Altering DNA After Birth

If anyone out there still believes that DNA is destiny and that claims to the contrary are so much bleeding-heart, PC drivel (my favorite is that parents' treatment of their children has no effect on their character, beliefs, behavior or values), neuroscientist Michael Meaney has some rats he'd like you to meet.
Since the 1990s, he and his colleagues at McGill University, Montreal, have been documenting how mother rats affect their offspring (dads don't stick around to raise the kids). Now they have scored what neuroscientist Robert Sapolsky of Stanford University, Palo Alto, Calif., calls "a tour de force": proof that a mother's behavior causes lifelong changes in her offspring's DNA.

A decade ago Prof. Meaney noticed that newborn rats whose mothers rarely lick and groom them grow up... well, there is a fancy biochemical description for it, but let's just say that they grow up a bit of a neurotic mess. Pups of attentive moms grow up less fearful, more curious, mellower.

Prof. Meaney and his team then showed that this wasn't a case of mellow moms having mellow kids and neglectful moms having maladjusted kids, as the DNA-as-destiny crowd would have it. When the scientists switch around the newborns so that rat pups born to attentive moms are reared by standoffish moms, the pups grow up to be extremely stressed out, nearly jumping out of their skins at the slightest stress. Pups born to standoffish moms but reared by attentive ones grow up to be less fearful, more curious, more laid-back, taking stress in stride.

Rearing, it turns out, affects molecules in the brain that catch hold of stress hormones. Licking and grooming increases the number of these receptors. The more such receptors the brain has in the region called the hippocampus, the fewer stress hormones are released; the fewer the stress hormones coursing through its body, the mellower the rat.

It turns out that all newborn rats have a molecular silencer on their stress-receptor gene. In rats reared by standoffish mothers, the silencer remains attached, the scientists will report in the August issue of Nature Neuroscience. As a result, the brain has few stress-hormone receptors and reacts to stress like a skittish horse hearing a gunshot.

But licking and grooming by an attentive mother literally removes the silencer; the molecule is gone. Those baby rats have lots of stress-hormone receptors in their brains and less stress hormone, and they grow up to be curious, unafraid and able to handle stress.

"In the nature/nurture debate, people have long suspected that the environment somehow regulates the activity of genes," says Prof. Meaney. "The question has always been, how? It took four years, but we've now shown that maternal care alters the chemistry of the gene."

The discovery overturns genetic dogma so thoroughly -- after all, how mom treats the kids isn't supposed to alter something so fundamental as their DNA -- that one researcher reviewing Prof. Meaney's manuscript at a prominent American science journal said there is no precedent for such a claim, asserted that he simply didn't believe it, and recommended that the journal not publish it. The scientists at Nature disagreed.

A key unanswered question is whether DNA can change even later in life. That is, can rats who grow up to be skittish, because they were reared by standoffish mothers, mellow out as the result of some experience? And does parental care, or other experience, alter DNA in people, too?

It would be astonishing if it did not. Altering genes by adding or removing silencing molecules is part of a new field called epigenetics. If epigenetics were a film, it would be "Fahrenheit 9/11," the hot new release and one that is causing more than a bit of consternation among traditionalists. This year's Nobel Symposium in Stockholm featured epigenetics, as did the A-list annual conference of the Cold Spring Harbor Laboratory in New York. Last month, the National Institutes of Health announced a $5 million grant to Johns Hopkins University School of Medicine, Baltimore, to establish the Center for Epigenetics of Common Human Disease, the first of its kind.

Genetic changes are mutations in which one or more of the four chemicals that make up the twisting double helix of DNA is, typically, deleted or changed. Instead of ATTCTG, for instance, you have ATTGTG; as a result, the gene no longer functions as intended.

Epigenetic changes, in contrast, leave the sequence of As, Ts, Cs and Gs untouched. But the DNA acquires some new accessories, as it were: Certain small molecules glom onto the DNA, and suddenly a gene that was silent is active, or one that was active is hushed. That is what happened to Prof. Meaney's rats: A previously silenced gene began singing loud and clear.

The appeal of epigenetics is obvious to anyone who is or knows an identical twin. Despite having the exact same sequence of DNA, identical twins aren't identical, especially when it comes to diseases such as cancers and mental illness. Something has altered their DNA sequence so that disease-causing genes turn on or disease-suppressing genes turn off. I'll explore epigenetics further in next week's column.