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The Explosive Science of Epigenetics

The health choices you make today could affect the expression of your kids’ (and grandkids’) DNA — and maybe their risk for disease

The “nature versus nurture” debate has been raging for thousands of years. Are people the products of their DNA, or of their upbringing and environment? The writings of both Plato and Shakespeare discuss this question. As recently as the past century, some big thinkers still subscribed to the philosopher John Locke’s “blank slate” theory, which held that each individual is born “formless” and is shaped by their environment and upbringing. Even more recently, some genetic scientists argued in favor of biological determinism, or the view that everything about a person is predetermined by their DNA.

Today, experts recognize that nature and nurture — far from being independent or at odds — engage in a complex dance. While DNA has a lot to say, a person’s genes and environment interact throughout their life to produce any number of outcomes. And the science of epigenetics lies at the heart of this interaction.

“Epigenetics describes how the human genome can adapt to cope with environmental factors,” says Jian Feng, an assistant professor in the Department of Biological Sciences at Florida State University. Specifically, epigenetics is the study of things that change the way genes are expressed — that is, whether they’re turned on or off. Changing gene expression can fundamentally alter the activity of that gene without giving it a mutation.

For example, a 2018 study from the Icahn School of Medicine at Mount Sinai found that giving cocaine to mice changed the activity of genes in the reward centers of the rodents’ brains, and these gene modifications led to addiction-like behaviors. “Substance use changes gene expression in ways that promote abuse,” Feng says, summarizing the study’s conclusions. Research has also found evidence that abused children undergo epigenetic changes that may increase their risk for obesity, heart disease, depression, and other medical conditions later in life.

“We know that there are all these molecular marks and processes around the DNA that regulate how the DNA functions,” says Michael Skinner, a distinguished professor and founding director of the Center for Reproductive Biology at Washington State University. Basically, these molecular marks and processes can turn genes on and off, he says. As a result, they have the potential to influence “every area of biology.”

Skinner says more and more research has found that many diseases have overlapping epigenetic signatures, meaning certain genes are predictably turned on or off in people who have the disease. Just last month, a new Harvard Medical School study reported that people with Alzheimer’s disease seem to share certain epigenetic characteristics. This is a big deal because, to date, most of the research on non-epigenetic DNA mutations has failed to find patterns of overlap in people who develop Alzheimer’s, cancer, and other diseases.

“The diseases you have today may be due to your grandparents’ environmental exposures.”

“If we look at disease populations,” Skinner says, “we often see that 90% of the individuals with a disease have an epigenetic signature that directly links to the disease.” He says research into the role of epigenetics in disease should yield insights that inform better treatments. For example, knowing about the epigenetic characteristics of certain forms of breast cancer could help doctors identify women who are candidates for special treatments with much greater accuracy.

Besides targeted drug therapies, epigenetic diagnostics could also point people toward diets, exercise habits, or other lifestyle changes that are most likely to lower their disease risks.

While smarter, more effective medical care is the bright side of epigenetic research, there’s a dark side — albeit a controversial one.

Genetic scientists have long believed that epigenetic modifications to DNA are not heritable in humans — meaning they can’t be passed from one generation to the next. It was thought that, like a car wash, DNA is rinsed of its accumulated epigenetic detritus as it passes from parents to offspring. But Skinner and some other scientists believe that certain epigenetic adaptations can be passed from one generation to the next, and that the inheritance of these epigenetic changes could help explain the rise in obesity, diabetes, and other heretofore uncommon diseases.

For example, Skinner’s research has identified epigenetic mechanisms through which exposure to the insecticide chemical DDT changes gene expression in ways that can be passed from parent to offspring, and that may contribute to the development of obesity in successive generations. “DDT exposure doesn’t cause obesity, but it promotes susceptibility to obesity,” he says. “In the 1950s, almost every pregnant woman in America was exposed to DDT, and now, three generations later, we have a 45% obesity rate.”

While DDT is now banned in the United States, Skinner says that glyphosate — one of the most commonly used herbicidal chemicals in the country today — has also been linked to disease-promoting transgenerational epigenetic changes. “So, glyphosate exposure today probably won’t affect us, but our grandkids may have elevated disease risks,” he says.

Not all scientists buy into the idea that epigenetic adaptations are heritable. “The evidence for transgenerational epigenetic inheritance… is not (yet) conclusive,” argued the author of a recent review of the research in the journal Nature Communications. Summarizing the view of many geneticists, he wrote, “For now, I remain skeptical.”

But others say the experimental evidence in animals is compelling, if not conclusive. “If you change a female rat’s diet, you can see changes that are passed down for two generations,” says David Nielsen, an associate professor and director of the Toomim Laboratory for Psychiatric Genetics at Baylor College of Medicine. There’s also evidence that the grandchildren of people who endure lengthy food shortages or starvation may be more susceptible to metabolic disease.

“The diseases you have today may be due to your grandparents’ environmental exposures,” Skinner says. Likewise, the choices a person makes today — the foods they eat or avoid, the drugs they experiment with — could promote epigenetic changes that affect the health of their kids, their grandkids, and successive generations. While scientists are still teasing apart and debating the role of epigenetics in inherited risk, Skinner says that what we know already should inform the choices we make. “We need to be much more conscientious today about what we do to our bodies and our environment,” he says.

Markham Heid


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