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Fraud case raiser deeper questions

analysis

By David P. Hamilton

Some three years after a series of experiments in an MIT biomedical laboratory appeared as a relatively obscure scientific paper in the journal Cell, investigators are still sifting through masses of evidence to determine the truth about allegations of fraud and scientific misconduct.

Despite the seriousness of these charges, however, the important issues raised by the investigation are not confined to the problem of scientific error, whether propagated accidentally or intentionally.

Instead, this incident raises questions about such disparate topics as the ability of institutions to objectively examine allegations of misconduct, the freedom junior researchers enjoy to question results achieved by their superiors, and the extent to which Congress should act to ensure that publicly-funded research is carried out free of misconduct.

The case has attracted national attention largely because of the involvement of David Baltimore '61, a Nobel laureate and director of the Whitehead Institute for Biomedical Research. A prominent national spokesman for biomedical issues as well as a highly-honored researcher, Baltimore has emerged as the spokesman for the paper's authors, although he was only peripherally involved in the research under question.

The real controversy involves research performed by Thereza Imanishi-Kari, formerly of the MIT Center for Cancer Research and now a professor at Tufts University. According to Margot O'Toole, a former post-doctoral student of Imanishi-Kari's, the experimental data supporting the paper's central thesis was misleading or false, rendering the paper's major contribution untenable.

After raising her concerns with faculty members at both MIT and Tufts, O'Toole complained that the resulting institutional reviews of the research were flawed by "false and damaging" statements, misrepresentations, and the investigators' failure to press for the correction of the paper's false claims, which she characterized at the time as error, not fraud.

At the same time, O'Toole claimed that her career began to unravel as the result of hostility on the part of unnamed MIT faculty members and Imanishi-Kari, who she said requested that O'Toole not be allowed to return to an appointment at Tufts.

The paper's authors have put forth a very different account. Baltimore, for instance, has acknowledged that the paper contained scientific errors, but argued that the MIT and Tufts reviews were fair and thorough and that they found the errors so minor as to warrant no correction.

Baltimore also denied that any fraudulent behavior ever took place. In a letter to MIT investigator Herman Eisen later that year, however, Baltimore complained that Imanishi-Kari had withheld information about a particular experiment, writing, "Why Thereza chose to use the data and to mislead both of us and those who read the paper is beyond me." Baltimore has since explained the letter as the result of a "misunderstanding" based on language difficulties.

Through the actions of two unofficial fraud investigators from the National Institutes of Health, O'Toole's case came to the attention of the House Subcommittee on Oversight and Investigation. The subcommittee, chaired by Rep. John Dingell (D-MI), was pursuing an investigation into other incidents of scientific fraud with the intent of gauging institutional response to allegations of misconduct.

Between the actions of the subcommittee and a reopened NIH investigation, the paper's authors recently have been under significant pressure. The subcommittee has subpoenaed laboratory data and correspondence, scheduled interviews at short notice, and brought in the Secret Service to perform forensic analysis on laboratory notes and data.

In response, Baltimore has marshaled the prestige and resources of the Whitehead Institute in an impressive defense of the authors' research. Colleagues wrote Op-Ed pieces in newspapers such as The New York Times and The Wall Street Journal decrying the Dingell "witch-hunt" and painting Baltimore as a natural target for publicity-hungry congressional investigators, while the Whitehead public relations staff devoted itself to preparing a defense for Baltimore's appearance at subcommittee hearings last May.

The subcommittee has also caused a certain amount of trouble for itself, as its investigation has at times been sloppy. One subcommittee aide, Peter Stockton, carelessly told the Boston Globe last year that "at certain times, it appears to be fraud and other times, misrepresentation." The Secret Service spent hours analyzing an autoradiograph that appeared in the paper, eventually concluding it was a composite of several pictures, only to learn that composite autoradiographs are common practice in presentations of immunological research.

These mistakes have provided ammunition for Baltimore's defenders, who write passionately about overzealous prosecutors and the spectre of a stultified research environment in which "all the fun" is taken out of science by too much federal regulation. Meanwhile, the investigators and their allies remain suspicious of untidy loose ends in the scientists' story, such as the postdating of Imanishi-Kari's lab notes.

Almost lost in the fray is any discussion about the environment that allowed a relatively minor scientific dispute to blossom into such a full-blown conflict. O'Toole has argued that it is nearly impossible for junior scientists to entertain serious disagreements with their seniors when these very scientists may one day be sitting on tenure committees or reviewing grants. Similarly, if institutional review procedures, and even NIH investigations, appear easily influenced by entrenched interests within the university, the foundations of academic freedom are a bit less steady.