Stanford misconduct probe of president stumbles as new journal launches inquiry

Allegations of scientific image manipulation are threatening Stanford University President Marc Tessier-Lavigne, a neurobiologist and former biotech leader. Tessier-Lavigne came under fire last week after an investigation by the school’s student newspaper revived long-standing concerns about several publications on which he was a co-author. In response, Stanford announced a misconduct investigation centering on “certain scientific articles,” including two papers in Science and one in Cell dating back more than 20 years.

The inquiry has rattled the field of neuroscience, where Tessier-Lavigne is a respected figure, as well as the broader academic community, where some question Stanford’s handling of the matter. The university’s board of trustees, on which Tessier-Lavigne sits, designated five other members to lead the inquiry. One stepped aside after the paper, The Stanford Daily, revealed his investment firm has a $18 million stake in Denali Therapeutics, a company Tessier-Lavigne cofounded.

The initial controversy triggered scrutiny of other papers Tessier-Lavigne co-authored and revealed additional problematic images. Image manipulation experts say at least some of the errors appear minor. Still, Tessier-Lavigne should step aside during the probe, one observer suggests. “The in-house investigation will have more credibility,” says Richard Smith, a former editor of The BMJ. “And his position as president is compromised when facing these serious accusations.”

In a 5 December letter to faculty, Tessier-Lavigne said, “I welcome” the review and that “the integrity of my work is of paramount importance to me, and I take any concerns that are expressed very seriously.” Although he took responsibility for any paper on which he was involved, Tessier-Lavigne noted that he was senior author on just the three papers in Science and Cell and that  flagged images in papers in other journals, such as Nature and The EMBO Journal, for example, were prepared by collaborators’ labs. Indeed, co-authors elsewhere have already taken responsibility for errors in various papers.

Some outsiders think Tessier-Lavigne’s scientific reputation will remain intact. “A lot of important and very solid work came out of Marc’s lab, as well as inevitably some studies that seemed a little overhyped. I was relieved when I clicked on the links to see that it was not some of Marc’s more seminal papers that were attracting such scrutiny,” says neurobiologist Barry Dickson of the Queensland Brain Institute. The Science and Cell papers “comprise a rather small fraction of the overall body of work … for which Tessier-Lavigne is well known and widely admired,” adds Harvard University neurobiologist Joshua Sanes.

Tessier-Lavigne, 62, a former president of Rockefeller University who was also once chief scientific officer at Genentech, is known for groundbreaking research in the 1990s on proteins dubbed netrins. He and others showed the molecules govern the growth of nerve fibers called axons in the developing spinal cord, work for which he and two colleagues won the prestigious 2020 Gruber Prize in Neuroscience. The 1999 Cell paper and two 2001 Science publications now under scrutiny, produced when he was at the University of California, San Francisco (UCSF), came after his initial landmark netrin discoveries.

Questions about certain images in the papers first surfaced 7 years ago on PubPeer, an online forum where scientists identify and discuss possible problems in published research, often anonymously. Some posts suggested various Western blots, which document a protein’s presence in a sample, were repeated in more than one figure or altered. In other cases, images or parts of images appear to have been cut and pasted into other figures.

Elisabeth Bik, a specialist in spotting manipulated images, reexamined the three papers and other Tessier-Lavigne publications noted in PubPeer at the request of the Daily. She calls some image changes “beautification” that did not affect the papers’ conclusions but describes others as “more serious.”

Stanford told the Daily it discussed concerns about the papers with Tessier-Lavigne when he was under consideration for university president in 2015. He submitted corrections for both Science papers, but the journal never posted them “due to an error,” said Holden Thorp, editor-in-chief of the Science family of journals. Tessier-Lavigne says another error has since been identified in one of the Science papers; Thorp says the Stanford president has been “very collaborative” in discussing possible solutions.

Tessier-Lavigne also reported errors in the Cell paper in 2015, but at the time its editors found no correction was necessary, the publisher Cell Press said in a statement. Last week, Bik found another manipulated image in that paper, which she says appears to be “deliberately changing the results” and could indicate data falsification. Cell Press said the “new concerns … warrant a closer look” and it now plans to investigate. The only authors on all three challenged papers are Tessier-Lavigne and a postdoc then at UCSF who apparently hasn’t published a paper since 2012. She did not respond to emails from Science.

Some scientists pointed out that regardless of the source of the alterations in the three papers, Tessier-Lavigne was the leader of the work. He was “responsible for the integrity of the data,” Bik says. All problematic papers that Tessier-Lavigne co-authored should be reviewed, she adds. “This investigation should be much wider [involving] all his collaborators’ institutions.”

Tessier-Lavigne’s troubles are a warning to investigators everywhere to keep an eye on how lab members edit images of data, some say. “In this day and age, it’s very easy to manipulate digital images. There’s a lot of trust built into science and trust can be abused,” says neurobiologist Tim Kennedy of McGill University. “On the flip side, science is a self-correcting enterprise.”

source: sciencemag.org