A Unlikely Star of Science

Jonathan Freedman Looks to Microscopic Roundworms to Document the Effects of Toxic Chemicals p.3

  “We know basically everything about the development of this particular organism through its entire lifespan,” says Portier. “Since we’re interested in finding something that, while it won’t be definitive, can warn us about chemicals that could potentially affect development, this is an extremely good model for doing that.”

  Using standard rats and mice, “we can only do so many assays is a given year,” he adds. “It’s just a matter of resources, space and availability of animals. So the idea is to develop an inexpensive, fairly sensitive screen that can give us guidance on what to test.”

  “Potentially if we get enough information put together and we feel comfortable enough with C. elegans, it may in fact replace the rodent. But for now what we’re looking for is something that helps us set priorities on what to test in rodents.”

  In a separate collaboration with scientists at the NIEHS, Freedman is using knockout roundworms to help answer a question that has come out of research in his lab: why more than 400 separate genes of the nematode species seem to be affected by the toxic metal cadmium.

  He suspects that one reason the number of those genes is so large is that many of them are actually involved in damage control rather than responding to the metal itself. “There are bunches of genes that respond to damaged DNA,” he explains. “There is a bunch that respond to damaged protein. There are also membrane repair genes. Others turn on to a whole defense mechanism that responds to reactive oxygen,” he adds, referring to a trait of cells under toxic assault to release damaging forms of oxygen compounds.

  Cadmium is among the “transition metals,” a group of 37 elements classified by the arrangements of their electron shells and their consequent positions on the Periodic Table. It has been a longtime focus of Freedman’s lab to study “what metals do inside cells,” he says. “A lot of these responses have nothing to do with toxicity.”

  In some cases, his group investigates what he calls “sub-toxic effects.” As one pointed example, he cites the fact that every cigarette contains 1-2 micrograms of cadmium. “Every time you smoke a cigarette or inhale the smoke second hand you’re getting a dose of cadmium,” he says. “So why don’t you develop lung cancer immediately?

  “Your body has a certain response to defend against these metals. Before you see a toxic response your body is adapting. So I’m looking into what those responses are and how they’re regulated.”

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