Years after questions were raised about their integrity, two of the University of Minnesota’s most famous scientific discoveries were retracted in one week — one that offered hope for the therapeutic potential of stem cells and another that offered a promising path to treating disease of Alzheimer’s.
The studies are more than a decade old and have been superseded by other discoveries in their fields. But the withdrawal of the Alzheimer’s report on Monday and the stem cell paper on June 17 are setbacks for an institution struggling to climb the U.S. rankings for academic reputation and federal research dollars.
Both studies were published in the prestigious journal Nature and have been cited nearly 7,000 times in total. Researchers all over the world were using these documents to support their work years after they were challenged.
That shows the damage from the protracted university investigation and the journal’s retraction, said Dr. Matthew Schrag, a neuroscientist who studied the 2022 Alzheimer’s report outside of his work at Vanderbilt University. “We are wasting not only resources but the trust and reputation of our profession by failing to deal with obvious misconduct.”
The university said in a statement Tuesday that there are many ethical requirements that were not in place when those documents were released, which should prevent future disputes and retractions.
The discoveries were remarkable in their day because they offered unexpected solutions to vexing scientific and political problems.
Dr. Catherine Verfaillie and colleagues reported in 2002 that they had induced mesenchymal stem cells from adult bone marrow to grow numerous other types of cells and tissues in the body. Only stem cells from early-stage human embryos have shown such regenerative potential at the time, and they are controversial because they are derived from aborted fetuses or leftover embryos from infertility treatments. President George W. Bush banned federal funding for embryo research, fueling the search for alternative sources of stem cells.
Dr. Karen Asch and colleagues similarly drew global attention in 2006 when they discovered a molecular target that appeared to influence the onset of Alzheimer’s disease, which remains incurable and a leading source of dementia and death in America’s aging population. Mice mimicking this molecule, amyloid beta star 56, showed worse memory loss based on their ability to navigate a maze. Asch theorized that a drug targeting this molecule could help people overcome or slow the debilitating effects of Alzheimer’s.
The issues that led to the withdrawal were strikingly similar. Colleagues at other institutions struggled to replicate their findings, prompting others to take a closer look at the imaging of cellular or molecular activity in mice on which their findings were based.
Peter Oldhouse first raised concerns in 2006 about the discovery of stem cells as a science journalist and San Francisco bureau chief for New Scientist magazine.
“The big claim that they are essentially the same as embryonic stem cells and can differentiate into anything, no one has been able to replicate that,” he said.
Verfaillie and colleagues corrected the 2007 Nature paper that contained an image of cell activity in mice that looked identical to an image in another paper that was supposed to come from different mice. The U then launched an investigation into complaints of duplicate images or manipulation in more of Verfaillie’s papers. It ultimately cleared her of wrongdoing, but accused her of inadequate training and supervision and alleged that a junior researcher falsified data in a similar study published in the journal Blood. This article was retracted in 2009.
Concerns resurfaced in 2019 with a Nature stem cell paper, when Elizabeth Bick, a microbiologist turned research detective, found more examples of image duplication.
Bick has also emerged as a key critic of Asch’s findings on Alzheimer’s disease, raising concerns about the imaging in her Nature paper and related research. Much of the blame falls on co-author Sylvain Lesnay, the U neuroscientist who was responsible for the published images. Lesne did not respond to a request for comment, but authorized the university to disclose that it had completed its internal investigation into the Nature article without finding evidence of wrongdoing. Reviews of other publications from Lesne’s lab are ongoing.
Changes over the past decade at the university have sought to reduce academic scandals, including a system added in 2008 for anonymous reporting and to manage allegations. All researchers conducting research at the U are now trained to avoid conflicts of interest, plagiarism, and misconduct.
The withdrawals are “painful,” but the university accepts the journal’s decisions and remains committed to ethical research, said Shashank Priya, vice president for research and innovation. “What I do know is that the vast majority of researchers … go into their labs, fields or classrooms every day with a strong sense of purpose and integrity.”
Although the papers continue to be cited, researchers have turned to other targets. Asch turned to the search for a drug that could prevent dysfunctional tau proteins from destroying the brain’s thought cells, or neurons.
Ash said she agreed to Nature’s retraction reluctantly because she had published follow-up research that offered new evidence for her findings and recommended a correction to the Nature paper that would further confirm those findings.
“However, when the editors decided not to publish the correction, I decided to retract the article,” she said in an email, adding that “we are encouraged by the results of ongoing experiments on Abeta*56 and continue to believe that we may advance our understanding of Alzheimer’s disease and the development of better treatments.”
Lesne was the only co-author who disagreed with the retraction, although Nature said the paper contained “excessive manipulation, including splicing, duplication, and use of an erase tool” to edit the images.
Verfaillie led the university’s stem cell institute and continued to be involved in its research even after returning to Belgium in 2006. The recently retired did not respond to an email for comment, but said in a translation of a Belgian newspaper article that the withdrawal was a “spot.” on our reputation.” Nature called for a correction because Verfaillie and other authors could not find authentic images to prove the validity of their research.
“There really is a problem with a photo,” she said. “We didn’t find the right photo twenty years after the research was done. But even without that photo, the conclusion stands.”
The controversy over the utility of mesenchymal stem cells became less important in 2007 when Shinya Yamanaka revealed a process to reprogram mouse skin cells so that they could mimic the flexibility of embryonic stem cells. Others were able to repeat the process, which earned the Japanese researcher a share of the 2012 Nobel Prize in Medicine.
Aldhus said it was disappointing that it took years to resolve questions about the Alzheimer’s paper and much longer to do the same on the stem cell paper. He said he did not believe the university had adequately addressed whether the researchers had made repeated mistakes or engaged in intentional misconduct. The junior researcher accused of errors in one stem cell paper was not involved in other disputed papers, he noted.
However, he said it may be more important to quickly correct the scientific record so that faulty or unsubstantiated research does not influence other scientists and send them in the wrong direction.
“Why did we have to wait so long to send this to the trash can?” he asked. “This should have happened years ago.
