Stanford president dodges research misconduct questions

Amid Tessier-Lavigne’s defense, unanswered questions and contradictory statements

April 25, 2023, 2:15 a.m.

Stanford President Marc Tessier-Lavigne was abruptly withdrawn as a speaker at a major alumni event this winter on the back of a Daily investigation exposing years of research misconduct allegations. “In the wake of the MTL controversy, he will no longer be a speaker at this event,” read an email sent by Stanford’s own fundraising office that was later obtained by The Daily. He was replaced at the event by a subordinate, Stanford’s Vice President for Development.

Over the past several months, Tessier-Lavigne, who faces an increasing number of research misconduct allegations, has repeatedly avoided answering questions about his published studies, both in public and in writing. He has canceled public appearances, demanded retraction of The Daily’s reporting through his lawyers, deactivated the website for his public office hours and declined to respond to dozens of inquiries. And, as Tessier-Lavigne’s public comments have grown increasingly contentious, questions have grown among faculty about whether Tessier-Lavigne can do his job.

Tessier-Lavigne, in a statement provided by his lawyer last month when The Daily reported on increasing discontent among faculty and calls for him to resign, remarked that he continued to “remain focused on the responsibilities of the President by supporting all of our faculty and our students in the mission of truth-seeking, and the advancement of knowledge.”

When he has commented on the allegations surrounding his work, Tessier-Lavigne has routinely provided accounts that contradict publicly available information. And despite sending messages to faculty and staff in his defense, desire for his resignation has continued among some. Hank Greely, a professor of bioethics, recently told The SF Standard, “it’d be very, very hard for him to survive as president.” (In subsequent emails to The Daily, Greely explained that this assessment depends on the allegations against Tessier-Lavigne being proven true; Greely was quick to note that he does not desire Tessier-Lavigne’s resignation and personally hopes that the charges are inaccurate, but is waiting to see what is proven.)

Meanwhile, Tessier-Lavigne continues to evade questions. After a recent event with Colombian president Gustavo Petro, Tessier-Lavigne was approached by a Daily reporter about his research. To two questions, Tessier-Lavigne responded with silence: “Why did you publish Alzheimer’s research you knew wasn’t reproducible?” and “What was the decision-making process behind not retracting that paper?” To a third question, “What do you have to say to people who are wondering why there are so many allegations of research misconduct from your lab?” Tessier-Lavigne told the reporter, “very nice to see you and look forward to corresponding.”

He did not respond to a subsequent email that once more offered the opportunity to answer questions.

Tessier-Lavigne has not responded to numerous inquiries about his research over the past several months. When he has responded, some of his statements have been significantly contrasted by the accounts of fellow researchers, Genentech and the scientific record.

Discrepancies in statements

Doctored images in his studies “do not affect the data, results or interpretation of the papers.”

This comment has been roundly dismissed by scientists and forensic image analysts who have examined Tessier-Lavigne’s work. Elisabeth Bik, one of the world’s most prominent research misconduct investigators, said she would “testify in court” that one Cell paper of Tessier-Lavigne’s had been intentionally manipulated and that it “appears to be altering results.” The journal Science, where several of the studies facing concerns of image manipulation were published, said in an Editorial Expression of Concern that in light of the image manipulation “not all specific conclusions related to these panels are supported by these figures.”

The image manipulation reported in more than a dozen papers on which Tessier-Lavigne served as an author, and the half dozen where he served as the senior or corresponding author, does affect the results and interpretations of these papers, according to several independent researchers.

Of a seminal 2009 Alzheimer’s paper: “the data that led to [the] proposals [of the study] were reproducible.” And, “Let me underscore this: the data were reproducible.”

This statement is untrue, according to independent experts unaffiliated with Tessier-Lavigne or his research who analyzed the scientific record at the request of The Daily. These scientists confirmed that the paper’s central conclusions — that a specific protein fragment makes a specific bind to another protein with the help of specific enzymes, triggering a signaling cascade that causes neurodegeneration in Alzheimer’s disease — were refuted by later studies. (N-APP cannot bind DR6, beta secretase and caspase 6 are not required as described, caspase 3 — which was explicitly ruled out by the paper — is required and the APP-DR6 pathway seems to have no relation to Alzheimer’s.) And Genentech, where the research was conducted, confirmed in a recent statement that “Prior to publication of the paper…senior leaders at Genentech including Dr. Tessier-Lavigne knew” that “the binding interaction between DR6 and N-APP could not be reliably reproduced or confirmed.”

Tessier-Lavigne has not answered several questions about the apparent contradiction in these statements. In his written communications to the community, Tessier-Lavigne has emphasized that certain aspects of the paper remained viable, even while its central conclusions regarding the role of N-APP and DR6 in Alzheimer’s did not hold up.

“I understand that Genentech has also communicated to you that… there was a regular Research Review Committee (RRC) review of the program [that] did not raise issues.”

Genentech has never claimed that the review raised no issues. When asked directly whether the review raised any issues, Genentech has repeatedly declined to comment. And in a subsequent statement, the company confirmed that there were “duplicate images” and “a composite of two images” in the paper.

The company said it did not know the origin of potential image manipulation in the 2009 paper, and did not rule on whether the anomalies were innocent. Nowhere has the company said that no issues were raised. The company also confirmed The Daily’s earlier reporting that at the time of the review, “scientists outside of Genentech also were having difficulty reproducing the binding of DR6 and N-APP” and “one senior leader in gRED [Genentech Research and Early Development] urged that the 2009 Nature paper should be retracted or corrected in light of the inconsistent binding results.”

While in a recent statement Genentech said it did not find evidence of an “investigation of fraud, fabrication, or other misconduct involving the 2009 Nature paper or the research leading to it,” the company also acknowledged that “there are other documents or evidence that the diligence team was unable to find or that no longer exist.” A senior executive involved in the research program at the time told The Daily that he informed Genentech he believed the research to have been falsified. Genentech chalked it up to “speculation.” Still, the company acknowledged “abnormalities” in the paper.

When The Daily asked Tessier-Lavigne about the discrepancy between his portrayal of Genentech’s statements and what the company wrote, Tessier-Lavigne did not respond. When he later released several letters from his lawyer publicly, the inaccurate sentence about Genentech’s statement was redacted.

Unanswered questions

Tessier-Lavigne, who has been under investigation by the Board of Trustees since November, has left a number of questions about his research unanswered. Daily reporting revealed allegations of “overtly problematic” image manipulation in a number of papers on which he served as senior author, as well as the allegation that he kept the findings of a review of his Alzheimer’s research from becoming public. Genentech also disclosed an additional instance in which a postdoctoral scholar co-authored a manuscript with Tessier-Lavigne that had to be withdrawn because of fraud in the research. Here are some of the questions The Daily sent to Tessier-Lavigne to which he did not offer a response.

“When was the [Board of Trustees] first informed of issues in your papers?” — November 2022

Tessier-Lavigne said he was informed of potential image manipulation in his papers in 2015, just as he was under consideration for the role of president of Stanford. According to Tessier-Lavigne, he submitted corrections for several papers at that time that were not published due to an error at the journal Science. Science has confirmed that an error at the journal kept the corrections from being published, but has not said what caused this error. Holden Thorp, Science editor in chief, told The Daily that Tessier-Lavigne had not followed up in seven years about the unpublished corrections.

The Daily has been unable to confirm what the Board of Trustees or presidential selection committee knew and when. Tessier-Lavigne did not respond to this question when it was emailed on Nov. 29, 2022. A spokesperson for the Board of Trustees and several trustees themselves have not responded to similar questions.

“Why did you not issue a public statement responding to allegations of manipulation when you were first informed in 2015?” — November 2022

In 2015, questions about Tessier-Lavigne’s research appeared in public on PubPeer, a site where scientists discuss anomalies in published work. Tessier-Lavigne was notified by email and said he worked to issue corrections for manipulated or duplicated images. But he did not respond to the allegations on PubPeer or in any other public forum, as authors often do. The first time he publicly commented on allegations of research misconduct in his published research was seven years later in response to The Daily’s reporting. Tessier-Lavigne did not respond to this question when it was emailed on Nov. 29, 2022.

“Do you believe that using an official Stanford website and email list to disseminate a personal defense was an appropriate course of action? Do you consider your language aggressive?” — March 2023

Several faculty senators, scientists and community members have expressed their discomfort with a statement emailed to all faculty and staff entitled “False allegations in the Stanford Daily.” Tessier-Lavigne wrote that The Daily’s reporting was “breathtakingly outrageous” and “replete with falsehoods.” The reporting was independently corroborated to the Board of Trustees just days later in an email obtained by The Daily.

Tessier-Lavigne, who also delivered an unprompted defense at a meeting of the Faculty Senate that was met with silence, did not respond to this question when it was emailed on March 4, 2023.

“How are you able to make the categorical statement that there was no fraud and with what evidence?” — March 2023

In Tessier-Lavigne’s public rebuke of The Daily’s reporting, he wrote that, “The Daily claims that the 2009 paper was the subject of an internal review at Genentech that showed falsification of data and that I worked to suppress its findings. This is a breathtakingly outrageous set of claims that are completely and utterly false. In fact, I was not aware of any allegations of fraud until the Daily raised them and to this day I remain unaware of any evidence whatsoever of fabrication.”

But, as several faculty members have said in interviews with The Daily, being “unaware of any evidence whatsoever of fabrication” is not the same thing as having evidence that the allegations are “completely and utterly false.”

Tessier-Lavigne, beyond his own denial and the statement of his friend and former colleague, Richard Scheller, who wrote weeks after The Daily released its article that he did “not recall any discussion” about wrongdoing in the paper and declined numerous interview requests in person and over email in the months leading up to the publication of the piece, has declined to provide evidence suggesting the suspected image manipulation and irreproducibility of his 2009 Alzheimer’s paper were due to innocent error. Tessier-Lavigne’s lawyer said he would provide “a full and corroborated refutation of all of the allegations” to the special committee formed by the Board of Trustees. When asked, he declined to share this refutation with The Daily.

Tessier-Lavigne did not respond to this question when it was emailed on March 4, 2023.

“Genentech reports additional image aberrations in the Nature 2009 paper. Do you still believe all the data to be accurate?” — April 2023

Tessier-Lavigne’s lawyer claimed that “the Paper’s original results were accurately reported.” But the paper has various duplicate panels and other areas of suspected image manipulation, according to independent analysis by several misconduct investigators and Genentech’s statement. Nature issued an Editorial Expression of Concern last month saying “readers are advised to use caution when using results reported therein.”

Tessier-Lavigne did not respond to this question when it was emailed on April 6, 2023.

“You say that ‘a full airing of the facts will vindicate my position.’ Why not sit down with us and walk through those facts as you understand them?”

The Daily has requested interviews with Tessier-Lavigne at least 11 times in the past six months, both in person and in writing. Tessier-Lavigne has declined them all.

This article has been updated to include additional comment from Hank Greely and to provide greater scientific clarity on the results of the Nature 2009 paper.

Theo Baker is the Vol. 263 Spotlight Investigations Editor. A frosh from Washington, D.C., he is the youngest ever recipient of a George Polk Award. Contact [email protected] for encrypted email. Find him on Twitter @tab_delete.

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