Surprise,

Medicine

"Anybody who says we've got this problem licked is a fool or a knave or both." Microbiologist J. Michael Bishop was referring to the slow, almost imperceptible progress in the search for a cancer cure. So when Bishop, 53, and colleague Harold E. Varmus, 49, were awakened early last Monday with word that the Karolinska Institute in Stockholm had awarded them the Nobel Prize for Physiology or Medicine, both were startled. Bishop called the news "surreal" and Varmus insisted on verifying the information. Others were less surprised. Said Dr. David Baltimore of M.I.T.'s Whitehead Institute, who won in 1975 the prize for research in the same field: "Their work established a new paradigm for thinking about cancer."

In a series of experiments begun in the mid-'70s at the University of California at San Francisco, Bishop and Varmus resolved a spirited debate over oncogenes -- the genes, or units of heredity, that cause cancer. Researchers had previously theorized that cancer genes were separate entities, unrelated to the healthy functioning of a cell. But in studies of a cancer-causing virus in chickens, Bishop and Varmus found that oncogenes were normal genes, vital to cell growth and development, that had somehow gone awry -- probably as a result of mutations induced by carcinogens such as cigarette smoke and radiation. The team thus helped explain the role of genetic damage in cancer development and established a common pathway by which all cancers seem to evolve. Observed Bishop: "We have the seeds of cancer in our own genetic dowry." Since then researchers have identified more than 40 slightly altered genes that cause cancer in humans. These discoveries will make it easier for doctors to diagnose and predict the occurrence of cancer.

The occasion was somewhat marred by the claims of a French researcher, Dr. Dominique Stehelin, that he deserved at least part of the prize. Stehelin, who assisted in the UCSF study but is now at the Pasteur Institute in Lille, France, called his omission "very unfair and rotten." But others who were present at the time of the original experiments said that Stehelin, though a key member of the research team, nevertheless worked under the supervision of Varmus and Bishop. The Nobel Committee stood by its decision.

Chemistry

Biology students used to be taught that there was a strict division of labor within living cells. The nucleic acids, DNA and RNA, served as repositories of genetic information, and certain proteins, called enzymes, did all the work. But research conducted in the past decade by Sidney Altman of Yale University and Thomas Cech of the University of Colorado at Boulder has forced scientists to alter completely their ideas not only of how cells function but also of how life on earth began. Last week the Nobel Prize for Chemistry went to Altman and Cech, with the citation that "many chapters in our textbooks have to be revised" as a result of their pioneering studies.

Working with a bacterium and a pond-dwelling protozoan, Altman, 50, and Cech, 41, independently discovered that RNA can act as an enzyme, a molecule that accelerates chemical reactions a millionfold or more and makes it possible for life to exist. Plants, for example, depend on enzymes to convert carbon dioxide in the air to sugar and starch. An enzyme in human saliva helps transform starch into glucose, the body's energy source. Until RNA enzymes were identified, all enzymes were thought to be proteins.

Cech also found that RNA can copy itself, suggesting that the first living organisms may not have depended solely on DNA, the principal carrier of hereditary information in plants, animals and bacteria. "Now that we know that RNA can both carry genetic information and serve as a catalyst," Cech wrote last year, "it seems possible that it was the key molecule at the origin of life."

Although Altman and Cech did not collaborate directly, each benefited from the other's advances. "Like a Ping-Pong match, the ball went from one to the other," according to Bertil Andersson, a member of the Nobel Committee. Cech heard of the award while in Boston accepting another prize. "I am obviously excited about it," he said. "It was something that everyone has been telling me would happen, but I had no way of knowing when." What will the researchers do with their $470,000 prize? "I'll just go back to the lab and do more work," Altman said. Cech had other ideas. Said he: "I have two young daughters who are very good at spending money."

Physics

Science does not progress through revolutionary discoveries alone. Important advances also occur as ingenious experimenters devise ever more clever methods for increasing the accuracy of their observations. The Nobel Prize in Physics this year celebrates the contributions of three scientists who have spent their careers elevating precision measurement to a high art. "It's nice to know that this type of work can be appreciated," said one of the recipients, distinguished Harvard University physicist Norman Ramsey. Upon hearing the news, Ramsey, an athletic 74-year-old who recently returned from a trek in Nepal, admits that he was startled. "Are you sure?" he asked the first reporter who called him.

Ramsey was awarded half of the $470,000 prize for his contributions in pioneering a method of measuring the minute movements that occur inside atoms. Ramsey's so-called separated oscillatory fields technique did not just become a valuable scientific tool; it also provided the basis for modern-day atomic clocks. Like the ticking of a pendulum in a grandfather clock, the rapid-fire (9,192,631.770 times a second) oscillations of cesium-atom nuclei, spinning like tops inside a magnetic field, can be used to pace off time.

Atomic clocks are the world's most accurate timepieces and have important applications in navigation and communication systems. These clocks have also been used to make direct measurements of continental drift, coordinate astronomical observations and test the ability of earth's gravity to slow down time. (It does so at the rate of a second every 10,000 years.)

Two other physicists -- Hans Dehmelt of the University of Washington in Seattle and Wolfgang Paul of Bonn University in West Germany -- are to split the remainder of the prize. They were honored for devising ways of "trapping" single electrons and charged atoms known as ions. Paul, 76, won fame for fashioning a vastly improved ion trap. Dehmelt, 67, who studied with Paul as an undergraduate, used such a trap to observe a single ion. Illuminated by laser beams, the imprisoned ion glowed "like a little blue star," he recalled.

Dehmelt has performed other small miracles as well. By creating an electromagnetic "cradle," he has kept a lone electron suspended in a vacuum for months at a time. He has also succeeded in observing the fabled quantum jump of a single trapped atom as it absorbed energy and then emitted it in the form of light.

Economics

Most winners of the Nobel Prize respond with joy and gratitude to the singular, once-in-a-lifetime honor. But Norway's Trygve Haavelmo bluntly criticized the award last week after he was named the 1989 laureate in economics. Haavelmo, 77, a modest and shy University of Oslo professor emeritus, told a reporter, "I don't like the idea of such prizes."

The reluctant laureate was honored for pathbreaking work in the early 1940s that laid the foundation for econometrics, which uses mathematical models to study the behavior of an economy. "Every time you open a newspaper and see an analysis of economic trends," said Assar Lindbeck, chairman of the economics- prize committee, "it is based on Haavelmo's econometric theories." Haavelmo's key contribution was to show that the relationship between such factors as income and spending was far more complex than had been thought, since those factors affect one another and the rest of the economy. For example, he demonstrated that an economist could not gauge the impact of a change in tax rates on consumer spending without using sophisticated statistical methods.

While Haavelmo has lived for years in contented obscurity, many prominent economists welcomed his selection. Said Lawrence Klein of the University of Pennsylvania, who won the 1980 economics award for his work in econometrics: "Haavelmo had a tremendous influence on me and on many other young econometricians in the 1940s." Concurred Robert Solow of the Massachusetts $ Institute of Technology, the 1987 laureate: "It's like giving the Nobel Prize for Physics to Thomas Edison. You slap your forehead and wonder why they didn't do it sooner."

In fact, Haavelmo's prize reflected a situation that is unique to the award for economics. The Nobel Prizes were first given in 1901, but the economics citation was not added until 1969, when it was established by Sweden's central bank. That late start has prompted the Royal Swedish Academy of Sciences to choose many older economists whose work could not be recognized when it was first published. "They're clearing up the backlog," says Harvard economist Zvi Griliches, who hailed this year's choice. "They haven't got to the point of recognizing something interesting that happened in the past five years." But when such awards are finally made, the work of the winners may show the influence of the feisty and reclusive Haavelmo.