Rewriting Heredity: Environment and the Genome

PRODUCERS: John Rieger, Jon Kalish, Vicki Monks

Our genomes are constantly at work, directing such vital functions as eating and breathing. Researchers are starting to understand that everything from diet to air pollution to stress has great influence on how our genomes function and what that might mean for our health.

When geneticists began sequencing the human genome, genes seemed all-powerful. But as researchers continue to try to make practical sense of information about the genome, they are learning that there is much more going on than they thought. At the most fundamental levels, geneticists are realizing that genes do not act alone. Beginning before birth, the environment around us triggers chemical changes to our DNA that influence health issues as complex as obesity and asthma.

Buying a hotdog on a busy Manhattan street corner, host John Hockenberry dodges environmental hazards big and small-from Mac trucks to tiny airborne pathogens. As he chomps on his quick lunch, he wonders why a diet of hotdogs might make one person overweight, while another person eating exactly the same thing would stay slim and trim.

The Pima Indians

Producer Vicki Monks picks up the story and travels to Arizona and Mexico to follow the story of the Pima Indians. The Pimas of Arizona have one of the highest rates of obesity and diabetes in the world. Their Mexican relatives, however, are much healthier, and slimmer. Researchers have studied the Pimas for almost thirty years looking for clues to their health problems. Sixteen years ago when Eric Ravussin began his work he thought he would find a few powerful genes at the heart of the Pima's obesity problems.

The "Thrifty Gene"
With this in mind, host John Hockenberry visits a facility with a metabolic chamber—a room in a hospital with vacuum-sealed doors. The chamber is a research tool that gives scientists almost complete control over the environment, and allows them to control physical activity and measure calorie consumption. The metabolic chamber, of course, is in stark contrast to what happens in the environment in the real world. Ravussin and his colleague, Peter Bennett, built one in Phoenix to test the hypothesis of the "thrifty gene"—the idea that the obesity-prone Arizona Pima might possess a specific gene that affected the ways in which they stored and used calories. But, as it turned out, the Pima were no different, metabolically, than people from the general population.

Similar metabolic tests on the Pima in Mexico produced similar results. No evidence for the thrifty gene. So what accounts for the differences in weight and health between the two genetically related populations? Researchers Leslie Schulz and Julián Esparza think it might be the way that environmental factors, like lifestyle and diet, are influencing the expression of the genes that control how and when the body decides it's had enough to eat.

Eric Ravussin has come to believe that many genes are involved, and that the environment, which includes everything from the loss of traditional diet and lifeways to levels of physical activity (and inactivity), exerts a powerful influence on how those genes are expressed.

Epigenetics: Controls Inside of the Cell but Outside of the DNA

The search for these genetic "control knobs" are the focus of the emerging field of epigenetics. Randy Jirtle, a researcher at Duke University, fed a special diet to obesity-prone agouti mice during pregnancy. The result? Their offspring, which were also genetically susceptible to obesity, were slim.

In a world in which we are constantly assailed by environmental factors as varied as diet, pollution and even maternal nurturing, the question being asked by geneticists is whether there are similar epigenetic mechanisms in humans.

Genes and the Environment: Asthma

Producer Jon Kalish considers another aspect of the interaction between genes and environment. He visits Long Beach, California, a place known for its high levels of ozone and smog due to the nearby port and shipping facilities. The asthma rate in Long Beach is twice as high as in the rest of California. Long Beach is part of a long-term study to determine how variations in genetic makeup may cause some people to be more susceptible or resistant to pollutants that cause respiratory illness.

As many as fifty genes seem to be involved in asthma. USC professor Frank Gilliland and biostatistician Jim Gauderman have been analyzing the work of several genes including GSTM1, the "garbage truck gene." As much as half of the world's population doesn't have this gene that is thought to clean up environmental toxins in the body. And it appears that people without it might be more susceptible to pollutants that trigger diseases such as asthma.

But as asthma researcher Donata Vercelli notes, there's no simple correlation between genes and environment. "What we see is that a certain gene can be associated with less asthma in a certain environment, with more asthma in another environment, and with no effect in yet another environment."

The complexity of diseases such as asthma and obesity is beginning to reveal that the most effective remedy to combat these illness may not be found in genes but rather the environment.