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.
Lately, as envirogenomics has taken off, scientists have begun to test for genetic markers in humans who are most heavily exposed to pollutants, an effort that got a huge boost in 2006 when Congress approved the $40 million Genes, Environment, and Health Initiative, a program administered by the National Institutes of Health (NIH). Since then the initiative has funded a range of projects that investigate the effects of common toxins such as mercury, ozone, diesel exhaust, and pesticides—as well as other environmental influences, like diet and stress—on disease. The project is also sponsoring the development of new biomonitoring technologies, including better ways to track everything from psychological stress events and blood-cortisol levels to chemicals that dissipate quickly in the body, such as phthalates. “We’re trying now to get relevant data on gene-environment interaction, to match exposure data with genetic data,” says Brenda Weis, a former project manager for the Genes, Environment, and Health Initiative and now with the NIH Office of the Director. “The initiative is still new. No one knows exactly what we will find or how the data will come out.”
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.
Meanwhile, at the Harvard School of Public Health, the similarly named Gene Environment Initiative is looking into how genes influence individuals’ responses to mercury and selenium exposure. Selenium, another chemical that appears in fish, may mitigate some of the harmful effects of methylmercury, although this is debated. The Harvard project is tapping into medical information collected as part of the Nurses’ Health Study and Health Professionals Follow-Up Study, which has tracked the health of 120,000 nurses in the Boston area and beyond since 1976. Dietary information is being gathered through questionnaires, mercury and selenium levels are being measured from toenail clippings, and genetic information is being acquired from blood and cheek swabs.
“Given the biologic relevance of mercury and selenium for human health and prior candidate gene studies demonstrating heritability, we anticipate discovery of major novel genetic regions that will greatly advance our understanding of the intersection between genes, dietary habits, and metabolism,” the research team told Harvard Public Health Now, a publication of the Harvard School of Public Health.
The Big Fish Gorge
Back on the Osprey, Churchman scoops up my halibut in his net and drops it on the deck. After he stabs it and drains some of its blood, we fish for another hour or so amid whitecaps and a steady, chilly wind before heading back to Bolinas Harbor with a second halibut and a rockfish. As the little boat rides the waves and the twin outboard engines roar, I wonder what my tests will reveal about my susceptibility to mercury. Do I have a supergene deep inside me to fend off heavy metals?
A few days later I eat the halibut, which I have cooked with butter and basil, and then, for dinner, a swordfish steak grilled with lemon juice. The next morning I have another nine millileters of blood drawn, and I give up another container of urine.
Soon I receive my test results. With just those two meals, my mercury level has spiked from 4 µg/l to 13 µg/l, well over the EPA’s recommended level of 5.8 µg/l. The results are even greater than when I ran the same test in 2006 with store-bought fish caught in the Pacific. That before-and-after test took me from 5 µg/l to 12 µg/l, a bump-up that prompted pediatrician and mercury expert Leo Trasande of the Mount Sinai School of Medicine in New York City to scold me for running a “fish gorge” experiment.
“No amount of mercury is really safe,” Trasande says, although my results are far less significant than they would be for children or for women of childbearing age. Children have suffered losses in IQ at 5.8 µg/l, he cautions. After my first “gorge,” Trasande had advised me not to repeat the experiment. I decided not to tell him that I had done it again.
My Genes and Mercury
Armed with my methylmercury data, I next go hunting to learn about the genes tucked into my cells that will or won’t let me eat large fish in the future. The journey begins with an e-mail to Trasande, who tells me that as a clinician he is not aware of human genes that are impacted by mercury or of tests to determine a patient’s genetic arsenal for coping with heavy metals. So I turn to animal toxicologists, who have identified several relevant genes in rodents, fish, dogs, dolphins, chickens, and fruit flies. Matthew Rand, a mercury toxicologist at the University of Vermont, has shown in fruit fly models that mercury binds to cells, including neurons, and interferes with signals being sent to the cells that control how they develop, replicate, and die.
Rand points me to a human study done by Karin Broberg, a molecular biologist at Lund University in Sweden who specializes in the toxic effects of metals. In 2008 her team published a study of 365 people that examined whether genetic variants influenced the elimination of total mercury in red blood cells. She concluded that mutant variations of two genes may impact a critical system in humans for flushing toxic metals, such as mercury, cadmium, and arsenic, out of the body.
Called GCLM and GSTP1, these genes help produce enzymes, such as glutathione-S-transferase, that maintain levels of glutathione, which plays a role in expelling metals from cells. Too little glutathione is one of the factors that cause metals to linger in cells, according to Broberg. “These findings suggest that GCLM polymorphisms [gene variants] that affect glutathione production also affect methylmercury retention,” she wrote to me in an e-mail, “and that GSTP1 may play a role in conjugating [chemically joining] methylmercury with glutathione.” Broberg’s lab has identified specific locations within the DNA sequences for the GCLM and GSTP1 genes that, when mutated, may indicate a slower elimination of methylmercury from cells.