The Riddle of Gender - Deborah Rudacille [148]
In the early years of his research on the effects of environmental estrogens, McLachlan found it difficult to publish in mainstream scientific journals. “Reviewers considered the work metaphysical, pointing out that these compounds weren’t really hormones. According to McLachlan, his detractors claimed that he was stretching the limits of endocrinology and that his work was more like toxicology. He himself characterized his research as crossing the boundaries of endocrinology, developmental biology, and toxicology without fitting neatly into any of the disciplines,” Professor Sheldon Krimsky writes in Hormonal Chaos, a study of the scientific and social origins of the environmental endocrine hypothesis, published in 2000. “He and his colleagues were creating their own branch of science and it would take some years before it became accepted.”
Part of the problem in gaining scientific acceptance for the environmental endocrine hypothesis was that it challenged the prevailing paradigm in toxicology, which linked potency to dose. The foundational assumption of toxicology, unchanged since its inception, was “it’s the dose that makes the poison.” The focus of testing was to determine at which dose a particular chemical would cause death (acute toxicity) or produce various types of morphologically apparent damage to experimental animals, especially carcinoma. Upping the dose of a toxin was expected to produce increasingly pernicious (and quickly observable) effects. “The higher the dose, the greater is the expected effect. However, in dealing with hormones and hormone mimics, small quantities might yield an effect, whereas large quantities of the same compound might shut the system off entirely, producing no effect,” says Krimsky Professor Milton Diamond, whose early experiments with guinea pigs showed the gender-bending effects of androgens on female fetuses, told me that when the research team attempted to feminize males with similarly large doses of estrogens, “we couldn’t do it. We got ioo percent abortions.”
Another difficulty encountered by the early exponents of the environmental endocrine hypothesis was that effects manifested themselves not in adult animals exposed to the chemicals, but in their offspring, and in many cases the effects were delayed. The authors of a 2000 paper published in the Quarterly Review of Biology contrasted the traditional toxicological approach based on carcinogenesis and acute toxicity, with the endocrine-disrupter approach, which “relies on a developmental model and delayed dysfunction.” A fetus exposed to an endocrine disrupter might not show any effect at all until puberty— like the first cases of cancer in DES daughters. The delayed effects of DES, DDT, and other estrogenic compounds allowed potential problems to escape detection for many years. Not until the mid-eighties did scientists begin to link the kinds of reproductive anomalies that had been observed for years in wildlife with possible human health effects. In 1990, pharmacist-turned-zoologist Theo Colborn published the results of an extensive literature search on the Great Lakes ecosystem, which revealed signs of reproductive anomalies in eleven of the fourteen species previously identified to be declining in population. Colborn found that though adult animals seemed unharmed by pollutants, “some of their offspring were not surviving, and those that did were afflicted with a variety of abnormalities of reproduction, metabolism, thyroid function, and sexual development.”
Around the same time, a reproductive physiologist named Frederick vom Saal published studies on what he called “the positioning effect,” showing that male mice positioned in the womb between two female fetuses receive extra doses of estrogen, and female fetuses positioned between two