I tell people I come from a different planet because the planet I arrived on is so unlike the planet of the 21st century. There were no plastics; there was less carbon dioxide. There were more fish in the sea. I come from the pre-Plasticozoic era.
— SYLVIA EARLE,
National Geographic explorer-in-residence
THE SAME YEAR THAT TIMMIE JEAN WAS EXCHANGING an ear tuck for a boob job, Rachel Carson published a book about the destructive power of pesticides. These two events had more in common than it might appear, for both heralded a new era of synthetic compounds that would forever alter breasts. In 1958, the nature writer and biologist had received a disturbing letter from Olga Huckins, a gardener in Duxbury, Massachusetts. It described how the local authorities had sprayed fuel oil and DDT (dichlorodiphenyltrichloroethane) to kill mosquitos, leaving scores of songbirds dead in her neighborhood and in her very backyard. Huckins wrote that birds fell from the sky. Others perished in grotesque postures around her birdbath, their claws splayed, their bills gaping open.
Carson was already known as a voice for nature. The first female biologist hired by the U.S. Bureau of Fisheries, she’d written several odes to the sea, including the wildly popular best seller The Sea around Us. It won a National Book Award in 1952.
Inspired by Olga’s letter, Silent Spring was a measured and eloquent argument against the indiscriminate use of synthetic pesticides, which Rachel Carson called “elixirs of death.” She described the little-known work of scientists showing how DDT and its ilk caused damage beyond their target insects, affecting birds, fish, and other vertebrates. She got a couple of things wrong in the book, such as the statement that few carcinogens exist in nature (in fact, there are many, including the sun, wood smoke, and numerous viruses and fungi). She could be melodramatic, describing a future lifeless world and quoting Keats (“The sedge is wither’d from the lake, / And no birds sing”). But history would prove her correct about the unanticipated effects of widely used neurotoxins in the environment. She introduced a nation to the idea that human actions and the natural world were inextricably linked, and that people had some obligation to protect that world. The United States’ seminal environmental legislation of the 1970s can be traced back to the wide constituency she built.
Carson made ecology a household word. Moreover, she placed the human body squarely within that ecology. She described the rising rates of cancer since World War II, which launched a new era of synthetic organic chemicals. She pointed out that we are now living with persistent industrial chemicals in a way our ancestors never did. “For the first time in the history of the world, every human being is now subjected to contact with dangerous chemicals, from the moment of conception until death,” she wrote. Or as The Who put it in 1966, “I was born with a plastic spoon in my mouth.”
Carson didn’t know that many of these compounds have the ability to alter human hormone systems, but she presciently described chemicals accumulating in the sex organs of birds and mammals and corresponding drops in sperm levels. She was struck by reports that roosters were losing their wattles and that sperm counts were found to be low in pilots who sprayed pesticides from the sky.
The term endocrine disruptor wouldn’t be coined for another thirty years, when a concerned group of wildlife biologists gathered to exchange research on everything from intersex fish to birds that refused to act like parents. To the scientists, the evidence was mounting that synthetic compounds in polluted areas, notably the Great Lakes, were altering the cells, bodies, and behavior of these animals in ways not seen before.
Until that time, most people thought synthetic estrogens showed up only where we intended them to, namely, in medication. But hormones are famously sneaky. They do their work in our bodies in infinitesimally small quantities. One molecule of a hormone fits into one receptor on a cell like a key in a lock, unleashing a chain of biochemical events. These are the keys that govern everything from cell division to metabolism to hair and breast growth to cognitive performance on spatial tasks. Hormonal changes during women’s monthly cycles affect how they smell things, how they perceive the faces and bodies of the opposite sex, and even how they think. Some studies show that when estrogen levels peak midmenstrual cycle, women reportedly get better at verbal and finemotor skills.
If a foreign imposter shows up on the receptor, however, the body’s responses become all but impossible to predict. Some foreign estrogens, called xenoestrogens, occupy the receptors so native estrogens can’t do their jobs. Others pass the security test and turn on estrogenic responses. Some seem to mess with the body’s feedback loops, causing the brain to release more or less hormone than it otherwise would.
It is now known that some imposters occur naturally, like estrogenic substances in plants. Why would plants bother to make estrogen mimics? For the same reason they make acids, poisons, and thorns. Plants are smart, or at least evolutionarily successful. One jaunty example is marijuana, which figured out how to make THC (tetrahydrocannabinol), a compound that happens to fit perfectly into pleasure receptors in the human brain, all but ensuring its spread around the world. Which begs the question, do humans cultivate marijuana, or is the plant actually cultivating its human growers? Marijuana also releases compounds that inhibit testosterone in people who consume it. Long-term male stoners are known to sometimes grow small breasts, and they also face increased risk of breast cancer. Is this a coincidence, or is the plant somehow benefiting from having less aggressive users who giggle easily and croon folk songs?
A couple of dozen plants are known to produce high levels of phytoestrogens, which essentially act as oral contraceptives, in order to knock back their predators. When sheep eat a particular strain of clover, they can’t reproduce. Humans have long taken advantage of these plant properties, using certain herbs and fruits to prevent pregnancy or induce miscarriage. Hippocrates knew that the seed of Queen Anne’s lace, when eaten, worked as a contraceptive and morning-after pill, as did an infusion of pennyroyal. Giant fennel, found by the Greeks in the seventh century BC, was so coveted for the contraceptive trade that it was harvested to extinction.
ALL OF THIS WAS FAR FROM THE MIND OF PATRICIA HUNT IN 1998, when she was working in her lab at Case Western Reserve University in Ohio. She is an experimental biologist with a fascination for aneuploidy, the chromosomal abnormalities that cause miscarriages or birth defects (like an extra copy of chromosome 21, which causes Down syndrome). These are the things that can go wrong in the earliest moments of conception and fetal development. Humans are supposed to have twenty-three pairs of chromosomes, but sometimes there’s a little, or big, miscalculation, especially in the eggs of older women. Hunt wanted to know why. She hoped studying mice would yield clues.
As was typical, she was working with mutant mice and some control, or normal, mice. One day, she noticed that her control mice, which were supposed to have healthy eggs, were producing a high rate—40 percent—of abnormal eggs, when the usual rate is 1 to 2 percent. Something had gone terribly wrong. “We checked everything,” she told me, “the air in the facility, were there pesticides coming in? It took us weeks. We finally noticed some wear and tear on the animals’ plastic cages.” It turned out a temporary worker was using the wrong detergent to clean the cages, and it was degrading the cage walls, causing a substance called bisphenol A to leach into the mice’s food and water.
Bisphenol A, or BPA, was an artificial estrogen developed in the 1930s as a possible drug to prevent miscarriages in women. It didn’t work for that, but the compound soon found other uses, like making polycarbonate plastic. BPA’s molecular structure is simple and elegant: two joined hexagons, each made up of six bonded carbons. When these are neatly stacked to make a long-chain polymer, the material is incredibly strong. You can drive over a polycarbonate water bottle and it won’t break. It’s also cheap, derived as a byproduct of refining petroleum. Unfortunately, BPA’s versatile ring structure bears a close resemblance to estrogen. Now produced in mind-boggling quantities of two million pounds per year in the United States, for annual profits in excess of $6 billion, it’s in everything from the lining of canned food to dental sealants, to consumer products like CDs, cellphones, and bike helmets, to the shiny paper receipts we get from the grocery store. It was also in lab equipment at Case Western Reserve.
“I don’t think anybody in the aneuploidy field really believed in environmental effects. I know I didn’t,” said Hunt, who’s petite and trim, with short, tousled hair. “That fad came and went in the 1970s.” That was when, spurred by the connections suggested in Silent Spring, scientists realized that it was much harder to attribute disease to pollution than anyone expected. “We knew that maternal age was the huge, main event [for abnormal eggs], and that trying to see any other effect would be like trying to see a snowball fight in the midst of an avalanche. That’s why this really caught our attention,” she said.
Another, much more personal, endocrine effect caught her attention five years after the leaching-cage problem. Hunt was diagnosed with breast cancer. She knew she was a so-called DES daughter (her mother had taken diethylstilbestrol while pregnant) ever since she’d received abnormal pap-smear results in college. In other words, in the earliest beginnings of her own life, she was exposed to a potent hormone that wasn’t supposed to be there. Ironically, the drug that replaced BPA in the 1930s to prevent miscarriage was DES, a more powerful estrogen (but alas, no better in hindsight at preventing miscarriage). Because of their early-life exposures, some DES daughters are known to suffer from rare, devastating reproductive cancers, malformed uteri, and higher-than-normal rates of breast cancer. When they’ve been able to bear children, their daughters are also more prone to breast cancer. DES sons have lower sperm counts and higher rates of genital birth defects. DES was not discontinued in pregnant women until 1971, nearly three decades after it was introduced. An estimated five million people were exposed through pregnancy, and many millions more consumed DES-tainted beef and poultry. Because of DES, scientists learned that chemicals can and do cross the placenta, which they once didn’t believe was possible.
Hunt has described these events as being twice struck by lightning. Two artificial estrogens were now determining her destiny. She’s since devoted her career to studying the strange and ominous effects of BPA in her mice. Hunt and numerous other researchers around the world have found that early-in-life exposures to BPA can cause early puberty, lower sperm counts, changes in mating behavior, predisposition to obesity, increased rates of breast and prostate cancers, and increased rates of miscarriages. All these troubles were observed in rodents, many of which were exposed while in their mothers’ wombs.
“The long-term ability to reproduce is my focus,” she explained from her immaculate lab, now housed in a spanking new building at Washington State University in Pullman. Her office is filled with “chromosome art,” prints and ceramics showing the spindly wormlike forms of the substance that begins all life. Her husband’s office down the hall sports a wooden lamp with a sperm-shaped pull cord.
Hunt showed me the basement “vivarium” where her strains of mice live, the breeders, the studs, and the babies. She no longer uses cages made with BPA. She saves that for her experiments.
When she doses her mice with BPA, she sees abnormal behavior or cells in the mother, the pup, and, later, the pup’s children, for what she terms a “grandmaternal effect.” One dose effectively damages three generations, just as some researchers are seeing with DES and humans. Hunt’s studies are controversial because sometimes the results haven’t been replicated. Hunt has a reasonable explanation for this: the effects depend precisely on when the mice are exposed. “The developing fetus is exquisitely sensitive to environmental factors,” said Hunt. “There are critical windows, sometimes just one or two days long, in which a tiny dose of chemical can send the wrong message to cells, and other days when the window has shut and the mouse will develop normally.”
Depending on that timing, in the mama mouse ovaries she often sees eggs in which the chromosomes aren’t lining up right. Normally, these eggs shouldn’t even be viable, but for some reason, the body’s quality-control checks aren’t working to destroy them. “We want to see the earliest possible defects, and here it is, bam. It means we can see things in the early stages of making an egg that should lead to mistakes, and they do.” She showed me a magnified image of scattered red wormlike chromosomes, the confounding mistakes in germ-cell scaffolding caused by BPA—a “funny little beast,” as she calls it. Pointing to the worm pattern, she noted, “The chromosomes are completely disorganized. I wouldn’t want my eggs looking like that spaghetti.”
Looking at the images, I could almost feel my ovaries twisting up. But these were mouse eggs. Did her work have relevance for us?
“That [multigenerational effect] for me was huge,” said Hunt. “It would be a fifty-year problem in humans. We think these effects are at doses that are environmentally relevant.” She was saying that people today are exposed to similar levels per body weight as her mice. “How would we see this in humans?” she asked. “Increasing rates of miscarriages, low sperm counts, testicular problems. We already do see that. How long will it be before we say, ‘Holy cow, are we crippling both sexes at once?’ “ Hunt is frustrated—passionate, even—that U.S. and many international agencies still have not taken a strong stance against BPA. (As of this writing, though, ten states have banned it for use in baby products. France has banned the substance from water bottles, and Denmark has banned it from food packaging meant for children under age three.) She reminded me of the once-staid climate scientists who have become some of the most outspoken critics of U.S. climate and energy policy. They know too much to keep quiet.
In the meantime, no one in her lab drinks out of a plastic bottle.
A COUPLE OF PAT HUNT’S OBSERVATIONS HAVE BIG IMPLICATIONS for breasts. The first is that diseases like cancer can start in the womb, even in the egg, in its earliest beginnings. The second is that synthetic chemicals that whack out our hormones are popping up in wholly unexpected places, like our grocery receipts. Since her first accidental discovery in the lab, hundreds of other scientists have also studied BPA, wondering, among other things, what it does to how the breast grows and develops.
Numerous studies have confirmed that BPA activates the estrogen receptors on breast cells and can cause cancer cells to replicate in a dish. In addition, BPA has been shown to cause normal breast cells to act like cancer cells, growing invasively when they’re not supposed to. BPA and similar compounds can turn on and off genes in breast cells in ways that foster cancer. When fetal or young rats are fed BPA, they can be more susceptible to getting cancer later on when they are exposed to other carcinogens. There is something about BPA that alters the way rats’ mammary glands grow and respond to later threats. In other rat experiments, prenatal exposure to low doses of BPA caused lesions in mammary glands. When researchers at Yale fed DES (a very strong estrogen) to some pregnant mice and BPA (a weak estrogen) to others at levels approximating those found in pregnant women, both offsprings’ mammary glands produced more of a protein called EZH2. Higher EZH2 levels are associated with an increased risk of breast cancer in humans. And it didn’t matter much to the glands whether they received the strong or weak estrogen. This was a chilling discovery for those toxicologists still clinging to the ages-old adage that the dose makes the poison.
Cancer isn’t the only concern. There is also some evidence that chemical exposures, delivered very early in life, can alter the way the milk-making structures grow, as well as re-jigger the timing of breast growth during puberty. In industrial countries, human breasts are appearing earlier in childhood (stay tuned for the next chapter), and women in the United States suffer from more problems breast-feeding than women in Africa or South America.
It’s treacherous drawing connections between lab rodents and people, but if our historical DES experience is any guide, the lab data can be telling. Our mammary glands are similar to those of rodents, and we are sensitive to the same hormones. These potent chemical signals are the ancient currency all vertebrates share. Estrogen is the oldest steroid of them all, with our cellular receptors originating over 550 million years ago. Our bodies inherited an eons-old ability to absorb it from our surroundings, even after we learned how to make it ourselves. We are a modern motif on an ancient device.
Why are our estrogen receptors such disappointing judges of character? Why are they so promiscuous, hooking up with many different kinds of compounds? Two reasons. One is a central theme of this book, so it’s worth saying again: organisms like us are designed to be biologically responsive to the world around us. Scientists call this “phenotypic plasticity.” It means we can tweak our bodies a little bit if it looks like we need to, regardless of our DNA. Our hormone receptors are sensors; they are one of the ways we gauge the world. The estrogen receptor, though, is confoundingly catholic in its tastes, more so than the other steroid receptors. Its lock will take any key with a carbon ring structure, and others besides. As bad luck would have it, this structure is the same building block used to make numerous synthetic compounds, including many plastics, solvents, and pesticides.
Our breasts, for better or worse, have more varied and more sensitive hormone receptors than other organs. If anything, their receptors veer toward oversensitivity. They need to sense the environment to store fat and grow at the optimal time and feed an infant in an uncertain world. What might have been handy once upon a time now looks increasingly like a liability.
This leads us to the second reason, which is that our receptors never before had to dance with so many bad actors. In the past, estrogen mimics were mostly plant estrogens, and many of them are weak and possibly even beneficial. Some phytoestrogens block our receptors in a good way. Some studies suggest that high-soy diets, for example, help prevent a recurrence of breast cancer in survivors, as well as delay breast development in girls, perhaps by protecting their cells from their bodies’ more active estrogens. We coevolved with plant estrogens, and that’s probably why we can metabolize these compounds quickly. We were also exposed to them seasonally and in limited amounts. BPA, on the other hand, comes to us in a daily drip and, notably, reaches us in the womb.
BPA was proved eighty years ago to act as an estrogen. You might wonder, as I did, why on earth, if BPA was known to behave estrogenically, did it go on to become the principle ingredient in ubiquitous polycarbonate plastic, an ingredient known to break down easily and escape into the environment?
The answer to that would be a long and sorry tale about the lack of government oversight, inadequate testing (in fact, virtually nonexistent testing) for hormonal effects in safety studies, and the phenomenal power of the chemical and pharmaceutical industries—à la Big Tobacco—to sow seeds of scientific doubt and maintain a favorable regulatory landscape.
If known estrogenic compounds such as DES and BPA could fly so long under the safety radar, what about the other thousands of chemicals in our world, especially the ones that are not obvious hormone disruptors? How safe are they? In the United States, seven hundred new chemicals come to market each year, joining the eighty-two thousand already in use. Of these eighty-two thousand, only a few hundred have ever been tested for health effects. Despite the thirty-five-year existence of government regulatory agencies and their guiding laws in the United States, including the Toxic Substances Control Act, only five chemicals have ever been banned. DES was still manufactured in this country as recently as 1997. Unlike in Europe, American companies are not required to perform safety studies on chemicals before they introduce them into the marketplace. In fact, they have a strong incentive not to perform them. In the United States, every chemical is assumed safe until proved guilty. The burden to do that falls on government and university scientists, who don’t have the institutional muscle or resources to keep up. It takes years of work to prove that a chemical causes harm, and a shield of proprietary industrial secrets has kept manufacturers from revealing which chemicals they are even using. These recipes may be private, but they swim in your bloodstream and in mine. Of the 650 top-volume chemicals in use, four billion pounds get released into the American water and air each year. Forty-two billion pounds are made here or imported each day for use in products and materials.
The U.S. government does occasionally single out some chemicals for lab-animal testing, and the Environmental Protection Agency has recently finalized new tests for routing out the top suspected endocrine disruptors. The official tests, however, focus on certain well-established endpoints: the liver, the kidney, the genitals, and the brain. “They leave the mammary gland in the trash can,” pointed out Ruthann Rudel, a toxicologist at the Silent Spring Institute, a Massachusetts-based nonprofit that advocates stronger environmental testing.
The mammary gland, once again, occupies a forlorn and forgotten place in science. This is especially disturbing since independent scientists have found that the mammary gland is the most sensitive organ to known culprits such as BPA, DDT, and a common weedkiller called atrazine. Banned in Europe but used in the United States to the tune of seventy-five million pounds a year, atrazine is a major contaminant of drinking-water supplies. In the body it appears to increase the activity of aromatase, an enzyme that converts testosterone and other hormones to estrogen. In affected frogs and fish, scientists are seeing damaged reproductive organs. Rats who are exposed early in life are showing signs of altered mammary gland development and increased incidence of mammary tumors.
The journal Cancer reported in 2007 that limited testing (mostly by independent scientists) has so far found 216 chemicals known to cause mammary gland tumors in animal studies. These include chlorinated solvents, products of combustion, pesticides, dyes, radiation, disinfectants, pharmaceuticals, and hormones. Twenty-nine are produced at levels greater than one million pounds per year in the United States. Seventy-three are present in consumer products or in food. Roughly one thousand chemicals have so far been shown to alter animal endocrine systems. These compounds include anti-androgens and thyroid impersonators, not just estrogens. One of Rudel’s projects is to corral various laboratories and agencies to develop standard tests for recognizing damage to the developing mammary gland.
WE’VE GENETICALLY MODIFIED OUR CROPS TO BE ABLE TO PROTECT them from the ill effects of pesticides, but we haven’t yet figured out how to modify our breasts or livers or brains. Perhaps someday we’ll have GMO breasts along with GMO corn. In the meantime, it’s next to impossible to draw a line between a particular chemical in our lives and a disease or symptom that might show up decades later. When we do notice a problem with a common drug or chemical, it’s because the resulting effects are either very unusual (rare vaginal cancers in DES daughters, mesothelioma in asbestos workers) or very obvious (shortened limbs in children whose mothers took thalidomide to prevent morning sickness).
With DDT, the effects have been more subtle and more varied. But the eventual catalogue of ills, recounted by Rachel Carson and many others, made the endocrine-disruption hypothesis possible.
A chlorinated hydrocarbon, DDT had a great run during World War II as an insecticide, sparing soldiers from grim deaths by typhus and malaria. After the war, its manufacturers were eager to grease its transition to civilian uses. As Brigadier General James Simmons rhapsodized, “The possibilities of DDT are sufficient to stir the most sluggish imagination. In my opinion, it is the War’s greatest contribution to the future of the world.” It was sprayed from airplanes over fields, suburbs, playgrounds, and country roads. It was aggressively marketed to housewives and farmers alike. By 1950, it was so widely used that 100 percent of houseflies were resistant to it. Still, its use continued unabated, and by the early 1970s, 1.3 trillion pounds had been sprinkled, sprayed, and dusted in the United States. Many adults today remember gleefully running or biking through the fog sprayed by DDT trucks and planes in the 1950s and 1960s.
After dead insects, birds were DDT’s first notable victims. Most famously, the pesticide wiped out populations of bald eagles, peregrine falcons, and brown pelicans because it weakened their eggshells and altered nesting behavior. It wasn’t long before scientists started looking for effects in other animals and humans. They measured it in human blood, umbilical cord blood, and breast milk, and they found associations between high levels of the pesticide and the incidence of diabetes, miscarriage, poor semen quality, shortened duration of lactation, preterm birth, low birth weight, and decreased cognitive skills in children.
DDT and its main breakdown product, DDE, are very difficult to get rid off. Fat-loving, stable molecules, they reside in animal tissues (as well as in soils and streams) and stay there for decades. Thirty years after the ban, these molecules are still detected in most human blood samples tested by the Centers for Disease Control and Prevention.
Several studies have compared the DDT levels in women with breast cancer to those in women without breast cancer. Nothing remarkable showed up. But then in 2007 researchers looked at blood samples collected from mothers in the 1960s. The younger women, the ones exposed to the most DDT as girls (at levels still measurable in their blood because of DDT’s long half-life), had a fivefold increase in breast cancer incidence later in life. The girls who were older than fourteen when DDT was introduced had no increase in the incidence of cancer. For the girls who received their hits in early youth, the blow was much worse. In other words, the timing of the exposure was critical, similar to the effects seen of radiation in bomb survivors and BPA in mice. This study may well help explain why women born after 1940 have much higher levels of breast cancer than women born before. There were simply more chemicals soaking their childhoods.
DDT was just the first in a line of troubling organic pesticides. Next came dieldrin, aldrin, chlordane, heptachlor, hexachlorobenzene, and others. After World War II, our thrumming petroleum and chemical-weapons machinery readjusted beautifully to civilian outlets. Cheap by-products of fossil-fuel production found myriad new uses. Benzene became a building block for BPA, flame-retardants, insecticides, and scores of other formulations. Today we use thirty times more synthetic pesticides than in 1950, nearly nine pounds per person. When Rachel Carson wrote Silent Spring, she noted that one out of four Americans would get cancer in their lifetimes. Now, the rate is 1 out of 2.5. An aging population accounts for much of that change, so it helps to look at age-adjusted rates for specific cancers. When we do, we see that the incidence is notably rising for endocrine-related cancers such as breast, prostate, and thyroid. We now know many chemicals have the potential to cause cancer and much more subtle effects, as we’ll see. It has taken three generations to find out.
Chemical World News reacted to the publication of Silent Spring by calling it “science fiction, to be read in the same way that the TV program, ‘The Twilight Zone’ is to be watched.” But the public responded to Rachel Carson, and by the mid-1970s, Congress had passed laws to begin to regulate the chemical industry. In 1972, DDT was banned.
Carson wrote, “If we are going to live so intimately with these chemicals—eating and drinking them, taking them into the very marrow of our bones—we had better know something about their nature and their power.”
She’d no doubt be discouraged by the extent to which chemicals are even more embedded in our food systems and personal lives than they were fifty years ago. But she’d be fascinated by our increased understanding of how they affect so many bodily processes.
Eighteen months after Silent Spring was published, Carson was dead at age fifty-six. She had breast cancer.
