October 29, 2019 – Fine particulate matter in the air. Prescription drugs taken by pregnant women. Radiation from CT scans. From before people are born to the time they reach adulthood, they are exposed to countless environmental factors that can influence their long-term health—and possibly the health of their children. Scientists are just starting to piece together the genetic and biological effects of these exposures across generations.
On October 18, dozens of experts gathered in the Snyder Auditorium at Harvard T.H. Chan School of Public Health for the 22nd annual John B. Little Symposium. “Early Life Impacts of Genes and Environment,” hosted by the John B. Little Center for Radiation Sciences, brought together scientists from a range of institutions and disciplines to present research on everything from new pediatric-oncology therapies to long-term studies on how environmental factors spur genetic changes.
“The John B. Little Center for Radiation Sciences is actively pursuing multiple lines of research to identify key vulnerabilities in early life,” said Michelle Williams, Dean of Harvard Chan School, in her opening remarks. She added her hope that the interdisciplinary nature of the event would help scientists across laboratories and institutions make connections that will ultimately help advance the research.
Among the presenters was Amy Berrington de González, radiation epidemiology branch chief and senior investigator for the Division of Cancer Epidemiology & Genetics at the National Cancer Institute, who discussed the negative long-term effects of both high-dose radiotherapy and computed tomography (CT) scans in children. She presented several studies she helped lead in the United Kingdom that focused on children who were exposed to these treatments in the 1990s. The studies showed that while the benefits of diagnostic scans and radiation outweigh the risks, cumulative overexposure in children can lead to adverse effects later on in life, including cancer. Berrington de González added that it’s still unclear why adults continue to show little to no serious risk from radiation therapy to treat cancer.
“We know certain organs are more radiosensitive in children. The most sensitive organs in childhood exposure below age 10 are red bone marrow, followed by the thyroid, breast, brain, and skin,” said Berrington de González, who co-led the first research team to suggest a direct epidemiological link between CT scans in children and subsequent cancer risk. The UK studies she discussed helped raise awareness of the issue, and, as a result, doses and exposure in children over the last decade have been significantly reduced. In recent years, radiologists have started delivering a therapy that minimizes harm to healthy tissue by using protons rather than x-rays to treat cancer, and they continue to mitigate diagnostic scan risks by avoiding and reducing unnecessary procedures.
The effects of other childhood exposures discussed at the event appear to stretch for generations. For instance, Marc Weisskopf, Cecil K. and Philip Drinker Professor of Environmental Epidemiology and Physiology at Harvard Chan School, presented on diethylstilbestrol (DES), a synthetic version of estrogen that was prescribed to pregnant women to reduce the risk of miscarriage and premature deliveries until it was banned 1971. Using data from the Nurses’ Health Study II, Weisskopf led a study that found an association between the mothers of the nurses—who were exposed to DES in the fetus—and low birth rate and preterm delivery among the granddaughters. He said the findings were an example of how gene expression can be altered by exposure to chemicals in the environment.
“The drug didn’t have much effect on first generation, but had effects on the later generation following in utero DES exposure,” said Weisskopf. “DES is no longer used, but endocrine disruptor exposures are currently ubiquitous in other pregnancy drugs and food and care products.” Another analysis presented by Weisskopf showed a correlation between mothers who smoked during pregnancy and a subsequent increased risk of attention-deficit/hyperactivity disorder (ADHD) among their grandchildren.
The all-day event, moderated by assistant professors of radiation biology in the Department of Environmental Health Zachary Nagel and Kristopher Sarosiek, also covered research on the cost of pediatric brain tumors, early findings in lung disease and lung cancer using 3D organoid models, and critical periods of brain development.
photo: Kent Dayton