System Failure

The chemical revolution has ushered in a world of changes. Many of them, it's becoming clear, are in our bodies.

Elizabeth Guillette, a University of Arizona Medical anthropologist, had been hearing the stories for years. Midwives and nurses in developing countries were reporting that children growing up in areas with high levels of pesticide use were displaying problems in learning and physical skills. In order to follow up on these reports, Guillette needed to identify two populations of children that were similar in every way but one--their level of exposure to pesticides.

In the torrid Yaqui Valley of Sonora, Mexico, she found what she was looking for. The Yaqui Indians of that area lived in two distinct groups: one in the valley lowlands, the other in the highland foothills. In the intensively farmed lowlands, Yaqui mothers had been exposed, over the course of numerous growing seasons, to high levels of pesticides, including compounds such as lindane and endrin, long banned for agricultural use in the United States. By contrast, foothill families lived simple ranching lives, rejecting pesticide use altogether--to the point of preferring to swat insects in the home rather than spray a pesticide.

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In all other respects--the most relevant being diet--the two groups lived essentially identical lives; in addition, they shared a common gene pool. They appeared to Guillette, therefore, to offer a unique chance to measure the developmental differences between groups of children who seemed to vary only in their exposure to pesticides.

Her research scheme was straightforward: She adapted a series of motor and cognitive tests into simple games the children could play, including hopping, ball catching, and picture drawing. She assumed that any differences between the two groups would be subtle. Instead, she recalls, "I was shocked. I couldn't believe what was happening."

The lowland children had much greater difficulty catching a ball or dropping a raisin into a bottle cap--both tests of hand-eye coordination. They showed less physical stamina too. But the most striking difference came when they were asked to draw pictures of a person.

As with any group of kids, there was variation in individual skills. But most of the pictures from the foothill children looked like recognizable versions of a person. The pictures from most of the lowland children, on the other hand, were merely random lines, the kind of unintelligible scribbles a toddler might compose.

Though it could take years of research to nail down precisely how the lowland children might have been harmed, it appeared likely they had suffered some kind of brain damage. Guillette based her working hypothesis--that pesticide exposure might be the cause--on her familiarity with an extensive body of animal research that had already proven that some pesticides and chemically related compounds interfere with test animals' endocrine (hormonal) systems. In both animals and humans, this system plays a critical role in nearly every aspect of development of a growing fetus--including proper formation and function of the brain and reproductive organs--and is also crucial for normal adult bodily function.

In fact, Guillette's Yaqui Valley findings bolstered not only her own hypothesis, but the growing notion within the scientific community of the damage that may be caused by a class of compounds scientists call "endocrine disruptors," or EDs. These include a much broader range of chemicals than are found in pesticides, and can not only harm developing animal embryos and fetuses in dramatic ways, but can have similar impacts on human fetuses, growing children, and even adults.

In the years since World War II, a veritable chemical revolution has swept the globe. Scientists in commercial and academic laboratories have synthesized some 75,000 new compounds--some 15,000 of which are currently under investigation as potential endocrine disruptors. Relatively few of these chemicals, suspected EDs or not, have received exhaustive study and testing, even as a great many have found practical applications in industrial processes and consumer products--including such presumably benign items as dental sealants, plastic toys, and plastic intravenous bags. They have, in short, become ubiquitous throughout the developed and developing worlds--meaning that it isn't just children in remote Mexican valleys exposed to pesticides banned in the United States who are at risk from these chemicals' untested and unintended effects.

Experts estimate that all of us carry in our tissues some 500 compounds that simply did not exist prior to this century. Virtually all of us harbor known EDs, including polychlorinated biphenyls (PCBs), chemicals banned in the 1970s but once widely used and still persistent in the environment; and dioxins, which are byproducts of industrial processes such as chlorine bleaching.

The first reports of the effects of endocrine disruptors on animals began to surface in the news media during the early 1990s. At the time, any notion that similar effects might be seen in humans (at least at the levels of contamination to which most of us are exposed) were routinely dismissed by the chemical industry and its allies as environmental fear mongering.

But more recently, mounting evidence has demonstrated that humans may indeed be at serious hormonal risk. Scientists have found striking evidence of problems with male reproductive systems in the developed world, including soaring rates of testicular cancer and plummeting sperm counts, and many attribute this to hormonal disruption in the developing fetus. A scattering of studies, including Guillette's, have shown clear evidence of neurological problems in children whose pregnant mothers were exposed to EDs. Recent experiments with mice indicate that, with some compounds, damage to gonads and abnormal behavior among a mother's offspring can occur even if she is exposed to amounts so tiny that she shows no effects whatever. Other recent animal studies have supported the hypothesized link between neurological problems and contaminants that disrupt the activity of the thyroid gland, which plays a role in normal brain function.

Theo Colborn, a toxicologist at the World Wildlife Fund, is widely credited with consolidating research on EDs and prodding her fellow scientists toward consensus about the damage these chemicals cause in animals, and perhaps in people (Mother Jones, March/April 1998). She has been influential in promoting her view that those most at risk from EDs are not adults, nor their young offspring, but developing embryos and fetuses. The pathway of exposure is a straightforward one: "The mother,"she says, "shares with her [fetus] the chemicals she has in her blood."

Starting shortly after a sperm cell enters an egg cell, hormones, first from the mother, and later from glands of the developing fetus, are critical to development of the reproductive system, brain, skeletal system, and other organs and body parts. Hormones function as biochemical messengers. Exceedingly tiny amounts--just a few molecules--will dock themselves on cellular landing sites called receptors. There, like tiny keys fitting into tiny locks, hormone molecules will trigger powerful bodily changes. The work of hormones in a developing organism is an exquisitely calibrated biological dance.

The reproductive system offers a telling example of how EDs operate: In a developing male fetus a precise wisp of male hormones at just the right phase of development signals the cells to form male gonads. But should foreign compounds that mimic natural hormones (PCB molecules, for instance) occupy and block the receptors, biological mayhem can ensue: Deformed gonads or even partial female gonads may be the result. Studies with mice have shown that doses of various estrogen-mimicking contaminants given to a pregnant female can cause her male offspring to be born with an enlarged prostate gland.

Laboratory and field studies are also demonstrating linksbetween endocrine disruptors and a variety of other developmental problems in people. Some of the earliest clues came from late-1980s research at Wayne State University in Detroit, suggesting that children whose mothers were heavy eaters of PCB-contaminated Lake Michigan fish were born with sub-par memory function, demonstrating deficiencies both in infancy and in a second round of testing at age four. The most recent follow-up report, in 1996, continued to note problems in the children, who were by then 11 years old. "The most highly exposed children,"wrote scientists Joseph and Sandra Jacobson, "were three times as likely [as a control group] to have low average IQ scores, and twice as likely to be at least two years behind in reading comprehension."

A team of researchers at the State University of New York at Oswego's Center for Neurobehavioral Effects of Environmental Toxics began an even more exhaustive effort in the early 1990s. According to SUNY-Oswego psychologist Tom Darvill, early results were crystal clear. Mothers who ate large amounts of contaminated Lake Ontario fish carried a more potent mix of PCBs in their umbilical-cord blood. (PCBs comprise a group of related chemicals, some more toxic than others.) And the newborn babies of those mothers responded poorly to standard motor and cognitive tests: They demonstrated poor reflexes, trembled in response to stress, and were easily startled.

Members of the SUNY-Oswego team also fed a group of lab rats the same Lake Ontario salmon that the human mothers had consumed, and compared them with rats that were fed clean salmon. The offspring of the experimental rat group showed problems that echoed the ones found in the human children. "They were hyperreactive to minor negative events,"says Darvill, "like a shift in a food reward from a large reward to a small."

A powerful clue to just how these compounds might have done their harm has begun to emerge. Medical science has long known that a severe deficiency in the thyroid hormone thyroxin can lead to congenital myxedema--a type of mental retardation once known as cretinism. And scientists have also known that even moderate thyroxin deficiency, caused by disease or dysfunction, can lead to motor and hearing problems in both lab animals and children.

More recently, in a series of experiments at the Environmental Protection Agency's Health Effects Laboratory, a team of scientists showed that small doses of PCBs given to pregnant rats led to lower thyroxin levels and subtle, but detectable, hearing problems in their newborn. According to the study, the link was rock solid: Injecting the rat "pups"with thyroxin got rid of the hearing problem. If PCBs are also found to reduce thyroxin levels in people--and given that lowered thyroxin is a known cause of human neurological problems--scientists will have identified at least one key pathway by which PCBs can harm developing fetuses.

Even as research on learning and behavioral problems among children has emerged, scientists worldwide have begun to raise new concerns about the potential link between endocrine disruptors and damage to the human--particularly male--reproductive system.

It had already been firmly established that certain estrogen-mimicking chemicals can damage the female reproductive system. From shortly after World War II until about 1970, doctors routinely prescribed the synthetic estrogen diethylstilbestrol (DES) to pregnant women to prevent miscarriage. The result of this unwitting experiment: Years later, after puberty, many of their daughters developed a rare clear-cell cervical cancer later linked conclusively to DES exposure in the womb.

Then, in 1992, stories about declines in male sperm counts blazed into the news media when European researchers announced that counts had declined by about half in Europe and the United States since World War II. The reports were followed by counterclaims from skeptics that the European studies were flawed. However, in the most comprehensive sets of analyses done to date, University of Missouri researcher Shanna Swan in 1997 confirmed the first reports. Swan, who says she was also an early skeptic, has found that sperm counts appear to have declined by about 3 percent per year in Europe, and about 1.5 percent per year in the United States between 1938 and 1990. (No one knows, as yet, why there's a difference.)

But, she says, these sperm problems are an ominous "red flag"for male reproductive health in general: Even as sperm counts have apparently declined, rates of testicular cancer have soared, doubling in the United States alone between 1973 and 1994. Meanwhile, rates of a condition in newborns called hypospadias doubled in the United States between 1968 and 1993, according to a 1997 report by the National Center for Environmental Health at the Centers for Disease Control. Hypospadias is a form of incomplete sexual differentiation in which the opening to the urethra appears somewhere on the genitals other than at the tip of the penis--in the worst case, as far away as the scrotum.

"Nobody can doubt that there's a clear increase in [these conditions], and that it's strongly associated with poor-quality sperm,"concurs Danish reproductive researcher Niels Skakkebaek. "We know,"he adds, "that when we give rats and mice estrogen in pregnancy we see damage to the testes of their sons. That leaves us with a strong hypothesis that giving chemicals that behave like estrogen to a fetusÉleads to a higher rate of reproductive health problems later on."

From elsewhere in the animal research world, evidence of ED-related problems keeps rolling in. In March, for instance, a study from the EPA's leading toxicology lab--building on a flurry of earlier studies--confirmed that groups of plastic additives called phthalates create havoc in the developing reproductive systems of male rats. Female rats whose mothers were exposed to the substances gave birth to male pups with single testicles or sacs of blood in the place of testicles. At the University of Missouri, scientists showed in 1997 that pregnant mice given infinitesimal doses of another common plastic additive, bisphenol A, gave birth to male offspring with abnormally enlarged prostates. In the same issue of the scientific journal in which the EPA study appeared, the Missouri team reported that tiny doses of methoxychlor, a common household pesticide, had the same effect.

Endocrine disruptors, unfortunately, seem to stick around for long periods of time. In 1997, a team of researchers reported in the journal Chemosphere that traces of PCBs and residues of DDT, both chemical compounds banned in the United States in the 1970s, were, along with dioxins, ubiquitous in supermarket foods ranging from chicken and pork to butter and ice cream. (The scientists also reported that a vegan diet, free of animal products, would expose a person to dramatically lower levels of the contaminants.) Says Colborn, these compounds are likely to be indicators of other, related ED poisons in the food supply--poisons that can make their way, quite naturally, from mothers to the developing brains and nervous systems of their children, with impacts we are only beginning to measure.

Amid all the grim reports, there have been some positive developments. In June 1998, representatives of more than 100 countries met in Montreal to begin negotiating a worldwide ban of 12 of the most noxious toxins, all of which are banned or restricted in the United States and Canada, but still used in developing countries and easily subject to worldwide dispersal via weather systems and consumer or agricultural products.

In the fall of that year, the EPA announced that a special advisory committee comprised of scientists, environmentalists, physicians, and representatives from major chemical companies and business trade groups had come to a firm and dramatic consensus: that an enormous number of compounds needed to be checked to see if they were hormonally active. Subsequently, the EPA announced that it would undertake the first phase of that effort, setting standards for and overseeing the testing of 15,000 pesticides, solvents, and various synthetic compounds.

"This is one of the key pieces that will help us deal with this problem,"says Gina Solomon, a physician who sat on the committee on behalf of the Natural Resources Defense Council.

The testing program, however, is off to a shaky start: The agency has dedicated only $4 million in its current budget to what most members of the EPA advisory committee believe should be a far greater effort to set up, standardize, and enforce a mandatory research program.

Congress did not appropriate enough money, notes Solomon with evident dissatisfaction, but she adds, "I can't say it's all

Congress' fault. The EPA and the Clinton administration didn't even request adequate funding."

As for Elizabeth Guillette, she says she finds herself hoping that the problems she found in lowland Yaqui children will recede as they grow and develop. But so far, the evidence hints, at least some subtle differences will linger.

On a follow-up trip in 1998, two years after her initial visit, Guillette found that both groups of children, who at that point were in primary school, had improved in drawing ability.

But while the lowland children's drawings looked more like people than they had before, the foothill kids were drawing far more elaborate and detailed images. And the lowland youngsters were still showing some motor problems, particularly with balance. "Some of these changes might seem minute, but at the very least we're seeing reduced potential,"Guillette says.

"And I can't help wondering how much these kinds of chemicals are affecting us all."

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