Miracle Molecule

Once just a messenger, RNA finds a higher profile

Medicine & Science

February 24, 2003|By Timothy B. Wheeler | Timothy B. Wheeler,Sun Staff

New Frontier

For decades, scientists have neglected RNA molecules, assuming that they were little more than messengers carrying genetic instructions from DNA to manufacture the proteins that rule our lives.

Now, thanks to a spate of discoveries in recent years, it appears that humble RNA assumes a surprising variety of other forms that do much more than deliver messages. Snippets of RNA actually become enforcers in the cell, interfering with the instructions from certain genes or shutting them down altogether.

The discoveries have electrified biologists, shaking up long-held theories of genetics. Science magazine declared the rapidly expanding understanding of what are called "small RNAs" the research breakthrough of last year.

Much remains to be understood about how small RNAs work, but research suggests that they play a role in the development of plants and animals, as well as in fending off illnesses. Several biotechnology companies have begun to work on translating the findings into new medicines.

As their names suggest, RNA and DNA are related molecules, strings of chemical building blocks called nucleotides that make up the genetic code. The instructions for making proteins -- which "build" and maintain everything from our muscles to the hemoglobin in our blood -- are copied from genes in the double-stranded DNA onto a single-stranded RNA, which then conveys the blueprint to the cell's protein-making factories.

The excitement is focusing on short stretches of RNA just 21 to 28 base pairs in length, which had been largely overlooked by researchers.

In 1998, Andrew Z. Fire of the Carnegie Institution of Washington, a private nonprofit lab in Baltimore, and others injected worms with "double-stranded" RNA, so named because the single-stranded molecule bends back on itself. They saw that the new molecules silenced the genes responsible for producing that RNA.

Researchers have since probed deeper into RNA interference, identifying a "dicer" enzyme that chops the double-stranded RNA into bits, which then silence genes by latching onto messenger RNA.

Studying yeast and a microbe found in freshwater lakes and streams, researchers found last year that small RNAs can permanently shut down or delete whole sections of DNA. The observations suggest that small RNAs play a previously unrecognized role in regulating cell division.

Careers: The two young men responsible for the DNA breakthrough continued along different paths for decades after winning the Nobel Prize.

By Timothy B. Wheeler

For most scientists, a Nobel Prize is the capstone of a career.

But in the 50 years since their breakthrough discovery of the structure of DNA, James D. Watson and Francis H.C. Crick have continued to pursue the frontiers of knowledge, albeit along different paths.

Watson, once the brash whiz kid from Chicago, has become the "dean of DNA," as one colleague calls him. Buoyed by his gossipy 1968 bestseller The Double Helix, he abandoned his laboratory bench for an administrator's desk, pushing for a cancer cure and a complete map of the human genome.

He stands today as the most visible figure in the continuing genetics revolution, though his penchant for speaking his razor-sharp mind has left a trail of enemies -- and admirers.

Crick, who was raised in a middle-class English family, remains a researcher at 86 and co-wrote yet another scientific paper that was published just last month.

After the 1953 coup, Crick pushed on to work out the mechanics of DNA before his restless mind led him to explore more cosmic questions, such as the origins of life on Earth. For the past two decades, he has searched for the scientific basis of human consciousness.

As the world marks the 50th anniversary of the discovery of the double helix with celebrations this week in New York and this spring in England, Australia and elsewhere, admirers are honoring Watson's and Crick's lifelong contributions to science, not merely the discovery that earned them the 1962 Nobel Prize.

At 74, Watson crisscrosses the country attending scientific meetings and ceremonies. In rambling lectures and interviews, he extols the promise of genetic research even as he recalls with self-deprecating humor how he and Crick made history.

"I think the biggest opportunity is curing cancer," he said recently while sipping coffee in his office at Cold Spring Harbor Laboratory in New York. "We really know a lot about that disease."

Watson is president of Cold Spring Harbor, the former biological field station on the north shore of Long Island that he took over in 1968 and steered toward a genetic cure for cancer. He relinquished administrative oversight nine years ago, but the institution's 350 researchers remain among the most frequently cited in scientific literature.

His wispy white hair remains as unruly as it was in his youth, as does his willingness to say whatever comes to mind.

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