Years after questions were raised about their integrity, two of the University of Minnesota’s most important scientific discoveries — one that offered hope for the therapeutic potential of stem cells and another that offered a promising path to treating Alzheimer’s disease — were retracted within a week.
The studies are more than a decade old and have been superseded by other discoveries in their fields.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 paper on Monday and the stem cell paper on June 17 are setbacks for the institution, which is struggling to move up the U.S. rankings in academic reputation and federal research dollars.
Both studies were published in the prestigious journal Nature and together have been cited nearly 7,000 times. Researchers from all over the world were using these papers supporting their work years after they were disputed.
This points to harm in the university’s lengthy investigation and journal retraction, said Dr. Matthew Schrag, a neuroscientist who researched the Alzheimer’s article in 2022 outside of his role at Vanderbilt University. “We are wasting not only resources but the credibility and reputation of our profession by not addressing obvious misconduct.”
The university said in a statement Tuesday that it had many ethical requirements that were not met at the time the documents were released, which should prevent future disputes and retractions.
The discoveries were remarkable for their time because they offered unexpected solutions to vexing scientific and political problems.
Dr. Catherine Verfaillie and colleagues reported in 2002 that they had converted mesenchymal stem cells from adult bone marrow to grow many other types of cells and tissues in the body. Only stem cells from early human embryos showed such regenerative potential at the time, and they were controversial because they were obtained from aborted fetuses or leftover embryos from fertility treatments. President George W. Bush banned federal funding for embryonic research, prompting a search for alternative sources of stem cells.
Dr. Karen Ashe and colleagues similarly gained global attention in 2006 when they found a molecular target that appeared to influence the onset of Alzheimer’s disease, which remains incurable and is the leading source of dementia and death in the aging US population. Mice mimicking this molecule, amyloid beta star 56, showed worse memory loss based on their ability to navigate a maze. Ashe believed that a drug targeting this molecule could help people overcome or slow the debilitating effects of Alzheimer’s disease.
The issues leading to the recall were remarkably similar. Colleagues at other institutions sought to replicate their findings, prompting others to take a closer look at the images of cellular or molecular activity in mice on which their findings were based.
Peter Aldhous first expressed concern over the discovery of stem cells in 2006 as a science journalist and San Francisco bureau chief for New Scientist magazine.
“The big claim that these were essentially the same as embryonic stem cells and could differentiate into anything, no one had been able to replicate that,” he said.
Verfaillie and colleagues corrected a 2007 Nature paper that contained an image of cellular activity in mice that appeared identical to an image in another paper that purported to be from other mice. The U then launched an investigation into complaints of image duplication or manipulation in several of Verfaillie’s papers. It eventually cleared her of wrongdoing, but accused her of inadequate training and supervision and alleged that a junior researcher had falsified data in a similar study published in the journal Blood. This article was retracted in 2009.
In 2019, concerns about the Nature stem cell paper resurfaced when Elisabeth Bik, a microbiologist turned research detective, found more examples of image duplication.
Bik also emerged as a key critic of Ashe’s Alzheimer’s discoveries, raising concerns about the images in her Nature paper and related studies. Much of the blame fell on co-author Sylvain Lesne, the neuroscientist at the U who was responsible for the published images. Lesne did not respond to a request for comment, but instructed the university to disclose that it had completed its internal investigation to the journal Nature without finding evidence of wrongdoing. Reviews of other publications from the Lesne laboratory 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 for managing allegations. All researchers leading the study at the U are now trained to avoid conflicts of interest, plagiarism and misconduct.
The withdrawal is “painful,” but the university accepts the journal’s decision 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 … walk into their labs, their fields, or their classrooms every day with a strong sense of purpose and integrity.”
Although the papers continue to be cited, researchers have turned to other targets. Ashe focused on finding a drug that can prevent dysfunctional tau proteins from disrupting the brain’s thinking cells, or neurons.
Ashe said she agreed to the Nature retraction reluctantly because she had published subsequent research that offered new evidence for her findings and recommended a correction to the Nature paper that would further confirm those findings.
“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 the ongoing experiments on Abeta*56 and continue to believe that it could improve our understanding of Alzheimer’s disease and the development of better treatments.”
Lesne was the only co-author to disagree with the retraction, although Nature said the paper contained “excessive manipulation, including splicing, duplication, and the use of the eraser tool” to edit the images.
Verfaillie ran the university’s stem cell institute and remained involved in its research after returning to Belgium in 2006. The recent retiree did not respond to an email for comment, but said in a translation of a Belgian newspaper article that the recall was a “stain.” on our reputation.” Nature demanded a correction because Verfaillie and the other authors could not find authentic images to prove the validity of their research.
“There’s a real problem with photography,” she said. “We haven’t found the correct photo twenty years after doing the research. But even without this photo, the conclusion still stands.”
Controversy over the utility of mesenchymal stem cells became less important in 2007 when Shinya Yamanaka revealed the process of reprogramming mouse skin cells to mimic the versatility of embryonic stem cells. Others were able to repeat the process, which earned the Japanese scientist a share of the 2012 Nobel Prize in Medicine.
Aldhous said it was disappointing that it took years to resolve questions about the Alzheimer’s paper and much longer to do the same with the stem cell paper. He said he does not believe the university has adequately addressed whether the researchers made repeated mistakes or willful misconduct. The junior researcher accused of errors in one stem cell paper was not involved in other disputed papers, he noted.
But he said it’s probably more important to quickly correct the scientific record so that flawed or unsubstantiated research doesn’t influence other scientists and send them in the wrong direction.
“Why did we have to wait so long to put it in the trash?” he asked. “This should have happened years ago.