Lab roundworm created to be thin may one day hold key to obesity treatment

Gene manipulation that created sleek and trim roundworms may ultimately help scientists develop new obesity treatments. <br><br>Harvard biologist Gary Ruvkun used a new technique to identify about 400

Wednesday, January 15th 2003, 12:00 am

By: News On 6

Gene manipulation that created sleek and trim roundworms may ultimately help scientists develop new obesity treatments.

Harvard biologist Gary Ruvkun used a new technique to identify about 400 genes in the roundworm's genetic code related to fat production and storage.

His team deactivated, or ``turned off,'' about 300 of the genes in experiments and ``the worms are thin and happy,'' Ruvkun said. When they knocked out the activity of the other 100 genes, worms grew fatter.

Details of the roundworm experiments and the new genetic technique appear in Thursday's issue of the journal Nature.

``If someone told me we'd be using this kind of protocol even three years ago, I'd have said that's crazy _ don't even think about it,'' Ruvkun said.

Scientists frequently conduct basic experiments with roundworms _ known by their scientific name as C. elegans _ because they are inexpensive and simple. Scientists can fit 100,000 on a lab dish, and they reproduce within four days.

Yet humans share about half of the roundworm's 19,000 genes, including 200 of the fat-storage genes. Whether the same gene knockout technique will work in humans is unclear, but obesity drugs might be developed based on the basic understanding of the genes, Ruvkun said.

Other biologists cautioned that drug companies would need at least a decade to safely develop a genetic therapy for obesity. One in five Americans is obese, and obesity is implicated in cardiovascular disease, diabetes and other illnesses.

``The worm studies will allow the identification of many more genes much more rapidly. It'll also speed up the process of figuring out how they work,'' said Leon Avery of the University of Texas Southwestern Medical Center in Dallas, which is conducting its own fat gene experiments with roundworms. ``For the drug companies, this means a much longer list of 'targets' that they can try to find drugs for.''

Ruvkun used a novel gene identification method developed at the Wellcome Trust/Cancer Research UK Institute in England.

Scientists study a gene by deactivating it and examining the organism in the gene's absence. But creating that version of an organism isn't always easy; scientists have needed up to six weeks to create a knockout roundworm.

In the new method, British researchers added genetic material from a roundworm to bacteria. When they fed the bioengineered bacteria to the worms, their immune systems recognized the genetic material carried by bacteria as foreign and destroyed that sequence in their own genetic coding. In doing so, the worms rapidly turned themselves into knockout versions.

The technique takes advantage of the roundworm's defense against viruses and ``jumping DNA'' from hijacking its own genetic code, said Julie Ahringer, a Wellcome Trust researcher and the author of the second Nature paper.

``We can inactivate hundreds of worm genes in a day,'' Ahringer said. ``It's amazing.''