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Mayo Clinic Admits Years Of Fraudulent Research

"It's surprising that a falsification could go on at such an extensive level for so long," added molecular immunologist Gordon Freeman of the Dana-Farber Cancer Institute. "It's the longest running pervasive falsification that I've ever heard of."

10 retractions and counting

Posted by Jef Akst

26th May 2010

In an unusually large case of misconduct, an immunology lab at the Mayo Clinic in Rochester, Minnesota, has pulled 10 papers so far, with about five more expected, and cancelled a clinical trial after a senior research associate was found guilty of falsifying data.

"I was shocked when I initially got the letter from Dr. [Larry] Pease" -- the head of the lab -- "stating the decision to retract all these papers (approximately 15)," Lieping Chen, co-author on some of the papers, told The Scientist in an email. "It is very unfortunate when anybody has such an associate in the laboratory," said Chen, based at The Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins University School of Medicine.

"It's surprising that a falsification could go on at such an extensive level for so long," added molecular immunologist Gordon Freeman of the Dana-Farber Cancer Institute. "It's the longest running pervasive falsification that I've ever heard of."

But despite the scope of the retractions, the impact on the field is likely to be minimal, researchers said. The loss will be "not too significant because it was a unique reagent with a unique proposed mechanism of action," Freeman said. "The damaging effect is clear but as far as I know the clinical projects derived were not of key importance for our understanding on how the immune system works," immunologist Ignacio Melero of the University of Navarra in Spain agreed in an email. "From the point of view of scientific knowledge, what will change is mainly the notion that dendritic cells could be stimulated through this pathway."

Starting in 2002, Pease and his colleagues published a series of papers about their discovery of a naturally occurring human IgM antibody, known as sHIgM12 (or B7-DCXAb). This antibody appeared to bind to a particular receptor called B7-DC on dendritic cells and upregulate the immune cells' function by promoting cell survival, enhancing the presentation of antigens, and increasing secretion of cytokines. This was somewhat surprising, as this group of dendritic cell receptors was generally believed to bind to T cells to regulate T cell function, but not dendritic cell activity.

The fact that the antibody appeared to be activating dendritic cell function suggested that it might be a good therapeutic target for increasing the immune response. "The antibody was claimed to be therapeutically active in a wide variety of diseases, [including] asthma [and] cancer, [and] to have really enormously strong effects," Freeman said.

But after continued research in the lab turned up "suspicious patterns of experimental results," according to one retraction notice, Pease and his lab members ran a number of blinded experiments that did not support the findings. The resulting investigation at the Mayo Clinic concluded that one of the lab's researchers, Suresh Radhakrishnan, "tampered with another investigator' s experiment with the intent to mislead toward the conclusion that the B7-DCXAb reagent has cell-activating properties," according to another retraction notice.

"I was surprised about this retraction from [Journal of Experimental Biology]" -- the lab's first publication about B7-DCXAb-- "because the groups involved enjoy an excellent reputation in the field," said Melero of the University of Navarra. "The message of that paper was interesting for us because it provided a tool to activate dendritic cells."

"I think [the retractions are] tremendously sad for science," Freeman agreed. "I think if something is too good to be true, it often isn't true."

So far, ten papers have been retracted, including one from Proceedings of the National Academy of Sciences and six from the Journal of Immunology. All together, the papers retracted thus far have been cited nearly 250 times, according to ISI, and more papers will be retracted "in the coming weeks," said Mayo spokesperson Bob Nellis.

PNAS and the Journal of Immunology both confirmed that the retractions were published at the request of the authors, but did not comment on how the papers slipped through the peer-review system.

Additionally, a clinical trial that planned to test the antibody as a potential therapy in patients with stage IV melanoma, in collaboration with the National Cancer Institute, has been cancelled, Nellis said.

"No other researchers were involved, [and] no patients were harmed," he said. Since the finding of misconduct, the "lab has refocused its efforts along other lines of research."

Pease was not taking interviews, according to Nellis. Radhakrishnan is no longer employed by Mayo, and the institute did not have any information about his current whereabouts.



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