Wriggling their way to scientific stardom

Tiny worms win growing respect for role in studying mysteries of life

Science

February 25, 2005|By Dennis O'Brien | Dennis O'Brien,SUN STAFF

One of the stars of the biological research world is a millimeter long and probably lives in your back yard.

Caenorhabditis elegans, a worm with no heart, bones or blood, has been used by one group of scientists to win a Nobel Prize and by others to explore how life works. The growing army of researchers who work with C. elegans appreciate it for practical and scientific reasons.

Most important, the tiny creatures have something in common with humans.

C. elegans became the first multicellular organism to have its genome sequenced in 1998. The feat - the culmination of an eight-year effort by British and U.S. researchers - attracted many scientists to the worm because it turned the organism into a kind of genetic Rosetta stone.

Because humans and worms evolved from the same one-celled organisms that dominated the planet until 600 million years ago, we share many of the same genes, including those linked to Alzheimer's, heart disease, aging and a range of birth defects.

"We know that whatever a gene is doing in a worm, it's doing the same thing in humans," said David S. Fay, who studies tumor suppressor genes in C. elegans at the University of Wyoming.

The worms are easy to use in the lab. They grow from birth to breeder in four days, live for two weeks, are easy to store, cheap to feed and, once there's a batch, they reproduce so rapidly there's no need to replenish supplies. What's more - they're transparent.

As simple as they are, the worms also intrigue scientists because they have a nervous system, a sex life, and some curious habits. They have been known to stand on one end and seemingly wave - no one knows why.

Another benefit: No one has complained yet about mistreatment of the worms.

"There may be some people out there concerned about the rights of these worms, but I've yet to see any," said Sir John E. Sulston, a British researcher and former director of the Wellcome Trust Sanger Institute in Cambridge who was knighted for his contributions to genetics.

Three years ago, Sulston shared a Nobel Prize with H. Robert Horvitz of Massachusetts Institute of Technology and Sydney Brenner, founder of the California-based Molecular Sciences Institute, for use of C. elegans to unravel mysteries about cell death, a process that plays a key role in AIDS, stroke, cancer and other diseases.

These days, biologists are using the worm to figure out how cells age, the genetics behind birth defects and the molecular machinery that fuels embryonic growth.

"The thing is, how a cell works is extremely complicated," Sulston said. "There's more going on in your basic bacterial cell than what you might find going on inside a 747."

Beautiful and tough

Some scientists seem passionate about the worms.

Geraldine Seydoux, a biology professor who studies them at the Johns Hopkins School of Medicine, uses words like "beautiful" to describe the gray creatures and their dew-drop-like embryos.

"You have all this information packed into one tiny animal," she said. "It's fascinating."

Seydoux and her researchers grow C. elegans in sealed dishes, create mutations with the help of a few chemicals and document how the mutated genes affect the resulting organism. They also are working to figure out why parts of the worm develop into its 2,000 or so reproductive cells while others form the approximately 1,000 cells used for the nervous system, skin and other survival tools. This cell differentiation begins within an hour of egg fertilization.

"What we're trying to determine is, how do you start with one boring egg and wind up so quickly with cells that are different," said Seydoux, who won a MacArthur Fellowship grant in 2001.

C. elegans are roundworms, as opposed to the earthworms used as fishing bait. Different genetic strains have different eating habits. Strains from the wild eat in groups, while lab-raised worms prefer to dine alone. But researches say that the lab worms will cluster and eat together if under stress, such as if oxygen levels drop in their environments.

Researchers have found that C. elegans - which live in any temperate climate - can survive on almost no oxygen. They also can enter a dormant, sleeplike stage that extends their lives when stressed.

"They're tolerant of almost anything we put them through," said Cindy DeRenzo, a graduate student in Seydoux's lab.

Easy to study

Researchers have been using C. elegans since the 1960s when Brenner and other scientists at the Medical Research Council Laboratory, a Cambridge facility funded by the British government, discovered that the worm's transparent skin made it ideal for studying cell division under a microscope.

By the early 1970s, MRC scientists were publishing studies showing how the worm could be mutated with chemical compounds during cell differentiation, the process in which cells specialize to form the various tissues and organs. The studies fascinated biologists worldwide, in part because of what they implied about human genetics and development.

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