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NEWS OF THE WEEK
NOBEL PRIZES: Molecular biology wins two awards
Research in molecular biology dominated this year's science Nobel Prizes. In chemistry, the prize was awarded to a chemist and a biologist who independently demonstrated that some ribonucleic acid (RNA) molecules possess enzymatic activity. The prize in physiology or medicine went to two research physicians who identified the origin of genes involved in cancer.
J. Michael Bishop and Harold E. Varmus, both professors in the department of microbiology and immunology at the University of California, San Francisco, will share the 1989 Nobel Prize in Physiology or Medicine for "their discovery of the cellular origin of retroviral oncogenes," according to the Nobel Assembly of Sweden's Karolinska Institute. The research solved a decades-old puzzle in virology while simultaneously revolutionizing the molecular biology of cancer.
Thomas R. Cech, professor of biochemistry and molecular biology at the University of Colorado, Boulder, and Sidney Altman, professor of biology at Yale University, New Haven, Conn., will share the 1989 Nobel Prize in Chemistry for their discovery that RNA acts as a biological catalyst as well as a carrier of genetic information. "The discovery of catalytic RNA has altered the central dogma of the biosciences," according to the Royal Swedish Academy of Sciences, and "has had a profound influence on our understanding of how life on Earth began and developed."
Both the chemistry and medicine prizes are worth $469,000, which will be split between Bishop and Varmus, and Cech and Altman.
In 1978, Altman and coworkers at Yale were the first to show that RNA was a necessary participant in an enzymatic reaction. The scien-
UCSF's Bishop (above) and Varmus share Nobel Prize in medicine
tists demonstrated that RNase-P, a bacterial RNA-cleaving enzyme that is a complex containing a protein molecule and an RNA molecule, loses its enzymatic activity when broken into its two components.
Cech was the first scientist to demonstrate that RNA molecules alone possess enzymatic activity. Cech and coworkers were studying the process by which the RNA transcript of deoxyribonucleic acid is processed into the messenger RNA that directs protein synthesis. That process involves splicing of the RNA transcript to remove intervening sequences, known as introns, that do not encode protein. The Colorado chemists were trying to isolate the enzyme responsible for the splicing reactions.
Working with the single-celled organism Tetrahymena thermophila, Cech discovered that the organism does not use a protein to catalyze RNA splicing. Instead, the intervening sequence adopts a conformation that contains an active site that sequence-specifically catalyzes the
hydrolysis of the phosphodiester bonds of the RNA backbone and rejoins them to remove itself from the molecule.
The discovery of RNA enzymes, of which more than 100 have now been identified, may also have practical applications. They likely will provide new tools for genetic technology, and could provide new strategies for antiviral therapies.
The Nobel Prize in medicine recognizes work begun in the early 1970s in which Bishop and Varmus probed what was an old problem in virology—the mechanism by which certain retroviruses induce cancer. The first such oncogenic retrovirus was reported in 1911 by Peyton Rous working at the Rockefeller Institute, research for which he would receive the 1966 Nobel Prize in medicine. Now known as Rous sarcoma virus (RSV), the retrovirus causes tumors in chickens.
Although numerous oncogenic retroviruses had been identified since Rous' original discovery, how they caused cancer remained a mys-
6 October 16, 1989 C&EN
tery. One idea favored in the 1960s held that a hypothetical viral gene, dubbed an "oncogene," could direct the transformation of a normal cell into a tumor cell.
In an effort to characterize the RSV oncogene, Bishop, Varmus, and postdoctoral fellow Dominique Stehelin compared two RSV strains provided by Peter K. Vogt, of the University of California, Los Angeles. One viral strain was capable of transforming cells into cancer cells and presumably contained the oncogene, and one was a variant that could not transform cells and presumably lacked the oncogene.
In research that would be routine today with the tools of modern molecular biology, but which was quite difficult in the early 1970s, the scientists developed a nucleic acid probe that could identify the RSV oncogene. Not surprisingly, the oncogene was shown to exist in chicken tumor cells transformed by the virus. Quite surprisingly, the scientists also found that a nearly identical version of the gene resided in normal cells as well.
In 1976, Bishop, Varmus, Stehelin, and Vogt published in Nature a paper in which they reached what the Nobel Assembly calls the "remarkable conclusion that the oncogene in the virus did not represent a true viral gene but instead was a normal cellular gene, which the virus had acquired during replication in the host cell and thereafter carried along."
Nobel chemistry prize cowinner Cech
The discovery that oncogenes are in some way abnormal versions of normal cellular genes (called proto-oncogenes or cellular oncogenes) that are ubiquitous throughout the animal kingdom changed the way scientists view cancer. All of the more than 40 oncogenes that have been identified since 1976 are involved in the systems that regulate the growth and division of cells. The dysfunction of proto-oncogenes, which can be caused by a number of mechanisms, leads to cell division run amok.
A discordant note was struck last week by Stehelin, now the head of the molecular oncology research unit at Louis Pasteur Institute in Lille, France, who complained that the Nobel Assembly overlooked his contr ibut ion to the research in awarding the prize to Bishop and Varmus. Stehelin told C&EN that he was "delighted" that the UCSF scientists had won the prize, but that he took issue with the way nominees for Nobel Prizes are evaluated. He maintains that his work was central to the discovery for which Bishop and Varmus received the Nobel Prize.
Neither Bishop nor Varmus would comment on Stehelin's complaints. A statement issued by UCSF for the scientists said that Stehelin performed difficult experiments, but that the work was carried out under the supervision of Bishop and Varmus.
Meanwhile, the 1989 Nobel Prize in Physics was awarded by the Royal Swedish Academy of Sciences for contributions of importance to the development of atomic precision spectroscopy. One half of the $469,000 prize was given to American physics professor Norman F. Ramsey of Harvard University for invent ion of the cesium atomic clock. The other half of the prize goes jointly to American physics professor Hans G. Dehmelt of the University of Washington, Seattle, and West German physics professor Wolfgang Paul of the University of Bonn for development of the ion trap technique, which has made it possible to study a single electron or a single ion with extreme precision.
Rudy Baum
NSF adds requirements for grant proposals The National Science Foundation has introduced two significant new requirements in the research grant proposal process. It is now requiring principal investigators to include in their proposals a statement describing how the proposed research project will contribute to the training of future scientists and engineers. And in a push to emphasize the quality of published research over quantity, it is limiting to 10 the number of publications that will be considered in reviewing a grant application.
The changes are psychologically important, says Kendall N. Houk, director of NSF's chemistry division. Houk points out that evaluating the effect of the proposed research on the infrastructure of science and engineering is already one of the four criteria used in reviewing a proposal. "This is just a way of saying we have to worry about the future, who the scientists are going to be, and that we want to do a good job in educating them. This is one way of putting it down in black and white."
Requiring principal investigators to list the names of all their graduate students and postdocs over the past five years, along with a summary of the total number of graduate students advised and postdocs sponsored, will give NSF an idea of how many people are being trained in a lab, Houk says. Given the choice between two borderline proposals that are equal in all respects, "it would be better to fund a program that has a history of training people and sending them on to fruitful careers in science."
But Houk also strongly emphasizes that the primary focus in reviewing a proposal will remain the quality of the proposed research. The changes in the proposal format aren't going to exclude anyone from the process, he says. "A great scientific proposal that doesn't involve students, say, from a theoretician who doesn't even work with students, will still get funded."
Limiting the list of publications to the five that have had the greatest impact, plus five that have the
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