“We asked just how stable is ‘stable,’” Crabbe told me when I called. “We did the identical tests in three different laboratories, trying to make every aspect of their environment identical, from the brand of mouse feed they ate—Purina—and their age, to their shipping history. We had them tested at the same hour on the same day with identical apparatus.”
So at the identical point—April 20, 1998, between 8:30 and 9:00 A.M. local time—all the mice from eight different inbred strains, including C57BL/6J, were tested. One test simply offered them a choice of drinking regular water or an alcohol solution. True to form, the liquor-lovers chose the rodent martini far more often than did other mouse strains.
Next was a standard test for mouse anxiety. A mouse is placed at the crossroads of two runways, elevated three feet off the ground. Two arms of the crossroads have walls while the other two are open, which can be scary. Anxious mice cower next to the walls, while more adventurous ones explore the open runways.
To the great surprise of those who believe that genes alone determine behavior, however, within a given strain some decided differences on the anxiety test were found from lab to lab. For example, one strain, BALB/cByJ, was very anxious in Portland but quite adventurous in Albany.
As Crabbe noted, “If genes were all, you’d expect to find no differences whatever.” What could have caused the differences? Certain variables were beyond control from lab to lab, like the humidity and the water the mice drank—and perhaps most important, the people who handled them. One research assistant, for example, was allergic to mice and wore a respirator while holding them.
“Some people are confident and skilled at handling mice, while others are anxious or too rough,” Crabbe told me. “My bet is that mice can ‘read’ the emotional state of the person handling them, and that state in turn has an impact on the mouse’s behavior.”
His study, featured in the prestigious journal Science, aroused a storm of debate among neuroscientists. They had to grapple with the disturbing news that minor differences from one laboratory to another, such as how the mice were handled, created disparities in how the mice behaved—which implied a difference in how the identical genes acted.3
Crabbe’s experiment, together with similar findings from other labs, suggests that genes are more dynamic than most people—and science for more than a century—have assumed. It’s not just which genes we are born with, but their expression, that matters.
To understand how our genes operate, we must appreciate the difference between possessing a given gene and the degree to which that gene expresses its signature proteins. In gene expression, essentially, a bit of DNA makes RNA, which in turn creates a protein that makes something happen in our biology. Of the thirty thousand or so genes in the human body, some are expressed only during embryonic development, then shut off forever. Others turn on and off constantly. Some express themselves only in the liver, others only in the brain.
Crabbe’s finding stands as a landmark in “epigenetics,” the study of ways the experiences we undergo change how our genes operate—without altering our DNA sequence an iota. Only when a gene directs the synthesis of RNA does it actually make a practical difference in the body. Epigenetics shows how our environment, translated into the immediate chemical surround of a given cell, programs our genes in ways that determine just how active they will be.
Research in epigenetics has identified many of the biological mechanisms that control gene expression. One of them, involving the methyl molecule, not only turns genes on or off but also tones down or speeds up their activity.4 Methyl activity likewise helps determine where in the brain the more than 100 billion neurons end up, and which other neurons their ten thousand connections will link to. The methyl molecule sculpts the body, including the brain.
Such insights put to rest the century-old debate on nature versus nurture: do our genes or our experiences determine who we become? That debate turns out to be pointless, based on the fallacy that our genes and our environment are independent of each other; it’s like arguing over which contributes more to the area of a rectangle, the length or the width.5
Simply possessing a given gene does not tell the whole story about its biological value. For example, the food we eat contains hundreds of substances that regulate a host of genes, turning them on and off like flickering Christmas tree lights. If we eat the wrong foods over a period of years, we can activate a combination of genes that will result in the clogged arteries of heart disease. On the other hand, a bite of broccoli offers a dose of vitamin B6, which spurs the tryptophan hydroxalese gene to produce the amino acid L-tryptophan, which helps synthesize dopamine, a neurotransmitter that stabilizes mood, among other functions.
It is biologically impossible for a gene to operate independently of its environment: genes are designed to be regulated by signals from their immediate surround, including hormones from the endocrine system and neurotransmitters in the brain—some of which, in turn, are profoundly influenced by our social interactions.6 Just as our diet regulates certain genes, our social experiences also determine a distinct batch of such genomic on-off switches.
Our genes, then, are not sufficient in themselves to produce an optimally operating nervous system.7 Raising a secure child, or an empathic one, in this view, requires not just a necessary set of genes but also sufficient parenting or other apt social experiences. As we’ll see, only this combination ensures that the right genes will operate in the best way. From this perspective, parenting exemplifies what we might call “social epigenetics.”
“Social epigenetics is part of the next frontier in genomics,” says Crabbe. “The new technical challenge involves factoring in the impact of environment on differences in gene expression. It’s another blow against the naïve view of genetic determinism: that our experiences don’t matter—that genes are all.”
GENES NEED EXPRESSION
James Watson—who won the Nobel Prize for his seminal discovery, with Francis Crick, of the double-helix design of DNA—admits to having a hair-trigger temper. But, he adds, he also gets over his anger quickly. That rapid recovery, he observes, stands toward the better end of the spectrum of how genes associated with aggression can operate.
The gene in question helps inhibit anger and can operate in two ways. In one, the weaker, the gene expresses extra-small amounts of the enzyme that controls aggression, and so the person angers easily, stays much angrier than most, and will be more prone to violence. People at that extreme can readily end up in prison.
In the other form the gene expresses lots of its enzyme, so, like Watson, the person may get angry but will recover quickly. Having the second pattern of gene expression makes life a bit more pleasant, so that irritating moments don’t linger too long. Some people with that pattern, apparently, can win the Nobel Prize.
If a gene never expresses the proteins that could direct the body’s functioning in a given way, then we may as well not possess that gene at all. If it expresses them a small bit, then the gene will matter a little—and if the expression comes full force, then the gene matters maximally.
The human brain is designed to change itself in response to accumulated experience. Possessing the consistency of butter at room temperature and locked into its bony cage, the brain is as fragile as it is complex. Part of this fragility results from an exquisite attunement to its surroundings.
It had long been assumed that gene-controlling events were strictly biochemical—getting proper nutrition, or (in a worst case) exposure to industrial toxins. Now epigenetic studies are looking at how parents treat a growing child, finding ways child rearing shapes that child’s brain.
A child’s brain comes preprogrammed to grow, but it takes a bit more than the first two decades of life to finish this task, making it the last organ of the body to become anatomically mature. Over that period all the major figures in a child’s life—parents, siblings, grandparents, teachers, and friends—can become active ingredients in brain growth, creating a soci
al and emotional mix that drives neural development. Like a plant adapting to rich or to depleted soil, a child’s brain shapes itself to fit its social ecology, particularly the emotional climate fostered by the main people in her life.
Some brain systems are more responsive to these social influences than are others. And each network of brain circuitry has its own peak period when social forces can shape it. Some of the most profound impacts seem to occur during the first two years of life, a period when the brain undergoes its biggest growth spurt—from a puny 400 grams at birth to a robust 1,000 grams at twenty-four months (on the way to an average of 1,400 grams in adulthood).
From this stage on, critical personal experiences in our lives seem to set biological rheostats that fix the level of activity for genes that regulate brain function, as well as other biological systems. Social epigenetics expands the spectrum of what regulates certain genes to include relationships.
Adoption can be seen as a unique natural experiment, in which we may evaluate the impact of the adoptive parents’ influences on a child’s genes. One study of belligerence in adopted children compared the family atmosphere fostered by their biological parents with that of their adopted families. When children who were born into families with a history of aggressive, belligerent violence were adopted by peaceable families, just 13 percent of the adoptees displayed antisocial traits as they grew up. But when such children were adopted into “bad homes”—families where aggression had free rein—45 percent went on to become violent themselves.8
Family life seems to alter the activity of genes not just for aggression but for a vast number of other traits. One dominant influence seems to be how much nurturing love—or cold neglect—a youngster receives. Michael Meaney, a neuroscientist at McGill University in Montreal, is passionate about the implications of epigenetics for human connection. Meaney, slight of build and a charming speaker, shows scientific guts in his readiness to draw conclusions for the human case from his elaborate studies of lab mice.
Meaney has discovered, at least for mice, a vital way that parenting can change the very chemistry of a youngster’s genes.9 His research identifies a singular window in development—the first twelve hours after a rodent’s birth—during which a crucial methyl process occurs. How much a mother rat licks and grooms her pups during this window actually determines how brain chemicals that respond to stress will be made in that pup’s brain for the rest of its life.
The more nurturing the mother, the more quick-witted, confident, and fearless the pup will become; the less nurturing she is, the slower to learn and more overwhelmed by threats the pup will be. Just as telling, the mother’s level of licking and grooming determines how much a female pup, in turn, will lick and groom her own pups one day.
The pups born to devoted mothers, who licked and groomed the most, grew up to have denser connections between their brain cells, particularly in the hippocampus, the seat of memory and learning. These pups were especially clever at a key rodent skill: finding their way around a physical layout. Moreover, they were less upset by life’s stresses and were more able to recover from a stress reaction when they had one.
The offspring of less nurturing and inattentive mothers, on the other hand, ended up with less dense connections between neurons. They scored poorly on solving mazes—the “IQ test” equivalent for mice.
For rat pups, the greatest neural setback occurs if they are completely separated from their mothers while still quite young. This crisis flips off protective genes, leaving them vulnerable to a biochemical chain reaction that floods their brain with toxic stress-triggered molecules. Such young rodents grow up to be easily frightened and startled.
The human equivalents of licking and grooming seem to be empathy, attunement, and touch. If Meaney’s work translates to humans, as he suspects it does, then how our parents treated us has left its genetic imprint over and above the set of DNA they passed down to us. And how we treat our children will, in turn, set levels of activity in their genes. This finding suggests that small, caring acts of parenthood can matter in lasting ways—and that relationships have a hand in guiding the brain’s continuing redesign.
THE NATURE-NURTURE PUZZLE
It’s all very easy to talk about epigenetics when you’re dealing with genetically hybrid mice in meticulously controlled laboratories. But just try to sort it out in the messy human world.
That was the daunting challenge undertaken in the massive study led by David Reiss at George Washington University. Reiss, famed for his astute research on family dynamics, teamed up with Mavis Heatherington, an expert on stepfamilies, and Robert Plomin, a leader in behavior genetics.
The gold standard for studies of nature versus nurture has been to compare children who are adopted with those raised by their biological parents. This lets researchers assess how much a trait such as aggression seems due to influences from the family, and how much to biology alone.
In the 1980s Plomin had startled the scientific world with his data from studies of adopted twins showing what portion of a trait or ability was due to genes and what to the way a child was raised. A teenager’s scholastic ability is about 60 percent due to genes, he asserted, while the sense of self-worth is only about 30 percent genetic, and morality but 25 percent.10 But Plomin and others using his method came under scientific fire because they typically assessed impacts only in a limited range of families, mainly those where twins were raised by biological parents compared with those raised by stepparents.
So the Reiss group resolved to include many more variations on stepfamilies, working far greater specificity into the equation. Their rigorous design demanded that they find 720 pairs of teenagers representing the entire range of genetic closeness, from identical twins to several varieties of stepsiblings.11
The group combed the nation to recruit families with just two teenage children in any of six specific configurations. Finding families with identical and fraternal twins, the standard procedure in their field, was no problem. Harder to find, however, were families where each parent had been previously divorced and brought only one teenager to the new stepfamily. Harder still, the stepparents had to have been married for at least five years.
After the excruciating search to find and recruit just the right families, the researchers spent years analyzing the resulting vast mass of data. Then came more frustrations. Some were due to an unexpected finding: every child experiences the very same family in sharply idiosyncratic ways.12 Studies of twins reared apart have taken for granted that every child in a given family experiences it alike. But the Reiss group research—like Crabbe’s with lab mice genetics—blew that assumption to bits.
Consider an older sibling versus a younger one. From birth the older one has no rival for her parents’ love and attention; then the younger one comes along. From day one the younger child needs to develop stratagems to compete for parental time and affection. Children vie to be unique, which results in their being treated differently. So much for the one-family-one-environment school of thought.
Even worse, these unique-to-one-child aspects of family life turned out to have great power in determining a child’s temperament above and beyond any genetic influences. So the way a child defines her unique niche in the family can follow any of countless modes, making them epigenetic wild cards.
Moreover, although parents have some impact on a child’s temperament, they are not the only ones. So do an array of other people in a child’s life, particularly their siblings and friends.
To complicate the equation further, a surprise factor showed up as an independent, and powerful, shaper of a child’s destiny: the ways a child comes to think about herself. To be sure, a teenager’s sense of overall self-worth depends much on how that child has been treated and almost not at all on genetics. But then, once formed, the child’s sense of self-worth shapes her behavior quite apart from the hapless ministrations of parents, the pressures of peers, or any genetic given.13
Now the equation for s
ocial impacts on genes takes another twist. A child’s genetic givens in turn shape how everyone treats him. While parents naturally cuddle with babies who flirt and hug back, testy or indifferent babies get less cuddling. In the worst case, when a child’s genetics lead him to be irritable, aggressive, and difficult, parents tend to respond in kind, with harsh discipline, tough talk, and their own criticism and anger. That route worsens the child’s difficult side, which in turn evokes more of the parents’ negativity, in a vicious spiral.14
The warmth of a child’s parents, or how limits are set, or myriad other ways a family operates, the researchers concluded, help set the expression of many genes. But in addition a bossy sibling or screwy buddy both have their impact.
The old, once seemingly clear distinction between the aspects of a child’s behavior that stem from genetics and those that derive from her social world blurs substantially. In the end, after all those millions of research dollars spent and the exhausting search for just the right families, the Reiss group yielded fewer specifics of the myriad complex interactions between family life and genes than they did puzzles yet to solve.
It appears too early in this science to track every epigenetic pathway in the chaotic fog of family life. Even so, from this mist a few crystal-clear bits of data are emerging. One suggests the power of life experiences to alter genetic “givens” in behavior.
FORGING NEURAL TRAILS
The late hypnotherapist Milton Erickson used to tell about growing up in a tiny town in Nevada early in the twentieth century. Winters there were quite severe, and one of his delights was to wake up and find that it had snowed during the night.
Social Intelligence: The New Science of Human Relationships Page 18
