Commentary: Using what works: genetics, epigenetics and chronic disease

Genetics-based therapies represent the pinnacle of medical science. Billions of dollars have poured into research to sequence genomes and develop tailored therapies. This is the basis of President Barack Obama's precision medicine initiative and his “moonshot” program to cure cancer that was announced at this year's State of the Union address.

Other than some hereditary genetic markers for rare diseases and limited ability to assess individual responsiveness to some therapies, however, there is little to show for all the investment. By contrast, epigenetics (how the body responds to external stimuli) shows enormous potential to treat and prevent chronic disease.

When President Bill Clinton announced the completion of the first human genome map in 2000, he predicted that genetic discovery would “revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases.” By 2010, the promise of more effective treatments remained largely unmet. The New York Times reported geneticists were “almost back to square one in knowing where to look for roots of common disease.”

Central to genetic research is a reductionist belief in finding single causal elements: that “flipping” molecular switches off or on can prevent or cure disease. It appears now that a host of rare genetic variants combine to cause common diseases rather than easily identifiable genes. Genetic origins of disease may be irreducibly complex and not discoverable.

Despite the lack of success, the National Institutes of Health invests over $30 billion annually in biomedical research projects. The NIH awards more than 80% of that investment through approximately 50,000 competitive grants to more than 300,000 researchers at more than 2,500 universities, medical schools and other research institutions. Given this enormous expenditure and the uncertainty of breakthrough outcomes, shouldn't there be a Plan B?

Biologists once believed that genes were static except for internal mutation. Researchers now understand that environmental factors alter genes throughout life and even across generations. These factors include diet, stress, lifestyle and even ancestral behaviors.

In a landmark Duke University study, Professor Randy Jirtle and post-doctoral student Robert Waterland fed female agouti mice a nutrient-rich diet before conception and assessed that diet's impact on the mice's offspring. Their November 2006 Discover Magazine article “DNA is Not Destiny: The New Science of Epigenetics,” described the remarkable results. A simple dietary change in one generation of mice significantly the next generation's risk for cancer and diabetes.

Almost all disease results from the interaction between genetic predisposition and external factors, such as diet, exercise, stress, smoking, environmental exposure and loneliness.

Epigenetics explains why smokers contract lung cancer. It also explains how the body sometimes reverses chronic disease. Environmental factors (diet, exercise, sociability) can trigger positive bio-chemical release that promotes healing.

Clinton underwent cardiac surgery in February 2010 to place two stents in clogged arteries. This surgery occurred six years after his 2004 quadruple bypass surgery.

Chelsea Clinton's orders were clear. Her father needed to lose weight to participate in her wedding ceremony. Following orders, Clinton became a near-vegan, exercised, lost 35 pounds and proudly walked Chelsea down the aisle. At the wedding, Clinton sang the new couple's praises and extolled the virtues of his new diet.

Caldwell Esselstyn, the head of Cardiac Nutrition at the Cleveland Clinic, advises Clinton on his diet and health. According to Esselstyn, people like Clinton who consume a plant-based diet become “heart-attack proof. They're bullet-proof from getting another heart attack.”

Esselstyn maintains that chronic diseases are manifestations of the body's reaction to unhealthy diets and lifestyles and are susceptible to epigenetic-based treatments. For example, a plant-based diet enhances the body's natural healing mechanisms and can prevent disease-causing genes from activating.

This explanation was not apparent to Bill Clinton's cardiac surgeon, Dr. Alan Schwartz, who observed that Clinton's need for two new stents “was not a result of his lifestyle or diet.” Similarly, Dr. Clyde Yancy, then president of the American Heart Association, stated at that time, “Coronary artery disease is a progressive process ... There aren't any cures.”

According to the Centers for Disease Control and Prevention, heart disease kills 610,000 Americans each year, accounting for 1 in 4 U.S. deaths. Despite significant surgical and pharmacological innovation, heart disease has remained America's leading killer for over 50 years.

These grim statistics frustrate Esselstyn. He observes, “All our cardiac interventions address symptoms, not the root causes of the disease.”

Irrefutable evidence from agouti mice to Bill Clinton demonstrates that epigenetic-based interventions can prevent and retard chronic disease, which consumes 86% of our national health expenditures. Medical science is spending billions of dollars searching for genetic-based cures for heart disease, cancer and other chronic conditions with limited success.

More of the same will not yield different results. Curing chronic disease requires reversing negative environmental factors. Epigenetics, more than genetics, holds the key.

David W. Johnson spent 28 years as an investment banker at Merrill Lynch, Citigroup and BMO Capital Markets before launching 4sight Health, a healthcare consulting firm.