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GEN News Highlights : Mar 14, 2014

RIKEN: No Misconduct Yet Found in Its Acid-Bath Stem Cell Investigation

  • Kevin Mayer

While acknowledging that “inappropriate handling of data” had occurred during the preparation of two prominent but controversial papers on stem cells, RIKEN asserted that the mistakes it has investigated thus far do not “constitute research misconduct.” RIKEN, however, also indicated that is continuing its investigation, weighing a number of questions raised by the papers, which appeared January 29 in Nature.

The papers immediately created a stir by reporting that simply exposing mouse somatic cells to external stresses—such as a mildly acidic bath—caused them to turn into pluripotent stem cells. Such a technique, if applicable to human cells, would open exciting opportunities, potentially leading to a range of stem-cell-based therapies.

The papers, the work of researchers at the RIKEN Center for Developmental Biology in Japan and Brigham and Women’s Hospital, also aroused skepticism, particularly when other investigators reported that they were unable to replicate the original studies’ findings. Also, questions were raised about the appearance of figures in the study and the possibility that some passages of text had been copied from other sources. Finally, after more detailed methods were released by RIKEN, other researchers noticed that they were inconsistent with the originally published methods.

In response to rising criticism of the studies, RIKEN opened an investigation February 13. Also, on March 10, one of the authors of the stem cell papers called for the study to be retracted. This author, Teruhiko Wakayama, Ph.D., a professor of developmental engineering at the University of Yamanashi, wrote in an email to the Wall Street Journal that there “is no more credibility when there are such crucial mistakes.”

Another co-author, Charles Vacanti, a Brigham and Women’s Hospital anesthesiologist, continues to stand by the paper. Earlier, in a February 17 Nature News article, Dr. Vacanti was reported to have recognized at least one mistake, but he also said that it did not necessarily undermine the paper’s conclusions. Later, in a Wall Street Journal article about Dr. Wakayama’s call for a retraction, Dr. Vacanti was quoted as follows: “It would be very sad to have such an important paper retracted as a result of peer pressure, when indeed the data and conclusions are valid.”

On Friday, RIKEN held a press conference to address concerns raised by the two Nature papers. RIKEN also issued a statement in which it said that its investigation is still in progress. “It will be some time before a final report can be issued,” the statement indicated. “Given the high interest in this case, however, the committee has issued an interim report on the six items it is investigating, including those for which it has reached conclusions and those items that are still being investigated.”

In its preliminary report, RIKEN finds no evidence of misconduct with respect to two of the items it is investigating. The first item concerns the “unnatural appearance of colored cell parts shown by arrows in d2 and d3 images of Figure 1f”; the second, the “strong resemblance between the rightmost panel in Figure 1b and the lower panel in Figure 2g, both showing a fluorescence image of mice placenta.”

The four items still under investigation include the following:

  • Paper 1: “In Figure 1i, lane 3 appears to have been inserted later.”
  • Paper 1: “A part of the Methods section on karyotyping analysis appears to have been copied from another paper.”
  • Paper 1: “Some of the description of karyotyping in the Methods section is different from the actual procedure that was followed.”
  • Paper 1: “The image of differentiated cells for Figures 2d and 2e and the image of chimera mouse immunostaining data are incorrect, and in the process of the investigation, it was found that these images closely resemble images used by [lead author] Dr. Obokata in her doctoral dissertation.”

More general remarks were offered in a statement by RIKEN president Ryoji Noyori: “The reproducibility and credibility of the STAP (stimulus-triggered acquisition of pluripotency) phenomenon must be rigorously validated, not only by RIKEN scientists, but also by others. I have instructed our people to cooperate fully with researchers at outside institutions in their efforts to replicate the STAP cell results.”

“It is extremely regrettable that significant discrepancies have been found to have been generated in the process of preparing the Nature articles for publication,” the statement continued. “We are investigating these discrepancies, with the understanding that it may become necessary to demand the withdrawal of the articles.”