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-

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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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