A Unlikely Star of Science
Jonathan Freedman Looks to Microscopic Roundworms to Document
the Effects of Toxic Chemicals p.2
Toxicity screening during development
evaluates chemicals by administering pre-selected amounts
to groups of animals while they are growing up, and then monitors
the outcomes. 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.
While rats and mice are the laboratory
standards for such work, Freedman said there would be a number
of advantages if the nematode were substituted for at least
the initial large-scale screening. For example, it takes just
3 1/2 days for the roundworm to develop from egg to adult.
And each adult worm is only 1 millimeter (1/25 of an inch)
in length, meaning that large numbers can be maintained and
tested in small spaces.
Because the roundworms are transparent,
researchers can directly monitor chemicals’ effects on the
worms’ developing internal organs.
In addition, strains of the roundworms
have been genetically engineered in Freedman’s lab and elsewhere
to make various cells change color or emit a fluorescent glow
if a chemical they’re exposed to is toxic.
As is the case 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 “knocked out” of
its genome through biochemical manipulation.
“To knock out one mouse gene can
cost $100,000 to do a genetics study that takes a year,” Freedman
says. “Whereas in C. elegans we just feed the roundworms
a strain of bacterium and the gene is knocked out.”
Unlike with genetically engineered
rodents, the knockout effect on specific nematode genes is
temporary. That’s because the roundworms themselves are not
engineered. Instead, their bacterial food is simply spiked
with “antisense” DNA designed to block the function of the
gene. The effect lasts only as long as the roundworms continue
to be fed that special diet.
Freedman’s funding agency, the NTP,
coordinates toxicological testing programs within the U.S.
Department of Health and Human Services and seeks to increase
scientific knowledge about potentially hazardous substances.
“As part of a new initiative to broaden and refine our investigational
methods, we are extensively evaluating C. elegans’
potential value to developmental toxicology,” says Christopher
Portier, an NTP associate director.
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