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22/03/2009

Are we posoning ourselves with mercury from fish?

When the halibut on my hook breaks the surface, writhing in a splash of seawater off the coast of Bolinas, California, I am thinking less of this fish’s fate than of my own. Considering that I plan to kill and eat it, this might seem cruel. Yet inside the fat and muscle cells of this flat, odd-looking creature is a substance as poisonous to me as it is to him: methylmercury, the most common form of mercury that builds up inside people (and fish). At the right dose and duration of exposure, mercury can impair a person’s memory, ability to learn, and behavior; it can also damage the heart and immune system. Even in small quantities, this heavy metal can cause birth defects in fetuses exposed in the womb and in breast-fed newborns whose mothers’ milk is laced with it.

Scientists have assured me that one serving of halibut contains nowhere near a dosage that might cause harm. These are the same scientists, though, who admit that no one knows for sure what the threshold dose is that causes mercury to subtly poison cells in the brain and the liver, two organs where it tends to accumulate.

As frightening as that sounds, most of us were born with a defense against exposure to mercury, initiated by specific sequences of genetic code that cause most people to expel the metal in 30 to 40 days. Not everyone carries this natural resistance, however. A small minority of people carry a genetic mutation that apparently causes their cells to retain mercury for far longer—in rare cases up to 190 days—greatly increasing the chance for cellular damage.

Such genetic differences may explain why some people are more susceptible to mercury poisoning than others. This possibility is driving a nascent but growing effort among scientists to link the impact of mercury and other environmental factors (everything from pollutants and diet to the sun’s ultraviolet rays) to the individual genetic proclivities that each of us is born with. “Toxicologists say that ‘the dose makes the poison,’” says mercury expert Jane Hightower, who practices internal medicine in San Francisco, “but it’s clear that some people are more sensitive to even small exposures than others.”

For lack of a better term, I’ll call this new science human envirogenomics, the fusing of environmental toxicology and genetics, two fields that until recently didn’t interact much with each other. Yet researchers are finding that the interplay of the two makes us who we are and often determines whether we are healthy or sick. “Recent increases in chronic diseases like childhood asthma and autism cannot be due to major shifts in the human gene pool,” says physician and geneticist Francis Collins, former director of the National Human Genome Research Institute. While acknowledging that changes in diagnostic criteria and heightened awareness may play a role, Collins says that much of the increase “must be due to changes in the environment, which may produce disease in genetically predisposed persons.” One day, envirogenomics could provide clues to a person’s sensitivity to environmental toxins (such as mercury) and the potential for damage based on that person’s genes. Doctors might then better understand how to prevent such harm and how to treat patients exposed to deleterious chemicals.

Man versus mercury
The possible connection between mercury and my own DNA is why I’m now holding a quivering fishing rod on the bow of the Osprey, a weathered 24-foot trawler. I am conducting an investigation: testing my mercury levels before and after eating this fish—assuming I land him—and checking my personal genetic code to see if I am one of the lucky ones who seem to expel mercury quickly. At the same time, I can’t help but wonder if this self-experiment is a sign that I am indeed sensitive to mercury and that it has already addled my brain. My hope is that these tests, plus discussions with experts around the world and a visit to an envirogeneticist in Maine, will help guide my decision when choosing between a large fish and, say, a bowl of pasta the next time I’m in a restaurant.

This exploration is the opening salvo in an extensive project in which I am treating myself as a human guinea pig, exploring four major new areas of personal testing: genes, environment, brain, and body. In essence I am aiming to answer two big, personal questions: How healthy am I at the very deepest level? And what can the seemingly endless profusion of new high-tech tests for various diseases and traits tell me about my health now and in the future?

My fish trial began a few days earlier when I gave up nine milliliters of blood and a cupful of pee to test my normal level of methylmercury—that is, the background level that I typically have in my body from living in 21st-century San Francisco. I’ll give up another round of bodily fluids after eating today’s catch for lunch and some store-bought swordfish for dinner.

In my “before” test for methylmercury, I registered a level of less than 4 µg/l (micrograms per liter), safely below the EPA threshold of 5.8 µg/l. This is a relief. But will my “after” level be higher?

Big fish are by far the most prevalent source of human mercury exposure, although researchers are exploring a number of other potential contributors. In 2008 a study at Boston University tested traditional herbal products manufactured in India and the United States and found lead, mercury, or arsenic in about one-fifth of them. Last year the FDA cited another potential source of harm for children and, through their mothers, fetuses: mercury contained in dental amalgams (those silvery fillings many of us have in our teeth). But the FDA has reserved judgment on health impacts for those of us who are not in early development and who do not have a medical condition making us more sensitive to mercury.

Methylmercury got into my fish from the coal-burning power plants that rim the northern Pacific Ocean, from the United States and Mexico to Japan and China. Expelled from tall stacks, mercury stays in the upper atmosphere until rain carries it down over the eastern Pacific, where it joins mercury from other sources as bacteria and other microorganisms transform it into methylmercury. After being absorbed by plankton, the mercury moves up the food chain: The plankton is eaten by small fish, which are then gobbled up by larger predators, each bigger animal accumulating more mercury with every meal. This process extends to the halibut that was now tiring and allowing me to reel it in as the Osprey’s captain, Josh Churchman—a man in his fifties with a stubbly beard, graying hair, and a faded baseball cap—leaned far over a gunwale with a net.

The Osprey experiment is a follow-up to tests I had run to check my internal levels of 321 common pollutants, a process called a chemical body burden test. Scientists were able to detect traces of 163 of those compounds, including mercury, flame retardants, DDT, polychlorinated biphenyls (PCBs), and phthalates (a pervasive chemical that makes plastics soft and facilitates the addition of scents to shampoos, soaps, lotions, and deodorants). These pollutants have been detected everywhere from North Pole to South Pole and deep in every ocean. In animal tests and in accidental high-level exposures of humans, the chemicals have caused a range of damage and disease, including cancers, sterility, and birth defects. But the compounds normally show up in humans in amounts so small—parts per million, billion, even trillion—that scientists only recently developed the tools to detect them and are only now beginning to figure out how harmful they really are.

The tests showed that my levels are mostly average or slightly above average—another relief—with a few outliers such as DDT, a pesticide I was exposed to as a child growing up in eastern Kansas before its 1972 ban. Yet even my high level of DDT (and of DDE, a metabolite into which DDT breaks down in the environment) is still so minute that there has been no obvious harm to me.

This time, to check my genetic fortitude against such toxins I will use data from more than 1.5 million DNA markers I had tested for this project. The tests look for differences in the DNA nucleotides adenosine, thymine, guanine, and cytosine (A, T, G, and C—the letters of the genetic code) between one person and another, or between one group of people and another group. My results contain clues about what makes me genetically different from other people, such as blue versus brown eyes or a higher risk of getting diabetes or heart disease. Other DNA variations have been identified as conferring either protection from or susceptibility to chemical pollutants, though most of this work has been done with animals.

Mercury moves up the food chain as plankton is eaten by small fish that are then gobbled up by larger fish, accumulating with every meal.

Mutant variations of two genes may impact a critical system for flushing toxic metals, such as mercury, from the body.

Chemicals interact with each other in a toxic soup inside our bodies and have an impact on possibly thousands of genes.


Without additional funding and attention, the uncertainties are likely to persist, says Christopher Austin, director of the NIH Chemical Genomics Center in Maryland. He is working with the Environmental Protection Agency and other groups to test the impact of pollutants on human and rodent cells. A much larger effort is needed—perhaps a Human Envirogenomics Project?—to really understand the implications of toxins and how they work on genes. Austin and others believe that the only way to create meaningful envirogenomics data is through a large prospective cohort study, collecting DNA samples and information about exposure to a variety of environmental factors from half a million to a million participants and following them for a number of years. This study would require a huge investment of time and effort and could cost as much as $3 billion (close to the cost of the Human Genome Project), according to a report issued in 2007 by the Secretary’s Advisory Committee on Genetics, Health, and Society at the Department of Health and Human Services.

“A comprehensive study of this sort might tell us everything is OK,” Sherr says, “though I suspect that it will tell us that some of these chemicals are not safe even at trace amounts.”

How to Tell If You're Poisoning Yourself With Fish
Researchers are creating genetic tests to determine if mercury hiding in that "healthy" dinner could be messing with your brain.

by David Ewing Duncan; photograph by Kathrin Miller

Published on line March 19th 2009: Genes and health magazine

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