In gene-speak, Broberg’s team found that individual letters in these genes are linked to how people retain or expel mercury. For instance, in one of Broberg’s markers within the GSTP1 gene, people whose DNA contains an A have an elevated risk of retaining mercury longer. Those with two of them have an even higher risk.
I am startled to learn that I am double-A, the higher-risk variation. Broberg’s study comes with a major caveat, however: This higher risk showed up only in those who consumed a high level of mercury. Another caution is that one marker considered in isolation does not take into account other genes and factors that might negate this singular result. As Rand says, “A much higher level of study with more subjects in the cohort would be required before concluding that a genotype [an individual’s particular genetic variation] is a risk factor.” Broberg also warns that these data are not yet ready to be used for evaluating an individual’s sensitivity to mercury. Yet it suggests the sort of testing that may become common in the future.
Fortunately, there is a simple way for me to avoid a potential mercury overdose: no more halibut or swordfish, and no more fish gorging. According to the FDA and most experts, small fish and young fish contain less mercury and are probably safer to eat.
Unfortunately, eliminating the source isn’t possible for most other pollutants that we breathe, eat, drink, and absorb through our skin whether we want to or not, including man-made chemicals such as phthalates and perfluorooctanoic acids, which are found in Teflon and other widespread products. The basic chemistry of these and thousands of other manufactured compounds incorporated in everyday products do not appear in nature; they have entered our environment so recently that our genes, cells, brains, and bodies have not yet evolved mechanisms for coping with them.
Mutant variations of two genes may impact a critical system for flushing toxic metals, such as mercury, from the body.
“The glutathione enzyme and other antioxidants are good ones to study,” says physician Mady Hornig of the Columbia University Mailman School of Public Health, whose lab studies the impact of toxins on the brain. “But I don’t think anyone should rest easy if they come out normal” in genetic tests that look at just one or a few markers. “There are likely to be multiple genes that might contribute.” Hornig says that the goal is to one day have a predictive genetic test that targets a person’s potential for neural disorders, such as autism, on which environmental toxins are likely to impinge. “We are also looking for markers in the blood, such as proteomic markers,” she says. Right now Hornig’s lab is studying umbilical cord blood preserved at birth, looking for differences between the blood of children who became autistic and the blood of those who did not. The results will be published later this year.
The First Evirogenomic Profile
Near Acadia National Park in northeastern Maine, I feel the frigid wind blow off the ocean at the Mount Desert Island Biological Laboratory, a cluster of buildings enveloped in snow and surrounded by winter-bare trees. I have come here to find out more about my body’s unique blend of environmental toxins and genetics from the scientists who run the Comparative Toxicogenomics Database (CTD), an online envirogenomics tool that cross-references thousands of chemicals, genes, and diseases. One of the coordinators of the NIH-funded project is Carolyn Mattingly, a tall, slender woman now wearing a thick overcoat and knit cap as she leads me through the snow to the building that houses the CTD staff.
Mattingly talks quietly and, like many scientists, responds to unfamiliar visitors as if interrupted from intensely absorbing work—which is fine, since her work is intensely absorbing. The researchers on the CTD team have examined 122,000 chemical-gene and chemical-protein interactions involving some 4,000 unique chemicals—including foods, vitamins, and naturally occurring compounds such as cholesterol. Along the way, they have looked at 13,500 genes in 200 species and their impact on 6,500 diseases. The team also integrates data from other sources on more than 60,000 chemicals.
Mattingly warns that this information as it applies to me, an individual, is incomplete. “We don’t really understand how many of these chemicals work and interact at a very basic level in cells and in the body, so being able to know how they affect different people with different genetic variations is problematic at best,” she says. Most researchers in the field agree. “The problem right now is that you don’t have all of the information,” says cancer biologist David Sherr of the Boston University School of Public Health, who studies the impact of chemicals like PCBs on breast cancer. “You have to understand the end point you’re measuring. You can find out whether the substance is active, but at what dose, and is there an adverse response or not? You need to have a clear end point and a clear algorithm to a have a truly predictive model.”
In a warm conference room overlooking a frozen cove, Mattingly opens her laptop and calls up my results for about 40 toxins that are present in my body at above-average levels: DDT, PCBs, flame retardants, metals, phthalates, and others. While I look on, she types “mercury” into the CTD search engine—a resource accessible to the public at ctd.mdibl.org—and up pops a menu offering links to peer-reviewed studies and media articles about genes and diseases tied to this pernicious metal. We find that there is information on 292 genes that have been tested for a response to mercury in 14 organisms, including mice, rats, dolphins, cows, ducks, and humans, with links to dozens of diseases from cancers to neurological disorders. Pulling up a grid with my results, Mattingly says that in this case, I came out normal in my genetic profile for gene variations associated with mercury sensitivity.
Next on the list is arsenic, which Mattingly studies in her own wet lab in a nearby building, testing its effects on zebra fish. The database lists more than 1,400 genes that are affected by arsenic in several animals, including humans. When I was tested for arsenic, my level was 12 parts per billion, safely under the official danger threshold of 23 ppb. This relatively low level of arsenic inside me was good news; Mattingly informs me that I have mutations in 22 of the 1,400 genes shown to interact with arsenic, including a variation in the ABCB1 gene that may inhibit my ability to expel the metal (and other toxins) from my body.
