Omens presents a series of historical vignettes, beginning in 1952, that, viewed now with the benefit of current scientific understanding, suggest that contaminants might have been interfering with the hormonal control of development in wildlife and in people. Examples covered include Bald Eagles in Florida (1952), river otters in England (late '50s), mink in Michigan (mid-60's), Herring Gulls in Michigan (1970), Western Gulls in California (early '80s), alligators in Florida ('80s), seals in northern Europe (1988), dolphins in the Mediterranean (early '90s), and sperm counts of men worldwide (1992).

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Hand-Me-Down Poisons describes the scientific odyssey taken by Dr. Theo Colborn that led to her synthesis of the theory of hormone (endocrine) disruption. The breakthrough came when, after reviewing hundreds of studies examining the health consequences of contamination in the Great Lakes (United States), Colborn realized that a theme running through many of the impacts observed was that they involved disruption of the hormonal control of development.

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Chemical Messengers introduces key work by Dr. Fred vom Saal, University of Missouri-Columbia, that explores the impact of tiny variations in hormone exposure on the development of fetal mice, and ultimately on adult characteristics of those mice when they mature. vom Saal discovered that natural hormonal gradients around each fetus in the womb of a mouse alter the development of its neighbors. vom Saal's discoveries lay the groundwork for understanding how tiny variations in contaminants that mimic hormones can also alter development.

The chapter also builds on vom Saal's work to present an overview of the control of development by hormones, and particularly the role of estrogen and testosterone in controlling sexual development.

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Hormone Havoc examines the tragedy of what can go wrong if the hormonal control of development is disrupted. It explores the classic case of diethylstilbestrol, or DES, a synthetic estrogen invented in 1938 and subsequently used by physicians to manage difficult pregnancies. Research ultimately revealed that not only did DES not help pregnancies, it did cause severe damage to individuals exposed to DES when their mother was treated while they were in the womb. Some of the impacts involved rare cancers, deformed fallopian tubes, and increased risk of endometriosis. In most cases, the DES impacts were not detected until after the victim had passed through puberty, even though exposure took place in the womb.

The DES case is particularly instructive because it proved definitively that the human body could mistake a synthetic compound for a hormone, with tragic results. It is also important because it reinforced the value of animal experiments in understanding human vulnerability. Time and again as scientists explored the impacts of DES on animals exposed experimentally in the laboratory, the results of these experiments anticipated human impacts.

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Fifty Ways to Lose Your Fertility explores key aspects of the ways that hormones work to control development, particularly the interaction of a hormone with its receptor. This interaction is crucial to understanding one of the best understood forms of endocrine disruption, when a hormone imposter like DES or DDT binds with the estrogen receptor. It was once thought that hormone-receptor binding was very specific, like a lock and key. Research has now shown that hormone receptors not nearly as discriminating as this old perception indicated. Many synthetic compounds bind with human hormone receptors.

The chapter also introduces plant estrogens, or phytoestrogens. These compounds are made naturally by plants and have the capability of binding with animal estrogen receptors. At least three hundred plants from more than sixteen different plant families are known to produce phytoestrogens. Studies of some of these phytoestrogens have shown they are capable of interfering with animal fertility.

Building on this basic information, the chapter then examines what is known about the impacts of various hormone mimics on reproduction and fertility. It describes work by Dr. Earl Gray (US EPA) who has studied how some synthetic chemicals disrupt male development by interacting with the receptor that normally binds testosterone, the androgen receptor. An important lesson from Gray's work is that hormone disruption is not limited to the estrogen system. Virtually every hormone-receptor interaction is vulnerable. If a disruptor hasn't yet been found for a particular hormone system among the 70,000-odd chemicals in modern use, it's probably because no one has looked very thoroughly.

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How much of a synthetic chemical does it take to disrupt hormone levels and do lifelong harm? This question is at the heart of the debate over the potential risks inherent in endocrine disruption. Research on dioxin summarized in this chapter indicates that an exceedingly tiny amount, so small and so brief that it defies the imagination to contemplate, is enough to alter the course of development, if exposure takes place in the womb.

The chapter highlights research conducted by Richard Peterson and his colleagues at the University of Wisconsin. Their work altered the landscape of what questions needed to be asked about the impact of contaminants on health. For a host of reasons, laboratory experiments with animals had focused increasingly on how high doses affected health outcomes. Peterson looked instead at the impact of low doses at crucial times during fetal development. They discovered exquisite vulnerabilities.

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The risks of hormone disruption are all around us, because of inadvertent experiments that expose us unintentionally to compounds that no one thought to question. Here, There and Everywhere delves into this, beginning with the description of a the discovery by Dr. Ana Soto and Dr. Carlos Sonnenschein that nonylphenol, a common additive to certain plastics, binds with the estrogen receptor and stimulates estrogenic responses in cells and living animals.

Soto and Sonnenschein's discovery is by no means unique even if their persistence against all odds was extraordinary. The chapter also describes the discovery that the basic building block of polycarbonate plastic, a compound called bisphenol A (BPA), also increases breast cancer cell proliferation rates. BPA, it turns out, was first synthesized in the great rush toward synthetic estrogens that led to the invention of diethylstilbestrol (DES). Polycarbonate plastic and hence BPA is everywhere in modern society. And as a result, so is exposure to hormone disrupting compounds. But the exposure is not limited to BPA. It comes from many, often unsuspected sources.

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The impacts of endocrine disruption are not just theoretical. Especially in the natural world, it is obvious that hormone systems are being disrupted and that animals are suffering. For better or for worse, because studies of animals allow experiment and sacrifice, we have better scientific understanding of what is happening with animals than with people. This chapter examines a series of examples of the impacts of hormone disruption on animals, several of which were highlighted in Omens, the book's first chapter. Among the examples covered are Beluga whales in the St. Lawrence River between the US and Canada, Florida panthers, seals in Europe, alligators in Lake Apopka, Florida, and frogs around the world.

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What has endocrine disruption meant for people? The answers are not yet clear. Evidence from wildlife, from studies of laboratory animals, and from observations of human exposure all indicate we are at risk. The fact is that basic physiological and developmental processes that are controlled by hormones have persisted relatively unchanged through hundreds of millions of years of evolution. Hence it only to be expected that risks for animals represent risks for people. As Rachel Carson wrote in Silent Spring, "our fate is connected with the animals."

Altered Destinies evaluates evidence available to date about what can be concluded from scientific studies about the impacts of endocrine disruptors on people. Many plausible impacts can be identified, including sperm count declines, prostrate problems, reproductive problems in women (including miscarriages, tubal pregnancies, endometriosis, and breast cancer), and effects on intelligence, behavior and disease resistence.

Scientific uncertainty plagues any conclusions, however. Defenders of some of the compounds that have been implicated may claim that there is no evidence. That is a distortion of the true circumstance. The limitations on what can be concluded arise largely because crucial studies simply haven't been carried out.

While there are a few (very few) studies of people who have been exposed in the womb through industrial accidents, these relatively high-dose exposures are only marginally relevant to contamination levels experienced by most people living in the real world. These high-level studies reveal problems. They don't tell us enough about the possible exposures taking place at background levels, exposures that in fact are comparable to those found through careful experiments with animals to have profound effects. There is too little scientific information available to state with certainty that concerns raised by animal studies are not relevant. The few that are available reinforce ideas raised in Our Stolen Future, that low level contamination by endocrine disrupting-compounds are causing a variety of health effects in people.

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The risks of cancer have dominated fears about the health consequences of cancer. Those fears are real and warranted, but they have blinded us to a parallel set of risks whose consequences can be even be more profound for the human prospect. Cancer kills individuals, mostly adults. Hormone disruption derails development, putting at risk the ability of individuals to participate fully in society. While it has been assumed that protecting people from the contamination risks of cancer will protect them from other health effects caused by pollution, it now appears that the opposite may be true. Because of the extraordinary low levels at which endocrine disruptors derail development, protecting against their health effects is likely to provide wide benefit for health, including cancer prevention.

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Given the reality that current regulations do not protect individuals from endocrine disruption, what should people do? In Defending Ourselves, we evaluate the choices people have to reduce their own risks and those of their family members, and also identify a series of changes in public policy that would be beneficial. While the facts in hand are cause for deep concern, trends are not destiny. There are many choices people have to protect themselves, and especially their children.

Our recommendations include suggestions for avoiding unnecessary uses of pesticides and reducing intake of contaminated food, both by choices in diet and changing the way that food is cooked. Don't microwave in plastic unless you are absolutely certain that the plastic does not leach endocrine disrupting compounds into the food it contains.

We also identify a series of changes in the way that contamination is regulated. Far from guaranteeing safety, the structure of current regulations do more to lower legitimate consumer concerns than they do to protect health.

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What does the future hold? The science of endocrine disruption is uncertain. Animal studies identify many plausible risks. Some data on people support them. For the most part, however, the crucial human studies have not been carried out. To do so carefully and definitely will take decades. We must ask, nonetheless, whether a series of disturbing social and behavioral problems have their roots in the impacts of contamination on human development. Are falling SAT scores linked to intrauterine exposure? What about global declines in sperm count? Or increases in societal levels of aggression. All these endpoints--cognitive, behavioral, reproductive--are shown vulnerable in animal studies to exposure to endocrine disruption. What can we conclude for people?

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In Flying Blind we step back from the details of endocrine disruption to ask why are we in this predicament and what must be done to get out of it? These questions are provoked unavoidably by what we have learned about endocrine disruption, but they arise from a larger consideration. Growth in human population and technological prowess over the past century has placed all of humanity, indeed all of the planet, in a series of unplanned, poorly monitored indeed often unwitting experiments. There is no uncontaminated place or people, no unsoiled valley anywhere. The scale of the human enterprise, our capacity to invent new substances and bring them to market far more quickly than science can hope to understand their unintended consequences, and the huge gaps in our knowledge of how the world works, together make us vulnerable to some of the very advances on which modern society is built.

"As we work to create a future where children can be born free of chemical contamination, our scientific knowledge and technological expertise will be crucial. Nothing, however, will be more important to human well-being and survival than the wisdom to appreciate that however great our knowledge, our ignorance is also vast. In this ignorance we have taken huge risks and inadvertently gambled with survival."

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