MOUNTAINS OF DATA
In the years since that conference, research on endocrine disruption has picked up speed; Colborn and her staff have built a database of 33,000 articles to make that research accessible. Chemical manufacturers have funded many studies that have almost uniformly concluded that endocrine disruption does not occur or, if it does, is not harmful. This is hardly surprising because a great deal of money is at stake. (To offer just one example: In 2002 U.S. companies produced 2.8 million tons of bisphenol A [BPA], a synthetic estrogen used to make baby bottles, plastic water bottles, dental sealants, and resin liners for metal food cans. At 94 cents a pound, this translates to sales of more than $5.3 billion in that year alone.) By contrast, federally funded academic researchers, who have no financial stake in the outcome of their work, have found much compelling evidence that synthetic chemicals, including BPA, do cause endocrine disruption and that the damage can be serious.
One discovery in particular changed the ground of all endocrine disruption research. Frederick vom Saal, a reproductive endocrinologist at the University of Missouri, established in 1997 that significant effects can be seen at extremely low levels of exposure, parts per billion and even per trillion. These levels are present in the blood of humans as well as animals.
The next logical step would be to expose human subjects to these chemicals, but it is considered unethical to subject humans to substances that might damage their endocrine function. So rats and mice have had to stand in for humans, just as they do in cancer research.
Over the last 10 years, vom Saal has studied the effects of BPA on mice, and others have followed his lead. Collaborating with Wade Welshons, a veterinary medical researcher also at the University of Missouri, he established in 1997 that male mice whose mothers were exposed to BPA during gestation routinely developed enlarged prostates. Further research found that BPA has many other impacts. In male offspring, exposure of the mother results in decreased sperm counts, decreased motility of sperm, an increase in malformed sperm, and smaller testes. In females, researchers have observed early onset of puberty, larger uteri, polycystic ovaries, deformed and incomplete vaginal structures and tissues, enlargement of mammary ducts and milk glands in the breast, and an increase in miscarriages. Damage by BPA, vom Saal notes, is not limited to reproductive effects. Structural changes in the brain; immune-system damage; learning problems; hyperaggression; and changes in sexual behavior, social interactions, and play behavior have also been documented.
Chemical manufacturers have worked hard to counter this academic research, hiring chemists to study and discredit the results. Vom Saal and others have had to spend enormous amounts of time and money defending their work, resources better devoted to moving forward onto new ground. Researchers funded by industry, curiously, tend to find that every chemical is safe. In 2004, vom Saal tallied up results of all the studies he could find on BPA. He discovered that of 104 studies done by independent researchers, 94 found adverse effects and 10 found no effects. Of the 11 studies conducted by industry-supported researchers, zero identified adverse effects. Marian Stanley, a spokesperson for the American Chemical Council, which represents the interests of chemical manufacturers, says, "We are unaware of any big discrepancies between the experimental research supported by industry and by others. Animal studies -- that is, credible experimental research -- from all sectors show basically the same results across the board."
In fact, Colborn observes, academic researchers have been able to demonstrate the effects of chemicals at very low doses, but industry labs have not been able to replicate their work, and use their lack of results to claim that the chemicals are safe. Colborn says that independent researchers have identified possible causes of these discrepancies. Diet is key; animal chow that has more soy, which itself is mildly estrogenic, may skew results. Housing rats in plastic cages or stainless steel may throw things off since some plastics disrupt endocrine levels but metal does not. Intrauterine position can affect results: For instance, a male rat that grew in utero between two female rats will be born with higher levels of estrogen in its blood than one that grew between two male rats. Controlling for all these variables is hard and expensive. The most contentious variable has been breed of rat. Early in the process, researchers determined that the Charles River Sprague Dawley rat was so tough that it barely responded to estrogenic compounds. Many scientists whose work is funded by chemical manufacturers have continued to use this strain, a practice deplored by Colborn and other independent researchers.
Pat Hunt, a geneticist at Washington State University, was shocked when she discovered how great a difference a worn-out plastic cage could make. Suddenly, 40 percent of the healthy control mice in an experiment began to make eggs with grossly abnormal chromosome behavior where she expected to see a rate of 1 to 2 percent. She traced the problem back to BPA they were exposed to when it leached out of their cages and water bottles. She spent five years on the problem, making certain of her results before publishing "because I was going to say exposure to this chemical used in plastics can cause miscarriages." Today, at conferences, Hunt urges fellow scientists to take endocrine disruption seriously. "The mouse is an incredibly robust breeder while we humans are, comparatively, so fragile." She is concerned about delay. "If we wait till we see an increase in chromosomally abnormal [human] miscarriages or a sharp drop in sperm count, by the time that big an effect comes up on the radar screen, we need to ask ourselves if we are going to be reproducing as a species or not."
Research on male sex hormones, or androgens, has shot forward in the past decade, and the man most responsible for this progress is Earl Gray, a toxicologist who works for the Environmental Protection Agency in Research Triangle Park, North Carolina. In 1995, he started by administering very low doses of the fungicide vinclozolin to pregnant rats.
Vinclozolin was widely used until 2002, when the EPA began to restrict it because of its potential health effects. Gray found that the rats' male offspring were born with nipples, malformed scrota and testes, vaginal pouches, and cleft phalluses with hypospadias (urethral openings in the wrong place, along the shaft of the penis or in the scrotum). This finding is particularly resonant for human health, since the rate of hypospadias in human infants doubled for no known reason between 1968 and 1993. The animals in this experiment also displayed delayed puberty, lower sperm counts, and reduced fertility.
Gray went on to examine trenbolone acetate, a synthetic steroid used as a growth promoter in beef cattle in the United States and as a performance-enhancer by athletes who purchase it illegally over the Internet. Trenbolone, excreted in animal waste, shows up in rivers and streams where, Gray believes, it may affect aquatic animals. After experiments on the fathead minnow, Gray concluded that trenbolone was a powerful androgen: Female offspring of mothers exposed to the compound grew tubercles, part of the reproductive system usually seen only in males, and had fewer babies. Observers of wildlife are beginning to report similar effects around the world. Effluents from pulp and paper mills are sufficiently androgenic to sex-reverse female fish in Florida, the Baltic Sea, and New Zealand.
Gray is an extraordinarily productive researcher, at the top of his field. One can only wonder how much more he might discover if he had more resources. Because of a hiring freeze at EPA, Gray's staff of technicians has shrunk from three to one, limiting the number of experiments he can do.