She calls up her analysis for PCBs, another class of chemicals detected inside me. Sherr and others have shown that PCBs, dioxins, and other organic pollutants seem to activate the aryl hydrocarbon receptor (AhR), which, among other things, contributes to cancer. One cause of cancer is healthy cells’ growing out of control and losing their identity: They forget that they are programmed to be liver or heart cells and go rogue, not dying in the usual manner but instead continuing to replicate into more rogue cells. “In a normal cell, AhR causes the cell to grow if needed,” Sherr says. “It’s a basic part of life for many organisms. Certain chemicals make the AhR think it’s being activated. The right kind of PCBs turn on the AhR, and it becomes a persistent signal that can contribute to cells’ becoming cancerous.” Sherr says that certain gene variations may be at work inside some people, putting them at higher risk for AhR activation by environmental chemicals. “It would help tremendously to know more about these genes and who is at risk,” he says.
Chemicals interact with each other in a toxic soup inside our bodies and have an impact on possibly thousands of genes.
Mattingly checks on DDT, important given my high readings from my Kansas childhood. She finds close to 300 references to studies in the CTD, including a few on humans. A study in France in 2004 investigated the impact of various doses of DDT and three other pesticides from the same chemical family on two genes associated with a class of proteins known as cytochrome P450; the genes produce enzymes that metabolize a broad range of drugs and chemicals. This and other studies suggest that DDT and the other pesticides may alter not only specific genes but also pathways of genes that collectively control the immune system or other systems that can be altered by chemicals.
I’m not liking what I’m hearing, I tell Mattingly with a nervous laugh, but she reiterates that the data on human toxicity and the impact of pollutants on genes remain sketchy. As with other genetic studies linking diseases to DNA markers, her research tends to compare populations who have one variation of a genetic marker with those who have a different variation—a comparison that has limited application to individuals. Most genetic links need to be tested and confirmed in clinical settings with multiple patients; scientists also need to better understand how a given genetic marker causes sensitivity to a chemical. Neither the chemicals nor the genes work in isolation inside us. The chemicals interact with each other in a toxic soup in our bodies and may influence hundreds and possibly thousands of genes. “We have not had any way to test all of these interactions,” Mattingly says. “The data are not robust; there are so many variables in multiple exposures. We can only look at footprints. There are some data on how groups of genes are impacted by one chemical, and other genes are affected by different chemicals. We are only beginning to look at this.”
As snow fell outside and I began to squirm over what she was telling me, Mattingly kept describing other gene-chemical interactions. But I’ll stop here, since much of the rest is equally unsettling and equally preliminary. Yet Mattingly and others insist this sort of analysis is on track to become more meaningful and perhaps useful for individuals in the next two or three years for some better-understood chemicals such as mercury and arsenic.
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.”
Our Toxic World
I ponder all this one night while sitting on my roof in San Francisco, where I have a great view of the bay and the extraordinary hive of human activity in the city spread out below, much of it dependent on chemicals that have shown up inside me. Interstate 280 and the Bay Bridge swim with tides and eddies of automobiles; a partially shut-down power plant releases a steady white plume of effluents from a tall stack. Far to the north, a massive oil refinery and a storage depot spread across a hillside. Ships move up and down the bay, and jets roar overhead. Farther north is Bolinas and the Osprey, though I cannot see that far from here.
As a modern urbanite, I find this scene breathtaking and reassuring. I don’t feel frightened or anxious, but I do feel an edge of unease, mostly because I lack the information to know what (if anything) all this human activity is doing to me, and to all those around me. Deep down, however, I suspect that there are trade-offs for our spectacular civilization that we have barely begun to understand, even as our technology is beginning to provide clues.
Read about more of the author’s findings in Experimental Man, published by John Wiley and Sons.
