A Scientist's Nightmare: Software Problem Leads to Five Retractions

Until recently, Geoffrey Chang's career was on a trajectory most young scientists only dream about. In 1999, at the age of 28, the protein crystallographer landed a faculty position at the prestigious Scripps Research Institute in San Diego, California. The next year, in a ceremony at the White House, Chang received a Presidential Early Career Award for Scientists and Engineers, the country's highest honor for young researchers. His lab generated a stream of high-profile papers detailing the molecular structures of important proteins embedded in cell membranes.

Then the dream turned into a nightmare. In September, Swiss researchers published a paper in Nature that cast serious doubt on a protein structure Chang's group had described in a 2001 Science paper. When he investigated, Chang was horrified to discover that a homemade data-analysis program had flipped two columns of data, inverting the electron-density map from which his team had derived the final protein structure. Unfortunately, his group had used the program to analyze data for other proteins. As a result, on page 1875, Chang and his colleagues retract three Science papers and report that two papers in other journals also contain erroneous structures.

"I've been devastated," Chang says. "I hope people will understand that it was a mistake, and I'm very sorry for it." Other researchers don't doubt that the error was unintentional, and although some say it has cost them time and effort, many praise Chang for setting the record straight promptly and forthrightly. "I'm very pleased he's done this because there has been some confusion" about the original structures, says Christopher Higgins, a biochemist at Imperial College London. "Now the field can really move forward."

The most influential of Chang's retracted publications, other researchers say, was the 2001 Science paper, which described the structure of a protein called MsbA, isolated from the bacterium Escherichia coli. MsbA belongs to a huge and ancient family of molecules that use energy from adenosine triphosphate to transport molecules across cell membranes. These so-called ABC transporters perform many essential biological duties and are of great clinical interest because of their roles in drug resistance. Some pump antibiotics out of bacterial cells, for example; others clear chemotherapy drugs from cancer cells. Chang's MsbA structure was the first molecular portrait of an entire ABC transporter, and many researchers saw it as a major contribution toward figuring out how these crucial proteins do their jobs. That paper alone has been cited by 364 publications, according to Google Scholar.

Read more about this at: http://www.sciencemag.org/cgi/content/full/314/5807/1856