Whistle-Blowers’ Tactics Against Nobel Laureate Raising Questions

Two federal researchers, with budding reputations as gadfly whistle-blowers, are conducting a campaign accusing Nobel Laureate David Baltimore, one of America’s most widely respected scientists, of publishing “grossly misleading” scientific data.

Baltimore categorically denies the allegations, which come at a time of unprecedented concern over reports of irregularities in biomedical research. He calls the methods of his accusers “totally improper.”

But more than a tale of scientific intrigue, the dispute is also raising ethical questions about when a zealous effort to ferret out an alleged error becomes potentially more damaging than the alleged misconduct itself, according to authorities on scientific misconduct familiar with the case.

The dispute, which is likely to be aired at two congressional hearings next week, centers on highly technical immunology research. The questioned article by Baltimore, a professor at the Massachusetts Institute of Technology, and five co-authors was published in the prestigious journal Cell on April 25, 1986.

Complex Discussion

The paper is an extremely complex discussion of how normal mice and mice into whose genes a new immune system gene has been inserted differ in their production of infection-fighting molecules called antibodies. “Some of the evidence was quite surprising, so it was published in an eminent journal,” Baltimore said.

His accusers--Walter W. Stewart and Ned Feder, nerve cell researchers at the National Institutes of Health--say some of the data in the paper are contradicted by the original laboratory notebooks.

The research involved a collaboration between Baltimore’s laboratory and another MIT lab headed by Thereza Imanishi-Kari. Imanishi-Kari, who currently works at Tufts-New England Medical Center, did not return several telephone calls.

Feder and Stewart became involved soon after the publication. They claim to have learned about “possible problems” with the paper from an “uninvolved party,” according to documents obtained by The Times on Friday from the NIH under the federal Freedom of Information Act.

Raw Research Data

Subsequently, a MIT postdoctoral fellow conducting related research in Imanishi-Kari’s laboratory furnished them with copies of 17 pages of raw research data, according to a detailed letter Feder and Stewart mailed to numerous other scientists in April, 1987.

The two said they compared this data with the published results and found that “some of the original data were presented in a grossly misleading and inaccurate way.” As a result, they concluded that the paper was “seriously defective.”

They wrote: “Because this paper is being relied upon by dozens of scientists everyday, we feel we may have a professional obligation to speak out.”

But Baltimore said: “This was a totally improper procedure. It was not data that (the postdoctoral student) had accumulated, but data from other people’s laboratory notebooks. . . . If you take selected pages from a lab notebook, you can prove anything.”

Arbitration Suggested

Last Spring, Baltimore suggested to his accusers that the dispute be arbitrated by a group of independent immunologists assembled by the NIH. But Stewart and Feder refused, in part because they balked at his request that they agree to apologize if the review upheld the article, according to a letter Stewart sent Baltimore.

Subsequently, the two submitted their own article entitled “Original Data Contradict Published Claims: Analysis of a Recent Paper” to Cell, which rejected it last fall.

The wide circulation of this unpublished manuscript among other researchers has drawn sharp criticism from Baltimore as well as prominent scientists who have been drawn into the dispute.

“I think (what they are doing) is a very ambiguous process at best,” said Patricia K. Woolf, a sociologist affiliated with Princeton University. “In the name of peer review and solicitly responsible opinion, they may be disseminating incendiary comments which can damage the reputations of responsible scientists.”

‘No Good Evidence’

Another widely respected researcher, who was sent an unsolicited copy of their unpublished manuscript, took Stewart and Feder to task for “papering the world with this” when “they had no good evidence that there had been misconduct.”

Stewart and Feder declined to be interviewed, citing the “incredibly complicated” situation and the fact that they were “working” with other reporters.

In a telephone interview, Baltimore said, “There is an exact correspondence between the original data and what is in the paper.”

He added: “It doesn’t strike me as appropriate for two scientists who have no background in immunology to set themselves up as judge and jury over whatever paper comes to their attention. . . . They may themselves be perfectly well-meaning people, but their activities are already having an inhibitory effect on scientific communication.”

Baltimore said MIT and Tufts officials have reviewed the allegations and found them groundless.

NIH Investigation

In addition, he said he helped initiate an ongoing confidential investigation by the NIH’s office of extramural research and is cooperating “fully.” This is the normal procedure when allegations are made about any federally funded biomedical research, such as the MIT study.

The results of that inquiry will not be made public until the review is complete, a process that can take months to years. (While Feder and Stewart work at NIH, they have no connection to the official probe.)

Feder and Stewart have used similar tactics in the past. In a highly publicized case, they took to task the co-authors of an ambitious Harvard University heart researcher who fabricated data that formed the basis for more than 100 journal articles. A key difference is that these allegations were based on a review of published articles, not raw laboratory data.

Their controversial 1983 paper on that case finally appeared in the British journal Nature in January, 1986, after prolonged negotiations.

Feder and Stewart are scheduled to testify on scientific misconduct Monday before a House subcommittee of the Government Operations Committee and on Tuesday at a similar hearing being held by a House subcommittee of the Energy and Commerce Committee. Neither subcommittee has scheduled testimony from either Baltimore or any of his co-authors, subcommittee staffers said Thursday.

Baltimore, 50, the director of the Whitehead Institute for Biomedical Research in Cambridge, Mass., won the Nobel Prize in 1975 for research on the biology of retroviruses, a class of viruses that includes the AIDS virus. He served as co-chairman of the Institute of Medicine’s 1986 Committee on a National Strategy for AIDS and addressed a special 1987 session of the California Legislature on the AIDS epidemic.