Is there a tonic in the toxin?
One day, however, the mail brought an advertisement for a meeting on radiation hormesis, the idea that radiation can kick-start the body's defenses and improve health. Reminded of his mint plants, Calabrese wondered if anyone had looked at this notion in chemicals. He decided to test the idea and began to find various examples of toxins doing some good for plants and animals at low doses.
His colleagues scoffed, arguing that it must be a rare and insignificant effect. So Calabrese and colleague Linda Baldwin did a survey of some 4,000 toxicology studies reported in science journals. They found that about 350 showed chemicals had opposite effects at low levels. And the actual prevalence could exceed that, as most of these studies weren't designed to tease out subtle effects that happen at tiny doses.
These days, most toxicologists accept Calabrese's general premise that tiny doses can have strange effects. As Linda Birnbaum, director of the experimental toxicology division of the Environmental Protection Agency and president of the Society of Toxicology, says: "Just looking at a high dose when we are killing animals or causing very overt, obvious problems may not tell us what is happening at the low-dose region. The real challenge for the next years is to understand how we approach this complexity." Still, while interest in low doses has grown, the emphasis has generally been on overlooked harms.
Calabrese courts controversy because he doesn't discount the possibility that low doses could improve health. As a result, "people tend to think of hormesis as a beneficial response," says Birnbaum, who believes it's not so simple. Low doses of certain chemicals might help some body systems while hurting others. They could, for example, help prevent cancer but also interfere with the immune system or fertility.
Good and bad. Calabrese doesn't disagree. "Some people describe it as a beneficial effect at low doses. I don't do that," he says. "I have tried to emphasize that there are opportunities for good and bad here." For example, he and colleagues have a study next month in Reproductive Toxicology that shows that higher levels of lead can delay puberty in mice, while lower levels can speed it up. So, should regulators try to push lead levels as low as possible, or not? "It challenges regulatory risk assessment concepts," he says.
Despite his willingness to consider that toxins can sometimes be beneficial, Calabrese seems to enjoy needling industry just as much as challenging environmentalists. He's taken industry-unfriendly positions like the notion that a single brief exposure to a carcinogen might be enough to trigger cancer, and in one political fight over the cleanup of a military site, he argued for a more rigorous cleanup than even the EPA.
But intellectually, Calabrese says, he thinks hormesis should "win." And even as he lays siege to his profession's sacred pillar, he acts surprised that anyone would feel threatened, as if this toxicology debate were like a baseball game or a bike race where everyone goes for the gusto and then shakes hands at the end. The disconnect helps explain why this scientist who is so comfortable with chemicals' paradoxical effects has trouble understanding how people on every side of a debate can find his work so alarming. "I view myself as quiet and mild-mannered," Calabrese says with a sort of mystified shrug, "but I seem to get embroiled in controversy."
Born: Aug. 10, 1946
Family: Married for 31 years, two sons
Education: Ph.D. in physiology/toxicology, University of Massachusetts-Amherst, 1973
Public service: Worked with National Academy of Sciences panels on issues like clean water and air quality
advertisement
