Curious, Don and 20 of his relatives each sent a vial of blood to the Cleveland Clinic, where the research was being conducted. Eric Topol, a cardiologist and genetics researcher at the clinic, spent a year studying their DNA. Each person’s genome comes with millions of individual variations, but Topol was looking for something distinctive—and shared only by the members of the clan with heart trouble. The mutation he and his team finally spotted, in a gene called MEF2A, produced a faulty protein. “We knew we had something,” Topol says. “But the question was: How does this sick protein, present at birth, lead to heart attacks 50 years later in life?”

Topol himself is as lean as a greyhound and weathered in a cowboyish way. He talks slowly and eats minimally: salads for dinner and high-fiber cereal for breakfast. He doesn’t eat lunch at all. Like almost every cardiologist I’ve talked to, he takes statins preventively, and his cholesterol count is a low 135. His children, 22 and 25, also eat uncommonly well for their ages. “People have looked at the cadavers of men in their 20s who died in car accidents or as casualties of war, and nearly all had arterial cholesterol deposits,” Topol said as we walked to his lab. “This disease starts much earlier than people realize.”

Using endothelial cells (which line the inside of the artery wall) grown in culture, Topol set about figuring out what the MEF2A mutation does. He and his coworkers created some cells carrying the Steffensen variant, and others with the normal form of the protein. Both cell proteins were tagged fluorescent green so their locations could be visualized on a computer screen. The resulting images revealed a striking difference.

In a normal cell, all the MEF2A protein was inside the nucleus; on the screen, the cell resembled a fried egg with a fluorescent green yolk. But in the cells carrying the mutated version, the nucleus did not glow; instead the cell membrane was edged by a thin, luminous green line: a layer of MEF2A protein, trapped where it cannot serve its usual purpose. Topol believes that this defect affects the integrity of the coronary artery walls, rendering them more vulnerable to cracking when the plaque embedded in them ruptures. And each crack brings an increased chance of a heart attack.

Since this discovery, the Steffensens have become famous, appearing on shows like 60 Minutes II. Their mutant gene turns up in a Robin Cook novel titled Marker, about a health insurance company in New York that secretly screens patients for the MEF2A mutation and then kills them to preempt future medical-care payouts. Lively reading, but the Steffensen gene is an unlikely target for an insurance company, in part because it is an uncommon genetic defect.