U.S. Study Clears Noted Scientist of Alleged Research Misconduct

The National Institutes of Health has cleared Nobel Laureate David Baltimore and his co-workers of scientific misconduct charges, but sharply criticized them for failing to take “appropriate action” to adequately correct errors in their work, according to government documents made public Wednesday.

The long-awaited decision said that Baltimore, one of America’s most widely respected scientists, and his colleagues did not commit “fraud, misconduct, manipulation of data, or serious conceptual errors” in an important 1986 scientific paper published in the prestigious journal Cell.

But Dr. James B. Wyngaarden, the NIH director, concluded that the authors of the research study failed for more than two years to “consider seriously the allegations” and that they still have not adequately corrected “several inaccuracies” that were found in their work.

In addition, Wyngaarden said that an acknowledgement of “three instances of misstatement” published as a letter to the editor in Cell in November did “not deal with all the issues which require attention.”

The NIH director instructed the paper’s authors to prepare a more extensive letter of correction that “should be sent to me prior to your sending it to the journal, so that we may review it for completeness and accuracy.”

“I feel vindicated,” Baltimore, the director of the Whitehead Institute for Biomedical Research in Cambridge, Mass., said in a prepared statement. The NIH review has “put to rest accusations of improper conduct and error” and supports “my original judgment that this research work would be a significant contribution.”

But in a telephone interview, the Nobel Laureate declined to say whether he would comply with Wyngaarden’s directive to prepare a more complete letter of correction. “This is a matter of scientific judgment,” Baltimore said. “If we can be convinced (that further corrections are necessary), we would be happy to respond appropriately.”

The NIH decision also appears to represent at least a partial vindication for Margot O’Toole, a former Massachusetts Institute of Technology postdoctoral fellow, who claimed that her scientific career was severely damaged by criticism from superiors after she raised private questions about the research more than two years ago.

The NIH report calls on research institutions to provide “an environment in which scientists, especially junior ones, have the freedom to air their concerns without feeling that they may be branded as troublemakers.”

Since it was first publicized last April, the “Baltimore affair” has emerged as a key test of the NIH’s ability to detect and deter irregularities in biomedical research. The federal agency, which supports the work of about 50,000 scientists and has an annual budget of more than $6 billion, has been under criticism for lagging in efforts to ferret out scientific misconduct.

The highly publicized case involves complex, NIH-funded immunology research. Baltimore’s lab and an MIT lab headed by Thereza Imanishi-Kari conducted a series of experiments in genetically engineered mice, seeking to gain new insights into how specific genes regulate immune system function.

The results of the experiments were published in the April 25, 1986, issue of Cell in a paper authored by Baltimore, Imanishi-Kari and four other scientists, most of whom were or are now affiliated with either MIT or the Tufts University School of Medicine.

Subsequently, O’Toole, who was conducting related research in Imanishi-Kari’s laboratory, raised questions about the study. She brought her concerns to the attention of MIT officials as well as Walter W. Stewart and Ned Feder, two NIH researchers with reputations as gadfly scientific whistle-blowers. The two began to investigate the matter on their own; in a detailed letter mailed to numerous other scientists in April, 1987, they accused Baltimore and his colleagues of publishing “grossly misleading” data.

Although NIH officials had been aware of the allegations since October, 1986, their inquiry did not begin in earnest until April, 1988, after the matter was aired at two congressional hearings.

The NIH review was conducted by a three-member panel of independent scientific experts, as well as senior institute staff. The review centered on whether two statistical tables in the paper accurately reflected the experiments that had been performed and whether the limitations of some of the methods used in the research were adequately explained. For example, the expert panel found that, based on an intensive review of raw data, two experiments reported in the tables had apparently not been performed.

But the review panel tempered such criticisms with praise for the “amount of work done in support of the studies” and “the completeness of the records” that were kept.

In a Jan. 31 letter to Baltimore and his co-authors, Wyngaarden said the review identified “inaccuracies” in the two tables and raised “serious questions” about the reliability of some of the biochemicals used in the experiments.

In addition, Wyngaarden said that if the paper’s authors had taken “appropriate” and timely action to correct their errors, a full investigation of the contentious dispute might have been “unnecessary.”

“It is unfortunate that despite the growing challenge to the validity of their research, the co-authors apparently did not undertake a comprehensive review of their data until they met with the NIH scientific panel,” the federal report stated.

The NIH’s Stewart, who was instrumental in publicizing the charges against Baltimore, declined to comment on the report. But a spokesman for a U.S. House subcommittee, which has retained Stewart as a consultant, said “we are not finished with (the matter).”

“The report is adequate as far as it goes . . . (but) frankly we are puzzled,” the spokesman for the House subcommittee of the Energy and Commerce Committee said. “The NIH panel concludes that certain published experiments were never done, that other published data contained factual misstatements and inaccuracies and that the previous correction two years after the fact was inadequate. But the panel states that they found no evidence of misrepresentation of data.”