Fraud - So Much Fraud

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Fraud, So Much Fraud

Charles Piller and the team here at Science dropped a big story yesterday morning, and if you haven't read it yet, you should. It's about Eliezer Masliah, who since 2016 has been the head of the Division of Neuroscience in the National Institute on Aging (NIA), and whose scientific publication record over at least the past 25 years shows multiple, widespread, blatant instances of fraud. There it is in about as few words as possible.

As is so often the case, image manipulation is at the heart of the scandal. Readers here will be all too familiar with the techniques of cutting and pasting Western blots in order to make them tell the story the authors want told, and of re-using images and parts of images over and over even when they're supposed to be produced from different experiments at different times. That's what we're seeing here, and a 300-page dossier has been assembled with examples of it. Splicing, cloning, overlaying, copy-and-pasting, duplication of the same image with different captions about different research in different journals: a great deal of effort seems to have gone into carefully doctoring, cleaning, beautifying, and spicing up these papers digitally. After looking over examples, I find the evidence convincing and impossible to explain (at least in my mind) as anything other than sustained, deliberate acts of deception lasting for decades. Hundreds of them. Again and again. The dossier references 132 papers with apparent problems. Unfortunately, these include many highly cited papers on mechanisms of synaptic damage (Masliah specialized in Alzheimer's and Parkinson's mechanisms, particularly around the alpha-synuclein protein).

The article has a range of reactions to this news from co-workers and others in the field. Everyone seems to have been overwhelmed (as I was) by the scope of the manipulations, and there are plenty of angry and incredulous responses to the news. Along, of course, with some "No comments" and people who refused to reply to emails and would not pick up the phone. Just who knew about these faked-up results over the years is a topic we may never really get to the bottom of: some co-authors have died over the years, and others appear to be running for cover. But at the same time I have a lot of sympathy for the honest scientists who have worked with Masliah over the years and who now have to deal with this explosion of mud over parts of their records.

As the article details, this all has some direct drug discovery implications, particularly for an antibody called prasinezumab which targets alpha-synuclein. All four of the fundamental papers about prasinezumab (as cited on the web site of its developer, Prothena) are full of manipulated images, unfortunately. Prothena and Roche reported results in a Parkinson's trial with it in 2022, and the antibody was found to have no benefit at all (it's undergoing another trial now). Given the difficulty of neurodegeneration therapy, it's hard to say if that result is an honest failure of a worthwhile idea, or whether the entire effort has been built on data that simply aren't real. But we cannot rule out the second possibility, at all.

There's also a proposed Alzheimer's therapy called cerebrolysin, a peptide mixture derived from porcine brain tissue. An Austrian company (Ever) has run some small inconclusive trials on it in human patients and distributes it to Russia and other countries (it's not approved in the US or the EU). But the eight Masliah papers that make the case for its therapeutic effects are all full of doctored images, too. A third drug, minzasolmin, is supposed to prevent misfolding of alpha-synuclein and Masliah and co-workers published the original papers that make the case for its effects. Papers which have doctored images in them. Masliah co-founded a company (Neuropore) that has been developing the drug, and they have a partnership with Belgian drugmaker UCB. It has to be noted that this one has taken some fire already: a paper last year on its in vivo effects brought some pointed criticism that the drug's short half-life should have made it impossible for it to work under the conditions described. The authors responded that they had other evidence of the drug's mechanism, and I'm glad to hear it, because in addition to the original papers, their previous paper on the drug had images in it credited to Masliah that also seem to have been digitally modified. Minzasolmin is currently in Phase II trials.

This is just a horrible situation in every direction. The NIH has stated that Masliah is no longer heading the Neuroscience division, but they haven't stated much else, honestly. An internal investigation starting in May of 2023 led to that decision, apparently but the statement also says that it was in reference to just two publications with duplicated images. It seems like a strange thing to take someone with a long and respected career and subject them to what would essentially be a Western blot and photomicrograph audit before offering them a big position. But if the NIH had done that in 2016, they wouldn't be in the position they're in now, would they? How many people do we need to check? How many figures do we have to scrutinize? What a mess.

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Derek Lowe’s commentary on drug discovery and the pharma industry. An editorially independent blog, all content is Derek’s own, and he does not in any way speak for his employer.

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