Not So Fertile Ground

By MICHAEL D. LEMONICK

The alarm went off with Rachel Carson's 1962 book Silent Spring and has been sounding ever since. We live, environmentalists warn, in a world laced with dangerous chemicals, from powerful pesticides to toxic industrial wastes like dioxin and PCBs. Despite periodic waves of public concern and efforts at government regulation (the 1972 banning of DDT in the U.S., for example), the chemicals are still found in small but measurable amounts in air, water, soil -- and our own tissues. Many scientists have long argued that even tiny doses of pollutants can cause cancer in humans, but the contention is hotly disputed. Other researchers maintain that traces of man-made chemicals are no more likely to cause tumors than are the countless chemicals produced by Mother Nature.

Now, even as the cancer debate continues, environmental groups are pointing to a different, previously unrecognized threat. Chemical pollutants, they say, can interfere with one of the most basic of biological functions: the ability to reproduce. The chemicals allegedly disrupt the action of hormones, those all-important molecular messengers that regulate just about all bodily activities, including growth and reproduction. The result may be a variety of harmful effects that could decrease fertility. Among them: testicular cancer and reduced sperm counts in men, uterine abnormalities and miscarriages in women. While there is no hard evidence that pollution is affecting human fertility in the U.S. or anywhere else, the theory is likely to grab the attention of millions of couples who have trouble conceiving.

The Environmental Protection Agency is expected to raise the issue this week when it releases a major report on the effects of dioxin, one of the most ubiquitous of the suspect chemicals. Dioxin is the name given to a class of chlorine-containing compounds that are waste by-products of many industrial processes such as paper making and waste incineration. Although the release of dioxin has been curbed in recent years, traces of it still permeate the environment.

According to sources familiar with drafts of the EPA report, it will say that dioxin remains a serious potential threat to human health and that possible links between the chemical and health problems, among them reproductive ills, should be further explored. "This study ranks with the Surgeon General's pronouncement that smoking causes lung cancer," says Sierra Club pollution expert George Colling, prematurely and hyperbolically, in the latest issue of the organization's monthly newspaper. And Peter deFur of the Environmental Defense Fund predicts that the document will lead to much tighter regulations, and in some cases even a ban, on the release of dioxin and related chemicals.

Well, maybe. But many scientists who have looked into hormone-disrupting chemicals say the issue is much more complex than environmental activists would have people believe. In high doses, the compounds in question, many of which contain chlorine, are clearly toxic and carcinogenic. On the other hand, the case that humans are being affected by very low concentrations remains far from certain. The existing evidence is largely circumstantial, based on extrapolations from animal studies, laboratory work on the chemistry of dioxin and other molecules, and statistics on human disease that may or may not turn out to be accurate or relevant.

But most investigators agree that although the danger has not been proved, it is too plausible to ignore. The chain of reasoning goes something like this: animals exposed to high doses of these pollutants in the wild develop reproductive abnormalities. Animals exposed to low doses in the lab do too. Humans absorb comparable low doses simply by breathing, drinking and especially eating. Some of the suspect chemicals have physiological effects similar to those of estrogen and other sex hormones, or they at least interact with them; they might reasonably be expected to interfere with processes involving these hormones, such as the menstrual cycle and sperm production.

Finally, several hormone-related human disorders, including low sperm counts, testicular and breast cancers and endometriosis (a painful condition in which uterine cells migrate to other parts of the pelvic area), have arguably been on the rise in the decades since DDT, dioxin and the like first entered the food chain. Says Thomas Burke of the Johns Hopkins School of Public Health: "What we have now is identification of a potential hazard, and that's all we have. What the implications are we don't know yet, and we need to clarify that."

Suspicions about hormone disrupters were raised a few years ago by Theodora Colborn, a zoologist with the World Wildlife Fund who did a study on the reproductive health of Great Lakes wildlife in the late 1980s. Colborn discovered that the young of 16 predator species, including fish, birds, reptiles and mammals, were failing to survive to adulthood or could not reproduce if they did. All the animals ate fish from the Great Lakes, which were contaminated with a variety of hormone-like chemicals.

Colborn suspected a cause-and-effect relationship between pollution and fertility problems -- and by extension a possible danger to humans. She began collecting human epidemiological studies, which suggested to her that human fetal exposure to such chemicals as PCBs could produce disorders affecting behavior, immune-system functioning, memory and learning. She also surveyed the literature on humans exposed to diethylstilbestrol, or DES, a synthetic drug that is related to estrogen. DES can be used to prevent miscarriage, treat prostate and breast cancer or reduce the symptoms of menopause; it can even promote growth in sheep and cows. But in 1971, after studies linked its use by pregnant women with reproductive-system abnormalities, infertility and cancer in their offspring, the FDA decreed that DES should no longer be used to prevent miscarriage. In 1979 the drug was banned in livestock because traces were showing up in meat.

Since no one seemed to be studying the impact of chemicals on reproduction in any systematic way, Colborn organized a 1991 meeting in Racine, Wisconsin, and invited 21 scientists representing 17 disciplines ranging from toxicology to zoology to endocrinology. "No one seemed to know what the others were doing," she says. "Most of the people didn't know anyone else in the room." Colborn also recalls that some of the participants were skeptical about the whole thing. Nonetheless, when they got down to discussing the problems Colborn and others had found in animals exposed to chemicals -- thyroid damage, immune deficiencies, sexual abnormalities -- a pattern emerged. Most of the problems involved malfunctions of the endocrine system that is responsible for producing hormones. Among the chemicals fingered by the group as probable culprits were DDT, kepone, triazine herbicides, certain PCBs and dioxins, styrenes and the alkyl phenols found in some detergents and plastics.

The conference gave rise to numerous collaborations, and participants began trading lab samples with one another and with a growing number of additional interested scientists. "We had gonads flying around the country," says Colborn. As the researchers compared notes, the evidence began to mount. During the mid-1980s, Colborn learned, mortality rates for alligator eggs in Lake Apopka, Florida, soared to 96%, in contrast to 57% in most Florida lakes. The almost certain cause: a 1980 chemical spill that included DDT. In 1993 researchers found that terns in PCB-contaminated Buzzard's Bay, Massachusetts, had reproductive-tract abnormalities including the presence of ovarian cells in male birds. Earlier studies had found similar problems with birds in California and the upper Midwest.

While most of these reports involve heavy doses of chemicals, evidence from laboratory studies suggests there are also effects at lower concentrations. Endocrinologist David Crews has discovered, for example, that small PCB doses can dramatically influence the ratio of male to female offspring in red-eared slider turtles. When University of Wisconsin toxicologist Richard Peterson investigated the impact of dioxin on male rats, he found that the dose needed to cause reproductive-system problems was relatively high. "But when we exposed pregnant rats to a dose 1/100th as large," he says, "we found the male offspring showed signs of reproductive dysfunction," including smaller sex organs, reduction in sperm counts and feminized sexual behavior. Peterson also found defects in lake-trout embryos exposed to dioxin.

What is especially disturbing about Peterson's work is that the levels of dioxin needed to do that kind of damage were as low as 64 nanograms per kg of body weight -- only a little greater than the 5 or 10 nanograms of dioxin and comparable chemicals found in a typical kilogram of human tissue. It is not surprising that these compounds are so biologically active, since they are metabolized in a fashion similar to natural chemicals. Says Linda Birnbaum of the EPA's Health Effects Research Laboratory, who was one of the driving forces behind the agency's decision to study dioxin: "You name almost every hormone system in the body, and dioxin interacts with it. And when you're dealing with hormones, they all talk to each other. When you ring one bell, many others chime."

But -- and this is a big but -- some species are more sensitive to dioxin than others. Just because rats and fish are affected in certain ways does not necessarily mean that humans will have comparable reactions. And doses that harm animals are not necessarily large enough to damage people. On the other hand, humans soak up many different chemicals, and the results may be cumulative.

Whatever the impact of pollutants on men and women, solid evidence is hard to come by. Even when a cause-and-effect relationship is established, as in major industrial accidents, the data are confusing. In the years after a large dioxin release in 1976 in Seveso, Italy, for example, the incidence of leukemias, lymphomas and soft-tissue cancers in men and gall-bladder and bile- duct cancers in women rose -- but breast and endometrial cancers in women actually went down. Possible reason: dioxin may sometimes interfere with the hormone system in beneficial ways.

When scientists look for hormone disruption in the general population, the evidence is murkier still. Birthrates go up and down for many reasons that have nothing to do with pollution. While there are anecdotal reports that the number of infertile couples is on the rise, the phenomenon could be a result of their waiting too long to try for children. The incidence of testicular cancer is higher than it was two decades ago, but that could be because of better reporting. Even the strongest piece of evidence, a Danish study that seems to document a drop in sperm counts over the past 50 years, is considered inconclusive by some scientists.

None of these uncertainties will be cleared up quickly or easily. The fact that environmentalists and a group of concerned scientists have raised the issue of endangered fertility is likely to spur much-needed research. The evidence so far may not be strong enough to support sweeping government action, but it ought to prompt some companies to consider whether there are practical, economical ways to reduce their emissions of suspect chemicals.

With reporting by J. Madeleine Nash/Chicago and Mia Schmiedeskamp/Washington