Genes That Once Supported Survival May Be Hazardous to Health Today

What has kept humans alive for 8,000 generations may be what’s killing them today, said Lee Goldman, M.D., at APA’s 2017 Annual Meeting in San Diego.

Pre-industrial humans evolved genes to protect our Paleolithic ancestors from starvation, dehydration, injury, and physical attacks, Goldman pointed out in his lecture. Today, those adaptations are Too Much of a Good Thing—the title of Goldman’s book (Little, Brown and Company: 2015). Not only are these traits less useful in the contemporary world, but their presence may actually lead to more deaths than the hardships for which they evolved to protect us.

Modern scourges like heart disease, high blood pressure, obesity, inopportune blood clotting, and depression are the genetic leftovers that once conferred adaptive advantages to ancient humans, said Goldman, a cardiologist and executive vice president and dean of the College of Physicians and Surgeons at Columbia University.

For instance, in a world with uncertain access to calories, genes that help the body store fat were a good thing. So was eating whatever food was available, whenever it was found. Innate biological preferences for sugars and proteins kept people alive. Yet when sustenance demanded wandering about all day looking for food, there was little risk of obesity, said Goldman. Today, 30 percent of the U.S. population is obese, and 15 percent have type 2 diabetes, a result of overloading humans’ calorie storage cells.

“People eat if food is available,” he said. “Ice cream used to be a treat; now it’s a basic food.”

Similarly, a predisposition for more effective blood-clotting mechanisms that would have saved lives in ancient times can now be considered detrimental if it increases the risk of heart attacks and ischemic strokes.

Goldman also highlighted hypervigilance as a trait particularly relevant to the psychiatric community today. In prehistoric times, being aware of the surrounding environment was critical to avoid dangerous animals (or humans). Today, the world is statistically much safer. Murder and fatal animal attacks are relatively rare events. However, genetically driven hypervigilance and fear may contribute to the growth of mental disorders including depression and anxiety. Genes favoring depression may induce submission to dominant group members and contribute to survival, and anxiety may be a lifesaving trait in a world of physical danger.

All of this leads to a genetic mismatch between the needs of modern humans and their historic genetic programming, said Goldman.

Since the start of the 20th century, improvements in medicine and public health have shifted illness severity in the United States. Chronic diseases surpassed the infectious kind as the leading causes of death. Perhaps 70 percent of deaths in hunter-gatherer societies come from infectious diseases, compared with 4 percent among high-income North Americans. This shift has produced longer life expectancy, from 43 years in 1900 to 65 years in 1950 to 81 years in 2014. But it has also paradoxically increased the health burden on individuals and society by increasing the importance of chronic, noncommunicable conditions.

That paradox might be attacked in several ways, he said. Goldman is skeptical that passing laws and enforcing regulations would work. Behavioral change is almost as difficult.

“Our bodies just don’t want us to lose weight,” he said. “It’s not because of immorality or a faulty psyche. We can’t do it because we can’t do it.”

Perhaps evolution might come to the rescue, since it got us into the problem—but don’t hold your breath. A genetic mutation with a 1 percent advantage would take 3,000 generations or 60,000 years to spread through the species. Even if the benefit were an unlikely high 25 percent, a thousand years would have to pass. Lactose tolerance confers a 4 percent to 10 percent advantage and is found in 95 percent of northern Europeans, but it took 350 generations and 7,000 years to achieve that.

Biomedical science may have the tools to address genetic mismatch, however.

Some advances have already been made. Medications are available that can reduce natural cravings to eat or inhibit overactive receptors that can cause depression or anxiety.

The next step may sound more radical: Seek out and target genes responsible for regulating traits that supported survival in the past.

“It may be possible to find genes we don’t need anymore and knock them out if they are truly irrelevant,” Goldman said.

He pointed out several genes affecting triglycerides or cholesterol synthesis or absorption that reduce lipid levels and possibly risk of coronary disease in mice when knocked out. There are rare humans who lack or fail to express such genes and who appear otherwise healthy, suggesting that further research might be fruitful.

In all, Goldman is placing his hopes in the people in the white lab coats.

“If we don’t do something soon, we’ll see huge reductions in longevity in the industrialized world,” he said. ■