Years after questions were raised about their integrity, two of the University of Minnesota’s highest-profile scientific discoveries were retracted in a week: one that offered hope about the therapeutic potential of stem cells and another that offered a promising path toward treating Alzheimer’s disease.
These studies are more than a decade old and have been superseded by other findings in their fields. But the retractions of Monday’s Alzheimer’s paper and the June 17 stem cell paper are setbacks for an institution struggling to move up the U.S. rankings in terms of academic reputation and budget federal government for research.
Both studies were published in the prestigious journal Nature and have collectively been cited nearly 7,000 times. Researchers from around the world have been using these papers to support their work years after they were challenged.
This shows the harm caused by the prolonged academic investigation and the journal’s retractions, said Dr. Matthew Schrag, a neurologist who reviewed the 2022 Alzheimer’s paper outside of his position at the university. Vanderbilt. “We are not only wasting resources, but also the credibility and reputation of our profession by failing to address obvious misconduct. »
The university said in a statement Tuesday that it has numerous ethical requirements that were not in place when these articles were published and that should prevent future litigation and retractions.
These discoveries were remarkable at the time 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 many other cell types and tissues in the body. Only stem cells from early-stage human embryos had shown such regenerative potential at that 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 embryo research, fueling the search for alternative sources of stem cells.
Dr. Karen Ashe and her colleagues also attracted worldwide attention in 2006 when they discovered a molecular target that appeared to influence the onset of Alzheimer’s disease, which remains incurable and is one of the leading sources of dementia and death in the aging population of the United States. Mice mimicking this molecule, amyloid beta star 56, showed greater memory loss due to their ability to navigate a maze. Ashe hypothesized that a drug targeting this molecule could help people overcome or slow the debilitating effects of Alzheimer’s disease.
The issues leading to the retractions 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 claim that these were essentially embryonic stem cells and they could differentiate into anything, no one has been able to replicate that,” he said.
Verfaillie and his colleagues corrected the Nature paper in 2007, which contained an image of cellular activity in mice that appeared identical to an image in another paper purporting to be from different mice. The U then opened an investigation following complaints of duplication or manipulation of images in several Verfaillie newspapers. He ultimately cleared her of any misconduct, but blamed her for inadequate training and oversight and claimed a younger researcher had falsified data from a similar study published in the journal Blood. This article was retired in 2009.
Concerns resurfaced in 2019 about the Nature stem cell article when Elisabeth Bik, a microbiologist turned research detective, found other examples of image duplication.
Bik also emerged as a key critic of Ashe’s findings on Alzheimer’s disease, raising concerns about the images in her Nature article and related studies. Much of the blame lies with 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 allowed the university to reveal that it had completed its internal investigation into the Nature journal without finding evidence of misconduct. Analyzes of other publications from Lesne’s laboratory are underway.
Changes over the past decade at the university have sought to reduce academic scandals, including the addition of a system in 2008 for anonymous reporting and handling accusations. All researchers conducting studies at the University are now trained to avoid conflicts of interest, plagiarism and professional 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 do know is that the vast majority of researchers … go into their lab, field, or classroom every day with a strong sense of purpose and integrity.”
Although the articles continue to be cited, researchers have turned their attention to other targets. Ashe turned his attention to finding a drug that could stop dysfunctional tau proteins from disrupting the brain’s thinking cells, or neurons.
Ashe said she reluctantly accepted Nature’s retraction because she published follow-up research that offered new evidence for her findings and recommended a correction to the Nature paper that would have further confirmed those findings.
“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 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 use of an eraser” to edit images.
Verfaillie headed the university’s stem cell institute and remained involved in its research even after returning to Belgium in 2006. The recent retiree did not respond to an email for comment, but said in a translation from a Belgian newspaper article that the retraction is “a stain on our reputation.” Nature demanded this correction because Verfaillie and other authors were unable to locate authentic images to prove the validity of their research.
“There is indeed a problem with a photo,” she said. “We haven’t found the right photo twenty years after the search was carried out. But even without this photo, the conclusion still stands.”
The debate over the usefulness of mesenchymal stem cells became less prominent in 2007, when Shinya Yamanaka revealed 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, earning the Japanese researcher a share of the Nobel Prize in Medicine in 2012.
Aldhous said it was disappointing that it took years to resolve questions about the Alzheimer’s paper, and much longer for the stem cell paper. He said he didn’t think the university had adequately addressed the question of whether researchers made repeated errors or intentional misconduct. The young researcher accused of errors in a stem cell paper was not involved in other disputed papers, he noted.
However, he added that it is arguably more important to correct scientific data quickly so that faulty or unsubstantiated research does not influence other scientists and send them in the wrong directions.
“Why did we have to wait so long to throw this in the trash, basically?” He asked. “This should have happened years ago.”