Cruel to be Kind

Researchers are finding that a pinch of poison might ward off cancer and enhance longevity--an observation that could someday lead to radical new antiaging therapies. But should environmental regulations be revamped to expose us to toxins' beneficial effects?

Radiation is a bad thing, or so we're told. So it's not obvious why people with a little radon in their basements are less likely to get lung cancer than their radon-free neighbors are. Dioxin causes cancer in chemical workers who are exposed to large amounts of the compound. Yet mice that consume minute amounts of the carcinogen develop fewer cancers than untreated animals do. The answer to these mysteries might lie in a theory called hormesis, the radical notion that a little bit of poison--whether it be radiation, toxins, or other stressful stimuli--might somehow prime the body to resist and repair damage. Scores of studies show that animals subjected to low doses of such destructive agents live longer and are heartier and healthier than their stress-free counterparts. A growing number of researchers are investigating the mechanisms behind hormesis in the hopes that they might someday harness its benefits to thwart old age and stall the onset of disease. A few even wonder whether we might be wasting our time developing environmental regulations that could be too strict for our own good.

Although hormesis might sound exotic, it's commonplace. Take exercise, for example. From a purely biochemical perspective, a workout should harm the body, says biogerontologist Suresh Rattan of Aarhus University in Denmark. An hour on the racquetball court produces a tremendous number of free radicals and other destructive metabolites that damage cells and might accelerate the molecular deterioration that occurs with age. Although intense physical activity can cause injury and suppress the immune system, moderate exercise helps maintain muscle mass and motility and enhances the body's immune response.

Similarly, low doses of radiation appear to stimulate the immune system and boost cells' abilities to repair damaged DNA, says physician Myron Pollycove of the United States Nuclear Regulatory Commission in Rockville, Maryland. Mice treated with small amounts of radiation accumulate fewer mutations, develop fewer cancers, and live longer than untreated animals do. And the effect is not limited to exercise and irradiation. Toxicologist Edward Calabrese and his colleague Linda Baldwin of the University of Massachusetts, Amherst, have collected evidence from hundreds of publications suggesting that nearly every environmental contaminant imaginable--arsenic, cadmium, lead, mercury, and dioxin, to name just a few--elicits beneficial effects at small doses. In some cases, however, the quantities required to obtain these benefits are greater than the concentrations permitted by current pollution standards. This disparity has prompted Calabrese and other proponents of hormesis to question whether regulatory agencies might be wasting their time and money trying to eliminate low-dose exposures that could possibly enhance our health.

"We live in a low-dose world, but that's not what toxicologists study," he says. These scientists instead probe the potentially deleterious effects of high doses of chemicals. "This is not a willful disregard of hormesis or other low-dose effects," says toxicologist Michael Dourson, a former risk assessor for the Environmental Protection Agency (EPA), who now directs Toxicology Excellence for Risk Assessment, a nonprofit corporation based in Cincinnati, Ohio. "It's because low-dose effects are irrelevant."

Pollution standards are formulated to protect public health, so toxicologists focus on determining how much of an environmental contaminant is safe. To accomplish this task, they work downward from a high, toxic dose until they find a concentration that doesn't cause adverse effects in lab animals. They then convert this "no observed adverse effect level" (NOAEL) to an exposure that won't harm humans by building in a safety margin. The resulting "safe dose" is thus generally around 1/100th to 1/1000th of the NOAEL. But according to Calabrese, the benefits of hormesis in many cases kick in somewhere in between these values, suggesting that regulators might be able to refine the pollution standards so that we can reap the benefits of hormesis while remaining protected from the adverse effects of higher doses.

But regulators are not about to make such a change, says Christopher De Rosa, director of the toxicology division at the Centers for Disease Control and Prevention's Agency for Toxic Substances and Disease Registry in Atlanta. Hormesis is real, he says, and toxicologists are eager to understand how the phenomenon works on a chemical-by-chemical basis. But an uncritical, all-encompassing acceptance of hormesis could be "the slippery slope that some might try to use as a basis for explaining away the potential harmful effects of these chemical agents," he says.

Even if researchers find that hormesis applies to all toxins, regulators must consider a host of other issues before they can adjust pollution standards, says J. Michael Davis, a toxicologist at EPA's National Center for Environmental Assessment in Research Triangle Park, North Carolina. For example, a hormesis-sized dose that improves the health of a young adult might adversely affect children or seniors, whose susceptibility to environmental contaminants tends to be greater. Furthermore, our current background exposure may make hormesis a moot point. For example, studies of animals raised in clean labs on controlled diets suggest that minuscule quantities of lead might be essential for nutrition. But in this postindustrialized world, we already carry more lead in our bodies than lab rats do, says Davis, so we're probably past the point of reaping the rewards of hormesis.

Given the evidence and the controversy, Calabrese and other toxicologists are calling for a group of experts such as the National Academy of Sciences to evaluate the role that hormesis might play in risk assessment. In the meantime, even if hormesis holds the key to slowing aging and enhancing health, it's unlikely that coffee bars are going to start offering shots of lead with their lattes.

Rebecca Renner is a science writer in Williamsport, Pennsylvania. Hormesis or no hormesis, she prefers her lattes unleaded.