Book review A parable about environment and our daughters’ health Toxic Bodies: Hormone Disruptors and the Legacy of DES by Nancy Langston. Yale Press, 2010, US$30 (256 pages), ISBN 978-0300136074. David Sassoon Myology Group, UMR S 787 Inserm, Universite ´ Paris VI and Pierre et Marie Curie, 105 bd de l’Ho ˆ pital, 75634 - Paris Cedex 13, France In the early 1970s, a number of women visited a Boston clinic with gynecological symptoms caused by malformations of the uterus, cervix and vagina. This same clinic also recorded an increased frequency of a rare form of cervical cancer, so rare, in fact, that the young doctor involved won- dered why he was witnessing so many cases when he had been taught to expect one such cancer during his entire career. He discovered that these women all shared one historical trait, namely they were born to mothers who took diethyl- stilbestrol (DES), a potent synthetic estrogen, during preg- nancy, thereby inadvertently exposing their unborn daughters to massive doses of estrogen. DES was adminis- tered to millions of women between the 1930s and 1970s and used in livestock for much longer. In the early 1990s, the conserved genes underlying the formation of bodies and organs were being elucidated. Molecular embryologists discovered that formation of the heart and the eye of an insect was governed by the same patterning genes found in birds, mice and humans. During this time, several laboratories, including my own, focused on several of these patterning genes, which, as expected, are expressed at high levels in the embryo but barely detectable in the adult. Unlike other tissues, the female reproductive tract remains cellularly and molecularly a ‘work in progress’ throughout fetal and subsequent post- natal life, and therefore expresses levels of patterning genes rivaling the embryo; perhaps more importantly, these critical genes are subject to regulation by estrogen. One of these patterning genes, Wnt7a, was identified as being essential for proper uterine, cervical and fallopian development [1–3]. Morphological abnormalities in the Wnt7a mutant reproductive tract had all been reported in papers dating back to the 1940s describing the effects of exposure to DES in utero (cited in Toxic Bodies). A series of simple experiments demonstrated the obvious: DES exposure in utero shuts down expression of Wnt7a, leading to a hormone-induced copy of the mutant phenotype [4].A fetal reproductive tract exposed to DES transformed into a morphogenetic ‘house of cards’, perturbed at its foundation by hijacking of a developmental process that would render most exposed females sterile and put others at risk of cervical cancer later in life. In Toxic Bodies, Nancy Langston explores the DES story and the broader issue of endocrine disruptors in our environment from a variety of angles, including politics, the pharmaceutical industry, farming lobbies, government regulators, scientists who tried to warn of the risks and scientists who were bought off. The subject is fascinating and frightening, and although DES is no longer widely prescribed, this tale serves as a paradigm for regulators and risk assessment today. Specifically, Toxic Bodies takes us through the history of DES, first as a treatment proposed by the medical estab- lishment to maintain a woman’s sexual attributes during and beyond menopause, and then as a more wholesale approach to various female health issues, including morn- ing sickness, difficult pregnancies or simply as an elixir to produce healthy babies. Similar to the case for current estrogen replacement therapies, this was not a male-domi- nated effort, but was welcomed by women, perhaps misled by the pharmaceutical companies of the day (who sub- sequently made warnings available only to prescribing physicians) in an environment in which regulatory agencies were not strong enough to stand up to the power- ful economic interests at play. In this regard, the book is a parable of a struggle that continues to the present day in which a modicum of caution is cast aside for profit. The earliest studies on DES provided clear indicators that significant risks existed. Scientists were told then, as we are told today, that mice are not human, which is true of course, but they are one of the best examples of a ‘canary in a coalmine’ that we have at our disposal. Although this book is backed by scientific references, the cellular and molecular mechanisms underlying the fetal impact of DES are often referred to as complex, which is not really the case. A clearer mechanistic discussion, vital to non-scientists who make critical decisions on new drugs and chemicals that impact our safety, could have been provided through more careful presentation. Other- wise, Toxic Bodies provides a well-documented narrative that exposes the DES legacy and interweaves it with accounts of other estrogen-like contaminants that are saturating our environment, such as pesticides and plas- tics, which the author convincingly contends will have yet- to-be-identified harmful effects on our daughters for generations to come. References 1 Cunha, G.R. et al., (1999) The embryology of the uterus. In The Endometrium (Glasser, S.R. et al., eds), pp. 2–25, Harwood Academic Update Corresponding author: Sassoon, D. (david.a.sassoon@gmail.com). 335