Two hundred years ago, the Swedish parish of Överkalix was a rough place to grow up. The little township experienced months of darkness, followed by months of endless sun. The rocky soil and permafrost barely kept a few hundred farmers alive. In 1812, widespread crop failure led to outright famine.
But then came 1813 and ’14, good years—very good years. A veritable Överkalix bonanza of potatoes, bread, butterfat, and red lingonberries poured forth, and mothers urged their boys to eat, eat, eat.
Decades later, a strange phenomenon manifested: the grandsons of men who had been well-fed 9- and 10-year-old boys during Överkalix’s feast years started dying young. Grandsons of men who had been the same age during the famine lived longer. Even taking into account wealth and social status, the outcome was a 32-year difference in life span for boys.
Even more strangely, the scientific saga that begins with those long-gone men of Överkalix leads to modern-day Portland, where about 60 researchers at Oregon Health & Science University are investigating a potentially radical new approach to ending chronic disease. Their discoveries could upend our understanding of how traits pass from one generation to the next.
“This work has invigorated the scientific community,” says Dr. Kent Thornburg, who leads this area of research and experimentation at OHSU. “We used to think genetics—the gene code—explained everything, in addition to a few behavioral choices people made.”
Everyone knows that eating spinach in your lifetime won’t give you Popeye-armed sons, just as breaking a leg on a black diamond run won’t result in broken-legged offspring. So why would a boy’s diet in one generation have an effect on the life span of his grandson? Inherited traits are based on genes, not behavior. Random mutation and variation. Survival of the fittest. Darwin! Right?
Turns out, Darwin may have missed a few things.
Thornburg and his colleagues work in a new field of inquiry called epigenetics—literally, “above the genes”—which seeks to understand how behaviors and experiences in one individual’s lifetime can create inheritable changes across multiple generations.
The epigenome tells genes to be active, or not. The metaphor of a light switch invariably comes up when scientists try to explain the concept. Stresses—nutritional, environmental, and perhaps even social—can cause those molecules to switch parts of the genome on or off. In other words, though the underlying gene doesn’t change, the way it actually expresses itself does.
Scientists around the world are trying to figure out how epigenetic changes in one generation affect future generations on a wide array of health issues, including heart disease, alcoholism, obesity, and depression. In Portland, Thornburg directs the Moore Institute for Nutrition and Wellness at OHSU, where investigators have landed about $14 million in grants since 2009 to probe this new avenue for understanding health. The OHSU center is complemented by a Portland State University study center working on the practical policy implications of the research.
Slight, white-haired, and soft-spoken, Thornburg has a warmly earnest mien. He describes epigenetics as the “fastest-moving field in all of medicine.” He says things that are known now—unknown only five or 10 years ago—have the potential to transform how we approach conditions such as diabetes, obesity, and heart disease. “This will drive public health policy in a way that we haven’t seen before,” he says.
The potential importance of epigenetics in the modern era—in Oregon alone, diabetes and obesity rates have doubled in the past decade—only make the field’s origin story more unlikely: it’s a tale of old data and odd connections, with characters separated by decades and continents.