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Spring 2004

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Around the Pond

The Power of Poison
A radical theory shakes up the field of toxicology

-Christopher O'Carroll ’97




	Cure you or kill you? The toxicology establishment finally ingests Professor Ed Calabrese’s provocative theories about poisons. (photo by Ben Barnhart)

FOR YEARS, THE SCIENTIFIC ESTABLISHMENT spat out Edward Calabrese’s ideas as if they were pure poison. His unconventional thinking about toxic chemicals was routinely “maligned and kicked around,” Calabrese says. “It was marginalized and not believed to be true.” But he persisted in piling up research data, and has at last begun to see his controversial views breaking through to respectability.

Calabrese, a professor in the department of environmental health sciences, holds two UMass doctorates: a 1973 Ph.D. in entomology (with a specialty in pesticide toxicology) and a 1974 Ed.D. in science education. In the 1980s, he became a hero to environmentalists and a villain to the chemical industry with his research on carcinogens and his advocacy of strict environmental cleanup requirements. More recently, he has put his professional reputation on the line by attracting international attention as a champion of hormesis, the theory that many toxins, taken in small doses, are not merely harmless, but actually contribute to good health.

His hormesis research encompasses an extensive rogues’ gallery of poisons—arsenic, cyanide, carbon monoxide, cadmium, lead, mercury, dioxin and DDT. In large doses, these substances can kill outright or generate long-term health problems by causing cancer, heart disease and other deadly conditions. But in small doses, Calabrese maintains, they can stimulate the body’s self-repair mechanisms to promote disease resistance, longevity and other health benefits.

The so-called hormetic effect is similar to well-established biological phenomena. For example, weightlifters inflict small injuries on their muscles, thereby causing the body to rebuild the tissue bulkier and more powerful than it was before. Similarly, Calabrese’s research seems to indicate microdoses of deadly toxins can stress the body and provoke a beneficial overreaction. According to hormetic theory, the body responds to small-scale toxic assaults by marshalling more resources than needed to repair the minuscule amounts of damage the poisons have caused. This excess healing power not only repairs the immediate injury: it leaves the affected cells and organs more robust than if they had never been attacked.

As hormesis becomes better understood, it could help to revolutionize environmental protection policy. The theory also offers exciting potential in cancer, Parkinson’s and Alzheimer’s research. Its promise has prompted Calabrese’s work to be written up far beyond the realm of toxicology journals. He has appeared in the pages of such diverse publications as Science, Discover, The Times of London and The Wall Street Journal.
Despite his recent notoriety, the unassuming scientist admits “It’s been a battle” getting fellow toxicologists to give serious consideration to the counterintuitive notion that poison might be beneficial. When he began devoting himself to the subject, he says, “You couldn’t get an invitation to give a presentation on this at the big toxicology meetings.” Today, as an example of how things have changed, he points to the prestigious textbook Casarett and Doulls Toxicology: The Basic Science of Poisons. “The first six editions never had even a mention of the word.” But the seventh edition, published in 2001, finally included a discussion of hormesis, elevating the theory to the status of something that every student of toxicology needs to know.

Calabrese, who grew up in Bridgewater, traces his interest in hormesis to an accidental discovery during his undergraduate days at Bridgewater State College. “My attention first got drawn to the topic in 1966,” he says. “I was a junior in college taking a plant physiology course.” His professor instructed the class to treat a peppermint plant with a toxic chemical known to be a growth inhibitor, and to measure the effects. When the plant responded with increased growth—the opposite of the expected reaction—the surprised students checked the details of their experiment and discovered that they had unintentionally used a much diluted solution of the chemical. Administered in that low dosage, the inhibitor had acted as a stimulant.

Although Calabrese found hormetic response intriguing, he did not make it a central issue in his scientific career over the next two decades. It was not until 1985 that a conference on radiation hormesis (it appears that large doses of radiation can promote cancer growth, but small doses can help the body fight off the disease) revived his interest in those poison-loving peppermint plants. By 1990, the health benefits of toxic chemicals had become his main professional preoccupation.

He’s aware that scientific findings can often be distorted in public policy debates and that his research could be co-opted by political and industrial partisans who never met an anti-pollution law they didn’t hate. “My role,” he says, “is to provide the best science possible. The implications are huge and they’re really just beginning to be known.” Beyond any impact on environmental policy and medical practice, he sees hormesis as the key to a more profound understanding of the human body. “This occurs in every cell, every organ, every whole organism,” he says. “It speaks to our basic biology.”
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