Monday, Oct. 03, 1983

Commemorating a Revolution

By Frederic Golden

Watson and Crick are reunited to mark an epic event

The article was only 900 words long, but its contents helped usher in a revolution. With bland understatement, James Watson, then 25, a freshly minted Ph.D. in zoology from Indiana University, and Francis Crick, a 36-year-old dropout from physics who had developed a belated interest in biochemistry, announced the solution to a puzzle that had stymied the scientific world. Though neither was especially equipped by training or experience for so challenging a task, they had unraveled the structure of deoxyribonucleic acid, or DNA, the basic molecule of heredity.

In doing so, these two very junior scientific researchers at England's Cambridge University had beaten out some of the giants of biochemistry, including Caltech's future Nobel prizewinner, Linus Pauling. More important, in discovering DNA's now famous double-helical, or spiral-staircase, architecture, they also suggested how the magic molecule works: the two sides of the helix unzip, so that each can act as a template for making an exact copy of the original genetic material. Thus Watson and Crick not only described the three-dimensional geometry of DNA, which forms the genes in all living things, but also showed how it passes its message from one generation to the next.

Last week, 30 years after the publication of their stunning report in the scientific journal Nature, a star-studded group gathered in Boston to commemorate an event that has been compared to the appearance of Darwin's Origin of Species or Einstein's papers on relativity. For three days, speaker after speaker, among them five Nobel laureates including Watson and Crick, talked eloquently about recent findings of the biological revolution.

M.I.T.'s Alexander Rich spoke of his discovery of so-called lefthanded or "Z" DNA, which twists bafflingly in the direction opposite that of a normal molecule; Rich indicated that this seeming oddity may play a significant role in switching genes off or on, thereby allowing a cell to develop into one that is different from its neighbor. Biologist Mark Ptashne of Harvard discussed the activity of small proteins that somehow attach themselves to the coils of DNA and control how the molecule replicates. Nobel Laureates David Baltimore of M.I.T. and Howard Temin of the University of Wisconsin reported on the use of viruses, which are little more than coils of nucleic acid wrapped in protein, to transfer new DNA or its molecular cousin, RNA (for ribonucleic acid), into bacterial cells. In the process, the cells are genetically transformed.

The highlight of the conference, however, was a rare joint appearance by Watson and Crick. Both looked appropriately oracular: Watson with his aureole of thinning hair, Crick with a rim of silver. Still, there were flashes of the brash biochemists who had once electrified the scientific world. Watson displayed the pointed wit that he employed so deftly in his gossipy, irreverent 1968 history, The Double Helix (it began with the line "I have never seen Francis Crick in a modest mood").

Acknowledging his former partner, Watson said he would not heap praise on him because he had already done that earlier this year during a conference at Cambridge, which Crick had skipped. Crick, ever the gadfly, characteristically bombarded the Boston speakers, even Nobel laureates, with sharp-edged questions aimed at sinking their pet ideas. Sighed one participant: "Ah, the same old Francis."

Watson and Crick, the old collaborators, have gone their separate ways. Watson, a professor of biology at Harvard for 15 years, has since 1968 been director of the Cold Spring Harbor Laboratory, a center for molecular-biology research on New York's Long Island. It is focusing much of its attention on the basic mystery of cancer. Crick, after helping solve another important riddle about DNA--how it codes the genetic message within its spiral-staircase structure*--turned to other genetic puzzles. Initially, he worked on the problem of how the originally identical cells of higher organisms develop different characteristics in the embryo stage. More recently, as the holder of a special professorship at the Salk Institute in La Jolla, Calif, Crick has been concentrating on neurobiology, the formation and operation of nerve cells.

Watson and Crick both debunk the idea that current work in recombinant DNA, endowing microorganisms with new genes, presents in any way a public peril. Says Watson: "There is no evidence that it is dangerous." Adds Crick: "I live near a small California township called Del Mar, and when the housewives are spending their time worrying about re|combinant DNA, I really think it has gone too far." Both are convinced that many of the problems in understanding diseases like cancer will not be overcome until scientists learn fully how genes are switched off and on. Says Crick: "What we want to know is not only how to turn on a single gene. We want to know the hierarchical controls [that determine each level of development in an organism]."

Both men are convinced the revolution they helped start is still very much alive. Says Crick: "If we look back in ten years' time, what we'll find is there are lots of [genetically engineered] products that we haven't even thought of." Even cancer may yield its secrets, Watson adds. When that happens, he says, "you can really think, Is there a way to modify biochemically this protein that's gone wrong?' " For Watson and Crick, three decades after their great discovery, the answer would obviously be yes. -- By Frederic Golden. Reported by Jamie Murphy/Boston

*By an arrangement of chemical bases, at the steps of the staircase, which taken three at a time form the "words" of the genetic message.

With reporting by Jamie Murphy/Boston This file is automatically generated by a robot program, so viewer discretion is required.