Does Fate Have a Deadline?
Down at his Duke lab in 2003, Randy Jirtle was on to something. He suspected that smart lifestyle choices could affect a person's DNA. But he also thought there must be a critical time for when epigenetic behavior can be set. He was right.
With a deceptively simple experiment, he showed that an adult's disease risk can be affected by what her mother consumed while pregnant. In an animal study (geek out with us for a moment, if you will!), Jirtle studied two groups of pregnant mice, both of which carried a gene that made them yellow, obese, and prone to diabetes and cancer. He fed one group grain-based mouse chow; the others got the same, plus folic acid, vitamin Bi2, and a cocktail of suspected epigenetic-boosting compounds. Per everything that's known about DNA, both groups should have birthed chunky, yellowish mice. They didn't. The animals born to the second set were slim and brown, even though they'd inherited the disease-prone gene.
Jirtle then repeated the experiment, this time with pregnant mice that had been exposed to the known carcinogen bisphenol A (BPA). The BPA flicked on the obesity gene and the moms birthed fat, yellow babies. However, when Jirtle fed one group of BPA-exposed moms that same nutrient-rich diet, their offspring were born brown and trim. Like some crazy environmental tug-of-war, the BPA that turned on the gene was counteracted by a diet that turned it off again...and the science world went wild. (The year Jirtle published his initial study, around a thousand other epigenetics papers came out. Today, interest is so intense that 2011 alone saw nearly 5,000.)
"We now have evidence that our susceptibility to disease—obesity, diabetes, cancer—is influenced by what we were exposed to very, very early in development," says Jirtle. But don't freak out if your own mom swilled the occasional gin and tonic while you were in utero. "During development, epigenomes are very susceptible to environmental influences and can become set for life," explains Robert Waterland, Ph.D., who studies developmental epigenetics at Baylor College of Medicine. "But it may still be possible to reprogram your epigenetic mechanisms, even in adulthood."
Redirecting Your DNA
Say your mom was a smoker. Every time she sparked up a butt, she was, in turn, igniting epigenetic behavior, opening the door millimeter by millimeter for disease. Researchers recently showed for the first time that smoking can actually result in epigenetic changes associated with the development of cancer. And this epigenetic change may have been passed down to you, even if Mom never lit up while she was pregnant and you've never touched a cig in your life.
That said, you're not destined to get lung cancer. Just like Jirtle did with his mice, you can combat what you inherited. Scientists are beginning to work out specific solutions, but they do know that diet appears to be one of the biggest factors. For example, a 2010 study in Cancer Research found that just 12 servings of leafy greens a month reduced some people's risk of developing precancerous lung lesions by 20 percent; adding a daily multivitamin slashed that risk by 50 percent. Certain nutrients appear to turn tumor-squashing genes back on, and not just in the lungs.
"Diet plays a big role in putting you at risk for cancer, or preventing you from getting it, because 95 percent of cases aren't solely genetic—they may be caused by epigenetic influences," says Goel. In other words, it's not always troublesome DNA that makes you sick; it could be a misfiring epigenome. (A possible exception is with the inherited BRCA gene mutations that are known to greatly exaggerate a woman's risk for breast and ovarian cancers. In these cases, the DNA is missing a genetic component; there's nothing to turn on or off.) Goel, who studies gastrointestinal cancers, is currently focused on curcumin, a powerful antioxidant and anticancer agent found in turmeric. His preliminary research shows the spice could activate certain tumor-suppressing genes.
Beyond diet research, scientists are trying to decode the myriad ways exercise and toxic chemicals give marching orders to DNA. (For now, it's safe to say to embrace the former, avoid the latter.) And it appears stress can also play an epigenetic part. "It's quite possible that lifestyle stressors can change epigenetic marks inside the brain," says researcher James Potash, M.D., head of the department of psychiatry at the University of Iowa. Ready for the real shocker? "Some of those epigenetic changes can persist for a long time, which might explain why major childhood stress can make you more vulnerable to depression 20 to 30 years later," he explains.
Untangling the role of epigenetics in mood disorders could help scientists develop better drugs and intervention for patients and their offspring. Indeed, untangling the role epigenetics plays in just about every major health condition could lead to a biological revolution. "If we can figure out how to change epigenomes, we might be able to change the behavior of a diseased cell and force it back into a more normal state," says Sharon Dent, Ph.D., director of the Center for Cancer Epigenetics at the MD Anderson Cancer Center at the University of Texas. "And the ability to change cell behavior could provide more effective and less harmful therapies."
Therein lies the great hope: One day, you could turn off genes that promote diseases and turn on genes that prevent them.
Looking Ahead: Two New Drugs and The Future of Epigenetics
While the field of epigenetics advances at lightning speed, we're still a ways off from a roster of tried-and-tested therapies. However, the FDA has approved two: one, Vidaza, is an injectable drug used to treat certain blood and bone marrow diseases, possibly by reversing the epigenetic changes that turned cells malignant in the first place. The other, called Zolinza, comes in tablet form and is now used to combat a rare form of lymphoma; it's currently in trials to treat other forms of cancer. Needless to say, the future potential of both are huge.
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