National Geographic : 2012 Jan
can get the attention he needs. ( e boys' par- ents requested that we not publish their last name.) When John's bus drops him o at home, he races inside, and Sam ambushes him with an a ectionate hug. John laughs but doesn't speak. When Sam releases him, John walks to a box with stu ed animals and starts ap- ping his hands in excitement. He's back in his own world. Both boys were diagnosed with autism spec- trum disorder shortly before their second birthday, though John's symptoms are far more severe, including constant movement, trouble speaking, and di culty making eye contact. Sam has challenges too, mainly with social skills. e fact that they share a developmental disorder is not unusual. When one identical twin is diag- nosed with autism, studies have shown, there's about a 70 percent chance the other will be too. No one knows what causes the disorder, which is diagnosed in about one of every hun- dred children. Inheritance is thought to play a signi cant role, though experts believe autism may be triggered by as yet unidenti ed environ- mental factors. A study of twins in California last year suggested that experiences in the womb and rst year of life can have a major impact. John's parents wonder if that was the case with him. Born with a congenital heart defect, he underwent surgery at three and a half months, then was given powerful drugs to battle an in- fection. "For the rst six months, John's envi- ronment was radically di erent than Sam's," his father says. "Things written in pen you can't change. That's DNA, " says geneticist Danielle Reed. "Things written in pencil you can. That's epigenetics. " Shortly a er Sam and John were diagnosed, their parents enrolled them in a study at the Kennedy Krieger Institute in Baltimore. Blood samples from the boys were shared with a team at nearby Johns Hopkins University looking into the connection between autism and epigenetic processes---chemical reactions tied to neither nature nor nurture but representing what re- searchers have called a "third component." ese reactions in uence how our genetic code is ex- pressed: how each gene is strengthened or weak- ened, even turned on or o , to build our bones, brains, and all the other parts of our bodies. If you think of our DNA as an immense pi- ano keyboard and our genes as keys---each key symbolizing a segment of DNA responsible for a particular note, or trait, and all the keys com- bining to make us who we are---then epigenetic processes determine when and how each key can be struck, changing the tune being played. One way the study of epigenetics is revolu- tionizing our understanding of biology is by re- vealing a mechanism by which the environment directly impacts genes. Studies of animals, for example, have shown that when a rat experi- ences stress during pregnancy, it can cause epi- genetic changes in a fetus that lead to behavioral problems as the rodent grows up. Other epige- netic changes appear to occur randomly--- throwing a monkey wrench into the engine of nature versus nurture. Still other epigenetic processes are normal, such as those that guide embryonic cells as they become heart, brain, or liver cells, for example. "During pregnancy, many changes must oc- cur as cells commit to and become progressively specialized tissues, and we know that process in- volves a cascade of epigenetic programs," says Andrew Feinberg, director of the Center for Epi- genetics at Johns Hopkins School of Medicine. Feinberg's study focuses on a particular epi- genetic process called DNA methylation, which is known to make the expression of genes weaker or stronger. To better understand how it relates to autism, Feinberg and his team are using scan- ners and computers to search samples of DNA from autistic twins for epigenetic "tags," places The twins in the photo gallery at the opening of this story look alike---but how alike are they really? To learn more about their similarities and differences, see our iPad issue, available at itunes.com, or visit ngm.com/twins.