The Riddle of Gender - Deborah Rudacille [153]
The science of endocrine disruption is still in its infancy, so it is not surprising that no one has investigated possible links between human gender variance and exposure to EDCs. In some ways, “the concept is ahead of the science,” says my friend Jim Yager, senior associate dean for academic affairs at the Bloomberg School of Public Health at Johns Hopkins University. Yager, a toxicologist, has been studying the relationship between estrogens and breast cancer for more than two decades, and even in that well-studied endeavor there have been no definitive data establishing causality between exposure to EDCs and rising rates of breast cancer. Yager says that one of the challenges researchers have encountered in EDC research is that “we’re seeing [biological] effects at concentrations that we couldn’t even detect ten years ago.” Much of the laboratory research thus far has been carried out in vitro, and while it is clear that there are measurable biological effects on cells exposed to various EDCs, and on gene expression within those cells, “you can see an effect, but is it a biologically meaningful effect?”
Then, too, “estrogens are considered reversible cellular signals,” as John McLachlan writes in a 2002 review titled “Environmental Signaling and Endocrine Disruption,” meaning that when the estrogen is withdrawn, the effects of the estrogen fade—as any trans person who has gone on and off hormones could testify. “On the other hand, when estrogens are given to newborn mice, at least one gene under estrogen control is expressed persistently, even in the absence of estrogen,” McLachlan notes in the paper. “This leads to the question, how does a reversible signal became irreversible in the absence of a detectable gene mutation?” McLachlan says that “the actual mechanism underlying the molecular feminization of genes by estrogen still has not been elucidated.” Nonetheless, studies have shown that estrogen can “imprint” genes in such a way that “when a gene programmed to respond to estradiol at puberty is misprogrammed or reimprinted by developmental exposure to a hormonally active chemical, it will respond abnormally to the secondary cue, resulting in a functional cellular abnormality.” This process has been elucidated most clearly in chicken and frogs. But it does lead one to wonder what might be the effects on human fetuses whose gene expression may have been chemically altered by exposure to estrogens in the womb and who are then re-exposed again and again to estrogenic chemicals in the environment?
It’s a long way from cells in a dish to a complex human trait such as gender identity, but the path from cell to animal to human in biomed-ical research is a well-traveled one. The neurological basis of psychiatric conditions once considered the result of inadequate parenting (schizophrenia) or insufficient willpower (alcoholism and other addictions) is now recognized, even if the mechanisms that produce the condition remain incompletely understood. McLachlan points to one interesting example of a behavioral disorder gradually revealed to be a signaling problem in “Environmental Signaling and Endocrine Disruption.” The condition, once called “St. Anthony’s fire,” is today called ergotism and is recognized as a consequence of “the human body’s misreading of a fungal signal.” In the Middle Ages, individuals exhibiting the bizarre symptoms of St. Anthony’s fire were thought to be possessed by the devil. “This level of knowledge was consistent with the unpleasant consequences usually visited on such individuals,” McLachlan notes dryly. In later centuries, they were incarcerated in mental institutions. Eventually, the disorder was shown to result from eating moldy rye bread, and an understanding of the biochemical etiology of the condition led to a public health solution—“prevent mold from developing in rye flour or, if it does, don’t make bread from it.”
No one believes that an understanding of the manner in which gender identity develops will be so simple—nor do many believe that