A little poison, a big help?

Hormesis: The theory that low doses of toxins can prove beneficial is gaining wider attention.

Medicine & Science

March 15, 2004|By Julie Bell | Julie Bell,SUN STAFF

Can a low dose of poison be a good thing?

The answer is clear when it comes to aspirin: Take a couple and cure a headache. Take a bottle and risk ending up dead.

But government regulators long have presumed that isn't true when it comes to carcinogens such as certain pesticides. If they're harmful to people in large doses, they reason, they can't be beneficial in small ones.

Now, a re-emerging but still marginal theory posits that regulators are wrong, calling into question the models the government uses to predict how much of a toxin is bad for you and - potentially - the regulations themselves.

"The implications are clearly there," said Edward J. Calabrese, a University of Massachusetts toxicology professor and the theory's leading, modern-day proponent. "Hormesis is now basically arguing for a seat at the table."

The controversial theory, first championed by a German pharmacologist in the late 1800s, was dismissed by mainstream scientists for decades because of its association with discredited homeopathic remedies such as radium-spiked water.

But Calabrese's research, funded by a combination of industry and government sources, has resurrected the debate.

Scientists say the theory is certain to be discussed at this month's annual meeting of the Society of Toxicology in Baltimore.

It was the subject of a Washington panel discussion last month for journalists, as well as a recent story in the journal, Science.

And for the first time, a leading toxicology textbook includes mention of it in a new edition.

Calabrese first ran across the effect when he tried to poison a peppermint plant as an undergraduate in a 1966 plant physiology course. He apparently diluted the poison and got a brief growth spurt instead.

His interest was piqued again in the mid-1980s, when a flier from an industry-sponsored research group touted the positive effects of low levels of radiation.

But his work, which largely consists of documenting hormesis in the published research papers of others and collecting it in a database, didn't spark great attention until last year.

That's when a commentary he co-authored appeared in the prestigious journal Nature, proclaiming "the predictive models that all regulatory agencies use are based on a fallacy."

The criticism was aimed at how regulators work: by testing high doses of toxins in animals, then using one of two models to predict the effects of low doses. For carcinogens, they presume that any dose, no matter how low, could cause harm. For other chemicals, they assume that there's a low-dose threshold below which exposure isn't harmful.

Moderate imbibing

But Calabrese argues that neither theory takes into account the peppermint plant experiment or others like it.

A striking, everyday example of hormesis is alcohol. Imbibing in moderation has been shown to lower the risk of one kind of heart disease, while heavy drinking can contribute to another kind. Scientists have also observed the effect when using drugs to study memory retention in mice. Low doses stimulated retention; higher doses inhibited it.

Calabrese's database contains nearly 6,000 experiments that exhibit evidence of hormesis. They include a 1978 Dow Chemical Co. experiment in which dioxin inhibited rat liver tumors at low doses and increased them at high ones.

In another study, fruit flies lived longer than normal when exposed to low levels of ethanal, a chemical used to make perfume and polyester resins, but were killed off by higher doses.

Regulators remain skeptical, though, of even using the term hormesis, much less putting it into practice as a predictive tool. A major objection is that the theory doesn't conclude that all toxins are good in low doses. It merely describes situations in which low doses stimulate a biological response, while high doses of the same substance inhibit it.

The only way to tell whether the responses are good or bad is case by case, Calabrese acknowledges.

When scientists exposed neonatal mice to low doses of natural or manmade estrogens, for example, the mice had enlarged prostates later in life - a negative effect. Large doses were associated with decreased prostate size.

"There are clearly different things happening in the low-dose region than in the high-dose region," acknowledged Linda S. Birnbaum, director of the EPA's experimental toxicology division, at the recent Washington forum, sponsored by the nonprofit Environmental Media Services.

About "the idea that low doses of things have a good effect" she said, "we have to be very, very careful."

Birnbaum points out that toxic substances can have multiple effects, stimulating one response in an organism - say, shrinking tumors - but inhibiting another that might not be noticed, such as weakening the immune system.

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