Author: By Judy Foreman, Globe Staff

Date: 05/06/1991 Page: 27



Colin Nickerson of the Globe Tokyo bureau contributed to

this report, as did journalists in Sao Paulo: Alvaro

Pereira, editor in chief of Noticias Populares, and

Claudio Csillag, a reporter at Folha de Sao Paulo.

Thereza Imanishi-Kari, a once-obscure immunologist who has never held a tenured academic appointment, now seems destined to go down in history -- as the woman who blackened the image of one of America's most prominent scientists, Nobel laureate David Baltimore.

Accused by a National Institutes of Health panel in March of committing numerous instances of research fraud, Imanishi-Kari is clinging by her fingernails to a career that friends say is "ruined."

Though she has an appointment as an assistant professor at the Tufts University School of Medicine -- Tufts won't say for how long -- federal money is the lifeblood of any scientist, and she has none. She has lost all her NIH funding.

She has published only three papers since the one she published with Baltimore and others in April 1986 that got her in so much trouble.

In the worst-case scenario -- and the five-year long "Baltimore affair" seems to have had nothing but worst-case scenarios -- she could even, as a resident alien, face deportation to her native Brazil, though her lawyer views this as speculative. Imanishi-Kari herself declined to be interviewed.

If NIH's final report confirms the March draft report by an investigating team -- Imanishi-Kari has until this week to rebut the charges against her -- she could be indicted on criminal charges of lying to the federal government, according to sources close to the investigation. If convicted, she could face deportation.

While the NIH panel faulted Baltimore's actions in hushing up problems with the scientific paper as "deeply troubling" and "difficult to comprehend," it said Imanishi-Kari committed outright fabrication of data -- forging lab notebooks in experiments on antibody production in mice.

On Friday, government sources leaked documents in which Baltimore said he now feels he was "too willing to accept" Imanishi-Kari's explanations. He added that he now feels he "did too little to seek an independent verification of her data and conclusions."

Though the five-member NIH panel did not agree on all instances of alleged fraud, they did agree on one point: that Imanishi-Kari had completely fabricated the so-called "June subcloning data" that she provided to answer earlier questions about a table published in the paper.

To her friends, among them Joan Press, an immunologist at Brandeis University, the whole thing is a travesty.

Imanishi-Kari "is a great scientist. She is creative. She thinks about this stuff like crazy. I trust her implicitly. There is no way she fabricated this stuff. I think she should sue the hell out of the government for the lack of due process. They have literally ruined her life and career," Press said.

Imanishi-Kari's current graduate students and post-doctoral fellows at Tufts -- Theresa O' Keefe, Christene Huang and John Iacomini -- agree, adding that although she continues to do science, life in her lab these days is tense.

Iacomini fumes, "Thereza hasn't been given any due process. They are saying her data are fabricated, but. . .how reliable is their evidence? In any court where there are rules of evidence and a chance for cross-examination, this evidence would have been thrown out."

Huang feels Imanishi-Kari has been "terrific as a teacher," and O'Keefe agrees: "I had a project that stopped working for four months, I couldn't get anything to work, and she continued to support me."

But others, particularly those who knew her at Massachusetts Institute of Technology, are not surprised at how Imanishi-Kari's career has unravelled.

One colleague now in private industry says she "could be quite charming" but working with her was "a pretty miserable experience."

"I think in this case she believed in her hypothesis. But she was sloppy. She didn't run controls. So when it was pointed out to her that she had forgotten some things, it would have been embarassing, . . .so she covered up some. She was aware she was not as productive as MIT expected and was hoping this would be a big breakthrough."

Charles Maplethorpe, now a scientist in Washington, D.C., began working for Imanishi-Kari as a graduate student in 1981.

"She was a nightmare to work for," he says. "She had fixed ideas. She did not make conclusions on the basis of data. She demanded that she always be the center of attention, she was loud, demonstrative and enjoyed being domineering."

Though another MIT colleague, post-doctoral fellow Margot O'Toole, was the whistleblower who initially charged Imanishi-Kari with error -- and later, fraud -- Maplethorpe was the first to testify that Imanishi-Kari had committed fraud -- at a 1988 congressional hearing called by US Rep. John Dingell (D- Mich.).

Even before that hearing, Maplethorpe recalls being astonished at the way MIT reacted when O'Toole began raising questions after the paper was published in the journal Cell in April 1986. The university, Maplethorpe felt, was clearly trying to get rid of Imanishi-Kari -- as quickly and quietly as possible.

By late 1985, it had already become clear to everyone -- except Imanishi- Kari, her lawyer says -- that she would not get tenure at MIT, according to her lab colleagues; Gene Brown, dean of science; and Herman Eisen, now an emeritus professor.

Her critics believe this was because she had not published enough papers -- she lists 26 on her resume, not a large number for a mid-career scientist.

Eisen says MIT does not base tenure on the number of papers published, adding, "It was just the general level of interaction with people and the science she was doing. She was never brought up for tenure -- that decision was made and she concurred it would not be suitable."

With tenure ruled out and a flap brewing over the Cell paper, says Maplethorpe, MIT began to "cover up for her so as not to have any hitches in the process of getting rid of her. They were sending her over to Tufts and the most convenient thing for them was to keep it quiet while that was happening."

Even as questions mounted about Imanishi-Kari's research practices, ''Herman Eisen wrote her a recommendation that helped clinch the Tufts job," says Maplethorpe. "He had every reason to do that. Eisen never does anything on time, including review theses. But for some reason, he found the energy to move . . . on this recommendation right after Margot O'Toole came to him with the first indication of trouble."

Eisen, whose initial review of the Cell paper is now considered too lax by many scientists, tells a different story, as does Gene Brown. Imanishi-Kari was job shopping even before the controversial paper was published, Eisen says, because it was clear she would not get tenure. Imanishi-Kari says through her lawyer that she left MIT because she could not get graduate students interested in immunology.

Did he hustle her out? "She had several job offers, that's a fact," said Eisen. "How should I respond? That seems a crude way to look at it, and I don't believe it's true. I wrote a recommendation saying that she had a good track record in science and was an expert in a particular area of cell biology and that she was intensely committed and hardworking. I may have put in a couple of reservations -- that she may have had difficulties with personnel."

Brown agrees, "People at MIT were interested in her getting a reasonable job. We weren't trying to hustle her out because all this came out."

At Tufts, Imanishi-Kari began working with Henry Wortis, a professor of pathology and immunology and -- in one of the most ironic twists to this case -- with Margot O'Toole's husband, Peter Brodeur, as well. Wortis, who also conducted an investigation and who, like Eisen, found no serious problems, declined to comment for this article.

A Tufts spokeswoman also declined comment, citing policy on confidentiality for personnel matters.

The woman at the center of the mess was born 48 years ago in Brazil, one of five children of a Japanese farmer-couple in Indiatuba, a town in the bustling state of Sao Paulo.

Like her brothers and sisters, one of whom died of the auto-immune disease lupus, Thereza Imanishi grew up speaking Japanese and Portuguese. She has since learned German, Finnish, English, Spanish and French, all of which, she says through her lawyer, she speaks "badly." Like her sister, she has developed lupus, although not severely.

Her lawyer, Bruce Singal, says she developed an early interest in medicine which evolved into a passion for research. In 1967, she earned a bachelor of science degree from the University of Sao Paulo.

To this day, she remains well-connected in Brazilian circles, largely through an influential brother-in-law.

After her undergraduate years, according to a resume she submitted with a grant application to the National Institutes of Health, Imanishi-Kari says she received a master's degree in developmental biology at the University of Kyoto in 1970.

However, that university said in response to inquiries that it has no record of awarding a master's degree to Thereza Imanishi. Asked about this, her lawyer supplied a letter from the university saying that her two years' residence was "equivalent in quality" to a master's course.

In the early 1970s, she left Japan and moved to Helsinki.

On August 15, 1974, Thereza Imanishi, then 31, married Marrku Tapani Kari, a young Finnish architect.

The couple -- who have a 15 year- old daughter -- divorced in 1986. Efforts to reach Kari, who is licensed as an architect in Santa Monica, Calif., were unsuccessful.

In Finland, Imanishi-Kari's mentor, Ole Makela, confirmed by telephone that she received her doctorate in immunogenetics from the University of Helsinki in 1974. Together, according to her resume, Makela and Imanishi-Kari authored eight papers on antibodies, disease-fighting molecules made by immune cells.

Asked if Imanishi-Kari was a good scientist, Makela cut short the interview, saying, "I don't want to say more."

From Finland, she moved to Germany in 1975 to work as a post-doctoral fellow at the Institute for Genetics at the University of Cologne with professor Klaus Rejewsky, where she worked for about five years until her appointment ran out.

Rejewsky, reached by telephone, recalled her favorably as "an extremely engaged, motivated scientist." He still gives her "the benefit of the doubt."

"When I worked with Thereza," he said, "we discussed science and looked at data. Sure, I have faith in her. We produced two or three good papers." (Her resume lists 11 papers authored with Rejewsky.)

"I think the whole thing started from a tiny little problem, perhaps, and it just went on and on and has been blown up and now, it becomes something absolutely gigantic," he added.

Indeed, the controversy was small initially. In 1986, all O'Toole charged was that there was no data to support parts of the Cell paper and that other data, excluded from the paper, contradicted its central claim -- that a foreign antibody gene inserted into mouse embryos influences native antibodies in an unexpected way. This claim has not been confirmed by other published papers.

And if others had listened to Rejewsky, the dispute might have been nipped in the bud.

As is the practice in science, the Cell paper was reviewed before publication -- by Rejewsky, among others, but Rejewsky, citing confidentiality, declined to discuss his review.

Those who have seen the review, however, say Rejewsky raised serious questions about the paper prior to its publication. Some scientists speculate that because the paper carried Baltimore's prestigious name, it was published anyway -- a charge Cell editor Benjamin Lewis says is "absolutely not true." CORRECTION 1: Because of a reporting error, the story misspelled the name of the editor of the journal Cell. His name is Benjamin Lewin.

At this point in the controversy, it is anyone's guess how Imanishi-Kari will fare, but her friend, Joan Press, is worried.

"There's this McCarthyite stuff going on. Now if you're affiliated with Thereza or Baltimore, you're afraid you'll look bad, but I think David was right to support her and wrong to bail out."

Last modified: Wed Sep 20 20:40:08 EDT 2000