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Science, Fraud & the Baltimore Case

Early in 1985 I was invited to attend a symposium for journalists who write about science. Its purpose was to acquaint us with the then newly-identified virus that causes AIDS. Present were Robert Gallo from the National Cancer Institute and Luc Montaigner from the Pasteur Institute in Paris. Each of them had made independent identification of a virus that the French called LAV and the Americans called HTLV-III, and very soon their two laboratories had become engaged in a nasty patent dispute. In this connection, Gallo was also made the subject of an investigation for possible misconduct or even fraud by the National Institutes of Health, an investigation that had been demanded by Congressman John Dingell (D-MI). It took years before he was fully exonerated of, in effect, having stolen the work of the French scientists.

Also attending this symposium was David Baltimore. As far as I know, Baltimore was not then working actively on AIDS, but in 1970 he and another biologist, Howard Temin, had independently made an extremely significant discovery in cell biology for which the two men, along with Renato Dulbecco, would win the 1975 Nobel Prize for medicine. What they discovered was the existence of “retroviruses”—viruses in which the ordinary flow of genetic information from the double-stranded DNA to the single-stranded RNA is reversed. Indeed, the virus that causes AIDS is such a retrovirus.

Not being a biologist—not even having taken a course in biology—I had not gone to the symposium with the intention of writing anything, but simply out of an interest in a new and terrible disease. As the symposium proceeded, several questions occurred to me, but uncharacteristically I felt too shy to ask them. Afterward I decided to take a chance and write to Baltimore, who was then at MIT. Why, I wondered, had the AIDS virus suddenly erupted; had it been there all along, or were we now about to be flooded by a plague of brand-new viruses? And, I wondered, why a retrovirus? Why should this particular virus have chosen so eccentric a path?

Baltimore took the trouble to reply in a two-page letter that was so interesting I saved it. To my first question he responded:

My understanding of biology would lead me to believe that the AIDS retrovirus has been in circulation somewhere for eons. In all probability there was a low level person-to-person transmission in Africa; there the virus might have caused a little bit of disease but, like most viruses, it was probably largely innocuous. In the very particular circumstances of adult transmission via bodily fluids, the virus has taken on a terrifying aspect that may never have been evident before.

My second question—why this particular virus?—marked me as a physicist. In the community of physicists, there is a feeling of insult if something seems to exist with no purpose. But biology is quite different. If I asked a biologist why there are giraffes, I suspect he would respond along the lines of what John von Neumann said to me when, as a student, I asked if the computer would ever replace the human mathematician: “Sonny, don’t worry about it.” Baltimore was much kinder:

The particularities of a retrovirus make it a very good candidate for a cancer-inducing virus, but it does not seem especially well adapted to cause a disease like AIDS. Given a few paragraphs, I could justify why the virus might be able to have evolved this ability. But the short-form answer has to be that many viruses could have become the AIDS virus, in principle.

In other words, it just got there first.

What I did not know was at the very time Baltimore wrote this letter, he was participating in a laboratory experiment that would make him, too, the target of a congressional investigation and that would nearly destroy his career. Indeed, my next and only other contact with him was in the middle of that horrific episode. At the time—the fall of 1992—I was an adjunct professor at Rockefeller University. Baltimore had become president of Rockefeller two years earlier, but by the time of our meeting he had been forced to resign from that position and, although still staying on as a professor, was planning to return to MIT. He had asked me to drop by to discuss an article I had published about the efforts of the Nazis to make a nuclear weapon.

I recall having a very odd set of mixed feelings. I knew that Baltimore had made a lot of enemies among the senior faculty at Rockefeller, and also that he now stood accused of abetting a scientific fraud. The former was not very important to me. Academic politics is, I think, best characterized by the inverse of Lord Acton’s maxim: absolute lack of power corrupts absolutely. But the fraud: was it true? It seemed unlikely, but how could one know?

Our conversation never touched on the subject. But now, to all intents and purposes, we have the answer to the question. Thanks to a new book by Daniel J. Kevles, The Baltimore Case,1 the matter can be put to rest. There was no fraud.

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In discussing Kevles’s book I should make it clear that I did not follow the science in detail. As I have already said, I am not a biologist, and a sentence like, “Thus the hypridomas in the vast majority of wells—119 plus 11, making a total of 130 in all—produced antibodies to NP with idiotypic birthmarks similar to the transgenes, but these antibodies had been generated by genes native to the normal Black/6 mice,” of which there are hundreds, is more than I am prepared to try to parse. Nor, from what I read, can I say why the experiments being discussed were important, or what their consequences were. Yet I still have confidence in Kevles’s conclusion. A well-known historian of science, he has interviewed everyone involved and has read all the transcripts of the hearings that took place over a period of some ten years as well as the vast peripheral literature that developed. Until anyone who still thinks Baltimore and his collaborators were guilty produces a book with comparable documentation, this one appears to me to be definitive.

What, then, was the Baltimore case?

After his work on the retrovirus, David Baltimore turned his attention to the general problem of how the immune system works. At this time, recombinant DNA—snippets of DNA that could be spliced into the natural DNA of a host—was being used for the first time in experimental cell biology. Baltimore learned that a Brazilian-born scientist named Thereza Imanishi-Kari, then working as a postdoctoral researcher in a laboratory in Germany, had discovered a way of tracking certain immune genes in mice.

In 1982, Baltimore had the idea of using Imanishi-Kari’s methods to see how specific antibodies operated when genetically engineered cells were introduced. Two of his own postdoctoral fellows—David Weaver and Rudolf Grosschedl—were working with him on this problem, but none of the three had the necessary experience in serology (the study of blood) to ascertain exactly which antibodies were circulating in the mice. So he invited Imanishi-Kari, by now an assistant professor at MIT, to join the group—or rather he persuaded her, since she was at a stage of her career where she wanted independent recognition.

Grosschedl soon left for another job, leaving Weaver as intermediary between Baltimore’s laboratory and Imanishi-Kari’s. Although the three scientists met regularly, it is unclear what hands-on work Baltimore did himself; this, indeed, may have been the source of problems later on. Then, too, although Imanishi-Kari spoke some seven languages, including Japanese, her English was apparently very difficult to follow—another problem in the collaboration and, once the investigations began, a disaster.

The results of the experiments, which required incredible care to conduct, were very surprising: the mice did not produce antibodies as anticipated. Why this should have been so, and why it matters to our understanding of the immune system, is a subject on which Kevles is not very helpful. But the work certainly merited publication, and it was duly written up and published in the April 25, 1986 issue of the journal Cell, with Baltimore’s name listed last among the authors. Usually this implies a certain detachment.

Enter Margot O’Toole, then a promising young biologist who in the spring of 1985 had met Imanishi-Kari at a party. Unfortunately, in addition to her talents, O’Toole had a history of time-consuming political activism and an apparent inability to follow a scientific project through to the end. Nonetheless, Imanishi-Kari, using grant money from the National Institutes of Health, hired her for one year as a post-doc on the understanding that at the end of that term she would have to generate her own support.

The two women clashed almost immediately, and things only went from bad to worse. A breaking point came when O’Toole tried to confirm Imanishi-Kari’s experiments in order to extend them; she was unable to get the experiments to work, and from this she drew the conclusion that Imanishi-Kari’s data must be wrong. Then, in May 1986, she came across seventeen pages of data in the notebook of one of Imanishi-Kari’s co-workers; to her, at least, the data appeared to contradict what had been published in Cell. Without asking permission, O’Toole xeroxed these pages and kept them. Her reason for this treacherous act was that she was now fully engaged in a higher task: exposing the supposedly flawed science in the Cell paper. Since this work had been supported in part by a federal agency, any or all of it was, she reasoned, public (i.e., her) property.

Imanishi-Kari was planning to move to Tufts, and so O’Toole decided to take her grievances to Henry Wortis, an associate professor at the Tufts Medical School who happened to have been her thesis supervisor. This resulted in a meeting on May 23 at MIT with both O’Toole and Imanishi-Kari present. Everyone agreed there were some errors in the Cell paper, and everyone thought they were minor—everyone, that is, but O’Toole, who insisted that the paper be retracted.

Next, O’Toole took her case to the dean of science at MIT, a biochemist named Gene Brown, who asked if she was charging fraud. When O’Toole replied no, only that a mistake had been made in Imanishi-Kari’s interpretation of the data, Brown suggested bringing in Herman Eisen, a senior MIT immunologist, to help sort out the issues. O’Toole drove to Cape Cod to meet Eisen, who found it difficult to understand exactly what her problem was. She wrote a memorandum laying out her complaints, again omitting any mention of fraud.

At this point Baltimore was brought in. He acknowledged that one of the tables in the paper was mislabeled—he had misunderstood something Imanishi-Kari had told him over the phone—but as this, too, was minor he did not think Cell would even bother to publish an erratum. It seemed clear that the only way the matter could be settled to everyone’s satisfaction was if an independent experiment were conducted—but once again O’Toole demurred. And she demurred yet once more when Baltimore suggested that she write a letter to Cell, outlining her own interpretation of the data. That, she felt, would be pointless: Baltimore could write an opposing letter, and he would be believed because of his reputation. As far as I can tell from Kevles’s account, at no time during any of these proceedings did Baltimore or anybody else utter a derogatory word about O’Toole’s scientific ability.

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Up to now, the dispute had remained within the local academic community; but it was about to escalate. O’Toole contacted an ex-graduate student of Imanishi-Kari named Charles Maplethorpe. Teacher and student had gotten on so badly that Imanishi-Kari ultimately refused to write letters of recommendation for Maplethorpe, thus making it very difficult for him to find a job. O’Toole turned over to Maplethorpe the seventeen pages of data she had purloined from Imanishi-Kari’s laboratory, and he then contacted Ned Feder and Walter W. Stewart of the National Institutes of Health.

These two men had just embarked on what would become their primary mission at NIH: the investigation of scientific fraud. After studying the seventeen pages, they decided that the data were indeed fudged and that Baltimore had been a party to the deed. Stewart and Feder now wrote to all the authors of the Cell paper threatening an internal audit of the data. Outraged, Baltimore entered into at least one very angry exchange with Stewart in which he threatened to sue. Then, late in the winter of 1988, Stewart and Feder opened discussions with two men who functioned as investigators for John Dingell, then the chairman of the House Energy and Commerce Committee, with jurisdiction over the NIH.

Dingell was on a crusade against scientific fraud, and here apparently was a case involving a Nobel Prize winner! What could be better? Traveling to Boston to interview O’Toole, Dingell’s two investigators found her and her family living with her mother; O’Toole herself was working for her brother at the Gentle Giant Moving Company—a consequence, she claimed, of her “whistle-blowing.” By now the press had picked up the story and was clearly on O’Toole’s side.

The NIH was now obliged to launch a formal investigation. One result was that the authors of the Cell paper wrote a letter to the journal outlining the various mistakes in the printed version but stating their strong belief that none of them invalidated its central results. In its own report, the NIH failed to stipulate fraud but proposed that the authors write an additional statement attesting to the paper’s problems. Once again, this did not satisfy O’Toole—and to make matters worse, the NIH report, which was supposed to be confidential, was leaked to the press.

In the meantime, Dingell’s committee had subpoenaed all documents in Imanishi-Kari’s possession that were related to the Cell paper. Some of them were even turned over to the Secret Service to check for the possible doctoring of dates—evidence of which the Secret Service duly announced it had uncovered. This information led to an open hearing in May 1989 at which the authors of the Cell paper were the star witnesses.

Although Baltimore had been warned not to attempt to “one-up” a member of Congress, he was unable to contain his distaste for the committee and in particular for Dingell, who was described when it was over as “very red in the face . . . clearly angry.” By contrast, O’Toole, who testified at the following session, got a cordial reception. After all, her charges were now firmly established in the public domain and widely reported in the press, as were the sufferings she was enduring as a truth-teller.

In January 1990, Imanishi-Kari was put on the NIH’s “Alert” list of people suspected of fraud or found guilty of misconduct; in April, one of her grants was canceled. The following year she was notified by the NIH that, according to its latest review, she was guilty as charged. This would have meant the end of her career, but there was still an appeals process and she began to explore it.

At this point one of the very few heroes of the story emerged: Bernadine Healy, director of the NIH from 1991 to 1993. Basically, Imanishi-Kari had been deprived of her legal rights to due process. Since she was not allowed access to her own lab reports once they were confiscated, she could not prepare a defense against the charge that dates had been altered. Bernadine Healy put a stop to this. Once given access to her material, Imanishi-Kari and her lawyers and their experts were eventually able to punch very large holes in the reports submitted by the Secret Service laboratory.

Healy also began a reorganization of the NIH office charged with the investigations, and another review was initiated. In October 1994, the NIH produced its final report, again stating that Imanishi-Kari was guilty as charged. One more appeal was possible. It took two years and hundreds of hours, but finally, on June 21, 1996, the appeals board issued a ringing verdict of innocence for Imanishi-Kari and a resounding condemnation of the previous findings of the NIH. A ten-year ordeal was over.

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As a practical matter, Imanishi-Kari was now awarded tenure at Tufts, where her position had been held in abeyance until she could clear herself, and her NIH grant was restored. As for Baltimore, who had never abandoned her even at terrible cost to himself, he became the president of the California Institute of Technology in 1997. In that limited sense, this dreadful story has a happy ending.

But there are some less happy lessons to be drawn from it. Science, when it is healthy, proceeds by constantly correcting and renewing itself. There is a marketplace of ideas, and if it is left alone, only the good ones survive—maybe not instantaneously, but certainly over the long and usually over the medium term. Moreover, outright forgery in science is quite rare.

Let me give an example of how the system works. On March 29, 1989, Stanley Pons and Martin Fleischmann, two electrochemists from the University of Utah, held a press conference to announce that they had succeeded in producing nuclear fusion in a simple chemical set-up that operated at something like room temperature: cold fusion, as it came to be called. This was an absolutely sensational discovery. Nuclear processes are about a million times more energetic than chemical ones. If what Pons and Fleischmann were claiming really worked, you would be able to produce electricity that was literally too cheap to meter.

But the very simplicity of Pons and Fleischmann’s set-up made it relatively easy to try to duplicate. You did not need machines costing hundreds of millions of dollars and attempting to reproduce the conditions in the center of the sun (where fusion is the energy source). You could do it, in a manner of speaking, on a tabletop. By the end of April 1990, several groups announced that they had been unable to reproduce Pons and Fleischmann’s data, even when using instrumentation more sensitive than theirs. Indeed, those data did not themselves appear to be internally consistent. As far as most observers were concerned, the idea was dead.

I do not know if Pons and Fleischmann had any conscious intention to deceive—which would have been fraud—or, as seems overwhelmingly likely, they simply made a mistake from which they would not back down. Certainly their behavior was strange: Pons’s lawyer went so far as to threaten to sue to prevent publication in the journal Nature of the results of an experiment claiming to refute theirs. But their behavior is not the point. There may still be some true believers in cold fusion, and hundreds of millions of dollars have been spent trying to revive the idea, but it took only about a month to cast sufficient doubt on the original experiment so that there was basically no farther interest in the subject.

That is why I think forgery in science is so rare (as opposed to honest mistakes, which are its heart’s blood). If one’s motivation is to make oneself celebrated—to become rich and famous—one has to produce experimental results that will be noticed. But these are just the results that can be most readily checked by others. Such a forger sows the seeds of his own rapid exposure.

As for forgery at a lower level, why bother? As far as one’s reputation and one’s career are concerned, it just does not pay. What had Imanishi-Kari and/or Baltimore to gain by promulgating false data? Since the results of the experiment seemed anomalous, it was bound to be repeated. The NIH, moreover, was the funding agency for much of the biological research done at MIT, including Imanishi-Kari’s. If fraud were established, such funding would almost certainly be withdrawn, with devastating consequences for all concerned.

So what went wrong in the Baltimore case? One thing that puzzled me in Kevles’s account is why the dispute was allowed to rise so high up the MIT administrative hierarchy. Surely the dean of science does not step in every time two groups of MIT researchers have a scientific disagreement. Why did he bother to get mixed up in this one? I can only speculate, but it seems highly plausible that beneath the excessive regard paid by all sorts of busy people to a minor spat over an inconsequential experiment lay that contemporary nemesis of academic life, political correctness.

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It would be nice to think that the hard sciences are immune to the influence of this doctrine, and that judgments on scientific questions are always driven by considerations of merit alone and never by any concerns based on “feelings,” much less on mere personal attributes like race or, in this case, sex. It would be nice to think that—but naive. The fact is that Margot O’Toole was able to get away with repeatedly rejecting a perfectly sensible and scientifically unimpeachable suggestion: that the experiment in dispute be conducted again by an independent researcher. Instead of being told that, in that case, the matter was finished and done, her complaints were accommodated—fatally.

Nor is the scientific community devoid of its fair quotient of fools and knaves, examples of whom, I am sorry to report, turned up in representative numbers in the Baltimore case. Here I do not have in mind the central characters so much as a few of Baltimore’s colleagues—including some very distinguished ones—who went after him with hammer and tongs when he was down. Some apparently felt that, in his confrontation with Dingell, Baltimore had jeopardized the government support of research—their research. For others, the matter seemed personal: Baltimore, who in the view of some had gotten too far too fast, was finally getting his. (It seems that Baltimore did have a reputation for arrogance, though as I have indicated, that was hardly the impression he made on me.)

Among those who took off after Baltimore in this way was James Watson, the man who with Francis Crick had first illuminated the character of DNA in one of the greatest scientific discoveries of this century. Ever since I read Watson’s 1969 book The Double Helix, I have thought him a scientific genius and a silly person. Watson decided that Baltimore not only was guilty of abetting fraud but had stolen his work on retroviruses from Howard Temin, and that therefore his Nobel Prize should be annulled. (Temin repudiated this idea in no uncertain terms.)

Joining the fray with Watson were the distinguished Harvard biologists Walter Gilbert—also a Nobel-Prize winner—and Mark Ptashne, both of whom had been friends of Baltimore and his wife. After the vindication, Ptashne had conciliatory things to say, but Gilbert apparently still believes Imanishi-Kari committed fraud and that Baltimore was wrong to challenge Dingell the way he did.

What I am saying is that, in science no less than in other professional endeavors, human error and human subjectivity abound. Unlike in many other professional endeavors, they are compensated for by the community’s intense scrutiny of itself: the most searching reviews of one’s work are the reviews one will receive from one’s peers. This is, indeed, the great glory of science. What the Baltimore case shows is just how precious a glory it is, and also how fragile—which makes it all the more crucial that it be guarded with zeal from the forces that in so many other callings have undone so many.

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Footnotes

1 Norton, 448 pp., $29.95.

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