How should we deal with fraudulent research? Photo credit: CDC via Unsplash
In June, a paper published in Nature in 2002 by Professor Catherine Verfaillie of the Stem Cell Institute at the University of Minnesota was retracted—22 years after its publication, following years of raised questions regarding the legitimacy of the data provided in the paper.
…this the most highly-cited paper ever to be retracted.
Being cited over 4,500 times, this the most highly-cited paper ever to be retracted, and hence, the news has drawn much attention.
The paper investigated the cell specialisation ability of a specific type of stem cell called a “Multipotent Adult Progenitor Cell” (MAPC). A stem cell is a cell that can form many different types of body cells. However, not all stem cells have infinite flexibility with regards to what they can turn into. Embryonic stem cells (found in embryos during the early stages of development) are the most versatile type of stem cells, with the ability to become any cell within the body and lead to the formation of an entire organism. In contrast, multipotent stem cells (most often found in adult bone marrow) can only divide into a select number of cell types within a tissue type.
…embryonic stem cells possess a much greater potential for stem cell therapy.
Therefore, embryonic stem cells possess a much greater potential for stem cell therapy, such as stem cell engineering for the treatment of disease. However, the use of embryonic stem cells is greatly debated within the scientific community and beyond, with many “pro-life” arguments raised against the destruction of embryos. Hence, when Verfaillie’s paper suggested that, under specific conditions, MAPC (a type of multipotent stem cell from adult bone marrow) could show the same amount of versatility in cell formation as an embryonic stem cell, and form most (if not all) body cells, this provided a less controversial alternative.
In addition to these in vitro results of the ability of MAPCs to form many body cells under certain circumstances, the paper also stated that when given intravenously in vivo, the MAPCs migrated to the bone marrow and engrafted. This describes how the cells are able to integrate into the bone marrow, and can start giving rise to other cells, such as blood cells, suggesting these altered stem cells could function physiologically.
This publication seemed extremely promising and highlighted great potential for treating disease.
This publication seemed extremely promising and highlighted great potential for treating disease. Yet issues began to surface in 2007 when the New Scientist magazine flagged the paper, alleging that there were flaws in the data. Following this, a correction was published in Nature, concluding that despite the issues with the data, those issues ‘do not alter the conclusion of the article’.
However, this was not the end of the discrepancies. In 2019, Dr Elisabeth Bik, an expert in examining image integrity, reported problems with some of the images in the article. Some of the images showed bone-marrow samples, and, according to Bik, two of the photos that were claiming to be separate samples were, in fact, the same. Furthermore, she identified the use of Photoshop on another image in the paper. Verfaillie’s team could not provide the original images when asked to do so and other researchers in the field could not reproduce the results presented in the paper, both raising further questions about the data.
…she identified the use of Photoshop on another image in the paper.
At the request of the University of Minnesota (the institution in which Verfaillie was based at the time of publication), the paper was retracted in 2024 following an investigation into the claims and the decision that the editors ‘no longer have confidence in the reliability of the data reported in this article,‘ according to Nature.
It was concluded that a PhD student working on the research in Verfaillie’s team had falsified data. However, the student stated these were ‘honest errors’ and were a result of ‘inexperience, poor training and lack of clear standards’. So, while Verfaillie was criticised for poor supervision of her research team, all members involved were cleared of intentional misconduct due to insufficient evidence.
With that said, it should be noted that a total of four publications associated with Verfaillie have been retracted over her career so far.
With that said, it should be noted that a total of four publications associated with Verfaillie have been retracted over her career so far. One of these was a paper in the Blood journal, which was retracted in 2009 also on the grounds of image manipulation and falsification. Once again, Verfaillie was shown not to be responsible for the manipulations.
…these mistakes could undermine a lot of subsequent research.
This result in the investigation has far reaching implications. With regards to Verfaillie, though she continues working on stem cell research, she states, ‘it’s a stain on my reputation’. Additionally, this is a greatly cited paper and, hence, if the conclusions made were incorrect, these mistakes could undermine a lot of subsequent research. Despite the potential flaws in the data, it appears that the potential for adult stem cells to be induced to form embryonic stem cell-like cells could still be feasible. More recently, it has been shown by Yamanaka and his colleagues that by genetically tweaking the production of four different chemicals within adult mouse cells, it is possible to create cells that are virtually indistinguishable from embryonic stem cells. Therefore, despite the controversy, many of the concepts Verfaillie presented still stand, and further research into the conversion of adult stem cells into embryonic stem cells is still ongoing worldwide.
