Genentech discloses unreported research misconduct in Stanford President’s lab, says it did not find ‘intentional wrongdoing’ in 2009 paper

Genentech, where Stanford President Marc Tessier-Lavigne once served as chief scientific officer, confirmed on Thursday that there were concerns about Alzheimer’s research Tessier-Lavigne co-authored even before publication and that a senior scientist at the company later called for the paper to be retracted, an action Tessier-Lavigne did not take. The company also disclosed previously unreported research misconduct in Tessier-Lavigne’s laboratory.

Tessier-Lavigne was the senior author of a 2009 paper published in the scientific journal Nature that Genentech had called “groundbreaking basic research about an entirely new way of looking at the cause of Alzheimer’s disease.” What the company didn’t say publicly at the time is that “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,” according to a statement Genentech issued Thursday. Tessier-Lavigne, in a letter provided by his lawyer last month, had claimed: “Let me underscore this: the data were reproducible.” The company said it had not found evidence of purposeful fraud, but five independent executives and senior scientists at Genentech who were involved with the research or its subsequent review at the time have claimed the irreproducibility was due to fabrication.

Genentech wrote in its statement that its legal department “interviewed more than 35 current and former Genentech employees” to compile its findings on allegations that were first presented in a Feb. 17 Daily article. The Daily reported that four high-ranking Genentech scientists and executives alleged Tessier-Lavigne’s Alzheimer’s research had been based on “falsified data” and that after a 2011 internal review discovered this, Tessier-Lavigne declined to retract the paper. Tessier-Lavigne has repeatedly denied the claims, calling the allegations “breathtakingly outrageous” in an email to all faculty and staff entitled “False allegations in the Stanford Daily.” A fifth source later independently corroborated the allegations in private correspondence to the special committee that has been investigating Tessier-Lavigne since concerns over suspected image manipulation in several of his papers were reported by The Daily in late November.

The company did not explicitly confirm or deny that the paper had been based on falsified data and wrote, “we recognize that there are other documents or evidence that the diligence team was unable to find or that no longer exist. We also recognize that interviewees may not have complete recollections of events occurring so long ago.” Still, the company reported that “none of the current or former employees who were interviewed reported observing or knowing of any fraud, fabrication, or other intentional wrongdoing in the research leading to and reported in the 2009 Nature paper.” But at least one person interviewed by Genentech in connection with its review told the company that the research had been falsified, the person told The Daily. This high-level executive requested anonymity due to fear of retribution. Genentech did not immediately respond to a question about why this allegation was not included in the readout.

The five-page document did not comment on the terms of Anatoly Nikolaev’s exit. Nikolaev, the Columbia Ph.D. postdoc in Tessier-Lavigne’s lab who was lead author of the 2009 paper, left Genentech in 2011. He adamantly denies that he was fired. The report also did not comment on recent allegations that were made to the Board of Trustees, alleging that Nikolaev was asked to repeat his results with reagents that were switched without his knowledge and that when he returned with the same results, it was clear he was falsifying data. Nikolaev denies this allegation or that he engaged in any misconduct. Tessier-Lavigne wrote that the allegation “does not even have the ring of plausibility.”

Genentech’s findings also revealed information about previously unreported misconduct claims, saying that “there was a complaint in mid-2010 alleging scientific misconduct by another postdoc working in Dr. Tessier-Lavigne’s laboratory.” The postdoctoral researcher, who was not an author of the Nature 2009 paper, co-authored a manuscript with Tessier-Lavigne that was submitted for publication. But “the complaint led to a formal investigation by the company, resulting in withdrawal of that manuscript and termination of the postdoc’s employment in August 2010.”

Steven Neal, chairman emeritus of Cooley who represents Tessier-Lavigne, sent a letter to The Daily demanding retraction of its reporting and claiming that the “Genentech Findings categorically refute the Daily’s reporting regarding the 2009 Nature Paper.” As of the time of publication of this article, Tessier-Lavigne has not responded to several questions about the review, including a question about his prior statements about the reproducibility of the research and another about the new allegations of research misconduct in his laboratory raised by the Genentech statement.

The company also disclosed new concerns about the 2009 paper, writing that it had “concluded that two sets of figures… include duplicate images” after consulting an expert who “also concluded that a Western blot panel for Caspase 6 in Supplementary Figure 6d appears to include a composite of two images.” The company said it had “not determined how these anomalies occurred” but reported them to Nature, where the study was published. Nature, on March 15th, issued an editorial note saying that it will investigate the paper and that “readers are advised to use caution when using results reported therein.”

The Daily had previously reported that Tessier-Lavigne was urged by senior executives at Genentech to retract the 2009 paper when concerns were raised after its results could not be reproduced by outside researchers and a subsequent 2011 review by Genentech’s Research Review Committee. Genentech confirmed this in part, writing that “at least one senior leader in gRED learned that scientists outside of Genentech also were having difficulty reproducing the binding of DR6 and N-APP.” The company confirmed that the research then received a review, but said it was not “investigation of fraud, fabrication, or other misconduct.”

Genentech wrote that “one senior leader in gRED urged that the 2009 Nature paper should be retracted or corrected in light of the inconsistent binding results. Other senior leaders recognized at the time that this was an action only Dr. Tessier-Lavigne or another co-author could take with the journal.” Tessier-Lavigne has declined to answer several questions over the past few months about how he responded to concerns raised over the paper.

The special committee to investigate Tessier-Lavigne, meanwhile, has not reached out to many of The Daily’s sources or to the scientists who a Stanford professor said would have knowledge of the events in an email to Jerry Yang, chair of the Stanford Board of Trustees, later obtained by The Daily. The committee put out an update recently that it had “made significant progress.” Jeffrey Flier, former Dean of Medicine at Harvard University, said he was interviewed by representatives of Kirkland Ellis when the law firm assembled its scientific panel. Flier said he was told the review would be completed by January. Aidan Ryan, Edelman senior vice president of crisis communications and spokesperson for the committee, wrote in an email that “the committee was not planning on finishing its review by the end of January and did not make any such representations to the panel.”

This story is breaking and will be updated.

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