In 2009, Marc Tessier-Lavigne, then a top executive at the biotechnology company Genentech, was the primary author of a scientific paper published in the prestigious journal Nature that claimed to have found the potential cause for brain degeneration in Alzheimer’s patients. “Because of this research,” read Genentech’s annual letter to shareholders, “we are working to develop both antibodies and small molecules that may attack Alzheimer’s from a novel entry point and help the millions of people who currently suffer from this devastating disease.”
But after several unsuccessful attempts to reproduce the research, the paper became the subject of an internal review by Genentech’s Research Review Committee (RRC), according to four high-level Genentech employees at the time; two were senior scientists and two were scientists who also served as executives. Three spoke on the condition of anonymity because of the sensitivity of the allegations and non-disclosure agreements. The scientists, one of whom was an executive who sat on the review committee and all of whom were informed of the review’s findings at the time due to their stature at the company, said that the inquiry discovered falsification of data in the research, and that Tessier-Lavigne kept the finding from becoming public.
Tessier-Lavigne denies both allegations. Genentech said in a statement that “as part of our diligence related to these allegations, we reviewed the records from that November 2011 RRC meeting and saw no allegations of fraud or wrongdoing.” The company acknowledged that “given that these events happened many years ago … our current records may not be complete.”
After the review, which began in 2011, Genentech canceled research based on the paper’s findings. Till Maurer, a senior scientist at the company from 2009-2018 who said he was assigned to develop drugs based on the 2009 paper, told The Daily that his superior informed him that, in Maurer’s words, “the project is being canceled and it’s because they found falsified data.”
Tessier-Lavigne, who became Stanford’s president in 2016, has been under investigation by the Stanford Board of Trustees since late November, after The Daily revealed concerns that several other papers he had co-authored contained altered imagery. But these latest allegations, about a different paper, are more serious because they involve what was once considered a promising treatment target for Alzheimer’s disease — and because people involved in the review allege that Tessier-Lavigne tried to keep its findings hidden.
Tessier-Lavigne declined multiple requests for interviews over email as well as in person. Stephen Neal, chairman emeritus of Cooley, a prominent law firm representing the president, responded in writing to questions sent to Tessier-Lavigne.
“Dr. Tessier-Lavigne is not aware of any internal investigation of the Paper,” wrote Neal. “Given that there was no investigation of the Paper, Dr. Tessier-Lavigne categorically disputes any allegation by unnamed scientists that he ‘covered up’ any findings regarding such investigation or was opposed to allowing such (non-existent) findings to become public.”
Genentech, in a written statement to The Daily, confirmed that an internal review took place in 2011, a fact that was not previously public. The company characterized the review as “routine.” When asked whether this was accurate, the scientist whom The Daily confirmed belonged to the research review committee said, “no no no no no no.”
“There have not been any formal investigations, allegations, claims or complaints regarding scientific fraud or misrepresentation involving the Nature 2009 paper,” wrote Susan Willson, a Genentech spokesperson. “The project received a regular review by Genentech’s Research Review Committee (RRC), as is routinely done for Genentech’s drug discovery projects.”
She wrote that “neither the RRC meeting nor the decision to conduct follow-up experiments was due to any concern about fraud in the Nature 2009 paper.” Willson would not answer multiple questions about whether any issues were ever discovered in the paper.
The research review committee authorized subsequent experiments to further analyze the paper’s conclusions, Willson wrote, and “based on the results of the genetic experiments at Genentech, the RRC terminated the Genentech research project in 2012.” She would not answer repeated questions about whether there were ever attempts to replicate the experiments in the 2009 paper and if the research was found to be reproducible.
Matthew Schrag, an Alzheimer’s expert with no relation to Genentech or Tessier-Lavigne who reviewed the scientific literature surrounding the paper at the request of The Daily, concluded that parts of the paper implicating a specific pathway in Alzheimer’s “were found in later studies to be inaccurate.” Schrag, who did not have knowledge of the internal review and based his analysis on published information, made clear that “this is not, by itself, evidence of misconduct.”
According to the four senior scientists, including the scientist who served as a member of the research review committee, the committee found that the fundamental science underpinning the 2009 study’s conclusion was fabricated. In the face of a finding of fabrication, retraction of the paper would have been the expected outcome, according to Nature’s policies. The Committee of Publication Ethics, a nonprofit that supports journal editors around the world, recommends retraction in the case of “clear evidence that the findings are unreliable, either as a result of major error (eg, miscalculation or experimental error), or as a result of fabrication (eg, of data) or falsification (eg, image manipulation).” But Tessier-Lavigne “was unwilling to clean up the mess,” said the scientist and former Genentech executive who participated in a series of 2011 meetings about the paper.
Neal, Tessier-Lavigne’s lawyer, asserted the conclusions of the 2009 paper that did not hold up, revolving around caspase 3 and caspase 6, beta secretase, N-APP binding to DR6 and DR6 playing a role in Alzheimer’s disease, were the result of “the normal march of science.” He continued, “no one involved in the experiments described in the Paper forged gels, falsified assays or fabricated experiments.” He did not answer a question about whether any concerns had been raised over the paper or if he believed there were any “issues with the paper.”
A “miracle result” that didn’t pan out
Each of the four senior Genentech scientists was contacted individually by The Daily and was unaware of the others’ accounts. Their independent accounts, given over several hours of interviews, were highly consistent with each other, and also consistent with publicly available information about the research.
Two days after the 2009 paper came out, Genentech’s letter to shareholders called it “groundbreaking basic research about an entirely new way of looking at the cause of Alzheimer’s disease.” At the time, Paul Greengard, a Nobel Laureate, called it “a very exciting paper,” saying “it’s going to have a major impact on the Alzheimer’s field.” And the news wing of Nature published an article entitled “Alzheimer’s theory makes a splash.”
People within the company were similarly excited, at first. One of the senior scientists recalled that Tessier-Lavigne’s initial presentation of the research left the room stunned. “This came out of nowhere,” said the scientist. Another senior executive in the room said, “We all thought: holy shit. This is Nobel Prize stuff…It was the miracle result.”
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