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Havoc In the Hormones
By Jon R. Luoma

Pollutants like dioxin and pesticides have upset the reproductive systems of alligators and gulls. Now, researchers theorize, the contaminants may be threatening humans.

Louis Guilette, a University of Florida wildlife endocrinologist with salt-and-pepper hair and matching beard, is stalking an alligator, one of dozens with which we presently share a large cage.

This is not high adventure. The alligators are babies - the young of the year, a foot or so long. They scramble away from Guillette, scurrying among potted plants or diving and swimming furiously across the shallow pool in the center of the cage's concrete floor. They are fast and nimble, but Guillette soon has one in his hand, a male about 14 inches long. He grips it like a sort of huge, green hypodermic, nestling its torso in his palm, its head between two crooked fingers.

"There is no way in the world, just looking at this little alligator, that you could tell there was anything wrong with him," says Guillette, stroking the animal. The little reptile certainly seems robust, pumping its stubby legs in the air and squeaking the curious distress calla quasi-electronic chirp of a baby alligator in the clutches of predatory danger. But beyond its present predicament, something is indeed very wrong with it

Guillette turns the alligator upside down and opens a pinkish genital structure on its abdomen. The oddity of this strikes me for a moment: that I have traveled all the way to Gainesville to look at an alligator's penis.

There isn't much to a baby alligator's penis; it is small, almost threadlike. But although a layman wouldn't know it simply by looking, this one is smaller than it should be. And that's part of a larger story that perhaps should have us all sounding an alarm.

The upshot of the story is this: In the past decade, scientists like Guillette have been finding more and more evidence that molecules of some chemical pollutants--ranging from pesticides to polychlorinated biphenyls (PCBs) and from dioxins to additives in some plastics and industrial detergents can behave like hormones in the bodies of both animals and humans. Mimicking natural hormones (or blocking, amplifying, or otherwise disrupting them), these pollutants have already created biological chaos in the bodies of some exposed animals, like this alligator. And since such pollutants abound in ecosystems, as well as in animal and human tissues, some scientists worry that the problems seen so far represent only the tip of an iceberg.

Hormones are the body's chemical messengers. Secreted in infinitesimal amounts into the bloodstream, they can trigger dramatic changes in the body, like the alert, hair-raising, heart-pounding sensation brought on by a surge of adrenaline, or the exquisite sequence of timing in the ovulation cycle. Hormones also exert enormous control over fetal development, enhancing the growth of skin, the nervous system, and some brain cells, and determining whether an embryo will develop the body of a male or a female.

A hormone molecule functions by docking onto a cell structure called a receptor, which has an affinity for the hormone's unique chemical design. Like a molecular key fitting into a specially designed keyhole, the hormone essentially flips a biochemical switch, which in turn can trigger a cascade of physical changes. But, says Guillette, "we now know for certain that some pesticides and other chemicals act like keys too - as fake messengers."

The alligator Guillette holds in the palm of his hand was born near Orlando on Lake Apopka. There, pesticide residues from agriculture as well as contaminants from a factory owned by the Tower Chemical Company continue to pollute the food chain even now, more than a decade after the plant was closed. As a bizarre consequence of that pollution, this alligator may not, in fact, be a male at all.

In terms of its hormonal chemistry, it seems to be closer to a female. Like other "males" born on the lake, its blood is high in estrogen and low in testosterone. As it matures, its penis could grow to as little as one-fourth the normal size; the animal is likely to be, like many of the Apopka alligators, "reproductively incompetent," as Guillette puts it.

It took Guillette and a group of colleagues years to piece together the puzzle of Lake Apopka's alligators. Since the mid-1980's they had known that something had caused the population to crash and that the alligators had strange anomalies. For instance, when he examined the ovaries of young female alligators, Guillette found that they were producing abnormal eggs, with multiple nuclei, and more than the usual one egg per egg follicle. A critical puzzle piece fell into place in 1992, when fellow endocrinologist Howard Bern visited Guillette's lab.

Bem, of the University of California, Berkeley, is a well-known expert on the now-banned drug DES, a synthetic estrogen that was prescribed for millions of women in the 1940's, '50's, and '60's; years later, the daughters of DES-exposed mothers began to have severe gynecological problems. During his visit, Bern showed Guillette and his students slides of the ovaries of laboratory mice that had been exposed to DES.

"A chill went up my spine," says Guillette. "It was the same pattern that I'd seen in my female alligators. But DES is a synthetic estrogen. I wondered where in the world my alligators were getting estrogen."

As Guillette accumulated data, the picture became clear. Pesticides (including dicofol - a close relative of DDT - and some DDT that had been produced as a contaminant during dicofol manufacture) had moved into the food chain of the Lake Apopka ecosystem Studies by other scientists working with birds and laboratory rodents had shown that these kinds of pesticides, from a class of chemicals known as organochlorines, were not only tenacious once they entered animal tissues but also could mimic, amplify, or block natural sex hormones like estrogen and testosterone. Indeed, Guillette has been able to duplicate the resultant gender-bending effects in his laboratory by infusing clean alligator eggs with similar pesticides.

Guillette's discovery was far from isolated. If this were a problem with one pesticide and one species, the story of the alligators would be little more than a scientific oddity. But Theo Colborn, a zoologist and senior scientist with the World Wildlife Fund, says the phenomenon is all too common: Chemicals that disrupt the endocrine system now abound in three ecosystems and, at least in the most polluted areas, are causing obvious problems. "We're seeing this same pattern of anomalies linked to endocrine disrupters across a whole suite of animals and humans around the world," she says.

In fact, from Europe's North Sea to the Great Lakes to the California coast, scientists have been piecing together remarkably similar puzzles, from seals with immune-system disorders to gulls with vestiges of both male and female gonads to fish that fail to mature sexually -all carrying high amounts of synthetic chemicals, most notably organochlorines.

Further, some scientists believe that the ubiquitous synthetic pollutants that virtually all of us now carry in our own fatty tissues could explain, for instance, why rates of breast and testicular cancer have soared, and why male sperm counts in the industrialized world have plummeted by a startling 50 percent since the dawn of the "chemical revolution" that began after World War II.

Theo Colborn has often served as the synthesizer who, beginning in the late 1980's, has helped bring together researchers who had made largely isolated discoveries about pieces of this puzzle. Yet for her, the discovery that the puzzle existed at all was an accident Hired in 1987 by the World Wildlife Fund to assemble a report on Great Lakes environmental problems, Colborn began to pore over articles that highlighted problems observed in wildlife in the Great Lakes ecosystem: terns and double-crested cormorants born without eyes or with twisted, crossed beaks; salmon in polluted waters that failed to mature; gulls that showed no interest in nesting. She was intrigued by what she sensed was a pattern, but, she says, "I just couldn't sort out how all these pieces fit together."

Eventually, after she began plugging the data into a chart, a clearer pattern began to emerge. Virtually all the affected species were top predators, mostly fish eaters. Although data showed that they had relatively high levels of compounds like PCBs, dioxins, and a wide range of pesticides, most of the problems were not showing up as defects in adults. Rather, the adults were either failing to reproduce or producing offspring that failed to thrive. Eagles, for instance, that had recently migrated to the shores of industrially contaminated bays bore healthy chicks. Yet those that had fed on contaminated fish for years were either failing to reproduce or were bearing chicks with defects like beaks so mangled they were unable to eat.

Colborn also ran into studies by developmental psychologists Joseph and Sandra Jacobson at Wayne State University, in Michigan, suggesting that children born of mothers who had regularly eaten contaminated fish weighed less than average at birth, had smaller heads, and, as they matured, began to show decreases in short-term memory and attention span. Once again, the mothers seemed healthy.

Since the adults were fine, Colborn concluded that something was happening at the embryonic or fetal level, that somehow pollutants, accumulated by the mother were affecting the offspring. But how? Just as Guillette, an endocrinologist, was led into the world of toxicology, more digging led Colbom, who was trained in wildlife toxicology, into the world of hormones.

Studies by Michael Fry, an avian toxicologist at the University of California, Davis, helped provide the tip-off. By the early 1980's, Fry had managed to replicate in his laboratory a bizarre anomaly he'd found in the 1970's among western gulls off the California coast According to his research, male gulls in one DDT-contaminated area were ignoring breeding colonies, and females were nesting with females. (DDT use was restricted in the United States in 1972, but residues remain in food chains.) Dissecting some birds, he found that some males were functional hermaphrodites, with at least partially formed female sex organs. He was later able to reproduce this effect in his lab by infusing clean gull eggs with DDT or estrogens.

Colborn also found studies showing that laboratory rodents exposed to either natural hormones or a range of environmental toxicants, including dioxin, could literally have their sexual orientation altered. In one study by University of Wisconsin toxicologist Dick Peterson male rats whose mothers had been injected with dioxin not only were disinclined to mate with females but moved into a female-like mating position when in the presence of normal males. Although adults exposed to the pollutants seemed unharmed except at high dosages, the rats exposed in utero produced only half the usual amount of sperm. Even tiny doses caused effects in offspring.

In a 1985 study at the Environmental Protection Agency's Health Effects Research Laboratory in North Carolina, female hamsters exposed to Xearalenone, a common fungicide, developed what EPA scientist Earl Gray calls masculine behaviors, including an inclination to mount another female in estrus. The scientists believe that exposure to the poison may have altered the organization of celLs in the brain that control sexual behavior.

In 1991 Colbom brought together many of the scientists studying this issue for a conference in Racine, Wisconsin. Among other things, participants agreed that pollutants can mimic or otherwise disrupt hormones, that "many wildlife populations are already affected" by endocrine-disrupting pollutants, and that because the same pollutants are accumulating in human cells, "a major research initiative on humans must be undertaken."

Colborn says, "This scares us all enough that we'd be delighted if someone could prove we're wrong." But she believes there is already enough evidence of risk to human health that federal regulatory agencies should insist that chemicals be tested for hormone-like effects before allowing them to be loosed upon the world.

Experimental studies can't be performed on humans. But the artificial estrogen DES may have served as a sad and unwitting experiment Just as with wildlife and experimental animals exposed to toxins, the drug appears to have had little effect on most mothers who took it. But when their daughters reached maturity, many suffered from infertility, had malformed reproductive tracts, or were afflicted with an otherwise exceedingly rare cancer, clear-cell vaginal adenocarcinoma. DES sons showed an increased rate of problems such as undescended testicles, testicular cancer, and reduced sperm counts.

At a January 1994 conference on "environmental estrogens" in Washington, D.C., Danish researcher Niels Skakkebaek and British reproductive biologist Richard Sharpe reported that similar problems among men have been rising since mid-century, including a tripling of testicular-cancer rates in the United States and Britain and a plummeting rate of sperm production across the industrialized world.

"Why should we be concerned about what's happened to wildlife?" asks Robert Kavlock, who directs the EPA's developmental-toxicology division. "One word: canaries [a reference to the old coal miners' practice of using a canary as a monitor for poison gas]. We know there are problems with reproductive health among humans. It's hard to know what the cause is. But we know that if the problem is the environment, it's going to show up first in species with shorter life cycles than ours. We know there are hot spots for wildlife where we've seen these kinds of problems. The issue we've got to address is whether there are problems in the general environment."

Steven H. Safe, a Texas A & M chemist whose work is partially funded by the Chemical Manufacturers Association - trade lobbying group - skeptical of the mounting research. In the April 1995 issue of the journal Environmental Health Perspectives, he flatly stated that "the suggestion that industrial estrogenic chemicals contribute to an increased incidence of breast cancer in women and male reproductive problems is not plausible." Although he agrees that reductions in such compounds in the Great Lakes "correlates with the improved reproductive success of highly susceptible fish-eating water birds," he points to naturally occurring hormone-like chemicals in some foods, like soy, as an estrogen mimic; further, he suggests that human intake of industrial compounds is too low to cause serious health problems.

However, Guillette and other researchers note that the human body has most likely evolved to cope with natural hormone mimics in foods, and that food-based compounds do not build up in fat cells, as do many of the synthetic industrial compounds. Guillette cautions, "Tying all of this into effects on the general human population at lower exposures is theoretical. But there are enough data to be concerned. There's no question that we have laboratory data showing that quite a few of these substances are endocrine disrupters. It's clear that in contaminated animals in the wild we have the same kinds of abnormalities we've produced in the lab. It's also true that in humans we're seeing increasing rates of these same kinds of problems. We're jumping ahead of the data if we try to say 'X causes Y.' But we aren't jumping ahead if we hypothesize and then support it with data. And it seems like the more data we collect, the more support we have...So far, we have not found data that falsify the hypothesis.

"People love to think that we're different from other animals, and certainly different from insects. But at the cellular level, we are fundamentally the same. If we design a compound to be toxic to an insect cell, why does it surprise us when we find out that the same compound is toxic to a human cell? We've always thought the issue was mass - that these things could be toxic to an insect without having significant effects in a much larger human. But how big is an embryo?"

Reprinted with permission from Audubon Magazine.

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