WHEN RESEARCHERS DISAGREE


WHISTLE-BLOWING WAS COSTLY FOR SCIENTIST


By Susan Okie
Washington Post Staff Writer
Monday, April 11, 1988 ; Page A01

In the spring of 1986, Margot O'Toole, a young scientist doing postdoctoral research at the Massachusetts Institute of Technology, reached a troubling conclusion. After poring over experimental data in a laboratory notebook, she became convinced that there were serious flaws in an important scientific paper recently published by one of her superiors and several other MIT scientists, including Nobel laureate David Baltimore.

O'Toole confronted senior scientists with her concerns. She has since left research, claiming she was driven out by the incident and its repercussions. And the case has given rise to a raging dispute that is not about scientific fraud, which is not an issue here, but about how legitimate disagreements over the conduct of scientific research are investigated and resolved.

The paper by Baltimore and his coworkers, published in the journal Cell in April 1986, became the target of an unofficial investigation by two National Institutes of Health scientists who are outspoken critics of the current system, a role for which they have been both praised and damned by their colleagues.

The scientists, Ned Feder and Walter W. Stewart, wrote in a letter to a fellow scientist that "some of the Cell paper's main conclusions appear to be contradicted, rather than supported, by the data." They are seeking to publish an article criticizing the NIH-funded research in a scientific journal.

NIH has appointed a panel to conduct an official investigation, and two congressional panels are scheduled to examine the case in hearings today and Tuesday.

Critics of the current system for maintaining scientific standards, under which the institution conducting research has primary responsibility for monitoring ethics and accuracy, say that the power and prestige of senior scientists often prevent whistle-blowers like O'Toole from getting a fair hearing. They argue that those who point out research flaws often lose grants or job opportunities. And because of close professional relationships among scientists, they say investigations of alleged misconduct are often marred by conflict of interest.

Defenders of the system say that in this case, and in others, it has worked well. Separate inquiries conducted by MIT and by Tufts University, where one of the authors is a faculty member, concluded that although some of the data allowed more than one interpretation, no errors in the Cell article were serious enough to warrant a published correction.

Baltimore, who is director of the Whitehead Institute at MIT, acknowledged in an interview that the paper, a highly technical immunology study, contained one "probable overstatement" regarding the accuracy of a test used in the research, which he called "a minor problem I'm sure I could find in most papers."

"The basic conclusions are solid, and a number of people have begun work that builds on it," he said. He called the dispute over the research "a tempest in a teapot" and said that O'Toole had been treated fairly.

But he agreed that the makeup of the three-member panel that NIH initially chose to investigate the case early this year did raise questions of conflict of interest. One of its members was a former student and scientific collaborator of Baltimore and another was his coauthor on a major textbook.

"It didn't seem to me at the time that it represented the independent investigation I would like to see," Baltimore said. The two are no longer on the panel and it is being reconstituted, according to Mary Miers, NIH institutional liaison officer.

O'Toole, who refused to discuss the case in detail before testifying at the Tuesday congressional hearing, said she still strongly believes that the data in the paper does not support its conclusions. After leaving her research job, she worked for a time for her brother's moving company and is now unemployed, she said.

"People at MIT have portrayed me as on a vindictive rampage," she said. "This has totally disrupted and upset my whole life. It has completely halted my career."

According to a written summary of the case by Feder and Stewart, O'Toole began to question some conclusions in the Cell paper when experiments she was performing under the supervision of one of its authors, Dr. Thereza Imanishi-Kari, failed to turn out as expected. O'Toole had been given a laboratory notebook containing data on which the paper was based to use as a reference. Her own analysis convinced her that the conclusions of the study, which dealt with production of certain chemical antibodies by the immune system of genetically altered mice, were not supported by its data.

O'Toole consulted Dr. Henry Wortis, her former teacher at Tufts University, who was attempting to recruit Imanishi-Kari for the Tufts faculty. Wortis reviewed the research with two other scientists, and they concluded there had been no deliberate falsification or misrepresentation. "Alternative interpretations of the experimental data can be made, but this is the stuff of science," he wrote later in a letter to a Tufts dean.

At MIT, Herman N. Eisen, an immunologist, conducted a separate inquiry. Eisen wrote in a memorandum to an MIT administrator, "O'Toole is correct in claiming that there is an error in the paper, but it is not a flagrant error. Correction would be too minor to rate a letter to the journal."

Enter Stewart and Feder, two NIH scientists who last year gained a reputation as critics of current scientific standards when they published a controversial study claiming that scientists who collaborated with Dr. John Darsee, a Harvard researcher who faked many of his findings, were negligent in not detecting and exposing Darsee's fraudulent research.

Stewart and Feder wrote in a letter to a colleague that, after hearing of the MIT case from a third party, they persuaded a reluctant O'Toole to send them a copy of the experimental data. Then they performed their own analysis, concluding that the Cell paper presented data "in a grossly misleading and inaccurate way" and that the data seemed to contradict some of the paper's main conclusions.

In late 1986, Stewart and Feder asked NIH to allow them to submit their critique of the study to a scientific journal. NIH administrators asked several other scientists to review their manuscript. All recommended against publishing a study based on a review of partial data without consulting the Cell paper's authors.

One reviewer wrote, "It must be asked what possible purpose would be served by exposition of these possible lapses in a manuscript from the laboratory of a famous scientist."

So Stewart and Feder sent copies of the manuscript to Baltimore, Imanishi-Kari and the study's other authors and requested access to more of the original data used in the Cell study. The authors angrily refused. In March 1987, Baltimore proposed in a letter to an NIH administrator that NIH appoint "a couple of immunologists" to check the paper and that Stewart and Feder promise "to send an apology to all concerned if the review group finds that the norms of scientific research were not transgressed."

The paper's other authors are David Weaver, Moema Reis and Christopher Albanese of MIT and Frank Costantini of Columbia University.

Stewart and Feder contend that Baltimore's prestige has prevented an impartial investigation of the incident. Stewart wrote in a memo to Miers, "He is widely considered to be a politically powerful scientist with considerable influence over funding and job decisions."

Baltimore disputed that notion. "That my power is so great that anybody in immunology has to kowtow to me, that is nonsense," he said. "I don't have any power."

He said that Stewart and Feder's investigative activities were damaging to science. "What they're doing will have a very serious inhibitory effect on the process of scientific publication and on the ability of people to collaborate," he said. "If they're going to say you must be judge and jury over everybody you deal with all the time, there's no trust left."

Stewart maintained that he and Feder are trying to make science better. "I think we as scientists have to take a more realistic view of scientific error," he said. "I see many of the things we are asking for as intrinsically likely to lead to an increase in trust."

NIH finally allowed Stewart and Feder to submit their manuscript for publication last fall, and Cell rejected it. In January, Dr. Katherine L. Bick, NIH's deputy director for extramural research, wrote in a letter to MIT's dean of science that "in view of unresolved questions and publicity regarding this matter," NIH had decided to appoint a panel to investigate the dispute. Miers said the panel has not yet begun its work.

Stewart and Feder are scheduled to testify today at a hearing of the House Government Operations subcommittee on human resources and intergovernmental relations and on Tuesday before the House Energy and Commerce subcommittee on oversight and investigations.

Articles appear as they were originally printed in The Washington Post and may not include subsequent corrections.