Collaborators: Daniela Kaufer (left) and Darlene Francis are working to better understand how external influences affect gene expression. Marcus Hanschen

Darlene Francis, clad in a blue zip-up hoodie and running shoes, is talking about the frontal cortex, decision-making, and high-stress profiles in rats, when she suddenly shifts the focus to poor, single, inner-city moms—that is to say, stressed-out humans. Working with rodents, the behavioral neuroscientist points out, makes it easier to study and talk about social problems without stirring up a political battle. But if you want to understand the effects of maternal stress on childhood development, Francis says, just look at her rats.

While still a grad student, Francis conducted a cross-fostering experiment in which she swapped pups between a litter of rats bred for calmness, and another that was predisposed to anxiety. The genetically calm mothers also tended to be better nurturers, licking and grooming their pups, than the less-attentive anxious mothers. But when a calm, nurturing mother raised the genetically anxious pup that had been added to her brood, the adoptee switched tendencies. The anxious rat behaved calmly throughout life, performed better in cognitive tests, and was more willing to explore new environments. The calm mother's behavior, Francis discovered, had caused permanent changes in the operations of the anxious rat's genes. Even more stunning: The acquired traits—calmness and nurturing habits—were passed on to the anxious rat's next generation.

In a rapidly developing field called epigenetics, scientists are discovering that nutrition, exposure to toxics, even a mother's touch (or lack thereof) can cause heritable changes in gene expression without any corresponding change in DNA sequence. This is a radically different view of heredity, one that adds another layer of complexity to the common conception of DNA as the complete and immutable set of instructions for life.

One oft-cited experiment in the emerging field was conducted by Randy Jirtle, a pathologist at Duke University, who in 2003 found for the first time that a mother's nutrition during pregnancy could alter gene expression. Jirtle discovered that simply by feeding Agouti mice four common nutritional supplements before, during, and after pregnancy, he could change the offspring from chubby and yellow to thin and brown. The nutrients, he discovered, added a chemical layer to DNA that slowed the activity of a gene involved in both coat color and appetite. The modification also lessened the animals' susceptibility to obesity, diabetes, and cancer. Nothing in the genome itself, however, had been changed.

Findings like these, which undermine the centrality of the genome and add a new twist to Darwin's theory of evolution, were bound to excite controversy. Early researchers in the field were warned that their careers would suffer if they persisted in looking outside the genome to explain human development and disease.

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