Darlene Francis 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.
As a graduate student, Francis conducted an 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 tended to be better nurturers, licking and grooming their pups more than the anxious mothers did. But when a calm, nurturing mother raised the genetically anxious pup 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 the question of nature versus nurture, we’ve embraced the view that our fates are written in genetic code. The news in recent years has been filled with reports about the isolation of genes said to “cause” everything from diabetes to voter turnout. Increasingly, though, researchers are finding that genes don’t tell the whole story.
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.
Francis’ work has been among the first to show that epigenetic influences go far beyond the common conception of “environment” to include things such as social interactions. With that in mind, her lab at the University of California, Berkeley, collaborates with scientists across the spectrum: in molecular biology, public health, psychology, and even moral reasoning. The links may strike some hard-core geneticists as alien territory, but with findings like Francis’, doubters may soon find themselves arm in arm with the “soft” sciences. Francis considers herself a member of both camps. “I’m a Ph.D. in neuroscience, but at heart a social worker,” she says.
In the 1990s Francis took a break from her graduate studies at McGill University to work with troubled young children in Montreal. She knew all about their early life experience–many of her charges were the children of friends she had grown up with. How, she couldn’t help but wonder, had she ended up in a Ph.D. program while her friends were visiting their kids in jail?
Such questions preoccupied Francis when she returned to school. She already knew that social, economic, and emotional deprivation could harm family relationships, and a resulting lack of nurturing could set up a certain type of brain biology for children. The young rats’ genes had been chemically repackaged in order to mobilize permanently against stress and routinely pump out high levels of hormones such as cortisol, in turn damaging learning capacity and heightening fearfulness. And yet, Francis was sure that the reactive behavior patterns apparently etched into the brain’s biochemistry could change. In working with troubled children and their mothers, for example, she had seen how transformative a simple thing like a weekend outing could be. The question was, how?
Francis set up experiments to investigate what could damp down the stress response in teenage rats. Enriched environments–cages with plenty of toys and social companionship–changed both hormone levels and behavior. Gene expression remained the same, however, suggesting that the rats compensated in some other way. To better understand what happens, Francis has begun a number of cross-disciplinary projects at Berkeley on stress response, decision making, and external influences on gene activity.
One of her closest collaborators is integrative biologist Daniela Kaufer, whose work documents the role of RNA–long dismissed as DNA’s poor sibling–in switching the functions for which DNA codes. Under stress, Kaufer has found, molecules outside the genome change the RNA in new ways, trimming and rearranging it to alter gene function.
Kaufer says that if researchers can break down the reprogramming in the brain caused by early-life trauma or stress, possible interventions may present themselves. Physical exercise, for instance, is known to reset the molecular machinery. Yoga, meditation, and sleep all can alter the stress response, muses the former yoga teacher.
For Francis, the study of how stress can work itself into our biological inheritance remains deeply personal. “I’m a product of all this stuff,” she says, referring to her hardscrabble beginnings back in Montreal. Americans, Francis contends, think poor people are poor because they make poor decisions. Francis believes the experience of her rats points to something very different.
Sally Lehrman has reported for Scientific American and the Peabody Award-winning, NPR-distributed series The DNA Files (www.dnafiles.org). Reprinted from California(March-April 2008), the alumni magazine of the University of California, Berkeley. Subscriptions: $19.95/yr. (6 issues) from Alumni House, Berkeley, CA 94720; www.californiamag.org.
