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Genetically endowed worm may substitute for rodents in some toxicology testing

During this evaluation, his group plans to expose developing roundworms to 200 different chemicals, in collaboration with researchers at the NTP and Environmental Protection Agency. The group will also evaluate how chemicals affect a roundworm's neural systems at various stages of life.

Freedman foresees several advantages if researchers use nematodes instead of the rats and mice that are now the laboratory standards for such work, especially during the expensive initial stages that typically involve large-scale screening.

For example, it takes just 3 days for the roundworm to develop from egg to adult. Since each adult worm is only 1 millimeter in length, large numbers can be maintained and tested in small spaces.

Because the roundworms are transparent, researchers can also directly monitor chemicals effects on the worms' developing internal organs.

Toxicity screening during development evaluates how pre-selected amounts of chemicals affect groups of animals as they grow. Even if the animals do not sicken or die as they mature in the presence of toxicants, the chemicals may affect their organs in ways that can be investigated normally through surgery or necropsy.

As with laboratory rats and mice, Freedman and his workers can even produce "knockout" varieties of C. elegans to evaluate how the animal's physiology changes if specific genes are excluded from its genome through biochemical manipulation.

Unlike genetically engineered rodents, the roundworms themselves are not engineered. Instead, their bacterial food is simply spiked with "antisense" DNA designed to block the function of the gene.

"To knock out one mouse gene can cost $100,000 to do a genetics study that takes a year," Freedman said. "Whereas in C. elegans we just feed the roundworms a strain of bacterium and the gene is knocked out."

In addition, strains of th
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Contact: Monte Basgall
monte.basgall@duke.edu
919-681-8057
Duke University
27-Oct-2004


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