Endocrine Disrupters: An Overview of the Evidence
Air Date: Week of October 21, 1994
(Due to an overwhelming response, an update on the show which aired the week of July 8, 1994) Common chemicals are getting into our bodies and may be disrupting our immune and reproductive systems. They're called endocrine disrupters and they act like hormones interfering with normal growth in people and animals. In this second of a two-part series, host Steve Curwood explores the link between synthetic chemicals, such as pesticides, to reproductive abnormalities. An increasing body of evidence is gaining the attention of the medical and scientific community.
CURWOOD: This is Living On Earth. I'm Steve Curwood. Thirty years ago a marine biologist with the US Fish and Wildlife Service issued a warning. In her book Silent Spring, Rachel Carson detailed the dangers from synthetic chemicals, especially pesticides. "They have immense power," wrote Carson, "not merely to poison, but to enter into the most vital processes of the body and change them in sinister and often deadly ways." Now, 3 decades after this warning, and a half a century after these chemicals were first developed, a growing number of scientists believe that the sinister effects Carson had predicted are beginning to show up. Item: researchers say a pesticide spill in Florida caused alligators to be born with both male and female sex organs. Item: a large number of aquatic birds in the Great Lakes seem to be chemically castrated, and born sterile. Item: children whose mothers were exposed to toxic chemicals have developed neurological problems and reproductive deformities. Item: something seems to be dramatically disrupting the fertility of men worldwide.
SIEBEL: In this particular room this is where the male reproductive tract is focused on.
CURWOOD: Our story begins in a laboratory at the Faulkner Center for Reproductive Medicine in Boston, where Dr. Michael Siebel studies the increasingly common problem of male infertility.
SIEBEL: And then we have a number of slides that you can see with various color stains on them, in which the sperm samples are looked at.
CURWOOD: Can you put one under the microscope and tell us what you see?
CURWOOD: Dr. Siebel flips on a microscope and focuses on an all too familiar sight.
SIEBEL: This person has a problem of making too many immature sperm cells.
CURWOOD: And what could cause that?
SIEBEL: It could be a hormonal imbalance, or it could be a problem of his sertoli cells, which are the cells that make sperm, not functioning properly.
CURWOOD: Sertoli cells are responsible for the production of sperm in the testes of adult men. Dr. Siebel says the slightest disturbance in the balance of sex hormones during critical stages of fetal development can disrupt the sertoli cells and a man's fertility for life. Researchers like Dr. Siebel believe there's been a dramatic increase in the number of men suffering fertility problems. There is mounting evidence that the average man today produces only half as much healthy sperm as his grandfather did.
SIEBEL: I'm quite concerned about it because whether or not we're now getting down to the amount one really needs to have children is the question, and how much further we'll go is the concern.
CURWOOD: What do you think is going on?
SIEBEL: I think that it's a combination of things. Whether it's environmental concerns, whether it's the stress of living today, whether it is substances that we passively get indirectly through the foods and preservatives, I really don't know. But clearly something is happening.
CURWOOD: Something unusual seems to be happening to the reproductive systems of women as well. Endometriosis, a painful, abnormal growth of the uterine lining, is epidemic worldwide. Fifty years ago there were just 21 reported cases. Today, as many as 9 million women suffer from the disease in the United States alone. Many scientists think the rise in endometriosis, the rapid decline in sperm counts, and a litany of other human and animal health problems are connected. Dr. Theo Colborn, a zoologist and senior scientist with the World Wildlife Fund, believes she's found the link.
COLBORN: I think we have flooded the environment with a large number of chemicals that look like or interfere with hormones, neurotransmitters, growth factors, and inhibiting substances.
CURWOOD: Dr. Colborn calls these chemicals "endocrine disrupters." The endocrine system is the delicate network of glands which produce hormones: the powerful chemical messengers which regulate our most vital biological processes, including sexual development, immune response, and the way we react to stress. Natural hormones are intensely powerful, but quickly eliminated by our bodies. Synthetic chemicals which act like hormones, on the other hand, are much weaker, but our bodies don't know how to get rid of them, and they build up, mostly in our fat. Dr. Colborn worries that the most important impact of these substances may not be on the people directly exposed to them, but on the next generation: on their offspring. In pregnant women, Dr. Colborn says, hormone-imitating chemicals can leech out of fat cells, cross through the placenta, and wreak havoc on the fetus at the most vulnerable stages of development.
COLBORN: They look like hormones, and they are capable of getting into the body and interfering with the normal hormonal activity, and the messages, the normal messages, that control normal growth.
CURWOOD: Many of the chemicals that Dr. Colborn suspects are endocrine disrupters are tested for their ability to cause cancer and birth defects, but they are not tested for what she says may be their less obvious, but no less devastating impact.
COLBORN: We had been focusing on cancer and mutations. We've been sidetracked by that, and we've missed this other, really more insidious effect. If the immune system is affected maybe they're not well all the time. If their nervous system is affected, maybe they're not as smart as they should be. Maybe they have problems with behavior. Maybe we're affecting their fertility, so that population may not be able to reproduce eventually.
CURWOOD: And these chemicals are all around us now. All the time.
COLBORN: That's right. That's right. Steve, you're sitting there right now with at least 500 measurable chemicals in your body that were not there before 1940. And I think what's happening is that you can't predict what these chemicals are going to do.
CURWOOD: Some of the substances that Dr. Colborn suspects are endocrine disrupters are heavy metals. Cadmium, lead, and mercury. But most come from a class of chemicals called organochlorines. They are used in thousands of products from pesticides and plastics to pharmaceuticals. DDT and PCBs are organochlorines that were banned because scientists believe they cause cancer. But even that link is uncertain. In fact, so little is known about so many of these chemicals that critics charge Dr. Colborn's theory is just that: a theory and nothing more. But after years of analyzing research from around the world, Dr. Colborn is convinced by what she's seen.
COLBORN: There was a consistency to what I was finding. It's called what I call the weight of evidence approach.
(Sea gulls calling)
CURWOOD: Much of the early evidence came from research conducted around the Great Lakes. Along the shores of the Detroit River connecting Lake Erie and Lake St. Clair, a herring gull dives into the water in search of a fish to eat. The bird looks healthy, but its meal probably isn't. Biologist Dr. Michael Gilbertson of the International Joint Commission, which studies the Great Lakes, blames contaminated fish for problems he's seeing in the birds' offspring.
GILBERTSON: One of the things we first noticed in the Great Lakes was that the herring gull embryos, the male embryos, were in fact developing parts of the female anatomy, or retaining parts of the female anatomy. So they looked like hermaphrodites.
CURWOOD: Feminization also seems to be threatening the dwindling population of Florida panthers. Dr. Charles Facemire, an environmental contaminant specialist with the US Fish and Wildlife Service, says government scientists have found alarming levels of the female hormone estrogen in male panthers.
FACEMIRE: We think it means that the majority of the male panthers are feminized. We don't know that. But it would appear to be the case, when we have estrogen levels in males that are as high or higher than estrogen levels in females. In some cases, estrogen levels in 2 or 3 of the males exceed estrogen levels in most of the females.
CURWOOD: The Florida panther is almost extinct. The male animals have suffered a huge increase in testicular abnormalities and don't seem capable of reproducing. Dr. Facemire blames a host of chemical pesticides for the male panther's condition. Researchers have found similar reproductive effects in alligators.
(Sounds of swamp land)
CURWOOD: The lakes of Florida and Georgia are where Dr. Timothy Gross has spent the last 3 years searching for evidence of endocrine disrupters. Dr. Gross is a comparative endocrinologist with the University of Florida. He stumbled upon the effect while studying the long-term impact of a 1981 pesticide spill in Florida's Lake Apapka. The spill killed 90% of the alligators immediately. Scientists had expected the remaining animals would quickly repopulate the lake. Yet, 10 years later, they haven't. Dr. Gross set out to find out why. He was surprised with what he discovered.
GROSS: Reproductive development was abnormal in the offspring. In other words, we felt that contaminants building up in mom's basic physiological system, primarily her fat tissues, was dumping a series of contaminants that get into the egg. And the embryo therefore, as it develops, doesn't develop normally. Primarily, the males are very altered. They're not normal. They look semi-female, semi-male; they're halfway.
CURWOOD: Uh huh. When you say semi-female, semi-male, what do you mean exactly?
GROSS: Well, what I mean by that is, external features are slightly altered. They're not fully developed. In other words they have some parts of the gonad are slightly male, some are slightly female. And they're probably non-functional.
COLBORN: We're seeing populations of animals decline because the offspring can't survive, or the parents are losing their fertility.
CURWOOD: DR. Theo Colborn says what happened to Lake Apapka's alligators is only one dramatic example of what other scientists are beginning to find in animals worldwide.
COLBORN: They're not capable of reproducing at the rate that they need to reproduce to maintain a stable population. You lose species this way. It's a second-generation effect and you may not see anything visible at birth. This is the problem: there's no gross birth defect.
CURWOOD: And in people?
COLBORN: Some of the messages we're getting within the last year or two tell us that yes, these things seem to be happening in people, too.
CURWOOD: In fact, there's growing concern that the bizarre effects seen in the offspring of alligators, panthers, and birds, could also be affecting our children. In January of 1994, 300 researchers from around the world came to Washington, DC, to compare notes and suspicions at a conference sponsored by the National Institute of Environmental Health Sciences. Dr. John McLachlan is the science director of the federal agency.
MCLACHLAN: I'm certain that there are chemicals in the environment that can affect the sex of an animal, including humans. If the question is, am I certain that they do, then I think we have a bigger problem. There's evidence that they seem to, in wildlife, and it's biologically plausible that they do in humans. So it really, it's a big problem in terms of its public health implications, and it's, it's an equally big problem in terms of its biology and what it really means.
CURWOOD: The kind of direct research needed to establish whether there is a link to humans could never be ethically conducted on people. But a series of medical disasters provides researchers with the closest thing yet to controlled human experiments. The first involved the synthetic estrogen DES: diethylstilbestrol. Despite warnings as far back as the 1930s that the drug could alter the sex of bird embryos, DES was prescribed to millions of pregnant women in the United States between 1948 and 1971. It was supposed to prevent spontaneous abortions, but it never worked. DES didn't hurt the women who took it. The victims were the 10 million of their sons and daughters who years later suffered irreversible and sometimes fatal damage. Among those harmed was Margaret Braun of New York. Her mother had taken DES when she was pregnant. Then, as a teenager, Ms. Braun developed a rare form of uterine cancer. It gave scientists an early clue that something had gone terribly wrong.
BRAUN: Now, because of the cancer being seen in the DES daughters, the daughters were the first to be researched, and it was discovered that they had this range of structural anomalies, the most common being T-shaped uteruses rather than a U-shaped uterus to carry a baby.
CURWOOD: DES was banned when these problems began to appear in women. Eventually it became clear that the DES sons were affected, too, suffering a high rate of testicular and genital abnormalities and fertility problems. Two more cases add weight to the evidence. In 1973, women in Michigan ate beef contaminated with PBB, a fire-retardant chemical. It later showed up in high levels in their breast milk. Sons later born to these women have a high rate of malformed testicles. Meanwhile, Dr. Leon Guo of the National Chen Kung University in Taiwan has studied hundreds of women who ate cooking oil contaminated with PCBs, a close cousin of the chemical found in the Michigan beef. Dr. Guo's data suggest the sons of these women have significantly shortened penises. The PCBs seem to have arrested the boys' sexual development. In the same way, Dr. Guo says, as the pesticides in Lake Apapka affected the male alligators.
GUO: So the next question is to ask: do they have the same reproductive system disruption? And the answer is that there's some suggestion, but we're not sure at this point.
CURWOOD: The full extent of sexual and reproductive impacts on the Taiwanese boys will only become clear as the boys grow older. But other effects are already apparent. The children, both boys and girls, have developed discolored skin, abnormal gums and nails. They are shorter than normal children. And they consistently score significantly lower on intelligence tests than unexposed children. These neurological effects closely match what Michigan researchers found in children born to women who ate PCB-contaminated fish from the Great Lakes, as well as lab experiments on animals exposed to organochlorines. But contaminants in the air and water may not be the only environmental sources of endocrine disrupting chemicals. New evidence indicates that our exposure may be far greater than anyone had anticipated.
(Gusts of air from a flow hood; sound of metal instruments)
CURWOOD: A high-powered flow hood prevents Dr. Ana Soto's experiments at Tufts Medical School in Boston from being contaminated. She's vigilant about keeping estrogenic substances away from test tubes filled with human breast cells. But 4 months of work were ruined when something went wrong.
SOTO: It was all of a sudden that one day cells were growing very fast, as if they were in the presence of estrogens. So we suspected that we had an estrogenic contamination. We discovered that the tubes in which we stored this serum were leaching an estrogen. And that is a very, something very unexpected. How could a hormone be present in a plastic?
CURWOOD: The estrogen-mimicking compound turned out to be a substance called nonylphenol, which had leached out of Dr. Soto's new plastic test tubes. Nonylphenol is used in making many plastics, household detergents, and cosmetics.
FELDMAN: Estrogens are turning out to be very ubiquitous, or at least materials that have estrogenic activity.
CURWOOD: Dr. David Feldman also accidentally discovered that another estrogenic substance was leaching out of plastics in his lab and ruining unrelated experiments at Stanford University. The chemical in this case was called polycarbonate.
FELDMAN: It has hundreds or maybe thousands of uses, and baby food dishes are made of this plastic, and heated or something like that. It's conceivable that more of this would come out than would be good for babies or people exposed to the contents.
McCARTHY: I don't think we need to panic. Concerned, yes. Should we get answers? Yes. Should we get it quickly? Of course we should.
CURWOOD: Dr. John McCarthy is Vice President for Science and Regulatory Affairs for the National Agricultural Chemicals Association in Washington. NACA's been taking the endocrine disrupter research very seriously, because many of the implicated chemicals are pesticides.
McCARTHY: Not everything that causes something in a test tube or at some level of an animal is necessarily dangerous to people when they encounter it in products in everyday life. My point is this: we have systems in place which would detect this in our industry, because of the kind of tests that are required and done routinely.
CURWOOD: But current testing methods aren't specifically designed to detect endocrine problems. And there may be another serious flaw in the screening process. Right now, safe exposure levels are set by testing chemicals one at a time. But there are indications that supposedly safe amounts of the chemicals may interact with small amounts of other chemicals, to produce a dangerous endocrine disrupting effect. Dr. Ana Soto took supposedly safe amounts of 10 chemicals and combined them.
SOTO: And we found that that was able to produce a full response. In other words, they add up and work together; so that is the reason why I think it's very difficult to regulate them one by one. Because these don't exist in isolation, but they exist together with other chemicals that also produce estrogenic effects.
McCARTHY: The proof of the pudding really is what happens in the whole animal.
CURWOOD: Again, Dr. John McCarthy of the National Agricultural Chemical Association.
CURWOOD: What about Dr. Soto's claim that tiny doses of chemicals can add up cumulatively to something that would have an effect?
McCARTHY: I personally believe that that's not plausible. That would not happen. I think what you have to have in order to have this kind of a cumulative effect is that you've got to have each of them at some dose in which there's some pharmacological or toxicological effect in the first place. In the case of pesticide residues on food, for example, I know that's a very hotly debated subject, but we're convinced, as well as a lot of others are convinced, that the amount of exposure of residues in our food are such, are so far below levels where there could be any reasonable expectation of an effect, that for all practical purposes the effect would be zero. And so in those cases, zero plus zero is zero, unless there's some new math.
CURWOOD: But whether or not tiny amounts of these chemicals can add up to produce an effect, there is growing evidence that even by themselves, some substances are dangerous at far lower levels than had been thought . For instance,a new draft report from the US Environmental Protection Agency warns that dioxin, a suspected endocrine disruptor, may do irreversible harm even at the trace levels commonly found in the environment and in people throughout the US.
The endocrine disruption theory, once largely ignored, is now gaining acceptance and credibility. Industry, government, and the scientific and medical establishments are giving the issue serious attention. Researchers who once dismissed bizarre field reports as isolated now say that something seems to be going on. That abnormal development and dramatic declines in populations of birds, reptiles, fish, and mammals, may be linked. That they may be related to widespread reproductive and other health problems in humans. And that they may implicate a wide variety of synthetic compounds ubiquitous in the modern world.
The evidence is compelling, but it's also very preliminary and there are many more questions so far than answers. Suspected hormone-disrupting chemicals are far weaker than natural hormones - so why would their effect be so strong? We often consume natural hormone-mimickers in our food, and some of them are actually good for us. Do our bodies respond differently to these chemicals than to their synthetic cousins? And, most fundamental of all, how do these synthetic chemicals do their dirty work? Even scientists who believe that they're potentially dangerous, are only beginning to figure out how the chemicals actually function. Several new laboratory findings suggest that rather than mimicking the female hormone, estrogen, some of these substances may feminize by blocking the male hormone, androgen, from its receptor sites.
What people on all sides of these questions do agree on is that more research is needed - in the field and in the laboratory. The implications of the endocrine disruption theory are too critical to be left unchallenged. Substances which have helped bring us modern life may now be threatening our very survival.
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