Two of the University of Minnesota’s most significant scientific discoveries were retracted within a week after years of doubts about their integrity. One discovery raised hopes about the therapeutic potential of stem cells, the other offered a promising approach to treating Alzheimer’s disease.
The studies are more than a decade old and have been overtaken by other discoveries in their fields, but the retraction of the Alzheimer’s work on Monday and the stem cell work on June 17 are setbacks for an institution struggling to climb the U.S. rankings for academic prestige and federal research funding.
Both studies were published in the prestigious journal Nature and cited almost 7,000 times. Researchers worldwide were with these papers to support their work years after their challenge.
That shows how much damage the university’s lengthy investigation and the journal’s retractions have done, said Dr. Matthew Schrag, a neurologist who reviewed the Alzheimer’s work outside of his position at Vanderbilt University in 2022. “We are not only wasting resources, but also the credibility and reputation of our profession by failing to address obvious misconduct.”
In a statement on Tuesday, it said that many ethical requirements had not been met at the time of publication of these works and that this should prevent future disputes and retractions.
The discoveries were remarkable at the time because they offered unexpected solutions to difficult scientific and political problems.
Dr. Catherine Verfaillie and her colleagues reported in 2002 that they had induced mesenchymal stem cells from adult bone marrow to grow numerous other cell types and tissues in the body. Until then, only stem cells from early human embryos had shown such regenerative potential, and they were controversial because they came from aborted fetuses or leftover embryos from infertility treatments. President George W. Bush had banned federal funding for embryo research, which fueled the search for alternative sources of stem cells.
Dr. Karen Ashe and her colleagues attracted worldwide attention in 2006 when they discovered a molecular target that appeared to influence the onset of Alzheimer’s disease, a disease that remains incurable and a leading cause of dementia and death in the aging American population. Mice mimicking this molecule, amyloid beta-star 56, showed greater memory loss based on their ability to navigate a maze. Ashe suspected that a drug targeting this molecule could help people overcome or slow the debilitating effects of Alzheimer’s disease.
The problems that led to the retractions were remarkably similar. Colleagues at other institutions struggled to reproduce their results, prompting others to take a closer look at the images of cellular or molecular activity in mice on which their results were based.
Peter Aldhous, a science journalist and San Francisco bureau chief for New Scientist magazine, first raised concerns about the stem cell discovery in 2006.
“The big claim that these were essentially embryonic stem cells and could differentiate into anything, no one could reproduce,” he said.
Verfaillie and her colleagues corrected the Nature article in 2007, which included an image of cell activity in mice that appeared identical to an image in another article that was supposedly from other mice. The university then launched an investigation because there were complaints of image duplication or manipulation in other articles by Verfaillie. It eventually cleared her of wrongdoing, but blamed her for inadequate training and supervision and alleged that a junior researcher had falsified data in a similar study published in the journal Blood. That article was retracted in 2009.
In 2019, concerns arose again around the Nature stem cell study when Elisabeth Bik, a microbiologist turned research detective, found further examples of image duplication.
Bik also emerged as one of the main critics of Ashe’s Alzheimer’s discoveries, raising concerns about the images in her Nature paper and related studies. Much of the blame was placed on co-author Sylvain Lesne, a neuroscientist at the university who was responsible for the published images. Lesne did not respond to a request for comment but authorized the university to announce that it had completed its internal investigation into the Nature paper without finding any evidence of wrongdoing. The review of other publications from Lesne’s lab is ongoing.
Changes at the university over the past decade have been aimed at curbing academic scandals, including a system for anonymous reporting and dealing with allegations introduced in 2008. All researchers leading studies at the university are now trained to avoid conflicts of interest, plagiarism and misconduct.
The retractions were “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, their fields or their classrooms every day with a strong sense of purpose and integrity.”
Although the work is still cited, researchers have moved on to other goals. Ashe has focused on finding a drug that can prevent dysfunctional tau proteins from disrupting the brain’s thinking cells, or neurons.
Ashe said she reluctantly agreed to the Nature retraction because she had published follow-up studies that provided new evidence for her findings and recommended a correction to the Nature article that would have further supported those findings.
“However, when the editors decided not to publish the correction, I decided to retract the article,” she said in an email, adding: “We are encouraged by the results of ongoing experiments with Abeta*56 and continue to believe that it could improve our understanding of Alzheimer’s disease and contribute to the development of better treatments.”
Lesne was the only co-author to disagree with the retraction, although Nature stated that the work contained “excessive manipulation, including splicing, duplication and the use of an eraser” to edit the images.
Verfaillie headed the university’s stem cell institute and remained involved in its research after returning to Belgium in 2006. Verfaillie, who recently retired, did not respond to an email seeking comment, but said in a translation of a Belgian newspaper article that the retraction was “a stain on our reputation.” Nature requested the correction because Verfaillie and other authors could not find authentic images to prove the validity of their research.
“There is indeed a problem with one photograph,” she said. “Twenty years after the investigation, we still haven’t found the right photograph. But even without that photograph, the conclusion still stands.”
The debate over the usefulness of mesenchymal stem cells faded in 2007, when Shinya Yamanaka discovered a method for reprogramming mouse skin cells that mimicked the versatility of embryonic stem cells. Others managed to replicate the method, earning the Japanese researcher a share of the 2012 Nobel Prize in Medicine.
Aldhous said it was disappointing that it took years to resolve the questions about the Alzheimer’s study and even longer to do so about the stem cell study. He did not believe the university had adequately clarified whether the researchers made repeated errors or were guilty of willful misconduct. The junior researcher blamed for errors in a stem cell study had not been involved in other controversial studies, he noted.
However, he said it was probably more important to correct scientific findings quickly so that erroneous or unsubstantiated research results do not influence other scientists and lead them in the wrong direction.
“Why did we have to wait so long to basically throw this in the trash?” he asked. “This should have happened years ago.”