When Hardship Changes Biology

Most days, Charles A. Nelson III can be found down the street from Children’s Hospital Boston, working in an office suite in which small rooms are painted with colorful animals and are frequently occupied by young children. It could be mistaken for a pediatrician’s office—that is, if a pediatrician’s exam rooms had lots of computer and camera equipment and the kids sometimes wore odd-looking caps with wires coming out of them.

Although he is not a pediatrician, Nelson is a researcher who studies the brain and behavioral development of young children, focusing in particular on those children for whom early development has somehow gone awry (or is at risk for going awry), either as a consequence of adversity early in life or because of a biologically based disorder. He’s devoted years to studying the effects of institutionalization on Romanian orphans, and he is overseeing, with his Boston University colleague Helen Tager-Flusberg, a $2.5 million grant from the National Institutes of Health to study infants at risk of developing autism—which is where the high-tech caps come in.

Nelson, who holds the Richard David Scott Chair in Pediatric Developmental Medicine Research at Children’s Hospital, is also a professor of pediatrics, neuroscience, and psychology at Harvard Medical School and a professor in the department of society, health, and human development in the Harvard School of Public Health. He has been affiliated with the work of the Center on the Developing Child since its inception in 2006.

One of the central tenets of the Center’s mission is its commitment to building a multi-disciplinary science of child health, learning, and behavior that reveals the early roots of lifelong disparities. Part of doing that is to fund or facilitate the next generation of cutting-edge science that will help advance the field.

nelson-pullquote-1column2.jpgSo, in the fall of 2008, the Center provided seed funding for three years to a team of six Center-affiliated Harvard researchers, including Nelson, to study the biology of early childhood adversity. The 6 researchers were part of a 10-member Center working group called the Interdisciplinary Research Seminar on Disparities (IRSD).

The IRSD team’s project comprises five separate but integrated multidisciplinary studies that together are trying to understand the biological toll of early life adversity. They are examining the cellular and molecular consequences of such hardship as maternal neglect or traumatic injury in both human populations (three studies) and lab mice (two studies).

Historically, Nelson explains, when bad things happened early in life, the tendency was to look at them in terms of what the effects are on a person’s psychology. For example, does it put the person at greater risk for depression?

This research, however, is looking more at the mechanism for how experience can change biology. “It’s called biological embedding—how does behavior get interwoven with biology,” Nelson says.

In Nelson’s contribution to the IRSD work, he is extending the research of his Bucharest Early Intervention Project, which is a randomized controlled trial in Romania comparing the effects of foster care as an alternative to institutionalized care for young children who were abandoned at or shortly after birth and placed in institutions. Nelson and colleagues have already collected DNA samples (buccal swabs, in which loose cheek cells are swabbed from the inside of the mouth) of both institutionalized and non-institutionalized children. In this study, they plan to take additional samples from the same children at an older age. By analyzing the samples, they hope to identify changes to genes and chromosomes that have occurred as a result of adverse early experiences and that may be markers for a much greater risk of serious health problems later in life. For example, the researchers will examine the telomere region, which is a small cap that sits on the tip of a chromosome and wears down over time or with chronic adversity.

Nelson explains: “When you’re abandoned at birth and dumped into an institution—leaving aside that it leaves you emotionally scarred and with very low IQ and having no language and all those other things—is there a biological consequence of that, as well? For example, does it increase your risk of health problems? Does it reduce your lifespan? Does it increase morbidity and accelerate mortality?”

If the IRSD team’s other researchers see the same kinds of genetic damage in their samples, whether in the mouse or human studies, then the team will know it’s onto something that might help kids. “What’s important about the project as whole,” says Nelson, “is that if we can more clearly articulate the effects of adverse experiences on biological development and the effects on health, generally, then we might start to develop a different set of interventions and implement them at a different point in development.”

This kind of research could have public-policy implications down the road, Nelson says. That’s something he’s already seen from his work in Romania, where the government has barred the institutionalization of any children under 2, unless they’re severely handicapped.

“If what we’re doing works, we could actually use this as [a test] to look at the efficacy of different foster care programs,” Nelson says, by way of example. “What if—leaving psychology out of it—it turns out that in some states, their foster care program leads to much better biological outcomes than another state’s foster care program? Then we have a benchmark. Then we go back in, and we try to change the foster care program” in the other state.

In addition to his role doing basic research that could eventually inform public policy, Nelson also works actively to help bring current scientific findings to bear on the public sector as a member of the National Scientific Council on the Developing Child, which predates, but is now an initiative of, the Center. Its members are leading researchers and scientists from higher education institutions in the United States and Canada who write and speak frequently about child development research to audiences of politicians and policymakers.

Nelson says those activities feed his interest “in getting the word out, translating science into policy,” and, he says, they “need to be done.”

-- Millicent Lawton

Photo by Fred Field

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