One of the most important of those disease-causing glitches is probably stress, says Moshe Szyf, an epigenetics researcher and professor in the department of pharmacology and therapeutics at McGill University in Montreal. Not only can stress hormones change gene expression for the worse, but they are pervasive, he explains, traveling to every organ and tissue in the body. While a stressful situation—say, losing a job or fighting in a war—may subside, the fascinating part is that through those epigenetic marks, "the exposure is memorized in our genome," even though the hormones have stopped churning, explains Szyf.
And that can have serious consequences. Szyf has done recent research showing that males who were abused as children and later committed suicide had epigenetic changes that inhibited stress-regulating genes. Those changes weren't seen in the brains of the control group, males who had died (though not by suicide) and hadn't been abused or neglected in childhood. The speculation is that the subjects' exposure to abuse, a known risk factor for suicide, was a life-altering factor that actually changed gene expression. Profound abuse and suicide are extreme examples, of course, but the implications of stress on health operate along a gradient of severity, says Szyf.
That connection appears to go the other, and happier, way, too, demonstrated by earlier work Szyf did with collaborators at McGill. That research showed that rats that were well nurtured by their mothers in infancy, which means they were licked and groomed, cranked out less of the stress hormone cortisol and had a better-developed hippocampus, a part of the brain involved in mood and the stress response. The rat pups that were not well licked and groomed showed epigenetic marks suppressing genes in the hippocampus that normally quell the release of stress hormones. "When the gene's function is reduced, control of stress is compromised," explains Szyf. "This could lead to both behavioral and physiological consequences." More fodder for the stress theory: Szyf points to "very convincing" 2009 research out of the University of Chicago that showed rats that were stressed and isolated had altered gene expression and tumor growth and were more likely to develop breast cancer.
In the case of cancer, researchers are looking at whether epigenetic changes may actually spark new tumors. For example, two malfunctions in tumor-suppressor genes had been thought to be culprits behind the disease: a mutation that crops up and stops their protective effects, and the loss of a copy of such a beneficial gene during cell division. Both fuel the runaway growth of cancerous cells. But there appears to be a third way, says Jones, one that has become apparent only in the past decade: A "perfectly good" tumor-suppressing gene can be muffled. "That has enormous potential for treatment because all you have to do is turn it back on again," Jones explains. By accidentally discovering in the 1980s that precancerous cells were turned into muscle cells by exposure to a certain chemical and then connecting the process to the undoing of DNA methylation, Jones and his team essentially launched the field of epigenetics. Since then, he has worked to harness this process for the benefit of patients with myelodysplastic syndrome, a preleukemia. And in 2004, the first new epigenetic cancer drug was approved by the Food and Drug Administration. The drug, marketed as Vidaza, works by removing the DNA methylation marks that are keeping protective genes from playing their usual role as safeguards against tumor development. Now Jones, along with a group led by Stephen Baylin at Johns Hopkins University, is in the midst of a three-year research project testing several epigenetic drugs in patients with late-stage lung, colon, and breast cancers.