A TOXIN TWIST

A theory asserting that very low doses of many toxins are, in fact, beneficial has been around for several years and, while embraced by some, is viewed either as an interesting idea or doubted entirely by many toxicologists. But the theory, called hormesis, arrived for public consideration this week through the publication of a commentary in the highly respected journal Nature. If the theory is true, it would dramatically change the way scientists view risk from chemical exposure.

Edward J. Calabrese and Linda A. Baldwin, members of the Department of Environmental Health Sciences at the University of Massachusetts, Amherst, wrote the Nature commentary called “Toxicology rethinks its central belief.” They say the traditional ways of viewing risk as increasing linearly from either an initial presence of a toxin or from a threshold level is wrong. Instead, they say that low levels of dioxin, saccharin, X-rays and various gamma ray sources, for instance, actually reduce tumors in some species – that is to say, improve health. There is more: “Some anti-tumor agents (for example, suramin) that inhibit cell proliferation at high doses, where they may be clinically effective, become like a partial agonist at lower doses, where they enhance cell proliferation” – increasing the likelihood of tumors.

From other reports, examples of hormesis include reports that that those exposed to low doses of radon through granite house foundations have lower rates of lung cancer than those who have not been exposed. Low levels of toxic metals like cadmium and mercury are reported to promote the growth of marine algae. And very low doses of arsenic are said to have been shown to induce cell-protection mechanisms.

The implication of this work is enormous because it would mean that the way the nation’s top regulators view risk would be changed. Instead of a straight line of increasing risk as the dose increases, hormesis produces a U- or J-shaped line with the dip down representing opposite effects of that expected, then returning to the expected reaction as the dose increased. As the authors point out, their theory “challenges the belief and use of low-dose linearity in estimating cancer risks, and emphasizes that there are thresholds for carcinogens. The economic implications of this are substantial.” The last sentence is a monumental understatement – it could change carcinogen thresholds, certainly, and could also change how industry discharges are regulated and how pollutant cleanups are ordered.

Some toxicologists will conclude that the low levels being discussed in the commentary are so low that they cannot accurately be separated from the background noise of the experiments and so are inconclusive. They may be open to a debate on many other aspects of measuring risk, but not hormesis. However, the public – and lawmakers count among the public – does not have the training and experience to know how important commentary like this is so it depends on peer-reviewed journals to decide what constitutes good science. Nature is among the world’s finest, and it has put the idea in play for policymakers to consider. The response to the journal ought to be interesting.