Brenner doesn't do boring. A Nobel Prize winner and one of the founders of molecular biology, he keeps opening up new fields of research. After solving some initial problems and attracting clever collaborators, he then moves on to try something different. On this occasion, last March at HHMI's Janelia Farm Research Campus in Ashburn, Virginia, he was attending a conference on the nervous system. A senior fellow at Janelia, Brenner was making one of many stops on an ever-full itinerary. He spends much of his time flying around the world, giving talks and advice, running research projects, launching new alliances, stirring things up.

"I've been a rebel, or as I was once called, an enfant terrible," he said in a series of interviews later published as an autobiography, My Life in Science, by BioMed Central Ltd. "Being a rebel has always appealed to me, largely because I'm convinced that the standard parts of any activity are already petrified at the core."

In the late 1960s, for instance, "after cracking the genetic code, Sydney decided he wanted to understand how genes control the development and function of the nervous system," says Paul W. Sternberg, an HHMI investigator at the California Institute of Technology. "So he chose to work with the worm"—specifically, a tiny transparent nematode called Caenorhabditis elegans, that he seemed to pick out of obscurity.

"People thought I was crazy," Brenner recalls.

But these worms are only 1 millimeter long—a good size to study under an electron microscope—and easy to grow in bulk. Ten thousand can fit onto one petri dish, where they feed on Escherichia coli bacteria. And they take only three and a half days to grow from egg to sexual maturity, when they produce about 300 progeny apiece.

Brenner liked them for all these reasons and also because of what he called their "beautiful sex lives." C. elegans is usually "a self-fertilizing hermaphrodite," he notes, and "each animal is the result of a cross of itself with itself." This means the worms have a uniform genetic constitution, as if they are clones. Occasionally, some smaller, male C. elegans worms crop up, which researchers can use to move genetic markers from one animal to another in experiments.

Brenner hoped his worms would enable scientists to study how genes affect behavior "because there is no simple mapping that connects the two," he explains. "The link between genes and behavior resides in understanding the structure of the nervous system"—particularly, the brain. So, in the early 1970s, he began to find mutant worms with behavioral abnormalities and to map the sites of their genetic mutations. Brenner also started a program of cutting up the worms into serial slices and examining each slice with an electron microscope.

Ultimately, in 1986, he and his colleagues John White, Eileen Southgate, and J. Nichol Thomson published the structure of the nervous system of C. elegans.
(Some ten thousand electron micrographs from these studies are now archived and accessible for scientific review at the Albert Einstein College of Medicine. For more information, visit There's Gold in Those Archives.)

Photo: Tom Kochel

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