Harvard Public Health Review
Spring 2006

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Ray of Insight

Preventing AIDS in stable couples whwere one partner is HIV-positive

It's grueling and scary enough for adults to go through cancer treatments themselves. But inevitably, those fears are compounded by one for the future: "What risks might radiation and chemotherapy pose to my unborn children?"

Harvard School of Public Health (HSPH) alumnus John Boice, ScD '77, aims to answer that question. In February, Boice, who's spent three decades researching people exposed to radiation directly, helped launch a study of Danish and Finnish cancer survivors diagnosed from 1943 onwards to investigate radiation's indirect effect on their children.

"Cancer survivors who are able to have children often ask whether their kids will be okay," says Boice, a professor at the Vanderbilt University School of Medicine, in Nashville, and the scientific director for the International Epidemiology Institute (IEI) in Rockville, Md. "We're aiming to give survivors information about risks to their offspring associated with treatments that kept them alive."

That radiation causes cancer has been known for more than 100 years. Though radiation has never been overtly linked to birth defects in children born to people who have been exposed, the possibility that it might produce heritable defects can't be discounted, Boice says. After all, non-human species exposed to radiation in the lab--from fruit flies to mice--have been shown to bear abnormal young. And in humans, radiation can cause the DNA in cells to mutate.

Boice and his collaborators--at Vanderbilt, the Danish Cancer Society, the Finnish Cancer Registry, the International Epidemiology Institute, the University of Texas M.D. Anderson Cancer Center, and the Westlakes Research Institute in the UK--are asking: Is this lack of evidence real? Or does it result from the fact that birth defects and adverse pregnancy outcomes in the general population are common, making it difficult to detect incremental risks that might stem from radiation's ill effects in parents?

Unlike the United States, Denmark and Finland maintain extensive national disease registries loaded with patient and health information. The researchers will scour these to identify cancer survivors, their children, and adverse health outcomes. Drawing on chemotherapy and radiation treatment data, they will estimate exposures to the male and female reproductive organs. Dose-response relationships for cancers, birth defects, stillbirths, and newborn deaths will then be quantified. From a subset of people, blood samples will be drawn and assayed for genetic abnormalities.

How low should we go?
When Boice started crunching data, it wasn't clear how much radiation humans could tolerate before suffering ill effects. Was there even such a thing as a safe dose? At what threshold did radiation ignite tumor growth?

Today, Boice is considered the world's leading radiation epidemiologist; his seminal studies have helped spawn public policies to prevent radiation-induced illnesses, including cancers of the brain, breast, bladder, blood, and thyroid. "Everyone in the field knows who he is," says Isaf Al-Nabulsi, program administrator for the Veterans' Advisory Board on Dose Reconstruction, an independent Congressional advisory panel of which Boice is a member. "Boice doesn't need any introduction."

Finding creative ways of estimating radiation doses is Boice's forte. At HSPH, he took a class with Jack Little, now the James Stevens Simmons Professor of Radiobiology, Emeritus, and never looked back. For his doctoral thesis, Boice estimated doses to the breasts of female tuberculosis survivors by hauling out a 1920s-era fluoroscope like the ones used to X-ray their lungs. Gleaning additional data from medical charts and interviews with survivors and physicians, he calculated and added up the “fractionated” doses women had received from bi-weekly X-rays over many years. Boice showed that, for women under age 40, these exposures produced a linear dose-response, meaning that even the lowest doses were associated with above-normal risks of breast cancer. Moreover, the fractionated doses added up to breast cancer risks similar to that of a single dose experienced by atomic bomb survivors. These findings, published in 1977 and co-authored by Boice's thesis advisor, Richard Monson, currently a professor of epidemiology at HSPH, triggered changes in mammography machines, which now deliver radiation in doses 50 times smaller than those of the 1970s.

After graduating from HSPH, Boice joined the National Cancer Institute (NCI) and began building an international reputation. In 1984 he helped form the NCI's Radiation Epidemiology Branch and became its first chief. For 22 years, Boice published studies on radiotherapy's impact on internal organs, as well as on the health consequences of radon in mines and homes, occupational exposures in radiologic technologists and Chernobyl cleanup workers, and environmental exposures among people living near nuclear facilities. Many of these studies confirmed radiation's low-dose carcinogenicity.

In 1996, Boice joined the International Epidemiology Institute (IEI). With joint appointments at the IEI and Vanderbilt, Boice continues to probe the effects of small radiation exposures over time. "Many of us are trying to validate or modify current estimates of risk, which assume linearity down to the lowest doses," he says. The work is challenging, in part because the body constantly repairs radiation's damage to DNA. Moreover, some cancers--leukemia, for instance--don't follow a linear dose-response. All of these efforts add up to higher safety standards for occupational and environmental exposures, and heightened awareness in medicine.

"We have to be vigilant when it comes to the medical application of radiation," Boice says. For example, whole-body CT scans--particularly multiple scans in children--could escalate risks to a point of concern. "There's a need to constantly monitor new technologies so that exposures are as low as possible," he says, "without compromising the clinical benefits."

Charlie Schmidt writes about health, science, and the environment for Technology Review, Environmental Health Perspectives, and National Geographic Online.

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