Nature Medicine | Spoonful of Medicine

UPDATED: GSK inquiry reports signs of possible data fabrication in multiple sclerosis paper

An inquiry by the British pharmaceutical company GlaxoSmithKline (GSK) into allegations of possible data fabrication in a 2010 Nature Medicine paper regarding the role of specialized T cells in autoimmune disease has found what it sees as evidence of misconduct. Concerns regarding the paper surfaced last week, when news sources reported that the company had begun investigating the research conducted for the study at a GSK lab in Shanghai.

The paper, led by Jingwu Zhang at the GlaxoSmithKline Research and Development Center’s department of neuroimmunology in Shanghai, originally claimed to have found data suggesting that the signaling molecule interleukin-7 caused a subset of T cells known as T helper 17 (TH17) cells taken from people with multiple sclerosis to multiply. The finding complemented other research in the field suggesting that genetic differences in the cell receptor for interleukin-7 might put some individuals at risk for developing multiple sclerosis—an autoimmune disease thought to involve helper T cells.

According to Melinda Stubbee, a US-based spokesperson for GSK, Zhang, who served as the company’s head of research and development in China, has been dismissed. She adds that “a second employee has submitted their resignation and three others have been placed on administrative leave, pending a final review.”

GSK concluded that the data offered in the study as coming from cells taken from people with multiple sclerosis were either recorded from healthy donor cells “or cannot be documented at all,” says Stubbee. She stresses that the work carried out by Jian Hong, a coauthor at the Baylor College of Medicine in Houston, was not implicated in any wrongdoing by the GSK investigation.

GSK says that it will seek a retraction for the paper. Juan Carlos López, editor-in-chief of Nature Medicine, says that the journal’s policy on retractions states that all authors on a given paper must agree to a retraction and sign a document to express this consent. Should there be disagreement, then the situation becomes more intricate. “If some authors do not agree to retract, we can run a retraction signed by just a subset of co-authors,” López says. “If the authors do not want to retract, but their home institution wants the study retracted, we would retract the study, stating the rationale behind the decision.” The news section of Nature Medicine, which includes the Spoonful of Medicine blog, operates separately from the section of the journal that includes research manuscripts.

A message seeking comment from Zhang addressed to his GSK account received a bounce-back email with an ‘unknown address’ error.

Notably, a 2011 paper published in the journal Science Translational Medicine concluded that interleukin-7 has a more pronounced effect on T helper type 1 (TH1) cells, rather than TH17 cells. Hans Dooms, an immunologist at Boston University School of Medicine, says that his group also found this in a 2012 study of a mouse model of diabetes. “We did see the strongest effect on TH1,” Dooms says. This finding, he notes, “would agree more” with the Science Translational Medicine paper, which was led by researchers at Stanford University and Pfizer, than the one from Zhang’s group.

Despite the problems in the 2010 Nature Medicine paper, GSK maintains that interleukin-7 has an important role in autoimmune disease. The Zhang paper, Stubbee says, “has contributed to the progress of an asset that we now have in early stage development, but it has not been pivotal.”

Others in the field remain equally confident about the importance of interleukin-7, despite the allegations regarding the TH17 paper. “It will not deter us from working on the pathway,” says Vijay Kuchroo, a neurologist at the Brigham and Women’s Hospital in Boston who has studied the development and role of T helper cells. Nonethless, the alleged shortcomings of the Zhang paper come as a surprise to Kuchroo. “In science, when someone says something, you take it as truth,” he says.

UPDATE: Spoonful of Medicine was able to reach Zhang, who denies accusations of wrongdoing, and says he is “shocked” by GSK’s actions: “I must say I’m very disappointed for several reasons. One is that I was never involved in any data fabrication.”

“I’m not saying I’m free of any responsibility,” Zhang adds. “I’m a senior author. For that I should accept certain responsibility as the corresponding author, but not as currently accused.”

The first author on the paper, Xuebin Liu, says he has resigned from GSK and emphasizes that the data relating to the figure in question was described improperly in the paper because he forgot to update the manuscript when submitting it for publication. “At that time we had a little bit of rush,” says Liu. “I didn’t realize we should switch the description back to the normal human subjects.” He adds that “all the data is real, but the data comes from healthy individuals” and that he can repeat the data in question “in any lab, at any time”.

Liu says that at this point he has not signed paperwork requesting a retraction. He adds that Zhang “did not realize” the errors in the paper and did not participate in the data analysis.

When asked if he will take legal action against GSK, Zhang says, “I am considering my options and [will] see what I can do.”

Comments

There are currently no comments.