DNA Is Not Destiny The new science of epigenetics rewrites the rules of disease, heredity, and identity. by Ethan Watters From the November 2006 issue; published online November 22, 2006 Back in 2000, Randy Jirtle, a professor of radiation oncology at Duke University, and his postdoctoral student Robert Waterland designed a groundbreaking genetic experiment that was simplicity itself. They started with pairs of fat yellow mice known to scientists as agouti mice, so called because they carry a particular gene—the agouti gene—that in addition to making the rodents ravenous and yellow renders them prone to cancer and diabetes. Jirtle and Waterland set about to see if they could change the unfortunate genetic legacy of these little creatures. Typically, when agouti mice breed, most of the offspring are identical to the parents: just as yellow, fat as pincushions, and susceptible to life-shortening disease. The parent mice in Jirtle and Waterland's experiment, however, produced a majority of offspring that looked altogether different. These young mice were slender and mousy brown. Moreover, they did not display their parents' susceptibility to cancer and diabetes and lived to a spry old age. The effects of the agouti gene had been virtually erased. Remarkably, the researchers effected this transformation without altering a single letter of the mouse's DNA. Their approach instead was radically straightforward—they changed the moms' diet. Starting just before conception, Jirtle and Waterland fed a test group of mother mice a diet rich in methyl donors, small chemical clusters that can attach to a gene and turn it off. These molecules are common in the environment and are found in many foods, including onions, garlic, beets, and in the food supplements often given to pregnant women. After being consumed by the mothers, the methyl donors worked their way into the developing embryos' chromosomes and onto the critical agouti gene. The mothers passed along the agouti gene to their children intact, but thanks to their methyl-rich pregnancy diet, they had added to the gene a chemical switch that dimmed the gene's deleterious effects.
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