The Scientist

Three authors have retracted their 2006 Science article that found evidence of different cell lineage fates in two-cell embryos in a letter published today (July 26) in Science. The retraction comes one month after the University of Missouri (UM) found the study's lead author, Kaushik Deb, guilty of research misconduct, and more than a year after embryologists blew the whistle on potential fraud. The university university exonerated R. Michael Roberts of UM, whose lab headed the work, and the study's other authors, Mayandi Sivaguru and Hwan Yul Yong, of any wrong doing in February. "That's a terrible tragedy, to throw it all away," Robert Hall, associate vice-chancellor for research at UM, said of Deb. "Truly this sort of reprehensible misconduct is fatal to a scientific career," Hall told The Scientist. Hall said the university's investigation found Deb had "fabricated or falsified" some of the digital images in the publication. Microscopy experts pulled from inside and outside UM found certain images of embryos were reproduced in the article and presented as different embryos, Hall said. Additionally, original data are missing. "There's no doubt in my mind serious misconduct has occurred, and I'm ultimately responsible for that," Roberts, a professor in UM's Biochemistry Department and a member of the National Academy of Sciences, told The Scientist. "I think I was overly loyal and found it hard to believe that this could actually happen." Deb cannot be found, Hall said. "When a scientist is desperate enough to commit misconduct, I am not surprised to hear that they have simply disappeared," Hall said. At the time it was published, the retracted article fueled an ongoing debate regarding the stage at which asymmetry appears in embryos. It found that blastomeres from two-cell mouse embryos differentially express the transcription factor Cdx2, and one of the blastomeres is fated to become the trophectoderm, which ultimately becomes the placenta. Just months earlier, Davor Solter and Takashi Hiiragi at the Max-Planck Institute of Immunobiology in Freiburg, Germany, and their colleagues found asymmetrical patterning in embryos is not developed until later in development, in the blastocyst stage. The findings went against years of evidence showing patterning in embryos occurs later than the two-cell stage. "The results were so surprising as to raise doubts," Janet Rossant at the Hospital for Sick Children in Toronto, told The Scientist. After scrutinizing the paper upon its publication, Rossant, Solter, Hiiragi, and about a dozen others wrote a letter to Donald Kennedy, the editor-in-chief of Science, noting that they "find clear evidence of duplicate figures being used to apparently support different experiments." The March 8, 2006, letter, which The Scientist obtained from Solter, points out several of the figures that were ultimately found fraudulent by UM's investigation. "I was very suspicious from the beginning, and wondered how the review system in Science worked to make that paper published especially immediately after the Hwang case," Hiiragi, now at the Max-Planck Institute for Molecular Biomedicine, wrote in an Email to The Scientist. "In this specific case, any experienced mouse embryologists would have noticed their unnatural data, and this is a failure in the review system of Science." The international group requested that Science publish a technical comment, but their request was turned down. Meanwhile, independent labs attempted to replicate the results and failed. Solter, Rossant, and their colleagues alerted UM of possible fraud and an inquiry began. Solter told The Scientist that the paper should have been retracted much earlier, and in correspondence to Kennedy, Solter urged the editor-in-chief to take more aggressive action and "speed up your usual procedure, thus preventing further contamination of scientific literature." According to the Web of Science, the paper has been cited in 31 scientific publications. Solter said the result has been that the paper "significantly confused the field." Roberts said he did not immediately retract the paper after knowing there were fraudulent data because he was waiting for the investigation at UM to clear up. Hall said it is unlikely Deb will face criminal charges for wasting federal funds. Rather, he is certain to lose his scientific career. "That's the worst penalty I can think of for anyone," Hall said. By Kerry Grens mail@the-scientist.com Links within this article: Deb K. et al., "Cdx2 gene expression and trophectoderm lineage specification in mouse embryos," Science, Feb. 17, 2006. http://www.the-scientist.com/pubmed/16484492 Roberts R.M. et al., "Retraction," Science 317:450, 2007. http://www.sciencemag.org K. Grens, "Biologists cleared of misconduct," The Scientist, February 14, 2007. http://www.the-scientist.com/news/display/52847/ R. Michael Roberts http://www.biochem.missouri.edu/mroberts.php Robert Hall http://research.missouri.edu/division/hall.htm K. Grens, "University of Missouri probes possible fraud," The Scientist, November 14, 2006. http://www.the-scientist.com/news/display/36408/ Davor Solter http://www.immunbio.mpg.de/home/research/biol/solter/ Takashi Hiiragi http://www.immunbio.mpg.de/home/research/biol/hiiragi/index.html Motosugi N et al., "Polarity of the mouse embryo is established at blastocyst and is not prepatterned," Genes & Development, May 1, 2005. http://www.the-scientist.com/pubmed/15879556 Janet Rossant http://www.utoronto.ca/medicalgenetics/PIs/ROSSANT.HTM A. McCook, "Hwang faked results, says panel," The Scientist, December 23, 2005. http://www.the-scientist.com/article/display/22870