Science is generally regarded as a ‘holy cow’. Although many do not understand the details of a sophisticated scientific theory, they nonetheless believe in it implicitly almost with religious sanctity; if it’s okay with the scientists, it’s okay with them. There is no other recourse for ordinary people because science has become so very complex. But occasionally, once in a long while, a case of fraud or forgery in some scientific work makes it to the prime time evening news to engage the listeners’ attention. Such frauds or forgeries do not have any long-term ill effects on the progress of science because they are invariably detected in due time by other scientists who encounter anomalies in the data which they collect to replicate the previous work hoping to extend it further. Such frauds are committed by selfish, self-seeking, and overly ambitious scientists who want to make their name in the field, which is extremely competitive. Sometimes, the motive is money and greed also. Much of the ongoing scientific research is funded from the government sources (National Science Foundation, for example, in the U.S) and there is veritably hard and cutthroat competition for the grant funding. Those who have published some quality work in the past and have a constantly advancing track record of publications stand better chance in getting their proposals accepted by the funding agencies. “Publish or perish” is not a meaningless aphorism in the science arena; it is the hard reality of a scientific career

Fraud and forgery is rare in the science world but it’s there. One of the notable hoaxes of the twentieth century was in the field of paleoanthropology. It was dubbed the Piltdown man hoax. Charles Dawson, an amateur fossil hunter, claimed to find two old fossils of a
jawbone and a skull in the Piltdown quarry in Sussex, England, in 1912. These fossils were suggested to belong to the primitive hominids. Some of the most eminent British natural scientists espoused this ‘find’, which lent immediate credible authenticity to it. However, there were some doubters also. The doubters claimed that the jawbone and the skull were obviously from two different animals. The skeptical voices became more and more intense until the Piltdown man was revealed to be a hoax in 1953. The July 10, 1954 issue of Nature asserted, “It is agreed that the skull fragments are human and not of great antiquity; that the jawbone is ape; that they have no important evolutionary significance.”

The case that I want to describe here in some detail is the one in which a Nobel Laureate biologist was implicated around 1986. Dr. David Baltimore (1938- ) won Nobel Prize in 1975, at the age of 37, for discovering reverse transcriptase, which transcribes RNA into DNA. Until then, it was believed that DNA led to RNA, which in turn led solely to proteins. “Reverse transcriptase is an important factor in the reproduction of retroviruses such as HIV,” (http://en.wikipedia.org/wiki/David_Baltimore).

While at MIT, Dr. Baltimore collaborated with another MIT scientist, Dr. Thereza Imanishi Kari (IK). Their work pertained to immunology and antibodies. Dr. Baltimore turned his attention to studying the immune system after winning his Nobel Prize.

The white blood cells called lymphocytes in mammals are the main component of the immune system. They are in the body’s specialized immune organs such as the thymus, bone marrow, spleen, and lymph nodes and they are in circulation in the blood stream. According to wikipedia, “Two types of lymphocytes are central to the immune response in mammals: T cells, which are manufactured in the thymus, and B cells, which are generated in the bone marrow. Both eventually migrate to the lymph nodes and spleen, reacting there with invading agents such as virus or a bacterium. T cells perform several functions, one of which is to assist B cells in doing their job. B cells produce antibodies, which latch to and inactivate what the body takes to be hostile invaders.” In the life of an animal, antibodies are continuously produced with numerous incipient B cells, which together account for the diversity of his immune response. If somehow the process of antibody production is enhanced and facilitated in the mammal’s body, the immune response can become stronger. This was the idea that motivated Dr. Baltimore to undertake his research program to find out how to do it. At that time, it was quite a puzzle as to “how exactly the process of genetic rearrangement is simulated and controlled.”

One of the most powerful techniques for this purpose was recombinant DNA, which allowed the “scientists to snip out a gene from one organism and insert it to another – to put a human gene into a mouse, for example”. The immunology system can be made much more efficient in fighting infections if suitable kind of gene is artificially inserted in the body for enhancing the production of antibodies.

Dr. IK’s involvement in the work was based on some work she had done at Kyoto University in Japan around 1970 (IK’s parents were Japanese immigrants in Brazil). She had conceived of a method for tracking the behaviour of certain immune genes in mice by using a chemical called NP. At that time, she was a graduate student. She left Japan to go over to Finland where she completed her Ph.D. in 1974. She married a Finnish architect, Marrku Tapani Kari. She came to MIT in 1981 as an assistant professor. Her collaboration with Dr. Baltimore on the immunology work began in 1984 on a study of production of antibodies in a special breed of mice. She would use her NP technique in the experiments pertaining to the production of antibodies. Dr. Baltimore organized experimental program with his own independent method in his own laboratory. Although she had coauthored a few publications with Dr. Baltimore previously, she wanted to strike on her own independently. Dr. Baltimore involved her giving her a chance to contribute independently in the combined research project.

To cut a long story short, the planned experiments were completed in due time and the results were published in a paper called “Altered Repertoire of Endogenous Immunoglobulin Gene Expression in Transgenic Mice containing a Rearranged Mu Heavy Chain Gene” in the issue of April 25, 1986, Cell magazine. Besides Dr. Baltimore and Dr. Imanishi Kari, there were four other coauthors of the paper who were Dr. David Weaver, Dr. Moema Reis, Mr. Albanese and Dr. Constantini. Dr. Weaver had written the first draft of the paper.

There was a postdoctoral fellow, Dr. Margot O’Toole, whom Imanishi had hired to work in her laboratory in 1985 on a one-year appointment. Imanishi assigned Dr. O’Toole to continue experiments to extend the work, which she had collaboratively published in the Cell paper. That was the beginning of her nightmare.

O’Toole was born and raised in Dublin, Ireland, in a strong Catholic household. By temperament, she is very combative. Her mother remarked about her “she was virtually bred to confront trouble”. In 1966, at the age of 14, O’Toole moved to Boston with her family. She was graduated with honors in biology from Brandeis University in 1974. She went to Tufts University Medical School for her graduate work in immunology in 1974. She received her Ph.D. in 1979. She together with her husband, Peter Brodeur, also a biologist, was appointed as postdoctoral fellow at Fox Chase Cancer Research Center in Philadelphia before ending up with IK. Her postdoctoral appointment was funded by the national Institutes of Health (NIH). W.W. Norton observed on the professional life of postdoctoral fellows as follows: “Life was tense low down on the professional ladder, where fledgling scientists, ambitious to stay in the game, had to prove that they could fly on their own in the high-pressure atmosphere of creative research,” (http://www.businessweek.com/@@dE1ksyyAdW5cqwMA/ch…/ke vles.ht).

When O’Toole did her experiments as directed by IK, she failed to get the results agreeing with the earlier results (published in the Cell paper) obtained by IK and her laboratory staff. She brought it to IK’s attention. Some believe that IK attributed it to O’Toole’s incompetence to obtain the desired results. For example, Robin Lucas wrote in his review of Daniel Kevles’s book “The Baltimore Case: A Trial of Politics, Science and Character”, “O’Toole seems to have wanted a life in science .. but not the seven-day-a-week life exemplified by IK. This along with O’Toole’s inability to repeat an experiment performed by other members of Imanishi Kari’s lab and published in Cell in April 1986 led Imanishi Kari to wonder whether O’Toole had the necessary tenacity and devotion for science and made O’Toole increasingly unhappy and frustrated,” (http:/www.hms.Harvard.edu/dms/bbs/bulletin/june/Baltimore.h tml).

Initially, O’Toole disputed the effectiveness of a particular reagent and certain overstatements and misstatements in the Cell paper but when IK underrated her comprehension and interpretation of the Cell paper, she expanded her charges against IK and ultimately accused her of falsifying and fabricating the data.

Now the dispute came out in the open and unraveled to an extent that it would be investigated by NIH (Office of Scientific Integrity), Congressman John Dingell and the Secret Service, which would perform a forensic analysis of IK’s notebooks at John Dingell’s request. The dispute continued over a decade. The Secret Service concluded its analysis and said, “that critical data had been falsified because certain records indicated that they must have been created later than Dr. Imanishi Kari said.”

In March 1989, the Office of Scientific Integrity issued its draft report on Dr. IK and found her guilty of faking data and debarred her from receiving federal funds for ten years. This would later be overturned by the board of appeals, which was created later on. So, in a sense, these investigations were inconclusive. John Dingell’s stance was largely political.

The Office of Scientific Integrity was reconstituted in 1992 in the Department of Health and Human Services and called Office of Research Integrity. The reorganization included an appeals board, “which would, for the first time, give the accused their day in court.” Now IK got the chance of presenting her case and she promptly filed her appeal in the board.

The board constituted a Research Integrity Adjudications Panel consisting of three members for the purpose of hearing IK’s appeal. In its decision on June 21, 1996, the Panel exonerated IK of all charges. It said, “…that the Office of Research Integrity (ORI) did not prove its charges by a preponderance of the evidence. The Panel recommends that no debarment be imposed and determines no other administrative actions should be taken.”

Dr. Baltimore was not accused of any wrong doing in this infamous case. He was involved in this protracted dispute only because he was one of the senior authors of the Cell paper, which was the focal point of the whole issue. Although he could have stepped aside, he chose to support Dr. IK all the way. His support was consistent and unwavering.

At the conclusion of the case, IK heaved a sigh of relief and remarked in an interview, “It seems tacky, but I’m going to say it: I felt like Joseph K, the main character in ‘The Trial’, the Franz Kafka novel.” Her professional career was derailed for almost ten years. Tuft University, where she worked after leaving MIT, had warned her that she would be dismissed if she lost her appeal. There was no reason for Tufts to fire her because she won the case. She was reinstated and granted her tenure.

What about the whistle blower Margot O’Toole? According to Norton, “She has received several awards emanating from her actions, among them the Humanist of the Year award from the Ethical society of Boston, and the Ethics award of the American Institute of Chemists.” She is employed at Genetics Institute, a biotechnology company in Cambridge, Massachusetts.

In the end, the question remains: Were O’Toole’s accusations of fakery true or just misperception of IK’s experimental work? If IK was totally on solid ground she could have laid the case to rest by producing the evidence of the authenticity of her data. It is said that IK was sloppy in matters of record keeping. In the face of the missing data, she could have repeated the experiments in question to vindicate herself and showed that her results were indeed correct and replicable. It is also reported that IK indeed repeated the experiments but failed to get the agreement with the published work; her results were identical to O’Toole’s.

So, it appears that something was fishy. Where there is smoke, there is fire.