DNA doesn’t have the last word in inheritance, according to Larry Feig. Photo: John Soares

A New Twist on Heredity

The popular understanding of genetics boils down to the defining power of DNA. Mom’s and Dad’s genes are passed along to their children, and the DNA instructions within those genes mean the children are either blessed or cursed with particular characteristics. It has long been known that people differ from each other, for the most part, because the content of the four building blocks of DNA that make up genes differs slightly from one individual to another. These differences are acquired from one’s parents, who acquired them from their parents. But recent findings shine a light on another side of the inheritance process.

Larry Feig, a professor of biochemistry at the School of Medicine and a member of the biochemistry and neuroscience programs at the Sackler School of Graduate Biomedical Sciences, has discovered that young mice that frolic in a cage filled with stimulating objects not only get smarter—they also pass at least part of their increased brain power on to their offspring. The research supports a growing body of evidence that an organism’s traits can be acquired not only through differences in DNA that have been passed on for many generations, but also by biochemical alterations that occur in response to a parent’s environment.

Unearthing new forms of inheritance was not Feig’s original goal. He and his team had set out to investigate the biochemical machinations that lead to cancer. They knew that when a certain gene continually produced growth-promoting proteins, tumors would result. To gain insight into how that gene operates, they created some mice lacking the gene—knockout mice, as they are known. Such mice had weak memories. The researchers wondered if stimulation would help the mice overcome their neurological deficit. So they took fifteen-day-old females (early adolescents, by mouse standards) out of their no-frills lab cage and gave them a two-week holiday in a rodent wonderland full of toys, running wheels, and nesting materials. These indulged mice showed markedly improved memory, just as Feig had hoped.

The surprise came several weeks after the mice were returned to their standard, spartan living conditions. When they and their less-favored counterparts became pregnant and gave birth, babies born to mothers who had enjoyed the enriched environment possessed a distinct mental advantage, even though their genetic profile said they shouldn’t. “When my postdoc first told me the result, I said, ‘Get out of here!’ I didn’t believe it,” Feig recalls. It was as though his colleague had claimed that a girl who learns German in high school will give birth to children who have a propensity for German.

The type of mental test investigated is known as fear conditioning. If a mouse is given a mild electric shock in its cage, the memory of that experience will often cause it to freeze when it is returned to its cage. Ordinary mice typically exhibit this freeze behavior for about a week. Knockout mice, with their weaker memories, lose the response more quickly. But sure enough, adolescent knockout mice that spent time in an enriched environment showed almost the normal duration of fear conditioning—and so did their offspring. “He got a huge effect, and showed that it was transmitted to the next generation,” says Klaus Miczek, the Moses Hunt Professor of Psychology at Tufts, who consulted with Feig’s group. “It’s quite stunning—your jaw drops when you see it.”
The results, taken as a whole, are the first to “demonstrate that the benefits of an early enriched environment on memory can be passed along without a direct nurturing effect,” notes Tania Roth, a neurobiologist at the University of Alabama at Birmingham who has done related research.

The work of Feig’s team adds to knowledge of a broader concept called epigenetics—the idea that the amount of a particular protein a gene produces can be altered for the lifetime of an animal, and even in their future offspring. Epigenetics may explain, for example, why children with identical genetic anomalies sometimes have entirely different diseases. In one of the best understood examples of epigenetic inheritance, McGill University researchers showed that rats whose mothers had an unusually high tendency to lick and groom their young grew up to be “high touch” mothers themselves. “Even though the external signal”—the stimulating environment—“is gone, the impact on gene expression is still there,” explains Moshe Szyf, a McGill pharmacology professor and epigenetics specialist. Feig’s results with memory, he asserts, are “impossible to understand without invoking an epigenetic effect.”

It’s not entirely clear how the process works. Feig conjectures that the enriched environment triggers a hormonal change. Even though the mice are missing the gene that normally aids learning and memory, this hormonal change may turn on another gene that then pumps out memory-boosting proteins.

When the mouse is returned to its humdrum laboratory cage, its body keeps churning out the proteins, because the hormone responsible remains in its bloodstream. If the mouse gets pregnant long after its happy holiday, the hormone could be passed along to the fetus, whose genes it affects in the same way.
Are there implications for human inheritance? Roth, the Alabama researcher, thinks it “very likely” that the epigenetic effect Feig has found exists in humans or other primates. Szyf, of McGill, concurs, remarking that Feig has uncovered “a very basic thing—and basic things are common.” Feig himself, though, is more conservative, cautioning that the effect could prove to be “unique to mice.”

Feig points out that his findings are reminiscent of the biologist Jean-Baptiste Lamarck’s theory, proposed in the early nineteenth century, that acquired traits can be inherited. But the new results do not undermine modern evolutionary theory, Feig insists.

In fact, the findings “may support the survival-of-the-fittest aspect of Darwin’s theory of evolution.” Offspring of environmentally enriched mice may have a selective advantage over other mice. The message that nature is sending, Feig says, is that “if you had it good when you were young, that will help your offspring even if they don’t always have it so good themselves.”

HERB BRODY is a Boston-area science and technology journalist. He has been editor in chief of MIT’s Lincoln Laboratory Journal and an editor of MIT’s Technology Review.