Negative results

    Retracted papers require a thorough explanation of what went wrong in the experiments.

    At first glance it seems to be a shining example of the scientific method in action. Two papers published by biochemist Homme Hellinga and his students at Duke University Medical Center in Durham, North Carolina, claimed a breakthrough in rational enzyme design. Last year, another chemist found that Hellinga's enzymes didn't actually work, which led to the retraction of the two papers this February (see page 275). Then, this March, a third group published research showing that rational enzyme design really is possible. All has ended happily, it seems, with the field marching forward in triumph.

    But examined more closely, the episode reveals some less than happy aspects of science as it is actually practised. For example, the problems with Hellinga's enzymes were identified by John Richard at the State University of New York in Buffalo, who hoped to use the proteins in his own work. In effect, Richard and his two co-workers wasted seven months and tens of thousands of dollars failing to reproduce the results from Hellinga's lab. Richard's subsequent efforts to correct the scientific record thus came at considerable cost, with no discernable benefit to his own career.

    This is a perennial problem in science. Many researchers who come across non-reproducible work save themselves extra hassle and money by simply not pursuing it further. Meanwhile, those who refuse to let it go — like Richard — gain nothing.

    The process has been even more difficult for Hellinga's former student, Mary Dwyer. Hellinga accused Dwyer of faking data in the now-retracted papers, although he apparently had no evidence of intentional wrongdoing on her part. A Duke inquiry later cleared Dwyer of any misconduct, but her mentor's accusations could be more damaging to her career than the retractions.

    The situation highlights the vulnerability of students in the system of scientific mentorship. Indeed, Hellinga's decision to accuse Dwyer was questionable. As Dwyer's adviser, Hellinga was responsible for training her. If she made mistakes, they are ultimately his responsibility. Instead, by accusing her, he cut off any possibility of frank and open discussion.

    In the end, despite Richard's work, a misconduct inquiry and two retractions, the scientific community still does not know what went wrong, and may never know. This is perhaps most damaging to Hellinga, as the scientific community is now unsure whether to trust his prior and subsequent work. He and Duke owe the world a more thorough explanation of his conduct, and of his scientific work in question. Until then, this episode will continue to be a cautionary tale about the weaknesses — not the strengths — of the scientific process.

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    Negative results. Nature 453, 258 (2008) doi:10.1038/453258b

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