research misconduct

alzheimer’s-scientist-indicted-for-allegedly-falsifying-data-in-$16m-scheme

Alzheimer’s scientist indicted for allegedly falsifying data in $16M scheme

Alzheimer's, Cassava, CUNY, fraud, health, Hoau-Yan Wang, NIH, NIH grant, research, research funding, research misconduct, Science, Simufilam, Western blots / /

Funding Scheme —

The work underpinned an Alzheimer’s drug by Cassava, now in a Phase III trial.

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Alzheimer’s scientist indicted for allegedly falsifying data in $16M scheme

A federal grand jury has indicted an embattled Alzheimer’s researcher for allegedly falsifying data to fraudulently obtain $16 million in federal research funding from the National Institutes of Health for the development of a controversial Alzheimer’s drug and diagnostic test.

Hoau-Yan Wang, 67, a medical professor at the City University of New York, was a paid collaborator with the Austin, Texas-based pharmaceutical company Cassava Sciences. Wang’s research and publications provided scientific underpinnings for Cassava’s Alzheimer’s treatment, Simufilam, which is now in Phase III trials.

Simufilam is a small-molecule drug that Cassava claims can restore the structure and function of a scaffolding protein in the brain of people with Alzheimer’s, leading to slowed cognitive decline. But outside researchers have long expressed doubts and concerns about the research.

In 2023, Science magazine obtained a 50-page report from an internal investigation at CUNY that looked into 31 misconduct allegations made against Wang in 2021. According to the report, the investigating committee “found evidence highly suggestive of deliberate scientific misconduct by Wang for 14 of the 31 allegations,” the report states. The allegations largely centered around doctored and fabricated images from Western blotting, an analytical technique used to separate and detect proteins. However, the committee couldn’t conclusively prove the images were falsified “due to the failure of Dr. Wang to provide underlying, original data or research records and the low quality of the published images that had to be examined in their place.”

In all, the investigation “revealed long-standing and egregious misconduct in data management and record keeping by Dr. Wang,” and concluded that “the integrity of Dr. Wang’s work remains highly questionable.” The committee also concluded that Cassava’s lead scientist on its Alzheimer’s disease program, Lindsay Burns, who was a frequent co-author with Wang, also likely bears some responsibility for the misconduct.

In March 2022, five of Wang’s articles published in the journal PLOS One were retracted over integrity concerns with images in the papers. Other papers by Wang have also been retracted or had statements of concern attached to them. Further, in September 2022, the Food and Drug Administration conducted an inspection of the analytical work and techniques used by Wang to analyze blood and cerebrospinal fluid from patients in a simufilam trial. The investigation found a slew of egregious problems, which were laid out in a “damning” report obtained by Science.

In the indictment last week, federal authorities were explicit about the allegations, claiming that Wang falsified the results of his scientific research to NIH “by, among other things, manipulating data and images of Western blots to artificially add bands [which represent proteins], subtract bands, and change their relative thickness and/or darkness, and then drawing conclusions” based on those false results.

Wang is charged with one count of major fraud against the United States, two counts of wire fraud, and one count of false statements. If convicted, he faces a maximum penalty of 10 years in prison for the major fraud charge, 20 years in prison for each count of wire fraud, and five years in prison for the count of false statements, the Department of Justice said in an announcement.

In a statement posted to its website, Cassava acknowledged Wang’s indictment, calling him a “former” scientific adviser. The company also said that the grants central to the indictment were “related to the early development phases of the Company’s drug candidate and diagnostic test and how these were intended to work.” However, Cassava said that Wang “had no involvement in the Company’s Phase 3 clinical trials of simufilam.”

Those ongoing trials, which some have called to be halted, are estimated to include over 1,800 patients across several countries.

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Report: Superconductivity researcher found to have committed misconduct

Nature, Physics, research fraud, research misconduct, Science, superconductivity / /

Definitely not super —

Details of what the University of Rochester investigation found are not available.

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Image of a large lawn, with a domed building flanked by trees and flagpoles at its far end.

Enlarge / Rush Rhees Library at the University of Rochester.

We’ve been following the saga of Ranga Dias since he first burst onto the scene with reports of a high-pressure, room-temperature superconductor, published in Nature in 2020. Even as that paper was being retracted due to concerns about the validity of some of its data, Dias published a second paper claiming a similar breakthrough: a superconductor that works at high temperatures but somewhat lower pressures. Shortly afterward, that got retracted as well.

On Wednesday, the University of Rochester, where Dias is based, announced that it had concluded an investigation into Dias and found that he had committed research misconduct. (The outcome was first reported by The Wall Street Journal.)

The outcome is likely to mean the end of Dias’ career, as well as the company he founded to commercialize the supposed breakthroughs. But it’s unlikely we’ll ever see the full details of the investigation’s conclusions.

Questionable research

Dias’ lab was focused on high-pressure superconductivity. At extreme pressures, the orbitals where electrons hang out get distorted, which can alter the chemistry and electronic properties of materials. This can mean the formation of chemical compounds that don’t exist at normal pressures, along with distinct conductivity. In a number of cases, these changes enabled superconductivity at unusually high temperatures, although still well below the freezing point of water.

Dias, however, supposedly found a combination of chemicals that would boost the transition to superconductivity to near room temperature, although only at extreme pressures. While the results were plausible, the details regarding how some of the data was processed to produce one of the paper’s key graphs were lacking, and Dias didn’t provide a clear explanation. Nature eventually pulled the paper, and the University of Rochester initiated investigations (plural!) of his work.

Those investigations cleared Dias of misconduct, and he quickly was back with a report of another high-temperature superconductor, this one forming at less extreme pressures—somewhat surprisingly, published again by Nature. This time, things fell apart much more rapidly, with potential problems quickly becoming apparent, and many of the paper’s authors, not including Dias, called for its retraction.

The University of Rochester started yet another investigation, which is the one that has now concluded that Dias engaged in research misconduct.

The extent of this misconduct, however, might never be revealed. These internal university investigations are generally not made public, even if it might be in the public’s interest to know. The only recent exception is a case where a researcher accused of misconduct sued her university for defamation over the outcome of the investigation. The university submitted its investigation report as evidence, allowing it to become part of the public record.

Behind the scenes

That said, we have learned a fair bit about what has happened inside Dias’ lab, thanks to Nature News, a sister publication of the scientific journal that published both of Dias’ papers. It conducted a tour-de-force of investigative journalism, talking to Dias’ grad students and obtaining the peer review evaluations of Dias’ two papers.

The investigation showed that, for the first paper, Dias simply told his graduate students that the key data came from before he had set up his own lab, which explains why they weren’t aware of it. The students claimed that the ensuing investigations didn’t contact any of them, suggesting they were extremely similar in scope. By contrast, the students claim to have been more aware that the results presented in the second paper didn’t match up with experiments and, in at least one case, suggested Dias clearly misrepresented his lab’s work. (The paper claimed to have synthesized a chemical that the students say was simply purchased from a supplier.)

They were the ones who organized the effort to retract the paper and said that the final investigation actually sought their input.

Meanwhile, on the peer review side, the reporting does not leave Nature looking especially good. Both papers required several rounds of revision and review before being accepted, and even after all this work, most of the reviewers were ambiguous at best about whether the paper should be published. It was an editorial decision to go ahead despite that.

While things seem to have worked out in the end, the major institutions involved here—Nature and the University of Rochester—aren’t coming out of this unscathed. Neither seems to have taken early indications of misconduct as seriously as it should have. As for Dias, the reporting in the Nature News piece should be career-ending. And it’s worth considering that, in the absence of the reporter’s work, the research community would probably remain unaware of most of the details of Dias’ misconduct.

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Lawsuit opens research misconduct report that may get a Harvard prof fired

Harvard, Human behavior, lawsuit, psychology, research misconduct, Science / /
Image of a campus of red brick buildings with copper roofs.

Enlarge / Harvard’s got a lawsuit on its hands.

Glowimages

Accusations of research misconduct often trigger extensive investigations, typically performed by the institution where the misconduct allegedly took place. These investigations are internal employment matters, and false accusations have the potential to needlessly wreck someone’s career. As a result, most of these investigations are kept completely confidential, even after their completion.

But all the details of a misconduct investigation performed by Harvard University became public this week through an unusual route. The professor who had been accused of misconduct, Francesca Gino, had filed a multi-million dollar lawsuit, targeting both Harvard and a team of external researchers who had accused her of misconduct. Harvard submitted its investigator’s report as part of its attempt to have part of the suit dismissed, and the judge overseeing the case made it public.

We covered one of the studies at issue at the time of its publication. It has since been retracted, and we’ll be updating our original coverage accordingly.

Misconduct allegations lead to lawsuit

Gino, currently on administrative leave, had been faculty at Harvard Business School, where she did research on human behavior. One of her more prominent studies (the one we covered) suggested that signing a form before completing it caused people to fill in its contents more accurately than if they filled out the form first and then signed it.

Oddly, for a paper about honesty, it had a number of issues. Some of its original authors had attempted to go back and expand on the paper but found they were unable to replicate the results. That seems to have prompted a group of behavioral researchers who write at the blog Data Colada to look more carefully at the results that didn’t replicate, at which point they found indications that the data was fabricated. That got the paper retracted.

Gino was not implicated in the fabrication of the data. But the attention of the Data Colada team (Uri Simonsohn, Leif Nelson, and Joe Simmons) had been drawn to the paper. They found additional indications of completely independent problems in other data from the paper that did come from her work, which caused them to examine additional papers from Gino, coming up with evidence for potential research fraud in four of them.

Before posting it on their blog, however, the Data Colada team had provided their evidence to Harvard, which launched its own investigation. Their posts came out after Harvard’s investigation concluded that Gino’s research had serious issues, and she was placed on administrative leave as the university looked into revoking her tenure. It also alerted the journals that had published the three yet-to-be-retracted papers about the issues.

Things might have ended there, except that Gino filed a defamation lawsuit against Harvard and the Data Colada team, claiming they “worked together to destroy my career and reputation despite admitting they have no evidence proving their allegations.” As part of the $25 million suit, she also accused Harvard of mishandling its investigation and not following proper procedures.

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