The Academic Culture of Fraud. Альцгеймер. На английском

Aug 08, 2024 15:43

https://www.palladiummag.com/2024/08/02/the-academic-culture-of-fraud/

In 2006, Sylvain Lesné and seven coauthors published a paper on Alzheimer’s disease, “A specific amyloid-beta protein assembly in the brain impairs memory,” in Nature, the world’s most prestigious scientific journal. This was a major paper in the development of the “amyloid hypothesis,” a proposed mechanism for how Alzheimer’s disease afflicts its victims. About 50 million people suffer from Alzheimer’s disease, more than the entire population of California, making it the world’s most common cause of dementia. This population will grow as the world’s average population gets older. There is no effective treatment for Alzheimer’s disease, and its pathology is poorly understood. Any progress in understanding this disease represents a massive humanitarian victory. Encouraged by this paper and other promising studies, funding and talent poured into investigating the amyloid hypothesis. By 2022, such research had received over $1 billion in government funds.

That year, neuroscientist Matthew Schrag discovered doctored images in this and many of Lesné’s other papers, including others purporting to provide evidence for the amyloid hypothesis. These images had been manually edited and cropped together to falsely show support for the papers’ hypotheses. Notably, these frauds all made it through the formalized “peer review” processes of Nature and six other academic journals undetected, before eventually being uncovered by unrelated channels.

Schrag’s investigation that uncovered the fraudulent papers began as a tangent from his work uncovering doctored images used in studies supporting simufilam, an experimental drug for Alzheimer’s disease. The suspicion would prove vindicated when in June 2024 Hoau-Yan Wang, a paid adviser to simufilam’s developer, was indicted by a federal grand jury for fabricating data and images in simufilam studies for which he obtained $16 million in National Institutes of Health (NIH) grants, following a 2021 petition to the Food and Drug Administration, a method of reporting research fraud which is highly unusual if not unique.

Follow-up to evidence of Lesné’s fraud was slow. Schrag’s discovery kicked off two years of wrangling, eventually leading all of Lesné’s coauthors-but not Lesné himself-to agree to retract the 2006 Nature paper. As Science reported in 2022, “The Nature paper has been cited in about 2300 scholarly articles-more than all but four other Alzheimer’s basic research reports published since 2006, according to the Web of Science database. Since then, annual NIH support for studies labeled ‘amyloid, oligomer, and Alzheimer’s’ has risen from near zero to $287 million in 2021. Lesné and [his coauthor] Ashe helped spark that explosion, experts say.”

Scientists must now untangle the strands of fraud woven through decades of arguments stretching across a billion dollars worth of research. The paper’s contribution to the allocation of this billion dollars might also be a reason why such a widely-cited paper, presumably read by thousands of experts where some must have spotted the fraud, wasn’t reported earlier. Whether the amyloid hypothesis survives or not, this fraud has likely delayed the arrival of life-saving medication for tens of millions of people, perhaps by many years. If so, it is a humanitarian disaster larger than most wars.
No Consequences for Fraud

All the coauthors of the Nature study who have spoken publicly deny any knowledge or involvement in the fraud, but acknowledge that the images were clearly tampered with. So far, the perpetrator has been left safely in the passive voice. Who actually manipulated the images? Was it Lesné himself? Was it a coauthor acting with his knowledge? Was it a harried underling, acting alone and in secret to fulfill their supervisor’s harsh expectations? Circumstantial evidence suggests it was probably Lesné, but there is no hard proof yet.

In any case, Lesné’s employer, the University of Minnesota, is not interested in these questions. Lesné apparently remains a professor and continues to receive National Institutes of Health funding. The university has been investigating his work since June 2022. A spokesperson says the university recently told Nature it had reviewed two images in question, and “has closed this review with no findings of research misconduct pertaining to these figures.” There is no ongoing effort from the university to find the culprit.

Lesné’s apparent fraud is not an isolated incident. In 2023, Marc Tessier-Lavigne, then the President of Stanford University, was forced to resign after the revelation of falsified data in his earlier research at drug developer Genentech, including a now-retracted paper on the amyloid hypothesis which has been cited over 1,000 times. In a case of successful dynastic skill transfer, public reporting was spearheaded by Theo Baker, scion of an influential family of journalists, during his freshman year as a Stanford student. In 2024, Tessier-Lavigne bounced back, becoming the CEO of the newly-founded drug discovery company Xaira Therapeutics, with over $1 billion committed by its venture capitalist backers.

Once again, Stanford’s official statements do not finger the culprit, but blame Tessier-Lavigne’s “management and oversight of his scientific laboratories,” where “Multiple members of Dr. Tessier-Lavigne’s labs over the years appear to have manipulated research data,” according to the Stanford Board of Trustees’s official report. The report contains incredible positions like “the process through which the science of the paper was developed in Dr. Tessier-Lavigne’s lab, culminating in its publication in February 2009, lacked the rigor expected for a paper of such potential consequence, although the Panel did not find, based on the evidence available to it, that Dr. Tessier-Lavigne was aware of this lack of rigor.” The panel maintains that “it would not be reasonable to expect Dr. Tessier-Lavigne to have identified these instances of research data manipulation prior to or at the time of the respective papers’ publications,” even though many of the fabrications were later identified by visual inspection of the manipulated images. Stanford’s public position is that its researchers cannot reasonably be expected to know what happens in their own labs and gets published in their own names.

Once again, there is no effort to find the supposed true culprits. If the trustees’ report is taken at face value, then there must be several unidentified fraudsters in multiple laboratories, but they seem unconcerned with the obvious implication that these supposed fraudsters are continuing to make up fake data for critical medical research. The trustees maintain that the fraud arose from “lab culture and management,” and therefore implicitly that there is no single individual who bears moral or procedural responsibility for actually falsifying the data. As we saw with the University of Minnesota, this attitude is typical of academic overseers.

While Tessier-Lavigne was at least forced out, rather than enjoying total impunity like Lesné, this should not be mistaken for justice. Medical fraud at this scale is mass manslaughter. If you ripped medicine out of the hands of every man, woman, and child in Spain, that would be about as many people as suffer from Alzheimer’s disease worldwide, whose treatments-and perhaps someday a cure-were all delayed for the benefit of one man’s career. In a just world, the perpetrators would not simply bounce from one prestigious executive position to another. In a just world, the trials of Sylvain Lesné and Marc Tessier-Lavigne would be at least as widely publicized as that of Sam Bankman-Fried. If found guilty, they would be imprisoned for decades.
The Replication Crisis Replicates Across Fields

Medical fraud may be the most evil form of academic fraud, but it is not the only one, or even the most common. More famous is the “replication crisis” in academic psychology, where since around 2010 it has become widely known that most studies in psychology fail to replicate-which is a polite way of saying that the research is mostly fraud, statistical massaging such as “p-hacking,” or simple bullshit. This has had surprisingly little effect, and the field has proceeded with barely even any cosmetic changes, even though all informed observers now know that it’s mostly fake.

Intellectual discourse long assumed that psychology was especially bad compared to other fields, whether due to difficult-to-study subject matter in the “soft sciences,” political pressures, or whatever other cause. Yet even while the ivory tower grappled with the problem, academic psychology remained politically influential. Works like Nudge, the influential 2008 book of psychology and behavioral economics, provided tremendous support for the role of “experts” managing public opinion during the COVID-19 pandemic. In recent years, it has become clear that psychology was relatively good. The indifference to truth is endemic to all or most fields, and psychologists like the Nobel-winning Daniel Kahneman, the author of Thinking, Fast and Slow, a book which popularized many of these results, were able to publicly acknowledge and discuss these problems more than a decade ahead of their peers. This came almost a decade after Kahneman’s work, based in large part on studies which failed to replicate, had played a substantial role in inspiring the influential “Rationalist” movement.

Perhaps the most egregious example in psychology is superstar professor and bestselling author Dan Ariely, likely the most famous psychologist alive. He has had several issues with papers failing to replicate or clashes with research ethics bureaucracies, but the most blatant incident came to light in 2021. The blog Data Colada, which focuses on analysis of research misconduct in the social sciences, published an analysis by “a few anonymous (and fed up and frightened) whistleblowers” which showed that the data in a 2012 paper on dishonesty was clumsily fabricated to provide a positive result. All five coauthors agreed that the data is obviously fabricated and that Ariely, one of the paper’s coauthors, had been the one to pass on the fabricated data to his colleagues.

Ariely implausibly claims the data was already fabricated when he received it from the insurance company the authors partnered with, and the insurance company claims the manipulation occurred after they sent it to Ariely. This “dog ate my homework”-tier excuse was apparently enough for Ariely’s employer, Duke University, to sweep it under the rug. In 2024, Ariely said that a Duke University investigation determined he had not knowingly manipulated the data, although Ariely himself remains the only source for this claim and Duke told reporters “we are not in a position to confirm or fact-check anything on this.” While most reporting has focused on Ariely as the near-certain perpetrator of the fraud, it is also significant that of the paper’s four other coauthors, at best none of them bothered to look at their own data closely enough to spot that it was impossible nonsense. One wonders what they do with their time instead. Many of Ariely’s other papers do not pass the smell test, although no one has yet looked closely enough-and the underlying data may or may not be available-to identify the specific fraud.

This is not just a matter of picking up a few outliers that will inevitably occur in any massive endeavor. This is a systematic corruption of the culture of academia’s researchers, with the active complicity and encouragement of the administration. In the time it took to write this article, I passively stumbled across more examples of consequential research fraud by high-profile field-leading academics than I have space to describe here. If you want more examples, you can find them all day long. How many similar frauds remain undiscovered? One study found that, between 2000 and 2021, the fraction of European biomedical papers which were later retracted quadrupled.

And why not? If bureaucratized peer reviewers or even a paper’s own coauthors aren’t expected to pay enough attention to notice blatant fraud, if fraud is only revealed by third-party investigators when they choose to make a years-long personal crusade in the face of institutional headwinds, if those frauds which are uncovered don’t come to light until decades after the fact, then we can be confident that almost all of the frauds have gotten away with it. Why wouldn’t you report the splashy result that you promised the grantmakers? Why wouldn’t you accept the prestige and promotions and money? Would you be deterred by the fear that, in twenty years, there will maybe be some bad articles online but you keep your job while your colleagues rally around you?

Even in the case of Tessier-Lavigne being forced to leave Stanford to lead a billion-dollar startup, it seems that he is the exception that proves the rule, facing any consequences at all not because his fraud was especially bad, but because Theo Baker had the family connections to take a prominent scalp-for which he should be applauded, in this case. Hoau-Yan Wang may end up paying a steeper price, if he is convicted of fabricating simufilam research, but it is revealing that this is only possible because his accusers gave up on pursuing truth and justice through the system of scientific journals.

Instead of calling for a retraction, they appealed directly to federal regulators at the Food and Drug Administration, prompting an investigation by the Securities and Exchange Commission (SEC). In all the clearly-identified frauds I’ve looked at, I have never found one who was seriously punished by their scientific peers or their university employer, unless the university first came under extraordinary pressure from other leading power centers like journalists or federal prosecutors.
The Epistemic Bankruptcy of Academia

Academics should perhaps take a lesson from one of America’s other privileged guilds. Financiers have a sophisticated apparatus for catching those who break its rules and codes, however lax those codes may sometimes be. Federal bureaucracies like the SEC or the Treasury are staffed largely by former and future financiers and bankers, who move freely through the “revolving door” between private companies and government bureaucracies. As a result, they share much the same norms, the same sense of what’s fair, and the same sense of what behavior is illegitimate. In cases of outright fraud, the fraudster’s former peers in the federal agencies will come down like a ton of bricks, and their employer will swiftly cut them loose.

The SEC maintains a bounty program for whistleblowers, who are awarded between 10% and 30% of the fines the commission imposes as a result of their information, and regularly announces bounties in the tens of millions. Those caught are often sent to prison. Sam Bankman-Fried’s sentence of 25 years may arguably be too lenient for billions of dollars of theft and fraud, but that he is in jail at all gives the financiers a much firmer moral grounding than the Alzheimer’s disease researchers. This approach, of a professional society granted extraordinary privileges while also required to submit to Congressional oversight and to assist in self-policing, provides a much more functional model for oligarchic guilds which have been delegated core social functions.

The U.S. financial system is hardly the greatest edifice of justice in the world. Yet, it demonstrates a basic level of self-policing, effort to uphold professional standards, and accountability to the rest of society. Academic institutions fall far short of these minimal standards. Known serial frauds are sheltered by their bosses and feted by their peers. The culture encourages this at every step of the way, starting with PhD candidates ordered to produce a positive result by any means necessary, continuing with coauthors and grantmakers who can’t be bothered to look at the data and check whether it makes any sense, all the way to department heads and famous bestsellers being widely cited even after they’ve been caught. Those who do not commit fraud themselves usually tolerate it in their peers. The minority who will not tolerate frauds usually weed themselves out quietly. I have lost count of how many friends of friends entered a PhD program, had an adviser who tacitly or explicitly demanded they commit fraud to get publishable results, and quit in disgust without raising a public stink. What that says about those who remain is not encouraging.

Fraud is certainly not the only problem in academic science. Lesser crimes such as massaging data to create false positives and “HARKing” (hypothesizing after the results are known) are even more common. Plagiarism has increasingly become a scandal, most famously forcing the resignation of Claudine Gay from the presidency of Harvard University, the highest post in America’s entire academic system. And many fields are overrun by the publication of bullshit and word games, meaningless enough that classifying it as “true” or “false” is not even useful. Fraudulent data is the worst of these sins, responsible for the biggest pile of dead bodies, since the damage it does is hardest for other scholars to undo. Yet these are all symptoms of the same disease.

With some honorable exceptions, most academics don’t care very much about the capital-T Truth. Oh, they’d prefer Truth to lies, if Truth only cost two dollars. But if the cost is at all serious, they won’t pay it. It is a fault in the institutions that academics must choose between wealth and prestige and career success on the one hand, and pursuit of Truth on the other. But it is a fault in the professor’s character that he would turn his back on Truth, for this. Our civilization created the universities and carved out their special privileges because we recognize that the unencumbered pursuit of Truth is among the noblest callings, and also among the most useful. These people have been given a sacred trust, and they have abandoned it in order to secure a comfortable position. You cannot advance human knowledge by throwing venal careerists and apparatchiks at the problem, no matter how many tons of paper you print. Knowledge comes, and always has come, from insane people on a spiritual quest for Truth, who will neglect worldly concerns in pursuit of the insatiable drive to know. Today’s academics are living in the ruins of a temple built by better men.
Hope Rests with Truthseekers Outside Academia

I have little hope that academic science can be reformed from the inside. Frankly, it seems too far gone. If they want to prove me wrong, it will take a massive purge of the fraudsters and bullshitters, and probably a sharp reduction in the institutions’ total staff. There is some extremely rare precedent for imprisoning medical researchers for defrauding NIH grantmakers by fabricating data: in 2006 Eric Poehlman was sentenced to one year, in 2015 Dong-Pyou Han was sentenced to four years and nine months, and Hoau-Yan Wang might soon join their number.

One conviction per decade is not nearly enough to solve the problem, but it shows that the legal tools already exist. Perhaps the doctors can take a page from the financiers, and create an NIH department dedicated solely to catching and imprisoning fraudsters. Perhaps they can offer a bounty of 10% of the fraudster’s NIH grant for those who turn them in. Whatever the details, any hope of solving the problem from the inside will require imprisoning hundreds of perpetrators, and permanently barring thousands from all scientific institutions. I might also suggest a public cashiering, in which the university’s leaders ceremonially strip the offender of their academic gown and hood, and tear up their diploma.

Unfortunately I doubt that our scientific institutions have the stomach for interventions like these, or for anything else which could possibly work. These are ideas for what actions might actually fix the problem, not ideas for what actions might be within bounds for the institutions as they exist today. More likely, fraud will grow more and more common as young scientists realize that lies are the best way to advance their careers and that serious punishment is about as likely as being struck by lightning. A fringe of credentialed scientists with unusual integrity and courage will continue their efforts on their private blogs and newsletters to document and publicize the many, many known frauds. Universities will not support them, and the legal and social pressure to shut down these embarrassing windows into the sausage factory will slowly grow more intense.

More likely, reform will come through circumvention from outside the academic system. There is no shortage of people who pursue the sacred quest for Truth. Increasingly, they are not pushing forward the frontiers of knowledge in peer-reviewed journals and university campuses, but in fringe niches of internet discourse. Because the internet commentariat’s intellectual elite is more attentive to an argument’s substance than whether it observes the bureaucratic forms, these circles are much less vulnerable to the problems which afflict academia.

The most influential philosopher of recent times is Eliezer Yudkowsky, an uncredentialed blogger and fanfiction author who lacks even a high school diploma. The adoption of his thinking contributed to the formation of major AI labs such as OpenAI and later Anthropic. These same labs have made some of the biggest technological advances of recent years, primarily within industry and with only light involvement from the academic system, while poaching talent from it. A growing fraction of the intellectual elite are leaving behind the institutions for internet self-publishing. Even archaeology is seeing some efforts to work outside of the academy, with well-funded projects like the “Vesuvius Challenge” to decipher the Herculaneum Papyri. Unless the academy can somehow reverse course, this trend will spread to more and more fields.

This situation has a precedent. From the 1500s through the early 1700s, most of the world’s best scientific work was done by individual natural philosophers in their private capacity. They were in dialogue not through formal academic institutions but through loose informal networks of peers, like the “Invisible College” and the “Republic of Letters.” It was in these distributed conversations that modern science was developed and codified, and made its first major discoveries, establishing the intellectual authority of its practitioners. Over time these networks were gradually folded into the university system and to institutions like Britain’s Royal Society, which enshrined their intellectual legitimacy and preserved their epistemic virtues for centuries.

With a bit of luck and a great deal of effort, we might follow a similar path. The fringe internet intellectuals are not yet ready to bear the full weight borne by the academic system of old. As the academic system abdicates more and more of its responsibilities, the work will get easier, but there is a tremendous amount of work to do. Our output is too scattershot, and not nearly comprehensive enough. We mostly have not built the channels which can make our work legible to other elites or to the public. Perhaps most importantly, most of us don’t intend for our work to become widely accepted and contribute to the onward march of human knowledge, rather than just to know for ourselves. Our only advantage is that we hold the epistemic high ground. But in the long run, there is nothing that matters more.

Ben Landau-Taylor studies industrial economics and works at Bismarck Analysis. You can follow him at @benlandautaylor.

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