Defense Systems Under Fire

Strong evidence that certain toxic pollutants make wildlife more vulnerable to disease may also apply to people

10-01-2000 // Peter Jaret

THE MASSIVE DIE-OFF was one of the worst marine biologists had ever seen. Over the course of seven months in 1988, almost 20,000 harbor seals in the Baltic and North Seas perished mysteriously--half the population thought to live in northern Europe´s waters. Researchers quickly identified a previously unknown virus, called morbillivirus, that had infected the doomed seals. For a time, it seemed, the case was closed.

Defense Systems Under Fire magazine layout - Seal

Then, within a year, a new mystery emerged. Seals in Canada had also been infected with the virus, scientists discovered, but none of the animals had died. Searching for clues, researchers noticed that the dead seals in northern Europe tended to be from colonies in areas known to be heavily contaminated with toxic pollutants.

Many of the animals had unusually high levels of substances like polychlorinated biphenyls, or PCBs, in their fatty tissues--chemicals that are known to suppress the immune system in fish and laboratory animals such as mice. So scientists thought these substances may have made the animals more vulnerable to infection. Still, so far there was only circumstantial evidence.

To test whether contaminants actually were implicated in the seals´ deaths, research scientist Peter Ross of the Institute of Ocean Sciences in British Columbia began a simple experiment. In the early 1990s, he collected seal pups from an uncontaminated area in Scotland. Then he fed

one group of the pups herring from the Baltic Sea and a second group herring from Atlantic waters known to have very low pollution levels. After two years, seals eating the Baltic fish showed signs of dramatically weakened immune systems--a strong indication that pollution may have played a role in the massive die-off.

Beyond cancer: Today immunotoxicologists have evidence that contaminants widely dispersed in the environment are weakening the immune defenses of a wide variety of wildlife species around the world--from birds, to marine mammals, even to rats and cockroaches in particularly contaminated sites. The new findings are part of a growing understanding that the threats from such pollution can go way beyond cancer, the old standard for toxicity. And many experts, including Environmental Protection Agency scientists, are studying how toxic substances may impair animals, possibly including humans, in ways that range from fertility problems to neurological defects. Among the most troubling effects are compromised immune systems.

"What frightens me is that this could be a health time bomb," says immunologist David Ferrick of the Laboratory for Marine Mammal Immunology at the University of California at Davis. "The chronic accumulation of these chemicals may be making these populations more and more vulnerable until a pathogen or a change in the environment comes along and creates another massive die-off. And once that happens, it may be too late to do much about it."

Die-offs have continued to occur around the world, some of them linked at least in part to immune-suppressing contaminants in the environment. In 1990, morbillivirus struck again, killing more than 1,000 striped dolphins in polluted areas off the coasts of Spain, France and Greece. In 1994, bottlenose dolphins in heavily contaminated areas off the Texas Gulf Coast died of the same virus in record numbers. "And no doubt there are die-offs that we don´t observe, that occur far out at sea," says Ferrick.

The potential threat goes well beyond these dramatic deaths, "We´re also concerned about the more subtle effects of these chemicals, which may be making animals chronically sick, making them less able to fight off infections or less likely to reproduce," says Judith Zelikoff, an immunotoxicologist at New York University School of Medicine and a leading expert on the effects of pollution on fish.

Weakening the body´s defenses: Among the substances known to be immunotoxic are PCBs, certain pesticides, mercury and a range of dioxinlike substances. Many of these chemicals can linger in the environment for decades and can spread to seemingly pristine regions of the world with remarkable ease. Some have been found in wildlife in both the Arctic and Antarctica.

"Even at very low doses--a single exposure of no more than one millionth of a gram, for instance--some of these chemicals have been shown to disrupt immune function," says immunologist Steve Holladay of the College of Veterinary Medicine at Virginia Tech. "And we know that many of these chemicals have made their way into wildlife, sometimes at astonishingly high concentrations." Last year, for example, a team led by research scientist Ross found high levels of PCBs in 47 killer whales roaming the Pacific waters off the U.S. coast. Transient males averaged 251 parts per million--400 to 500 times more than levels in humans.

Killer whales, Ross thinks, are now the most contaminated mammals in the world. But plenty of other animals also carry heavy burdens of these chemicals in their tissues, including beluga whales in the St. Lawrence River, fish, herring gulls, cormorants, seals, dolphins and sea lions. Marine life in many coastal locations is at high risk because many of the contaminants wash into the sea from rivers and runoff.

The toxics then become more concentrated as they move up the food chain. "You may begin with fairly low levels in fish. But when a seal eats thousands of contaminated fish, the levels of those chemicals gradually build up," explains Zelikoff. Some of the contaminants also can be transferred from a mother´s fat into her offspring, whether in her eggs or in her milk.

An early warning system: What worries immunotoxicologists is that even fairly low concentrations may make animals less able to fight off disease. Some substances may disrupt the immune system´s ability to distinguish foreign invaders from the body´s own tissue, triggering destructive autoimmune reactions. Because the immune system is especially sensitive to toxics, in fact, it may serve as an early warning system of environmental degradation.

"The immune system depends on the ability of its cells to proliferate rapidly in response to a new infection," Holladay explains. "If a flu virus invades, for instance, a group of cells called T cells, which can recognize the invaders´ molecular fingerprint, must rapidly increase in number to rout the virus. Any substance that interferes with the ability of cells to divide will weaken immune responsiveness."

Studying colonial waterbirds, biologist Keith Grasman of Wright State University in Ohio has found evidence of widespread immune disturbance. Each spring for 10 years, he and his research team have searched out the nests of herring gulls and Caspian terns along the shores of the Great Lakes. Many of these birds nest near hazardous waste dumps and other contaminated sites, and many of them have high levels of PCBs and other pollutants in their tissues.

Three weeks after the chicks hatch, the researchers inject them with small amounts of substances foreign to the birds´ immune systems. The injections, though harmless, prompt protective immune reactions in the birds. Six days later, Grasman and his team return to test for signs of those reactions. "What we´ve found," he says, "is that gulls and terns hatched near these contaminated sites have very low levels of T cell activity--immune responses typically involved in fighting bacteria and viruses. The closer these birds live to contaminated sites, the weaker their immune systems."

In another series of field experiments, researchers at Virginia Institute of Marine Sciences collected fish from the polluted Elizabeth River and the more pristine York River, both in Virginia. Fish raised in the Elizabeth´s waters, which are contaminated with aromatic hydrocarbons from creosote factories, among other chemicals, had significantly reduced immune functions.

And last year, scientists at London´s Institute of Zoology reported on studies of harbor porpoises that have been stranded on the British coast in recent years. Among those that have died of infectious diseases, the average level of PCBs was 31.1 milligrams per kilogram of blubber, compared to only 13.6 in relatively healthy porpoises--evidence that contaminants made the animals more susceptible to fatal infections.

The danger may go beyond outbreaks of infectious disease. The immune system is thought to guard against the rise of cancer cells in the body. Mice exposed to aromatic hydrocarbons, common industrial pollutants, have suffered significant immune damage and died more quickly when exposed to even very small doses of bacteria. The same mice are also more likely to develop tumors when exposed to small amounts of cancer-causing chemicals.

The human factor: Could the same chemicals be putting us at risk? Some of the evidence suggests they might. A few examples: Farm workers exposed to high levels of pesticides after accidental spills have suffered immune abnormalities. In 1992, researchers reported that people exposed to the termite-killing substance chlordane in their homes or at work had weaker immune responses in tests than people who had not been exposed. Last year, scientists found that young adults living in Aberdeen, North Carolina, home of the Aberdeen pesticides dump--a national priority list Superfund site--were two times more likely than nonresidents to have shingles, a painful condition caused by a herpes virus.

Researchers suspect that children are likely to be at greatest risk because their immune systems are still developing. "We know that kids exposed to hydrocarbons show signs of abnormal immune development," says Holladay. "Those abnormalities may make it harder for them to respond to infections."

Some of the evidence comes from the Canadian Arctic´s Inuit, who consume large amounts of fish known to be contaminated with immune-suppressing PCBs and other substances. The breast milk of Baffin Island Inuit women, who consume meat and blubber of animals such as whales and seals, contains levels of PCBs five times higher and levels of the pesticide chlordane ten times higher than the breast milk of women in southern Canada.

Also, unusually high numbers of Inuit children suffer from infectious diseases, but researchers can´t say for sure if the cause is pollution or a life-style factor such as wood smoke in homes. In March, scientists from the University of Quebec reported that infants with the highest exposure to dioxinlike substances were almost twice as likely as unexposed children to develop ear infections.

New hopes for heading off disaster: Thanks to national and international bans, concentrations of some of the most worrisome chemicals, including PCBs and dioxins, already have leveled off or are declining in many parts of the world--although hot spots of high contamination still exist, particularly in some countries once part of the former Soviet Union.

Even at reduced levels, however, some of these chemicals will be around for decades as they seep out of hazardous waste sites. What´s more, new industrial chemicals are not routinely tested for their immunological effects. "So we may not know if they cause problems until the problems begin showing up," says Ferrick.

But at least scientists better understand the causes and effects. In the dozen years since harbor seals began to wash ashore by the tens of thousands in northern Europe, immunotoxicologists have developed increasingly sensitive tests, called assays, for measuring the immune health of animals. "In the past we made the mistake of thinking that a test that works well in whales will work in harbor seals," says Ferrick. But scientists now understand that the responses of different species may vary, especially to very specific assays. "Now we´re developing far more reliable tests that will tell us whether a particular animal is immunologically fit or not." Tests of the human immune system also have become much more sensitive and specific.

Eventually, experts say, they hope to have measures sensitive enough--and a monitoring system broad enough--to spot immunologic and environmental trouble in time to head off catastrophes like the 1988 die-off in the North and Baltic Seas.

California writer Peter Jaret is coauthor of a book about immunity, In Self Defense (Harcourt Brace Jovanovich, 1987).

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