THEREZA IMANISHI-KARI

Starting with a Clean Slate

For someone whose lack of organization has become a topic of conversation throughout academe and beyond, Thereza Imanishi-Kari has a strikingly tidy office. The Brazilian-born scientist was this past summer cleared of all charges of scientific misconduct arising from a tangled, decade-old controversy that reached into the halls of Congress and forced Nobelist David Baltimore, one of Imanishi-Kari's co-authors in a disputed scientific study, to resign as president of the Rockefeller University. Because of his indignant defense of Imanishi-Kari, the case became known as the "Baltimore affair," even though she was the only one of six collaborators to be accused of wrongdoing. Intense news coverage turned the saga into the most sensational case of alleged research fraud in U.S. history: three books about it are now in progress. Recently reinstated as an assistant professor in the pathology department at the Tufts University School of Medicine, Imanishi-Kari, currently in her early fifties, seems remarkably unbitter. Casually dressed and in an ebullient mood in her small room at the top of a cramped laboratory building in the New England Medical Center, she displays no anger toward her accusers, concluding that they should look to their consciences: "We all have to live with our mistakes." She finds it "very sad," however, that some scientists, notably Mark Ptashne of Harvard University, publicly sided with her accusers without ever discussing the evidence with her.

Moreover, press coverage of the controversy, Imanishi-Kari says, was "irresponsible"; she singles out the New York Times for handing out blame in 1991 on the basis of a condemnatory draft report by the Office of Research Integrity (then the Office of Scientific Integrity) of the Department of Health and Human Services. That leaked document became public before she knew the details of the allegations against her and before her lawyers had cross-examined witnesses. At that time, she says, she doubts "whether the scientists who were overseeing the investigation at the Office of Scientific Integrity actually had seen the evidence." She expresses agitation only in decrying the lack of due process that made that situation possible.

The research at the heart of the dispute, published in the journal Cell in 1986, concerned antibodies produced by genetically engineered mice. Imanishi-Kari, then at the Massachusetts Institute of Technology, and her co-authors reported that the addition of a gene to the mice made them produce a range of antibodies that was altered in a surprising way. The arguments started within a month, when Margot O'Toole, a researcher whom Imanishi-Kari had hired to extend the experiments, came to suspect that Imanishi-Kari's own studies did not support the published account. Early inquiries by scientists at the involved universities and by the National Institutes of Health found errors in the paper--it overstated the power of a key reagent, for example--but the errors did not threaten the paper's main conclusions, and the investigators found no evidence of misconduct. But in 1989 O'Toole upped the ante by charging that data reported in a published correction to the paper had been fabricated, and the NIH, under pressure from Congress, reopened its investigation of the affair.

The case against Imanishi-Kari turned on her laboratory records, which she has always agreed were not kept up-to-date and in good order. She readily admits that when she could not remember exactly what day she did an experiment, she "probably did" put vaguely remembered dates on records, months after the fact. That habit may explain why the matter went as far as it did: the Secret Service, called in by then Representative John D. Dingell of Michigan to investigate Imanishi-Kari's notebooks, concluded by analyzing paper and ink that their pages were not written when the dates on them indicated. That finding forced the Department of Health and Human Services to dig further. Imanishi-Kari has acknowledged that when the NIH first investigated her, she pulled together loose papers and incorporated them into her principal notebook in an attempt to organize the record. (She sent along to the NIH the empty manila folders that had earlier contained some of the data, she says, but never saw them again.)

Imanishi-Kari's career bottomed out five years later, when in 1994 Tufts asked her to take a leave of absence. The request came after the Office of Research Integrity issued a "final report" concluding that she had "intentionally and deliberately fabricated and falsified experimental data and results," a finding that rested heavily on the Secret Service's notebook analysis as well as on statistical analyses of data. Imanishi-Kari argued that there was no reason she should stop her research until her appeals were exhausted, but she had to accept a demotion to contract researcher. As a result, she could no longer teach.

Looking back--something Imanishi-Kari says she does not often do--she laments the loss to her science and to her private life. "It was just a lot of pain," she recounts. Her daughter, former husband and faculty colleagues were "very supportive," and, until she lost her teaching responsibilities, her students injected enthusiasm for learning that, Imanishi-Kari says, "kept me going." Her research during the blighted years proceeded slowly, especially when she was supported only by small grants from the American Cancer Society and the Leukemia Society. She denies harboring anger over her loss of earnings since 1986: although her salary "never increased very much" during the several investigations of her, she says she "never wanted to be rich." Lawyers worked on her defense pro bono, and scientific supporters met some of the legal expenses.

At this point in our conversation, I learn the truth about her neat-looking office: it has, she confesses, been tidied and organized in honor of my visit. The appeals panel that cleared Imanishi-Kari of all charges of misconduct did criticize her for sloppy record keeping, as well as her collaborators for allowing the paper to be published "rife with errors of all sorts." Besides the overstatement of the reagent's power, there were clerical mistakes and an incorrect description of the cells used in one set of tests (some of the errors have since been corrected). Imanishi-Kari says she is not sure that the disputed Cell publication has any more errors than most papers, a thought that might make scientific editors blanch.

Some observers have speculated that Imanishi-Kari's accented and imperfect English may have been a significant factor in the case (she came to the U.S. in 1980, having previously lived in Brazil, Japan, Finland and Germany). Miscommunication between the collaborators on the disputed paper accounted for at least one misstatement in the paper. But Imanishi-Kari insists that once the investigations started, she and her colleagues "did listen very carefully" to all O'Toole's concerns.

Imanishi-Kari is defiant about her innocence, but she regrets not having insisted that all charges, discussions and findings be formally recorded right from the earliest stages. Some initial meetings about O'Toole's accusations were not recorded, she says, and Imanishi-Kari believes that if they had been, things might have gone differently. "In my own head, I didn't see at that time that it was going to turn into such a nightmare," she declares. At first, according to Imanishi-Kari, discussions centered on which data had been used in the Cell paper, and she provided reasons for her selections. She now advises all scientists who get caught up in any disputes that go beyond normal scientific discourse to record allegations, rebuttals and findings and to get a lawyer as soon as fraud or misconduct is mentioned.

Lawyers, whom as a breed scientists love to hate, finally got Imanishi-Kari off the hook after scientists working alone had failed. The research integrity appeals panel, consisting of two lawyers from the Department of Health and Human Services and an academic immunologist, concluded this past June after a six-week hearing that much of the evidence against Imanishi-Kari was "internally inconsistent, lacked reliability or foundation, was not credible or [was] not corroborated." The panel was the first body not set up to look for misconduct to weigh the Secret Service's challenge to Imanishi-Kari's data. The panel's decision is scathingly critical of the Office of Research Integrity's findings, stating that the evidence is unreliable, in large part irrelevant and "disconnected from the context of the science." Many of the anomalies the office identified were in data that were never published, for instance. The office has lost all its recent big cases on appeal, and the secretary of health and human services is now considering options for changing the agency's responsibilities.

O'Toole, too, has paid a substantial price: she has said that as a result of her whistle-blowing she was unable to find work in science for four years. (She now works for Genetics Institute, a biotechnology company in Cambridge, Mass.) After the decision of the appeals board, she was quoted in Science, saying, "Given that this board tossed out the evidence, it is not surprising that they cannot believe that what I say happened, happened."

Imanishi-Kari, who if found guilty would have been barred from receiving federal funds, says she intends to continue her career in research. "Now I don't have to think about the investigation, I should be putting all my energy into something productive and something good," she remarks. She has published recent papers on the same system that was explored in her infamous 1986 publication, and although the effects she was studying are now no longer in the scientific spotlight, she expresses the hope that she might one day collaborate again with Baltimore. "You never end finding things," she reflects. "I think there's a lot of things we don't know."

--Tim Beardsley in Washington, D.C.