NEWS

Data From DNA Repair Studies Questioned As Leading Researcher Investigated

James Schultz

Because science depends on collaboration and experimental replication, even the slightest hint of fraud or neglect reverberates quickly throughout the scientific community. Such is the case with Steven A. (Tony) Leadon, Ph.D., considered by his colleagues a leading authority in the field of transcription-coupled DNA repair (TCR). Leadon has been accused of falsifying data related to the repair function of the BRCA1 protein and how BRCA1 absence or modification is associated with a higher incidence of breast and ovarian cancers.

The accusations may lead to the recall of several major papers on which Leadon was a co-author, and may force researchers to reverify previous findings connected with Leadon’s laboratory.

This June, the journal Science published a retraction of an Aug. 14, 1998, summary of findings on which Leadon was a co-author with four colleagues (none of whom have been implicated by the ongoing investigation). A subsequent article in the news magazine The Scientist reported that Leadon resigned this past March from his post as director of radiobiology at the University of North Carolina at Chapel Hill, after a five-member panel at UNC asserted that Leadon had tampered with an antibody assay examining TCR mechanisms.

Leadon’s original laboratory notebooks have been confiscated and sent to the Office of Research Integrity (ORI) at the National Institutes of Health. ORI will not comment on the case, citing confidentiality provisions. Leadon has retained Chapel Hill-area civil-rights attorney Alan McSurely to represent his interests. Experts continue to evaluate other papers that cite Leadon as a co-author for possible withdrawal or modification.

Leadon has steadfastly denied any fraud or deliberate wrongdoing. According to The Scientist, Leadon accepts responsibility for the flawed data emanating from his UNC laboratory, but contended "the pathway that we initially characterized is still a valid pathway." When contacted by JNCI, Leadon declined to comment on the case. "As of this stage, nothing has changed," Leadon said. "I really don’t have any more to say." Repeated calls to Leadon’s attorney were not returned.

If the most serious charges against Leadon are upheld, he faces loss of federal research funds for at least 3 years. If Leadon is found to have violated accepted procedures but is cleared of all other misdeeds, he would likely face administrative actions, such as ongoing supervision of federal grant applications and government-underwritten laboratory data. Serious or not, if the accusations against Leadon are upheld, he will nevertheless be prohibited from serving on any public health service peer-review committees. And ORI would continue to lead efforts to correct any published papers.

Colleague Response

Leadon’s colleagues appear confused, concerned, and anxious about the case. Those who have worked closely with Leadon and consider him one of best in the TCR field are struggling to find explanations. "It’s every scientist’s worst nightmare," said Philip Hanawalt, Ph.D., a TCR pioneer and professor of biology at Stanford University, Palo Alto, Calif. As a young post-doc, Leadon worked in Hanawalt’s laboratory. "I feel it’s essential not to leap ahead with conclusions. We have to sort out what is valid and what is not," he said.

Hanawalt praised Leadon as a conscientious, attentive scientist who was always careful about his experiments. While at Hanawalt’s laboratory, Leadon "made a major technological contribution" to TCR: the antibody-assay process that is now under question. According to Hanawalt, Leadon’s subsequent work was always consistent with the findings reported by other research teams.

"Those who know Tony are in a state of disbelief. Perplexing is an understatement," Hanawalt said. "This is so bizarre to me. I’ve had no reason to doubt Tony’s work until the recent events. But investigating committees are quite meticulous. They would not come out and make the kind of accusations they have unless they had very solid evidence that something was amiss."

When contacted for this news article, UNC-Chapel Hill would offer no comment other than an e-mailed statement on what events led to the Leadon investigation or its current status. In remarks attributed to Robert Shelton, UNC-Chapel Hill executive vice chancellor and provost, the statement read, "We investigate rigorously any allegation of scientific misconduct. If we find evidence of misconduct in research funded by a federal agency, we report it to the federal Office of Research Integrity. If ORI finds that a violation has occurred, it publishes a detailed account, which then becomes a matter of public record. State law prevents us from commenting on specific cases."

BRCA Work

Leadon’s research has focused on the roles played by inherited mutations of the BRCA1 and BRCA2 genes, which confer a marked predisposition to breast and ovarian cancer in women. The inheritance of a mutant BRCA1 allele dramatically increases a woman’s lifetime risk for developing those cancers. How precisely that happens, how a normal BRCA1 gene suppresses tumors, is still being investigated—and was by Leadon until his resignation.

"What has been called into question represents a small portion of this field," said Isabel Mellon, Ph.D., associate professor in the University of Kentucky Medical Center’s Department of Pathology and Laboratory Medicine. "There has been independent corroboration of at least some of the work. What will be required is independent reproducibility of some of the important observations that have been made. I hope [Tony’s] collaborators will be able to repeat some of these experiments."

Chris Pascal, J.D., director of ORI, said that although he was aware of media reports of Leadon’s situation, he could offer no specific comment until the ORI investigation had run its course and any appeal is made, a process that could last more than 2 years. Most cases, said Pascal, are resolved in 8 months or sooner if an accused researcher wants to settle quickly.

Pascal said that although there has been no apparent absolute increase in the number of research fraud-and-abuse cases, there does seem to be a substantial increase in the percentage of those involving active misconduct, such as deliberate fabrication and falsification. In part, Pascal said, it is because universities and other research-sponsoring institutions are more sophisticated and aggressive about pursuing suspected researcher conduct. The other portion, the personal motivations, remain a mystery.

"Why do researchers cut corners and fake data?" Pascal said. "Maybe people just want to get ahead. They want to be first. There are financial incentives. But these are just suppositions. It’s an issue for further scientific study."



             
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