Feb. 23 2016

Killer DNA

The genes that once helped us survive are now responsible for top causes of death, argues CUMC Dean Lee Goldman

To truly understand human health—what’s killing us and what can make us healthier—Lee Goldman, Harold and Margaret Hatch Professor and Dean of Columbia University Medical Center, believes we have to look back into history: 10,000 generations back. In a recent lecture at the Mailman School, Goldman, who also has an appointment in Epidemiology, outlined how the genes that helped us survive for millions of years are now the very ones responsible for killing us.

The course of human health history can be divided into three “encounters,” according to Goldman. Initially, public health challenges were centered on the natural environment and basic survival. In the second phase, which began with the Industrial Revolution around 1850, human health suffered from pollution and other man-made hazards. Today, we live in a “leisure era” where health risks stem from a combination of genetic mismatch and the reluctance of people and societies to adopt health-promoting behaviors and policies.

For most of human history, people battled starvation and our DNA adapted. “Our bodies are built to make us hungry, process all kinds of foods, and store fat—traits all genetically driven to avoid death by starvation,” said Goldman. But lifestyles have changed since the days of the hunter-gatherer—and today, those anti-starvation genes are causing people to face the opposite health issue: obesity.

Lee GoldmanAnother example of this, Goldman says, is childbirth, which is one of the riskiest moments in a woman’s life. To combat the dangers childbirth presents, our bodies became naturally good at clotting. Now, the diseases of clotting—heart attacks and strokes—are among the top causes of death in the developed world.

Progress against infectious disease has only come about more recently. In hunter-gatherer times, they were responsible for 70 percent of deaths. Today, that global rate is 17 percent—and just 5 percent in high-income North America and Europe. Most mortality today comes from problems our society created in the last 200 years: more than a third of everyone dies from manmade hazards like air pollution, traffic accidents, gun violence, drugs, and alcohol.

Can our genes catch up?

If 10,000 generations of history have taught us anything, it’s that the fittest survive. We know human DNA mutated and adapted to help our ancestors survive and make us who we are today. But can our genes evolve to provide the solutions to the health issues we face now? Not quickly enough, said Goldman, citing the example of lactose tolerance.

To encourage the weaning of young children and allow mothers to give birth to more babies, prehistoric humans developed an intolerance to lactose around age four or five. Around 10,000 B.C., when societies began domesticating dairy-producing animals like cattle and sheep, a genetic mutation appeared that allowed people to drink milk throughout their lives. This mutation was passed to future generations and now about 95 percent of northern Europeans can tolerate lactose as adults. The mutation is less common in regions like Southeast Asia where dairy isn’t a staple.

In evolutionary terms, the spread of the lactose tolerance happened rather quickly: it reached an enormous number of people in around 350 generations, or 7,000 years. But 7,000 years is a long time to wait for our genes to catch up to the health problems of today. Additionally, “genetic mutations won’t help if the diseases we’re afflicted with affect us after we procreate,” Goldman says. Mutations that help fight conditions of middle and old age like heart disease may appear, but most people don’t die or become disabled from heart disease until after they’ve had children. Without a survival advantage, any such mutation won’t proliferate.

Tackling our killer genes

If humans can’t count on evolution to help in time, we have to turn to other solutions for survival. On a personal level, this means behavior change. For example, avoiding the calorie-dense, fatty foods our bodies are programmed to crave. However, Goldman is pessimistic about behavior change on a mass scale. “I think we have put too many eggs in the behavior change basket,” he said. “Not that we shouldn’t encourage it—we should. But our genes are fighting against us, so for a lot of people, behavior change isn’t realistic or lasting.”

To achieve maximum impact we must change society’s code. Laws designed to curb intake of sugar-sweetened beverages, discourage smoking, and promote traffic safety can all have a substantial health benefit.  But investing in science may yield the ultimate weapon: a way to get a jump on evolution by influencing the effects of our own DNA.

We are increasingly able to isolate specific genes that lead to disease and to find ways to blunt or even neutralize their effects. “There’s enormous opportunity to try to find the genes that we no longer need, the ones that are causing more harm than good in today’s world,” says Goldman. “Genetic science might end up identifying a series of interventions that can mimic what beneficial evolution cannot do or will take too long to do.”