Years after questions were raised about their integrity, two of the University of Minnesota’s most prominent scientific discoveries have been retracted within a week: one that offered hope for the therapeutic potential of stem cells and another that offered a promising path to treating Alzheimer’s disease.
The studies are more than a decade old and have been superseded by other discoveries in their field. But the retractions of the Alzheimer’s article on Monday and the stem cell article on June 17 are setbacks for an institute fighting to move up the U.S. rankings in academic reputation and federal research dollars.
Both studies were published in the prestigious journal Nature and have been cited almost 7,000 times. Researchers worldwide were use of these papers to support their work years after they were challenged.
That shows the damage of the journal’s lengthy university research and retractions, said Dr. Matthew Schrag, a neurologist who reviewed the Alzheimer’s paper in 2022 outside his role at Vanderbilt University. “We are wasting not only resources but also the credibility and reputation of our profession by failing to address clear misconduct.”
The university said in a statement on Tuesday that there are many ethical requirements that did not apply when the articles were published. These requirements should prevent future disputes and withdrawals.
The discoveries were remarkable in their time because they offered unexpected solutions to difficult scientific and political problems.
Dr. Catherine Verfaillie and colleagues reported in 2002 that they coaxed mesenchymal stem cells from adult bone marrow to grow numerous other cell types and tissues in the body. Only stem cells from early-stage human embryos showed such regenerative potential at the time, 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 embryonic research, fueling the search for alternative stem cell sources.
Dr. Karen Ashe and colleagues also gained global attention in 2006 when they found a molecular target that appeared influential in the pathogenesis of Alzheimer’s disease, which remains incurable and a leading source of dementia and death in the aging US population. Mice that mimicked that molecule, amyloid beta star 56, showed more severe memory loss based on their ability to navigate a maze. Ashe theorized that a drug that targets that molecule could help people overcome or slow the debilitating effects of Alzheimer’s.
The issues that led to the withdrawals were remarkably similar. Colleagues at other institutions struggled 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 raised concerns about the discovery of stem cells in 2006 as a science journalist and San Francisco bureau chief for New Scientist magazine.
“The grand claim that these were essentially the same as embryonic stem cells and could differentiate into anything, no one could replicate,” he said.
Verfaillie and colleagues corrected the Nature article in 2007, which contained an image of cellular activity in mice that appeared identical to an image in another article supposedly from different mice. The U subsequently launched an investigation into complaints about duplications or manipulations of images in more of Verfaillie’s papers. It ultimately cleared her of misconduct, 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. That article was retracted in 2009.
In 2019, concerns about Nature’s stem cell article resurfaced when Elisabeth Bik, a microbiologist turned investigative detective, found more examples of image duplication.
Bik also proved to be a leading critic of Ashe’s discoveries on Alzheimer’s disease, raising concerns about images in her Nature paper and related studies. Much of the blame lies with co-author Sylvain Lesne, a U neuroscientist who was responsible for the published images. Lesne did not respond to a request for comment, but allowed the university to announce that it had completed its internal investigation into the Nature paper without finding evidence of misconduct. Reviews of other publications from Lesne’s 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 allegations management. All researchers leading studies at the U are now trained in avoiding conflicts of interest, plagiarism and misconduct.
The retractions 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 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.”
Even as the articles continue to be cited, researchers have turned to other targets. Ashe has focused on the search for a drug that can prevent dysfunctional tau proteins from disrupting the brain’s thinking cells, or neurons.
Ashe said she reluctantly agreed to Nature’s retraction because she had published follow-up research that provided new evidence of her findings and recommended a correction to the Nature article that would have further confirmed these findings.
“However, when the editors decided not to publish the correction, I chose to retract the article,” she said in an email, adding that “we are encouraged by the results of ongoing experiments with Abeta*56, and continue to believe that this could be possible. improve our understanding of Alzheimer’s disease and the development of better treatments.”
Lesne was the only co-author to disagree with the retraction, even though Nature stated that the paper 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 the 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 is a stain”. 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 is indeed a problem with a photo,” she said. “We still haven’t found the right photo twenty years after the investigation. But even without that photo, the conclusion still stands.”
The dispute over the usefulness of mesenchymal stem cells became less significant in 2007, when Shinya Yamanaka unveiled a process for reprogramming mouse skin cells so that they could mimic the versatility 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.
Aldhous said it’s disappointing that it took years to resolve questions about the Alzheimer’s paper, and much longer to do the same about the stem cell paper. He said he doesn’t believe the university adequately resolved whether the researchers made repeated errors or committed intentional misconduct. The junior researcher blamed for errors in one stem cell paper was not involved in other questioned papers, he noted.
However, he said it is arguably more important to correct the science quickly so that flawed or unsubstantiated research does not influence other scientists and send them in the wrong direction.
“Why did we have to wait so long to actually throw this in the trash?” he asked. “This should have been done years ago.”