The dog had been housebroken. Then Joseph von Mering and Oskar Minkowski decided to operate. They took out its pancreas--a tricky business in 1889 in the then-German city of Strassburg--so that they could better study how the body reabsorbs fats. The operation succeeded; the dog recovered. Then it started peeing on the floor.
A bewildered Minkowski checked the urine--it was full of sugar. The doctors had happened on proof that diabetes is caused not by the presence of some poison, but by the absence of something the pancreas secretes. So began the still-unfolding discovery that life and growth depend on the body's endocrine system, which churns out an endless series of messages in the form of hormones that make you hungry, affectionate, aggressive, or merely functional.
The dog died within days. It no longer had a way to regulate the digestion of sugar, which built up to poisonous levels in its blood. Von Mering and Minkowski couldn't put its pancreas back in, and they had no idea how to treat the disease they'd induced by accident. But at least they knew when they started that they were conducting an experiment.
During the subsequent century humans have created tens of thousands of chemicals for all kinds of good reasons: to purify water, protect food, prevent disease, insulate electrical equipment, make plastic. Some of these new chemicals--nobody knows how many--have an unexpected power, a power to cause reactions in the body every bit as unexpected as dog pee on the Strassburg laboratory floor. When eaten, drunk, inhaled, or otherwise absorbed into an animal, these chemicals can impersonate its own hormones. They're less potent than the real things, but these "endocrine disrupters" can still send counterfeit messages through the body or block genuine ones.
Take polychlorinated biphenyls, PCBs, until recently used to insulate and fireproof electrical equipment. They can interfere with thyroid hormones, which stimulate brain development in the growing fetus. "Only thyroxine (T4), bound to transthyretin, is capable of entering the fetal brain," Dr. Ted Schettler of Physicians for Social Responsibility told a July 14 symposium in Chicago on endocrine disrupters. "Some PCBs lower T4 levels and displace T4 from transthyretin" so it can't get in, a problem that might lead to hypothyroidism. PCBs are stored in body fat and are shared across the placenta between mother and child. "Longitudinal studies of humans over time show that even transient hypothyroidism at birth is associated with IQ deficits later in life."
You don't have to know the difference between thyroxine and transthyretin to get the point: endocrine disrupters are more likely to endanger offspring than grown animals. "The body's detoxifying agents take days to produce," explains University of Wisconsin zoologist Warren Porter. So mom's already mature organs probably won't suffer irreversible damage while her liver girds for battle. But fetal development runs on a tight schedule, and the lifelong patterns for her unborn infant's brain and sex organs may be laid down wrong.
This past February Illinois became the first state to publish its own list of human-made chemicals "associated with endocrine system effects in animals and humans or in vitro"--19 of them known, 29 probable, and 26 suspect. (The less cautious authors of the 1996 book Our Stolen Future claim "at least 51" as proven.) Most of the chemicals on the Illinois Environmental Protection Agency's list are pesticides, ranging from the long-banned DDT to the widely used herbicide atrazine. That may be an artifact of past research, which has tended to focus on agricultural chemicals and a few other bad actors such as PCBs and dioxins (also on the list). Of the state's 19 "known" endocrine disrupters, only 3 have been conclusively shown to affect humans--the pesticides kepone and DBCP and the drug DES.
The state EPA hasn't yet banned or regulated any of these chemicals for being endocrine disrupters. According to associate director Peter Wise, the mere fact that the agency put the list together was enough to make Illinois chemical manufacturers "irate."
On July 15, George Rabb, director of the Brookfield Zoo, spoke at a public hearing at the Ambassador West Hotel. "In some of the most recent investigations, frogs are being found dead in place. To find one like that is unusual. To find several of different species is extraordinary." A short, spare figure in a dark suit, older than most of the activists testifying this evening, he spoke in a dry, level voice. He didn't use his full four minutes and showed no inclination to pound on the table. He couldn't anyway, because the EPA's Endocrine Disrupters Scientific and Technical Advisory Committee hadn't provided one.
Endocrine disrupters are usually accused of deforming or sickening people or animals, not killing them outright. But Rabb and some other herpetologists speculate that they might have something to do with the disappearance of frog species around the world. Rabb mentioned the work of field biologist Karen Lips, who earlier this year found just 24 amphibian species in a protected Panamanian mountain forest that had sheltered more than 55 in 1995. "I found 54 dead or dying frogs belonging to 10 species," she wrote in "Froglog" (June), the newsletter of the Declining Amphibian Populations Task Force. "Many of the casualties still had a very life-like appearance; most were found during morning surveys, still sitting in a perched position." (Lips didn't mention endocrine disrupters in her report. She suspected a virus or other disease.)
"We're not just affecting humans--we're affecting all life," Rabb said, then paused. "And we'd better know what we're doing." He walked away from the microphone and out of the room.
When it comes to endocrine-disrupting chemicals, we know that they act on individual cells, that tiny doses harm laboratory animals, and that large doses harm wildlife and humans. We know that some are ubiquitous--PCBs are in everyone's body fat in low concentrations--but we don't know whether having endocrine disrupters around all the time in tiny amounts hurts people. In other words, we don't know what we're doing, any more than Minkowski and von Mering knew what that dog was in for when they whipped out their scalpels 108 years ago.
Different people draw different conclusions from this fact. Joanna Hoelscher of Citizens for a Better Environment (CBE)--along with many other environmentalists--thinks that if we don't know what we're doing we should stop. "In the absence of certainty, zero exposure to suspected endocrine-disrupting chemicals should be the goal," she says, at least "until the weight of evidence suggests that there is no risk to the public health posed by the EDC in question."
The Chemical Manufacturers Association says it agrees that people shouldn't be exposed to dangerous chemicals. But where CBE wants to know that suspect chemicals are harmless before they're turned loose, the chemical producers want to know that a compound is harmful before it's restricted or banned. As a representative of the Chemical Industry Council of Illinois put it at the July 15 hearing, EPA shouldn't regulate an endocrine disrupter unless it's been proved to have adverse effects "beyond any doubt." Translation: if we don't know what we're doing, let's keep on until we find out exactly what it is before we conclude that it's bad.
Along with synthetic chemicals, the body's endocrine system itself is a 20th-century discovery. "Before 1920 endocrinologists basically dealt with the unusual," Henry Anderson, chief medical officer of Wisconsin's Bureau of Public Health, told the July 14 endocrine-disrupter symposium. "They dealt empirically with patients who were too fat, too thin, too short, too tall, too tired, too hairy or not hairy enough, and those with all sorts of sexual problems." Experiments, as we have seen, were crude.
Outside the medical profession, people we might call folk endocrinologists had a better sense of how to manipulate the endocrine system. Women with unwanted pregnancies knew what teas to brew in hopes of disrupting their own endocrine systems. Their remedies sometimes worked, because plants had been mimicking and disrupting animals' hormones long before humans came on the scene. The Australian sheep industry was nearly destroyed in the 1940s, before scientists puzzled out that a new variety of clover was producing endocrine-disrupting chemicals that made the ewes miscarry or never conceive at all.
Some 173 plants are known to have estrogenic effects--and estrogens are only one kind of hormone. "Compared to the plant kingdom [the members of the Chemical Manufacturers Association] are second-rate amateurs," writes Jonathan Tolman in a recent report of the Competitive Enterprise Institute. "The botanical world is the original CMA."
With the discovery of insulin in 1921, humans began their own experiment in manipulating hormones, supplying diabetics with the vital sugar-regulating hormone their own pancreas couldn't produce. Sir Charles Dodds pushed the experiment along in 1938, creating an artificial estrogen called diethylstilbesterol or DES. Over the next few decades doctors prescribed DES to as many as four million expectant mothers to help them avoid miscarriages. They kept it up even after a 1952 University of Chicago study showed that the drug did no good. As late as 1957 the Journal of Obstetrics and Gynecology carried an ad promoting DES for "bigger and stronger babies."
Now we know that repeated ingestion of a potent estrogen can harm people, because it did. Daughters of DES-ingesting mothers are at extra risk for reproductive abnormalities, including sterility and a heretofore extremely rare vaginal cancer. (Their sons are also more likely to suffer reproductive abnormalities than unexposed men, though their fertility seems unaffected. Proportional doses to fetal mice produce similar problems.) As John McLachlan and Steven Arnold write in American Scientist (September-October 1996), the DES research provided "almost a kind of guidebook to outcomes" of other estrogenlike endocrine disrupters.
Trial and error showed the way again in 1975 when a Hopewell, Virginia, spill exposed workers to the now-banned pesticide kepone. Researchers found that kepone was a weak estrogen and that male workers exposed to the stuff had very low sperm counts. This effect became the subject of national scientific conferences in 1979 and 1985. A chemical designed for another purpose altogether, with a molecular structure quite unlike natural estrogens, had disrupted normal hormone-message transmission in the body. How many others could do that? With what results? Clearly the great human endocrine-disrupting experiment was already in high gear--an unintended experiment with no controls, on subjects who neither knew about nor consented to it.
Sensational consequences in the real world bring out the media, whether they involve young women who learn they can never have children or Florida alligators with miniature penises (victims of a hormone-altering pesticide spill in 1980). Subtler findings in the lab don't get the same attention, but they've been quietly undermining an important, long-cherished, and seemingly reasonable assumption of environmental science--that if a small amount of something does no harm, then a still smaller amount must be harmless too.
Aldicarb is a broad-spectrum insecticide used on potatoes, cotton, and soybeans. In 1987 University of Wisconsin zoologist Warren Porter and his colleagues found that it affects the immune system in mice in a startling way. Just one part of aldicarb in a billion parts of drinking water suppresses their immune response more than doses 1,000 times bigger. (The immune system is closely related to, but separate from, the endocrine system; Illinois EPA lists aldicarb as a "suspect" endocrine disrupter.)
"The lower aldicarb doses are far less than doses normally tested in toxicity studies," Porter and his colleagues wrote in the Archives of Environmental Contamination and Toxicology. They speculated on "the possibility of added danger to humans and animals exposed to a variety of low level stressors in combination with aldicarb."
One part per billion is not much. It's less than the ten parts per billion of aldicarb that Wisconsin allows in its groundwater. Porter--a lanky, genial fellow who seems never to raise his voice--contrasts the safeguards imposed on his laboratory animals with the comparatively lax rules in the outside world. "I could have experimented [with aldicarb] on children simply by taking them out and giving them a drink of water from wells in the county I live in."
A recent study of mice and DES by the University of Missouri's Frederick vom Saal and his colleagues also shows that less can be more. When male mouse fetuses were given DES in parts per trillion they grew up to have significantly and permanently enlarged prostate glands. But when they got a thousand times more DES (parts per billion), their prostates were reduced in size. In normal toxicology the dose makes the poison, and more is worse. In endocrine-disrupter land, high and low doses may have opposite effects.
The result made no headlines--it said little about whether endocrine disrupters promoted prostate cancer in humans, for instance. But it should have made headlines, because it shattered the assumption that everything would be fine if we just kept our exposure to endocrine disrupters below certain very low limits. That still might turn out to be true in particular cases, but it can't be assumed anymore.
Losing this assumption is a bit like losing the railing you were leaning on while looking out over the Grand Canyon. Illinois EPA tells us that releases of endocrine disrupters dropped by 50 percent between 1988 and 1994 and that such chemicals have been involved in less than one percent of all chemical spills since 1990. But that news just isn't as cheering as it once would have been. The campaign by Greenpeace and other groups for zero tolerance of endocrine disrupters--as opposed to the usual regulatory strategy of finding an acceptably low level of pollution and settling for that--begins to make sense.
On May 29 at the Metcalfe Federal Building, Warren Porter talked about endocrine disruption. Afterward an EPA worker asked him, "How can you know that what you decide is right?"
Porter answered in a flash. "Oh, you can never know that. You can only live with the consequences."
OK, powerful drugs and big spills can hurt people and wildlife. Small amounts hurt lab animals. Does any of this prove that small exposures hurt people? No. Mainstream scientists say the question remains open. Environmental Concepts Made Easy, an excellent Web site maintained by the Center for Biological Research at Tulane and Xavier universities in New Orleans (www.tmc.tulane.edu/ecme) states that "no simple conclusions can be drawn from the evidence." Specifically it's "impossible to predict what, if any, human and wildlife health risks exist from daily, low level exposure to natural and synthetic environmental hormones."
Repeated attempts to correlate breast cancer in women with exposure to various chemicals have been inconclusive. Some endometriosis sufferers are convinced that their mysterious disease is "all because there are chemicals in our environment" (as one representative of the Endometriosis Association puts it). But EPA's latest research summary describes the evidence for that theory as "very weak." On the male side, researchers haven't even agreed on whether sperm counts are declining, much less what the cause might be if they are.
This isn't to say that complacency is in order. If it were--if, for instance, the standard precautions in the manufacture, regulation, and use of pesticides were adequate--then we could expect that children born to professional pesticide appliers would do just as well as everyone else's.
They don't. In April 1996 Vincent Garry of the University of Minnesota and his colleagues published a study of 4,935 children born to state-licensed pesticide appliers (almost all male) between 1989 and 1992, comparing them to the 210,723 births in the state's general population over the same time. Three groups of babies had significantly more birth defects than the others: those born to the pesticide appliers; those born in western Minnesota, where chlorophenoxy herbicides and fungicides are used the most; and those conceived in the spring, when those chemicals are used the most. As epidemiological studies go, the odds ratios the authors found for birth defects aren't especially high. They describe the study as "an initial step" that shows "a clear-cut need for comprehensive examination of the health issues involved." At least five of the herbicides and fungicides involved are believed to be endocrine disrupters.
Since hormones guide fetal brain development, it's also reasonable to ask whether early exposure to endocrine disrupters changes how people behave. Estrogen exposure at key stages of development does masculinize the sexual behavior of female rats and demasculinizes that of male rats. But a 1993 comparison between DES-exposed women and the general population came up empty. "No clear-cut differences can be demonstrated to date between unexposed and DES-exposed women in gender-related behavior," wrote Retha Newbold in Environmental Health Perspectives in 1993. "Individual variation is more apparent."
Sex isn't the only issue, though it does help the media pay attention. How about learning, since thyroid hormone levels are critical to brain development before birth? In a controversial study that has lasted more than a decade, psychologists Joseph and Sandra Jacobson of Wayne State University in Detroit have tracked 212 western Michigan women and their children from birth to age 11. The children whose mothers had the highest levels of PCBs in their blood before birth still lag behind the rest in cognitive development. At age 11 they averaged six IQ points lower than their less-exposed peers. (Because everyone contains PCBs, there are no unexposed peers to form a true control group.)
"The most highly exposed children were more than three times as likely to perform poorly in terms of the scores for full-scale IQ, verbal comprehension, and freedom from distractibility and more than twice as likely to be at least two years behind in word comprehension in reading," the Jacobsons wrote in the September 12, 1996, issue of the New England Journal of Medicine. "These deficits are not attributable to maternal drinking or smoking during pregnancy, the quality of intellectual stimulation by parents, postnatal exposure to lead, or numerous other control variables."
You wouldn't notice such a small difference if you met one of these kids. It's what researchers call a "subclinical" or "population-level" effect. "Projected onto an entire population, this amounts to a large shift in the number of people at the high end and low end of a bell-shaped curve," says Dr. Ted Schettler of Physicians for Social Responsibility. "It is a biological phenomenon with enormous social consequences." But the Jacobsons' small sample wasn't randomly selected from the general population. Originally they sought to test mothers and babies with high exposure to PCBs, but they wound up with a group whose measured exposure is only "at the high end of normal," says Joseph Jacobson.
The Jacobsons' results have been partially confirmed by a larger North Carolina study, and they're consistent with what happened to children in a much worse accidental contamination case in Taiwan in 1979. (Contrary to what some critics have said, the Jacobsons correlate children's test results with their mothers' measured PCB levels at birth, not their memories of how many Great Lakes fish they'd eaten.) For what it's worth, the Jacobsons' study does offer some reassurance to breast-feeding mothers. Children in the study actually got much larger doses of PCBs from breast milk than they got in the womb, but it did them no detectable harm. Exposure before birth, not afterward, seems to be the problem. Sometimes it's the timing, not the dose, that makes the poison.
Joseph Jacobson is the first to say he doesn't know if these findings are the result of endocrine disruption. In fact, he doesn't endorse the environmentalists' desire to regulate endocrine disrupters as such. "There may be a compensating effect" rendering the disruption harmless, he says. In researchers' jargon endocrine disruption is a "mechanism," a way something happens, not an "end point," such as strange behavior or diabetes or death. "As a scientist, I'm very interested in mechanisms," Jacobson told the July 14 endocrine-disrupter symposium. "But just having a hormone disrupted may not lead to a serious end point."
Environmentalists involved in this issue find Jacobson's results more persuasive than his reasoning about policy. They want EPA to regulate or ban anything that disrupts the endocrine system, period. They don't want to wait to see if the endocrine disruption actually has any bad results. Jack Weinberg of Greenpeace laments, "The basic information-transfer system of life is being polluted with false information."
On August 4 at the Cook County Courthouse in Skokie, Jum Smith, chairman of the North Shore Mosquito Abatement District board, sat stiff and uncomfortable in his high seat as he submitted to questioning. Some of his constituents were upset that the NSMAD board abruptly decided in July to resume occasional spraying of the insecticide Scourge to kill adult mosquitoes. (Most of NSMAD's antimosquito efforts involve prevention, such as draining breeding places, and killing larvae--activities that have generated little controversy.)
Resident: You were quoted in the paper as saying that the chemicals in Scourge are safe. What was your basis for saying that?
Smith: I didn't say it was safe. I was misquoted.
Resident: Well, do you think there is any safety in Scourge?
Smith: I'm not answering that question. I don't know.
Smith was lucky that was the only pesticide he'd beeen grilled about. Although some endocrine-disrupter suspects--DDT, atrazine, PCBs, dioxins--have been studied quite a bit, many other widely used ones haven't been. Their effects are pretty much unknown. Also unknown are basic facts such as how much people are exposed to specific endocrine disrupters and how much effect the disrupters stored in body fat (such as PCBs) can have. Nor do we know much about the effects of mixtures of different chemicals. Even chemicals we think of as single compounds are often a number of different ones. PCBs, for instance, are a varying mix of some 209 chemically different "congeners," which differ in toxicity and ability to act as endocrine disrupters. Jacobson's results may actually understate the problem with PCBs, because when the original blood samples were taken he didn't have the technology to measure individual congeners.
The EPA has allocated $10 million a year to endocrine-disrupter research, but that money will have to be spread pretty thin, considering that the number of synthetic chemicals now in use exceeds 50,000. More than half of the 333 ongoing federal studies now listed on the EPA's Web site focus on PCBs and dioxins, while other high-production chemicals remain in the shadows. "We tend to be like the drunk who looks for his car keys under the lamppost--because that's where the light is," says Wisconsin's Henry Anderson. According to the Illinois EPA's report on endocrine disrupters, "Several chemicals on the list...are not 'captured' by any routine monitoring programs. As an example, p-Nonylphenol and bisphenol A are two chemicals with high production volumes which are not routinely analyzed in any of the Agency's programs" for water, air, or land pollution.
Chances are you've never heard of bisphenol A, a sealant that Illinois lists as a "probable" endocrine disrupter. It leaches out of polycarbonate plastic when heated, out of dental sealants, and out of sealed cans into food. Like most human-made endocrine disrupters, it's a much weaker hormone than natural estrogens, but that doesn't necessarily make it harmless. As little as five parts per billion provokes an estrogenic response in breast cells in the laboratory. Male mice exposed before birth to just two parts per billion of it grow up to have enlarged prostates. Dr. Ana Soto of Tufts University, interviewed on the Web, says, "About seven out of ten cans of food will contain something that leaches bisphenol A.
On August 3 in Deerfield: "We never fertilize, we never water, we never herbicide, pesticide, or degrub," says Loop lawyer Bret Rappaport, referring to his family's expansive suburban lawn. He's involved with the Chicago-area Yards for Nature campaign and president of a 2,000-member midwestern natural-lawn group called Wild Ones. "If you get down and look close, you'll see field grass, ajuga, and crabgrass in this lawn. It's no golf course. But when you stand up it looks fine. You can have a good-looking lawn without chemicals, if you're willing to accept a little less than what the lawn companies say is perfect."
Steadily encroaching on his greensward are unruly but planned patches of coneflowers, rattlesnake master, and other native prairie plants, some of them tended by the Rappaports' four children. "The easiest way to eliminate lawn pesticides is to make less lawn."
"This is a huge opportunity for industry and business to make a lot of money--by finding ways to control weeds without doing harm," says the University of Wisconsin's Warren Porter. People like the Rappaports have power, he figures, "because a change in market share of half a percent or less really elates or depresses [chemical company] CEOs. We want to educate the public gradually, not alarm them. It is a problem, but there's a very simple solution."
The market can be a simple and peaceful way of dealing with problems. But most pesticides are purchased and applied not by the general public, but by a tiny minority of the population, namely farmers. (And of course not all suspected endocrine disrupters are pesticides; some, such as bisphenol A, are obscure additives to common products.) Of the two and a quarter billion pounds of pesticides applied every year in the U.S., private households use only about 5 percent (though private households spread more pesticides per square foot than farmers). So if people choose less perfect lawns and more organic food, Porter's problem will be eased but not solved.
Even if consumers want to make changes in how they care for their own lawns, they still may not know what's in a given product. To choose wisely we need information, and pesticide makers have resisted releasing the names of the "inert" ingredients in their products on the grounds that they're trade secrets. One such "inert" ingredient in at least some products? Bisphenol A.
In any case, the Republican Congress has already ordered EPA to get busy on endocrine disrupters. Last year's Food Quality Protection Act set an impossibly strict timetable: develop a strategy for screening and testing potential endocrine disrupters by August 1998, be screening and testing them by August 1999, and report back by August 2000. As a result "the scientific and policy debates are occurring simultaneously," says EPA's Tony Maciorowski. "The policy issues will probably be decided before resolution of all scientific questions." That increases the chance of making a mistake. The agency might restrict the use of innocuous chemicals--or ignore dangerous ones.
Both kinds of mistakes have real costs--as Lima, Peru, discovered when it quit chlorinating urban water supplies because chlorine might be harmful and suffered a far more lethal cholera epidemic. Still, it's a lot easier to withhold a new compound than to remove it from the tissues of every creature on the globe afterward. You might as well try to put a pancreas back into a dead dog.
Art accompanying story in printed newspaper (not available in this archive): illustration by Slug Signorino.