Fascinating analysis. Great points on lost opportunity, costs to public in terms of health, trust, and public funds. Cost to scientific community at large, as well as to individuals who serve on reviews, committees, research time... and lots more. Sad, but very really reflection of the nature of humans. More readily apparent in some areas than others. I would like to think that scientists are more immune to temptations of glory money and power, but the reality is they're not. The question is were to scientists rank in terms of basic malign character relative to other professions, such as politicians, clergy, bankers, investment 'advisers', real estate professionals, car dealers, ....
Thanks for your comment Elan. The question of how scientists compare to other people in terms of their integrity and commitment to truth-seeking has been on my mind. Sadly, it seems people are driven more by incentives than theoretical principles and values. I'm currently reading a book called "The Betrayers of Truth". It's an old and now rather obscure book about scientific fraud coauthored by esteemed science journalist Nicholas Wade. (https://www.amazon.com/Betrayers-Truth-William-Broad/dp/0671495496). One of the main points of the book is that scientists are human - meaning they will often cheat if they think they will get away with it and accrue massive benefits as a result. All of this has been quite sobering for me. If you'd asked me when I was starting my PhD (in 2010) if I thought fraud was a problem in science I would have assumed it was barely an issue at all! I think collectively we trust our fellow scientists too much...
Disclaimer: I am involved in commercial AD research.
Throat clear: fraud is bad and we should absolutely tar and feather (not to mention fire) the fraudsters.
I want to push back a little and say that I personally think the impact of these frauds on clinical development is overstated.
For example, I do not know of any drugs in development which specifically target Lesné's Aβ*56 species, and yet his fraud is used to cast doubt on the whole Aβ field, including the approved monoclonal therapies (which of course have very small effects and all that, and that's a justified critique, but they're certainly not based on the fraud).
Same for prasinezumab: with or without Masliah, there is still a rationale to at least try and target alpha synuclein.
Cassava is a joke company and a meme stock, they will keep promoting their failed molecule for as long as people give them money. This one is for the SEC to solve, not scientists.
I never saw the "string links" formulation of the problem but I must say I kind of like it as a theoretical framework, as long as we admit that poor quality research should be discouraged and fraud should be punished.
When I was in academia, in an entirely different field, we all knew not to trust the results of certain labs (or colleagues!) without in-house replication. Correcting the record is extremely difficult, as is knowing intent, and not everyone has the persistence to pursue it. I think in practice a lot of shoddy and fraudulent research is just ignored by those in the know, which is like, not great! For sure. But it's workable, and that's the strong links theory in practice.
On the other hand I'm increasingly worried about how this interacts with the training of various knowlege-extracting LLMs which are increasingly used by researchers and often cannot see beyond the context of an abstract.
Hey -- I meant to comment earlier. That's very fair. Derek Lowe said something similar - very hard to say the effect of these frauds. The amyloid hypothesis was going to be dominant regardless.
I think a lot of the research from China and stuff in low tier journals can easily be disregarded as nonsense. It's the high level fraud in journals like the "CNS" journals (Cell, Nature, Science) that worry me more.
An example of a fraud that obviously had a huge negative effect is Andrew Wakefield's notorious Lancet article which helped create the modern anti-vax movement.
In the case of Masliah's fraudulent Cerebrolysin papers (and other Cerebrolysin papers), there seems to be some connection with the exploding popularity and use of the drug (I researched Cerebrolysin quite a bit for a previous post).
LLMs are mixed bag. Personally, I find https://elicit.org/ useful for literature searches, which has some LLM stuff under the hood.
Fascinating analysis. Great points on lost opportunity, costs to public in terms of health, trust, and public funds. Cost to scientific community at large, as well as to individuals who serve on reviews, committees, research time... and lots more. Sad, but very really reflection of the nature of humans. More readily apparent in some areas than others. I would like to think that scientists are more immune to temptations of glory money and power, but the reality is they're not. The question is were to scientists rank in terms of basic malign character relative to other professions, such as politicians, clergy, bankers, investment 'advisers', real estate professionals, car dealers, ....
Thanks for your comment Elan. The question of how scientists compare to other people in terms of their integrity and commitment to truth-seeking has been on my mind. Sadly, it seems people are driven more by incentives than theoretical principles and values. I'm currently reading a book called "The Betrayers of Truth". It's an old and now rather obscure book about scientific fraud coauthored by esteemed science journalist Nicholas Wade. (https://www.amazon.com/Betrayers-Truth-William-Broad/dp/0671495496). One of the main points of the book is that scientists are human - meaning they will often cheat if they think they will get away with it and accrue massive benefits as a result. All of this has been quite sobering for me. If you'd asked me when I was starting my PhD (in 2010) if I thought fraud was a problem in science I would have assumed it was barely an issue at all! I think collectively we trust our fellow scientists too much...
Disclaimer: I am involved in commercial AD research.
Throat clear: fraud is bad and we should absolutely tar and feather (not to mention fire) the fraudsters.
I want to push back a little and say that I personally think the impact of these frauds on clinical development is overstated.
For example, I do not know of any drugs in development which specifically target Lesné's Aβ*56 species, and yet his fraud is used to cast doubt on the whole Aβ field, including the approved monoclonal therapies (which of course have very small effects and all that, and that's a justified critique, but they're certainly not based on the fraud).
Same for prasinezumab: with or without Masliah, there is still a rationale to at least try and target alpha synuclein.
Cassava is a joke company and a meme stock, they will keep promoting their failed molecule for as long as people give them money. This one is for the SEC to solve, not scientists.
I never saw the "string links" formulation of the problem but I must say I kind of like it as a theoretical framework, as long as we admit that poor quality research should be discouraged and fraud should be punished.
When I was in academia, in an entirely different field, we all knew not to trust the results of certain labs (or colleagues!) without in-house replication. Correcting the record is extremely difficult, as is knowing intent, and not everyone has the persistence to pursue it. I think in practice a lot of shoddy and fraudulent research is just ignored by those in the know, which is like, not great! For sure. But it's workable, and that's the strong links theory in practice.
On the other hand I'm increasingly worried about how this interacts with the training of various knowlege-extracting LLMs which are increasingly used by researchers and often cannot see beyond the context of an abstract.
Hey -- I meant to comment earlier. That's very fair. Derek Lowe said something similar - very hard to say the effect of these frauds. The amyloid hypothesis was going to be dominant regardless.
I think a lot of the research from China and stuff in low tier journals can easily be disregarded as nonsense. It's the high level fraud in journals like the "CNS" journals (Cell, Nature, Science) that worry me more.
An example of a fraud that obviously had a huge negative effect is Andrew Wakefield's notorious Lancet article which helped create the modern anti-vax movement.
In the case of Masliah's fraudulent Cerebrolysin papers (and other Cerebrolysin papers), there seems to be some connection with the exploding popularity and use of the drug (I researched Cerebrolysin quite a bit for a previous post).
LLMs are mixed bag. Personally, I find https://elicit.org/ useful for literature searches, which has some LLM stuff under the hood.
What about my dad? He wrote a paper called the Amyloid Cascade Hypothesis. Gerry Higgins