Gary Strobel
Plant Sciences
Montana State University-Bozeman
The kernel of every scientific breakthrough or concept originated as a gem or spark in someone's imagination. Evidence, however, for the validity of the concept generally arises via the application of the scientific method and then is ultimately accepted as new knowledge after it has been independently confirmed by others. This powerful combination of processes has freed mankind of many dread diseases, provided ample food for most of the world's peoples, and given conveniences in travel, communications, and materials that have markedly changed and improved our lives. Those participating in the scientific enterprise have much to gain if their endeavors are successful, including fame, fortune, and a place in history. This entire system of scientific discovery must be guarded and protected by our society at all costs if we wish to further prosper and succeed. Any prostitution of this process could result in tragic consequences.
The Baltimore Case offers numerous examples of how this system for scientific discovery can be open to attack, thwarted, abused, or even destroyed when certain unwelcomed, but seriously self-serving forces, intrude into the system and desire to change it for reasons that are more selfish than altruistic. One should keep in mind that the entire case may have never happened had the scientific process been allowed to proceed. Instead it was short-circuited before the point where the data would have been independently confirmed, denied, or questioned by others. Instead, even before confirmation could be made, there were claims of abuse, fraud, and sloppiness.
In preparation of reading this book it is important to understand the development, support, and nature of the biological sciences in the United States in the past century. The evolution of the biological sciences began by one or two individuals working on a problem in the early 1900s and progressed to megagroups involving cross-disciplinary efforts and teams located at two or more laboratories at widely scattered locations by the late century. Likewise, the problems being tackled are some of the most mystifying to the mind, such as the cause and cure for cancer, the make-up and organization of the human genome, factors controlling the nervous system, the control of the immune system, and myriad others. Finding answers to these questions demands huge sums of money for space, equipment, and personnel.
Most of the basic work in these biological disciplines in the USA is funded from federal sources on a very competitive basis. Thus, as the competition for funds has increased, the stakes have also increased. The funding levels have not nearly been great enough to meet the demand, which was the case in the '50s and '60s. The result of this pinch has been the display of a number of human characteristics that rarely intruded into the labs of American science in the early part of this century when science was a kinder, gentler activity that engaged the spirit of only a few dedicated souls. Enter greed, avarice, power-seeking, fear, self-aggrandizement, and many other displays of human emotion that have absolutely nothing to do with the processes of scientific discovery. Each raises its ugly head in the Baltimore case.
The weighty work by Dan Kevles is the most unabridged account of the Baltimore case to date. In 1975, David Baltimore of MIT received the Nobel prize in medicine for his co-discovery of the reproduction of the retroviruses (reverse transcriptase RNA-DNA), which at the time went against the hallowed belief of how nucleic acids replicated. This discovery in the '70s led his group into the rapidly emerging and powerful field of recombinant DNA technology. In 1986, he co-authored a paper in the journal Cell (45, pp. 247-259) which claimed that the insertion of a foreign gene into a certain mouse strain caused changes in the production of its own antibodies. The result was significant and unexpected.
In late 1985, Dr. Margot O'Toole appeared in Baltimore's lab as a post-doctoral associate. Her lab supervisor was Brazilian born Dr. Imanishi-Kari, one of Baltimore's lab chiefs who was a principal author on the Cell paper. O'Toole, with a rocky record of post-doctoral work, was busy with a pregnancy and was taking on the Boston police as an alleged witness to police brutality. From the very first day in the lab, conflict arose between O'Toole and Imanishi-Kari. Basically, the stage was set for one of the scientific disasters of the 20th century.
Soon Margot O'Toole found inconsistencies between the behavior of the transgenetic mice in her experiments and those reported in the Cell paper. In fact, this led her to inspect the original lab notebooks from which critical aspects of the Cell paper were published. This aroused her suspicions even more, especially upon discovering that the original lab notebooks were a mess. Apparently, because of her confrontational (or combative) attitude, her junior position, and her personality conflict with Imanishi-Kari, she received little or no sympathy for her point of view from MIT scientists. Her personality, however, demanded justice. When she was unable to get satisfaction from her supervisor, she soon found herself in the clutches of two wannabe scientists at the National Institutes of Health, Ned Feder and Walter Stewart. Upon hearing of her circumstances, a kind of scientific vigilantism was hatched, and out of this brew grew the ingredients of a huge mess. The genuine sloppiness that O'Toole had observed in the original notebooks was now interpreted as scientific fraud--a very serious charge. It was at this point that the hallowed scientific process began to be thwarted: virtually no work had yet been done by an independent lab to corroborate the claims in the Cell paper. Instead, the process was in the early stages of being moved into the mode of a circus side-show with all sorts of players soon to be involved, including politicians, journalists, lawyers, administrators, and zealots for various causes.
Because of the public anxiety--not only about the prospects of fraud in science as portrayed in the 1983 book by Broad and Wade of the New York Times, but the phobias developing about the misuse of recombinant DNA technology--there was a backdrop for convening an NIH panel to hear the circumstances of the Baltimore case. A draft report of the hearing was leaked to a number of key people. It indicated that Imanishi-Kari was guilty of serious scientific misconduct and that Baltimore had covered it up. By now the international media, including newspapers, scientific journals, and news magazines, had taken up the issue and began a series of interviews, statements by investigators, and friends of the accused, and NIH administrators. Ultimately, this flurry of reports led Michigan Congressman John Dingell to establish a series of hearings in 1989 to root out fraud in the American science scene.
During one of the hearings, David Baltimore lost his composure under questioning by the committee when he defended his position and that of his coworkers. He alleged that the investigation represented a threat to scientific freedom. Dingell took umbrage with Baltimore and his attitude and used his congressional authority to rocket the case up one more notch by calling in the US Secret Service to examine notebooks, data tapes from scientific instruments, and other crucial evidence with refined techniques and methods. The Baltimore case was now causing misery for each of the scientific players. For instance, David Baltimore had just been appointed a President of Rockefeller University, and the publicity of this episode caused so much rancor among the faculty that he felt compelled to resign after only 18 months of service. Colleagues at Harvard and elsewhere in molecular biology (including Mark Pstahne, Wally Gilbert, and James Watson) had each independently looked into the case and thought that he was wrong to support Imanishi-Kari. In fact, long-held friendships were trashed as a result of these events. These detractors were probably not alone since many feared that the case had become so public and had so angered powerful Congressman Dingell that the fate of funding for all of science in America was threatened. David Baltimore was in an extremely precarious position. I consider him very lucky to have had the support of his wife, microbiologist Alice Huang, throughout the entire episode. In the meantime, after the hearings, Imanishi-Kari's NIH grants were terminated and her tenure at Tufts was placed on hold. This case also spawned the opening of the NIH Office of Scientific Integrity (OSI). This office would basically be the watch dog for all infractions of scientific integrity involving NIH grants and protect the interests of the public funding of science in America.
Finally, nearly ten years after the Cell paper was published and appeals made by Imanishi-Kari, a new hearing was convened. The result of that meeting was that she was exonerated of each of the 19 counts of fraud. Her tenured position was restored and her case and her grant position reinstated. Ultimately, not only she but several other labs confirmed the main tenants of their Cell paper. This is the critical thing that should have been done in the first place, before the investigations, hearings, and the media storm took place. It would have saved much time, unwanted anxiety, and a multitude of friendships. The key player, David Baltimore, was appointed president of Caltech and continues to flourish in his science as well as in his administrative duties.
While Kevles has written a detailed, reliable treatment of this complex affair, he fails to take note of the major lessons to be learned from this case. Namely the major, widening gap between those supporting science and those doing it. This is illustrated by the dumbing of America as school science test scores drop and few adults follow developments in science. Furthermore, most Americans don't understand how the scientific process functions, though traditionally they have been very trusting and supportive of it. Those in the scientific community have cause to be fearful when those who don't understand what is involved in doing it question their research. Perhaps as a result of the Baltimore case, scientists may change their attitude about who supports them and become more proactive in educating congressmen, legislators, the press, and the general public about what it is that they do. To not do so will invite other cases of this type in the future, especially as large sums of money are expended by a few for the presumed benefit of all. What is the other lesson to be learned? It would seem that people doing science on the public bill are obligated to keep reasonably neat notebooks of their activities. Failure to do so invites the kind of detonations that occurred in this case.
In 1988, I met Dan Kevles and his wife Bettyann when I was guest at Caltech to present a seminar on the events surrounding the Dutch Elm disease case. Both Dan and his wife are successful writers: he covers modern American science, while she writes novels. In The Baltimore Case, Kevles may have been so enamoured of the situation that the text is overly detailed, and, at times, the morass of events being described seems to leave the reader in a pile of minutiae. In fact, the science being described is quite complicated, and he may have been better served to have provided additional simplified illustrations to better show his points. He has thoroughly documented each event with copious notes at the end of the text. Happily, he very liberally and accurately used contemporary events involving other scientific personalities to embellish his story (e.g., the Gallo case and HIV). This certainly added a great deal to the text. The book, in spite of the copacetic outcome for most of the players in this case, will long serve the best interests of the American scientific enterprise because of the lessons learned in this ten-year episode. If you do science, you need to read this book.