TNFRSF21

A review did uncover a complaint “alleging scientific misconduct by another postdoc." Genentech has published the findings of its investigation into an alleged fraud and cover-up involving a 2009 Nature paper co-authored by Marc Tessier-Lavigne. None of the 35 current and former employees interviewed for the probe reported knowing of fraud, but the process did leave unanswered questions about image “anomalies” and brought an unrelated misconduct issue to public attention. In February, The Stanford Daily reported that an internal review “discovered falsification of data in the research” into the potential role of death receptor six (DR6) and amyloid precursor protein (APP) in Alzheimer’s disease, and claimed Tessier-Lavigne, Genentech’s former chief scientific officer, “kept the finding from becoming public.” The student-run newspaper ran a follow-up article last month after obtaining an email from a Stanford professor that said “there was discussion of fraud/fakery and MTL knew.” Genentech responded to the reports by conducting its own investigation. The findings (PDF) largely exonerate Tessier-Lavigne, now the president of Stanford, while still leaving loose ends that may simply reflect the challenges of investigating events that began around 15 years ago.  Here’s the top-line positive finding for the accused: “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.” Genentech was also unable to find any evidence that its Research Review Committee investigated fraud, fabrication or misconduct related to the work at the time, as was claimed in the original article. Other aspects of the review are less clear-cut. Genentech tasked “an independent, outside expert who specializes in detecting image manipulations in scientific publications” with looking at the paper. The expert found two sets of figures that include duplicate images and a Western blot panel that “appears to include a composite of two images.” “We have not determined how these anomalies occurred,” the report states. One challenge is that some of the original data and images are missing. Noting that the research took place nearly 15 years ago. Genentech said “some data and images were saved on electronic storage media that may no longer exist.” The report states “Genentech scientists and research associates had difficulty reproducing certain results reported in the 2009 Nature paper, in particular, the binding interaction between DR6 and N-APP.” Genentech researchers not involved in the 2009 paper achieved inconsistent results when they tried to replicate the study, an issue that some of them attributed to “the purity and quality of the reagents used.” The inconsistency was evident prior to publication and persisted across three years of research. “Senior leaders at Genentech including Dr. Tessier-Lavigne knew of the inconsistent binding results, and there was uncertainty and speculation within the Genentech Research organization about why the binding interaction between DR6 and N-APP could not be reliably reproduced or confirmed,” the report states. After Tessier-Lavigne left Genentech, a senior leader in gRED, the biotech’s research unit, urged that the paper should be retracted or corrected in light of the inconsistent binding results. Only Tessier-Lavigne or another co-author could take such an action.  Genentech decided to perform other experiments to evaluate binding and determine whether DR6 was a viable Alzheimer’s target. Ultimately, genetic experiments in two mouse models killed off the program. The experiments found amyloid plaques and other features of Alzheimer’s weren’t dependent on DR6, leading Genentech to stop work on the target in 2012. “Many scientists who worked on the project were disheartened by having devoted substantial time and energy to a program whose underlying biology was ultimately proven wrong. That sentiment gave rise to rumors about why the DR6 program failed,” the report states. The review did uncover a complaint “alleging scientific misconduct by another postdoc working in Dr. Tessier-Lavigne’s laboratory.” The complaint was dealt with at the time, leading to the termination of the postdoc’s employment and withdrawal of a manuscript. The complaint was unrelated to DR6.