Three generations: Dr. Lars Olov Bygren, with son Magnus and grandson Ludvig in Stockholm
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Since 2004, the FDA has approved three other epigenetic drugs that are thought to work at least in part by stimulating tumor-suppressor genes that disease has silenced. The great hope for ongoing epigenetic research is that with the flick of a biochemical switch, we could tell genes that play a role in many diseases--including cancer, schizophrenia, autism, Alzheimer's, diabetes and many others--to lie dormant. We could, at long last, have a trump card to play against Darwin.
The funny thing is, scientists have known about epigenetic marks since at least the 1970s. But until the late '90s, epigenetic phenomena were regarded as a sideshow to the main event, DNA. To be sure, epigenetic marks were always understood to be important: after all, a cell in your brain and a cell in your kidney contain the exact same DNA, and scientists have long known that nascent cells can differentiate only when crucial epigenetic processes turn on or turn off the right genes in utero.
More recently, however, researchers have begun to realize that epigenetics could also help explain certain scientific mysteries that traditional genetics never could: for instance, why one member of a pair of identical twins can develop bipolar disorder or asthma even though the other is fine. Or why autism strikes boys four times as often as girls. Or why extreme changes in diet over a short period in Norrbotten could lead to extreme changes in longevity. In these cases, the genes may be the same, but their patterns of expression have clearly been tweaked.
Biologists offer this analogy as an explanation: if the genome is the hardware, then the epigenome is the software. "I can load Windows, if I want, on my Mac," says Joseph Ecker, a Salk Institute biologist and leading epigenetic scientist. "You're going to have the same chip in there, the same genome, but different software. And the outcome is a different cell type."
How to Make a Better Mouse
As momentous as epigenetics sounds, the chemistry of at least one of its mechanisms is fairly simple. Darwin taught us that it takes many generations for a genome to evolve, but researchers have found that it takes only the addition of a methyl group to change an epigenome. A methyl group is a basic unit in organic chemistry: one carbon atom attached to three hydrogen atoms. When a methyl group attaches to a specific spot on a gene--a process called DNA methylation--it can change the gene's expression, turning it off or on, dampening it or making it louder.
The importance of DNA methylation in altering the physical characteristics of an organism was proposed in the 1970s, yet it wasn't until 2003 that anyone experimented with DNA methylation quite as dramatically as Duke University oncologist Randy Jirtle and one of his postdoctoral students, Robert Waterland, did. That year, they conducted an elegant experiment on mice with a uniquely regulated agouti gene--a gene that gives mice yellow coats and a propensity for obesity and diabetes when expressed continuously. Jirtle's team fed one group of pregnant agouti mice a diet rich in B vitamins (folic acid and vitamin B12). Another group of genetically identical pregnant agouti mice got no such prenatal nutrition.