Civilization expects a lot from scientists, perhaps especially from those in the biological sciences. Some expectations are straightforward: Citizens in the mature democracies spend large amounts of tax money to support research. They expect to sponsor work that is free of intellectual dishonesty. But the expectations are less clear when it is realized that misconduct can come in many forms, not all of them as clear-cut as falsifying data, say. What constitutes scientific misconduct? What about unclear cases? Can and ought scientists police themselves? In a broader context, what are the legitimate rights and responsibilities of researchers in the natural sciences?

The Baltimore Affair

The following annotated chronology, of what has come to be known as “The Baltimore Affair,” provides a lattice on which to develop an analysis of key issues and controversies in scientific practice. The case is perhaps the most well known in the recent history of scientific misconduct. Some key issues: What is the difference between fraud and misconduct? What are the responsibilities of researchers and team leaders? Who should police scientific practice? What is the proper role of whistle blowers? The timeline was created by Ken Goodman for use in the University of Miami’s program for educating science students in the responsible conduct of research.

April 25, 1986
Publication of Weaver D, Reis MH, Albanese C, Costantini F, Baltimore D, Imanishi-Kari T. Altered repertoire of endogenous immunoglobulin gene expression in transgenic mice containing a rearranged mu heavy chain gene. Cell 1986;45:247.

Summer-Autumn 1986
M.I.T. postdoc Margot O’Toole, acknowledged in the paper “for critical reading of the manuscript,” challenges key findings after discovering 17 notebook pages of conflicting data. She informally reported her findings to an advisor at M.I.T. He and two colleagues find nothing amiss after an informal examination.

Thereza Imanishi-Kari, the main author, learns of O’Toole’s report and dismisses her from the laboratory. David Baltimore describes O’Toole as a “disgruntled postdoctoral fellow.’”  [1]

O’Toole says that in a meeting with Baltimore, Imanishi-Kari and others, she urged that a correction be published. She says Imanishi-Kari admitted the discrepancy between the 17 pages and the published report. She says Baltimore told her that “this kind of thing” (i.e., the discrepancy) was not unusual, and threatened to oppose her attempts to correct the paper. [2]

M.I.T. and Tufts University (where Imanishi-Kari was seeking a job) investigate the charges but find no evidence of misconduct.

1989
An NIH panel (which at first had members with ties to Baltimore) conducts a preliminary investigation and concludes on Jan. 31, 1989, that “no evidence of fraud, conscious misrepresentation, or manipulation of data was found.’’

U.S. Rep. John D. Dingell’s House Committee on Oversight and Investigations holds hearings and brings in the U.S. Secret Service to examine Imanishi-Kari’s lab books and radiation counter tapes. Dingell and the committee are strongly criticized by scientists. It is found that that dates were changed and faked in lab books and that some counter tapes —offered in response to other challenges—were counterfeit.

Baltimore testifies before the committee in May 1989, dismissing the Secret Service forensic evidence. He said the dispute is “part of a process of self-purification that goes on continuously”  in science. However, the committee, he said, “wishes to do away with the standard criteria and substitute a whole new standard for judging science. They have chosen a prosecutorial style. The message is that you do your science with an eye facing towards prosecution. If the hearing here today represents the Congressional view of how science should be done, then American science as we have known it is in trouble. Science will become an enterprise based on form, not substance . . .” [3]

Prompted in part by the Dingell committee, the NIH’s Office of Scientific Integrity begins a 23-month investigation.

April 30, 1990
Baltimore tells an ORI investigating team that if data were fabricated, the NIH was partly to blame in that Imanishi-Kari “was driven by the process of investigation into an unseemly act.”  He also said:

“ . . . [In] my mind you can make up anything that you want in your notebooks, but you can’t call it fraud if it wasn’t published . . .”

March 1991
The ORI concludes in a draft report that Imanishi-Kari committed “serious scientific misconduct” by “repeatedly present[ing] false and misleading information” to federal investigators. Neither Baltimore nor the other four authors are charged with misconduct, but Baltimore is strongly criticized for continuing to defend Imanishi-Kari “as the evidence mounted that serious problems existed with the serological data in the Cell paper . . .”  O’Toole is praised as a “hero.”  [4]

April 12, 1991
O’Toole, in a New York Times Op-Ed article, gives her perspective and notes that “A retraction can be done with dignity, takes only a few lines in a journal and need not have disastrous consequences. The authors could not explain away my evidence, but they would not issue a retraction.” [5]

May 17, 1991
The paper is retracted “because of questions raised about the validity of certain data in the paper (Cell 1991;65:536). The retraction notes that “Two authors (Thereza Imanishi-Kari and Moema H. Reis) do not believe that the questions raised have merit and are not parties to this retraction.”

May-June 1991
Baltimore apologizes: “I now recognize that I was too willing to accept Dr. Imanishi-Kari’s explanations and to excuse discrepancies as mere sloppiness. Further, I did too little to seek an independent verification of her data and her conclusions. I commend Dr. O’Toole for her courage and determination, and I regret and apologize to her for my failure to act vigorously enough in my investigation of her doubts . . . This entire episode has reminded me of the importance of humility in the face of scientific data.” [6]

Imanishi-Kari insists she is innocent: “I know it sounds tacky, but I am innocent. I really refute all of this stuff.” However, she also admits that some key work on mice—work necessary for the paper’s central point (cf. the paper’s Table 2)—was not performed. [7]

Sept. 5, 1991
Baltimore, in a letter to Nature, writes “I believe that my science—including the Weaver et al. paper—is done with rigor and criticality. But, because the issue is one of judging historical events, the only way to judge that statement is by the traditional test of science: have the data proved reliable? . . . I do know that I have tried to ferret out the truth and I feel that I did reasonably well because the science has stood up to the toughest test of all, the test of history.’’ [8]

Dec. 2, 1991
Baltimore says he will resign as president of Rockefeller University, a position he had held for 18 months.

July 13, 1992
A federal prosecutor in Maryland decides not to prosecute Imanishi-Kari for fraud, saying the evidence against her was persuasive but might be too complex for a jury. Baltimore responds by saying,

“This seems a powerful statement that there is no validity to the Secret Service analysis. I will write to Cell and tell them I consider the paper a valid contribution to the scientific discourse and there is no longer any reason to doubt it. I see no reason that the scientific community should consider this a retracted paper any more.”

Dingell says “The decision not to prosecute does not change the fact that the Cell paper was retracted because of serious, and extensive, irregularities.’’

August 1992
The ORI is continuing an investigation into the M.I.T. and Tufts investigations, and into the initial NIH probe.

May 1993
Researchers at Stanford and Columbia universities say they have confirmed the results of the initial Cell paper.

June 1993
Science reports that “many of the glass plates used in the forensic analysis of data by the Secret Service were smashed, apparently accidentally, in shipping. Federal investigators believe that enough plates have survived for them to continue with the case, but the episode has raised concerns about the way this material was handled . . .  The plates are the record of the thin layer chromatography analysis that the Secret Service conducted on data tapes from Imanishi-Kari’s notebooks . . .”  [9]

December 1994
The ORI issues a final report, concluding that Imanishi-Kari fabricated data in the Cell paper and later tried to cover up those fabrications with additional deceptions. The U.S. Department of Health and Human Services says it intends to bar her from receiving federal funds for a decade. The findings are widely interpreted to constitute a vindication of O’Toole.

Imanishi-Kari tells Science that “I didn’t falsify my results, nor [did] anybody in my laboratory.” She files an appeal of the ORI ruling.  The case now goes to an HHS appeals panel.

June 21, 1996
The HHS appeals panel finds that ORI did not prove misconduct by Imanishi-Kari. The panel voids the proposed 10-year funding sanction. The ruling is widely interpreted to be a vindication of Imanishi-Kari and Baltimore. Following are passages from the appeal panel’s ruling, as quoted in Science: [10]

The Cell paper as a whole is rife with errors of all sorts ... [including] some which, despite all these years and layers of review, have never previously been pointed out or corrected. Responsibility ... must be shared by all participants [including Baltimore].

The credibility of [Imanishi-Kari’s] testimony before us was bolstered ... when much of the evidence in the record, and in particular some of the document examination evidence, corroborated her statements and directly contradicted representations made by ORI.

It is also important to consider ... whether Dr.  Imanishi-Kari had any conceivable motive for the allegedly false dating of the questioned pages. While some of the pages involved contained relevant data ... ORI offered no possible reason to fabricate other pages for which the same findings were presented.
We are concerned about the implications of involving a whistleblower too heavily in an investigation. Such involvement can compromise both the ability of the investigators to maintain objectivity and the ability of the whistleblower to avoid becoming too vested in the outcome. We think that happened here.

Comments criticizing the panel’s findings, taken from the Science report:

“It’s a goddamn sad day for science.” – Peter Stockton, a former Dingell staff investigator

The panel decision “is a stunning repudiation of the truth … In the long run, the truth will prevail.” – Suzanne Hadley, another former Dingell staff investigator

“Given that this board tossed out the evidence, it is not surprising that they cannot believe that what I say happened, happened.” – Margot O’Toole

And Dr. Bernadine Healy, former director of the NIH, wrote in an Op-Ed column:  “About half a century ago, Supreme Court Justice Robert Jackson wrote that ‘the most odious of all oppressions are those which mask as justice.’ This sentiment must resonate with the scientists who faced destruction. We must see that this sad story is never repeated.’’ [11]

Aug. 1, 1996
Tufts University reinstates Dr. Imanishi-Kari as an assistant professor of pathology.  “I think it was the only thing they could do,”  she said.

———————————————————
[1] Hilts PJ.  Hero in exposing science hoax paid dearly. The New York Times, March 22, 1991, national edition, pp. A1, A11.
[2] Hamilton DP. Baltimore throws in the towel. Science 1991;252:768.
[3] Hilts PJ. How charges of lab fraud grew into a cause célèbre. The New York Times, March 26, 1991, national edition, pp. B5, B6.
[4] Hamilton DP. NIH finds fraud in Cell paper. Science 1991;251:1552.
[5] O’Toole M. The whistle-blower and the train wreck. The New York Times, April 12, 1991, national edition, p. A11.
[6] Hilts PJ. Baltimore apologizes for data’s defense.  The New York Times, May 4, 1991, national edition, pp. 1, 7.
[7] Hilts PJ. “I am innocent,”  embattled biologist says. The New York Times, June 4, 1991, national edition, pp. B5, B8.
[8] Baltimore D. Open letter to Paul Doty. Nature1991;353:9.
[9] Anderson C. Secret Service analysis goes to pieces. Science 1993;260:1715.
[10] Kaiser J, Marshall E.  Imanishi-Kari ruling slams ORI. Science 1996;272:1864-5.
[11] Healy B. The dangers of trial by Dingell.  The New York Times, June 3, 1996, national edition, p. A11.