.

We can blame regulatory capture of the FDA for approval of failed drugs, rather than the scientific establishment. And we can blame Sylvain Lesné for Sylvain Lesné's fraud.

I would encourage those of us whose only knowledge of this topic is the word "amyloid" (I admit I am one of them) to read the scientists' comments and appreciate that there is more to this than we know. There are complexities, nuances, diverse perspectives and healthy disagreements. It's not just a political battlefield. Projecting culture war into it would be harmful to the scientific progress we all value and to the millions who suffer from Alzheimer's.

Their comments are not without self-interest. They all see the potential of their own funding being re-evaluated if they admit that any of their ongoing research build's on (or even references) Sylvain Lesné's work.

They have an interest in limiting the scope of the perception of fraud in the field.

And the people who want a change in direction have an interest in calling out any of that sort of thing that may be happening. So if it is, I hope to see it called out in a scientifically substantial way.

I recommend reading these instead:

Alzheimer’s amyloid hypothesis ‘cabal’ thwarted progress toward a cure (2019) https://news.ycombinator.com/item?id=31828509

How an Alzheimer’s ‘cabal’ thwarted progress toward a cure https://news.ycombinator.com/item?id=21911225

The amyloid hypothesis on trial https://news.ycombinator.com/item?id=17618027

Is the Alzheimer's “Amyloid Hypothesis” Wrong? (2017) https://news.ycombinator.com/item?id=17444214

Why, at this point should we believe any one scientist writing in that forum wasn't already sunk far deep into amyloid research in their career?

Not to mention that after a quick glance on the comments section, I fail to see where you get the idea that "They all disagree with the notion that Lesné's papers have been important to the field". Apart from the very first comment from karen Ashe (who will obviously be defending her research) and a few other who's working on related topics, other commenters seems to be keeping their suspicion at amyloid hypothesis.

Rather than just scrutinizing a single hypothesis for AD we must understand that it is a multi factorial disease and that there are other hypotheses as well (i.e., acetylcholine, tau, transport-clearance), which affect and complicate this disease. Furthermore, we know very little about the brain, hence why novel therapies consistently fail in the clinic compared to other diseases (i.e., cancer). Most of these antibodies that target amyloid don’t even cross the blood-brain barrier (<0.1% and need an effective dose of 1000x blood-plasma for effective amyloid lowering) - provided with this, can we really attest the failure of the amyloid hypothesis? Moreover, the commenters there are big names in the AD community

And how many of those commenters have a vested interest in the current research direction?

It's pretty disrespectful to signal (without evidence or elaboration) that researchers are not credible (or worse, broadly lying) in order to keep their research grants flowing. A hypothesis that turns out to be wrong is something both industry and government are obviously not going to invest further in. The people working in the field have skills to transfer to other departments and projects; these aren't the sort of scientists and engineers that are out of ideas or work to do.

It's also plenty obvious that there is no single, monolithic "current research direction" or even that this researcher's work was of fundamental impact when it was published - not to mention the number of people that were highly skeptical from the beginning.

Given everything we know about how research funding has been captured and shaky ethics in particular domains, skepticism is warranted, not disrespectful.

Also, “believe science” is the exact opposite of the scientific method.

“Hurl unfounded and baseless accusations of personal corruption” is not the scientific method either.

Trying to pass off conspiracy theorist “disprove the negative” arguments as reasonable discourse is intellectually lazy, at best.

Is that an accusation of bad faith or just a non sequitur?

There is that minor issue that we don't have nearly the same experience and resources as the scientists who say what they say. Are you implying we all becom biologists and figure out the source of Alzheimer's ourselves? As some point you have to trust people and choose someone.

I'm not asking for people to turn off skepticism or blindly trust researchers. It's not disrespectful to be skeptical.

What is disrespectful is not bothering to read what people have to say before dismissing them as liars who are too vested in "the current research direction" and/or money for their perspectives to matter. It only takes reading a few comments to see that's not happening - for starters, people were skeptical of this group's work for a while now.

It's not disrespectful to point out conflicts of interest. Recusing yourself is standard practice for good reason.

Harboring skepticism of the work people did with a seemingly fraudulent researcher is a good idea. Dismissing everybody in a field whether or not their work is fraudulent is disrespectful approach (not to mention useless).

It’s not even a good faith argument, people cannot prove they’re not biased.

It’s just your basic lazy conspiracy theory thinking dressed up as cynical aloofness.

lol

Based on the way that string theory keeps on going like a zombie in physics, I don't think its disrespectful at all to consider allegations that are pretty much indistinguishable from those. Although I think that heavily entrenched groupthink and biases are all that is required. I don't think they're consciously think that "I need to lie in order to keep the research grants flowing" but its instead that old adage that "It is difficult to get a man to understand something, when his salary depends on his not understanding it". To an external observer those are largely indistinguishable and have the same effect, but in the latter case the person has convinced themselves of the lie or the half-truth via financially inclined self-deception.

I think there is truth to the general principle you refer to, but I don't think it accurately describes what I saw skimming experts' comments in the linked thread. I'm an outsider to medical research but have experience in other parts of STEM research at universities. Here I saw a plenty of nuance, documentation of historical skepticism, concern over broad perception, and plenty disagreement over technical points. Far from a unified kool-aid drinker sort of situation. And I think there has been plenty of changes of opinions in the Alzheimer's field in recent years given the number of failed drugs - which goes against the idea that these scientists are following their career over the evidence.

But people who are motivated by a decade or two of having their salaries paid by the leading hypothesis aren't going to produce unified kool-aid drinker kinds of rationales to support it. They've had decades to internalize the arguments and they will be nuanced and multifaceted. They're experts and their defense of the old paradigm will look just like expert opinion. There can still be rotten core foundations at the bottom of it all.

I'm not claiming there are no overly stubborn PIs. But we should not be lazy and paint so a brush that we view the field as a monolith.

Nobody is actually arguing that everyone in the field is goosestepping in perfect synchrony like a cartoon.

But human bias applied by groups is actually very powerful.

See related :

"Alzheimer’s amyloid hypothesis ‘cabal’ thwarted progress toward a cure (2019)"

https://news.ycombinator.com/item?id=31828509

https://news.ycombinator.com/item?id=21911225

(also see dang's comment who lists 2 more thread https://news.ycombinator.com/item?id=32213973)

Parent comment is downvoted but it seems like most alzheimer's researchers have vested interest in amyloid hypothesis one way or the other.

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