Speculation In The Biomedical Community Abounds Over Likely Candidates for Nobel

Candidates For Nobel Author: NEERAJA SANKARAN Sidebar: Highly Referenced Scientists As one of the oldest and richest awards for intellectual achievement, the Nobel Prize is also perhaps the most coveted prize in the world. With nearly $1 million allocated to winners in the categories of physics, chemistry, physiology or medicine, literature, and economics, and a long selection process shrouded in secrecy, it is also one of the most prestigious. It's only natural then, in the weeks of tense anticipation preceding the annual announcements, that scientists in various disciplines speculate among themselves as to who might win this year. According to the terms of Alfred Nobel's will, the prize in the category of physiology or medicine is to go annually to the "person who shall have made the most important discovery within the domain of physiology or medicine." Factors that will undoubtedly be considered by the Nobel committee include the perceived importance of a discovery as well as the role played by the researcher under consideration. While it is impossible to know what the members of the committee might be thinking, there are certain indicators that have consistently pointed toward potential winners. One such sign is a scientist's citation ranking.Virtually all Nobelists are individuals whose work is of high impact and ordinarily is widely recognized as important, and thus frequently referenced in subsequent work by others. A second indication of recognition-in the form of awards other than the Nobel-is also illustrative of the relevance of an individual's work. Prestigious honors such as the Gairdner Foundation International Award and the Albert Lasker Basic Medical Research Award have long been considered "Nobel predictors": 43 Gairdner awardees and 52 Lasker winners have gone on to receive Nobel prizes. p53 PRINCIPAL: Will Bert Vogelstein's research on the tumor suppressor gene win him the Nobel Prize? Following Nobel's death, a special committee was set up to work out the criteria for what constituted "the most important discovery," explains Ingemar Lindahl, an associate professor of the theory of medical science at the Karolinska Institute in Stockholm, the Swedish medical institution named by Nobel to award the physiology or medicine prize. In addition, during the first decades of the prize, a pattern of informal criteria emerged. "Recent research on this period shows that the Nobel committee attached importance to whether the discovery be of wide-ranging significance both theoretically and practically; the results be verified by the scientific community, and brought to a point where the given problem had been solved entirely; all issues of priority had been established; [and] the work in question be clearly distinguished as the person's own," recounts Lindahl. "In order to make any sort of guess, it is necessary to understand something of the selection process," asserts Cecil Fox, a former researcher at the National Institutes of Health and currently president and CEO of Molecular Histology Inc., a research-services firm in Gaithersburg, Md. During his NIH tenure, Fox worked as a visiting researcher at the Karolinska Institute from 1976-79. The initial nominations may come from a variety of regular and invited international sources, from which the staff of the Nobel Foundation at the Karolinska Institute selects a short list of "up to 24 names in about eight topics," according to Fox. The Nobel committee, consisting of six members, investigates each of these candidates and presents a report for deliberation by about 75 members of the institute, which then makes the final decision. "The scientists on this [short list] have the best-researched bibliographies in the world," declares Fox. While the selection process and the identity of committee members themselves-some of whom change annually, others serving for longer terms-are not concealed, "actual proceedings are kept secret for 50 years and then published," remarks 1976 Nobelist Baruch Blumberg, Fox Chase Distinguished Scientist and scientific adviser to the president of the Philadelphia-based Fox Chase Cancer Center. "If a Nobel laureate really wanted to find out how he or she came to be chosen, all they have to do is outlive their prize by 50 years," he says jokingly. In forecasting potential winners, Fox avers that "it is important to know who is on the [Nobel] committees." He contends that the disciplines of the committee members would influence the subject areas they might be inclined to recognize as important and hence highlight in their reports. Historian of science Franz Luttenberger of Uppsala University in Sweden suggests that personalities also play a role in the choice of a particular winner (F. Luttenberger, Theoretical Medicine, 13:137-73, 1992). For instance, in his paper recounting the controversy among various people on the committee over the choice of Paul Ehrlich as the 1908 laureate, he proposes that among the factors influencing the final decision was physiologist J.E. Johansson's "position as a nonconformist at the Karolinska." Luttenberger recounts that "Johansson asserted that Ehrlich's ideas [on the nature of the immune response] was of little scientific value and therefore not worthy." The majority of the institute, however, opposed this view and "succeeded in awarding Ehrlich" the Nobel, he says. The high degree of secrecy of the committee's deliberations has left it open to many questions, criticisms, and even scandals. Just recently, articles were published in Swedish newspapers charging that the Karolinska Institute had been influenced by the lobbying efforts of an Italian drug firm, Fidia, to promote the candidacy of one of the 1986 winners-Rita Levi-Montalcini, then a researcher for the company-for her role in discovering nerve growth factors. Both the institute and Levi-Montalcini deny the allegations. Fox, however, claims that attempts to influence the people at the institute are not at all uncommon: "The number of scientists in the U.S. who find it convenient to give lectures at Karolinska during September [deliberations] is phenomenal." Whether such attempts have any real influence is debatable. Despite the controversies and criticisms, the process is undertaken year after year, and the Nobel Prize continues to hold the world in its thrall. And maybe because of the almost mystical veil of secrecy over the deliberations, "guessing who will win is a popular parlor game for scientists," as noted by Eugene Garfield in a 1990 commentary in The Scientist (Oct. 1, 1990, page 14). While declining to specify any people or research subjects, Joshua Lederberg, a professor and president, emeritus, at Rockefeller University, projects that new discoveries in "the area of infectious diseases" might capture the attention of the committee. Lederberg himself was a winner of the 1958 Nobel for his discoveries concerning genetic recombination and organization in bacteria. Another area suggested by Blumberg as gaining more prominence is "bioinformatics and the management of biological complexity. "It is unlikely that the Nobel committee can identify someone [in this field], but I think that prizes in the future will be given to someone who can understand and integrate information about biology and databases," he speculates. With respect to the present, he offers the ever-hot area of cancer research. "In recent years, there has been the development of new genetic models for cancer etiology," he observes. For instance, "the anti-oncogene-tumor suppressor gene model provides a significant advance in the understanding of the mechanism of familial and sporadic cases of cancer." Fox Chase Cancer Center researcher Alfred G. Knudson, Jr. formulated this model, and "there has been a considerable amount of experimental support for it," adds Blumberg. This year Knudson is also a special adviser to the director of the National Cancer Institute (Richard Klausner) as well its division of epidemiology and genetics. Work on another aspect of tumor suppressors-known as p53-has commanded considerable attention in recent years. Science magazine declared this the "Molecule of the Year" in 1993 (E. Culotta, D.E. Koshland, Jr., 262:1958, 1993). And some of the most highly cited papers and authors last year have been in this area, according to the Philadelphia-based Institute for Scientific Information. Pioneer p53 researcher Bert Vogelstein of Johns Hopkins University has been named as a possible Nobel contender by many of his peers. Last year, Vogelstein was one of the investigators with the highest number of "hot" papers (Science Watch, 6[2]:1, February 1995). He ranks second among the top-cited scientists in the period of 1981-1994 (see accompanying list). Fox, whose time at NIH was divided between the National Cancer Institute and the National Institute of Allergy and Infectious Diseases, has his own list of potential winners from the field of cancer research. "I believe that there are three discoveries that have been terribly important in understanding cancer" and providing avenues for its treatment, he remarks. The first he cites is in the area of apoptosis, or programmed cell death. He names as possible Nobel contenders Scottish researchers John F.R. Kerr and Andrew Wyllie, "who were the first to describe [apoptosis] in pathological terms." The numbers of publications referencing their seminal paper on the subject (J.F.R. Kerr et al., British Journal of Cancer, 26:239-57, 1972) have risen exponentially since its publication (see accompanying chart). The third key contributor to this work, Alastair Currie, died last year. Another field that Fox feels deserves attention is that of angiogenesis, which is the formation of new blood vessels around cancer cells. He points specifically to the work of M. Judah Folkman, an oncologist at Harvard Medical School. "He probably won't win it this year, since the work is still in progress, but I believe he should get it in a couple of years," Fox maintains. The increasing realization of the importance of Folkman's contributions to understanding the process of angiogenesis is apparent from the citation history of his papers on the subject: In the past decade, at least a dozen of his papers have been referenced more than 100 times in other publications. He also won a Gairdner award in 1991 for this research. JUDAH FOLKMAN: Some scientists predict that his work on angiogenesis will gamer him a Nobel Prize some day. One other area that Fox predicts "is eventually going to win something" is telomere research. "I can think of at least two scientists who should be considered in this area, although there are others, as well." The two, Elizabeth Blackburn at the University of California, San Francisco, and Calvin B. Harley at Menlo Park, Calif.-based Geron Corp., have both made independent seminal contributions in implicating telomere length to cellular growth and aging and thus, potentially, cancer. Upon examination of the citation histories of past laureates, it is apparent that most of these scientists have done work and published papers that have been referenced highly by their colleagues. The 12 most highly cited biomedical scientists during the period 1981-94 received anywhere from 27,700 to nearly 52,500 citations (see accompanying list). Of these, NIH HIV researcher Robert Gallo and signal transduction pioneer Yasutomi Nishizuka of Kobe University School of Medicine have consistently been highly cited and have won both Gairdner and Lasker awards. Gallo, however, is perceived by many as an unlikely choice of the committee, owing to the controversy over allegations that he misappropriated the virus from the Institut Pasteur, although federal investigations into the matter have been dropped. But even as scientists speculate on the winners, they remain aware of the fact that for every winner there are several "who were deemed worthy, but didn't actually get the prize," maintains Fox. And Lindahl points out that dramatic changes in the way science is conducted has further complicated selection of only one or two candidates over the rest. "It must be exceedingly difficult to fairly choose one, two, or three prize-winners at the most, when so much of science is so collaborative nowadays," he argues. Indeed, this trend is reflected in the number of prize recipients: In the last 20 years there have been only two unshared Nobels in physiology or medicine-in 1983 to Barbara McClintock for her discovery of "jumping genes," or mobile genetic elements, and in 1987 to Susumu Tonegawa for discovering the genetic basis of antibody diversity. And most agree that science is only getting more complex and collaborative. The validity of awarding the prize to only one or two individuals is thus now questionable. Says Lindahl: "We may have to change the way we look at the Nobel Prize." Sidebar: Highly Referenced Scientists (The Scientist, Vol:9, #19, pg., 10 , October 2, 1995) (Copyright © The Scientist, Inc.)

Speculation In The Biomedical Community Abounds Over Likely Candidates for Nobel

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