The Best American Science and Nature Writing 2014 (6 page)

Whether it's a pilot on a flight deck, a doctor in an examination room, or an Inuit hunter on an ice floe, knowing demands doing. One of the most remarkable things about us is also one of the easiest to overlook: each time we collide with the real, we deepen our understanding of the world and become more fully a part of it. While we're wrestling with a difficult task, we may be motivated by an anticipation of the ends of our labor, but it's the work itself—the means—that makes us who we are. Computer automation severs the ends from the means. It makes getting what we want easier, but it distances us from the work of knowing. As we transform ourselves into creatures of the screen, we face an existential question: Does our essence still lie in what we know, or are we now content to be defined by what we want? If we don't grapple with that question ourselves, our gadgets will be happy to answer it for us.

FROM
Pacific Standard

 

A
FEW YEARS AGO
, Gene Robinson, of Urbana, Illinois, asked some associates in southern Mexico to help him kidnap some one thousand newborns. For their victims they chose bees. Half were European honeybees,
Apis mellifera ligustica
, the sweet-tempered kind most beekeepers raise. The other half were
ligustica
's genetically close cousins,
Apis mellifera scutellata
, the African strain better known as killer bees. Though the two subspecies are nearly indistinguishable, the latter defend territory far more aggressively. Kick a European honeybee hive, and perhaps a hundred bees will attack you. Kick a killer bee hive, and you may suffer a thousand stings or more. Two thousand will kill you.

Working carefully, Robinson's conspirators—researchers at Mexico's National Center for Research in Animal Physiology, in the high resort town of Ixtapan de la Sal—jiggled loose the lids from two African hives and two European hives, pulled free a few honeycomb racks, plucked off about 250 of the youngest bees from each hive, and painted marks on the bees' tiny backs. Then they switched each set of newborns into the hive of the other subspecies.

Robinson, back in his office at the University of Illinois at Urbana-Champaign's Department of Entomology, did not fret about the bees' safety. He knew that if you move bees to a new colony in their first day, the colony accepts them as its own. Nevertheless, Robinson did expect that the bees would be changed by their adoptive homes: he expected the killer bees to take on the European bees' moderate ways and the European bees to assume the killer bees' more violent temperament. Robinson had discovered this in prior experiments. But he hadn't yet figured out how it happened.

He suspected the answer lay in the bees' genes. He didn't expect the bees' actual DNA to change: random mutations aside, genes generally don't change during an organism's lifetime. Rather, he suspected that the bees' genes would behave differently in their new homes—wildly differently.

This notion was both reasonable and radical. Scientists have known for decades that genes can vary their level of activity, as if controlled by dimmer switches. Most cells in your body contain every one of your 22,000 or so genes. But in any given cell at any given time, only a tiny percentage of those genes are active, sending out chemical messages that affect the activity of the cell. This variable gene activity, called gene expression, is how your body does most of its work.

Sometimes these turns of the dimmer switch correspond to basic biological events, as when you develop tissues in the womb, enter puberty, or stop growing. At other times gene activity cranks up or spins down in response to changes in your environment. Thus certain genes switch on to fight infection or heal your wounds—or, running amok, give you cancer or burn your brain with fever. Changes in gene expression can make you thin, fat, or strikingly different from your supposedly identical twin. When it comes down to it, really, genes don't make you who you are. Gene expression does. And gene expression varies depending on the life you live.

Every biologist accepts this. That was the safe, reasonable part of Robinson's notion. Where he went out on a limb was in questioning the conventional wisdom that environment usually causes fairly
limited
changes in gene expression. It might sharply alter the activity of some genes, as happens in cancer or digestion. But in all but a few special cases, the thinking went, environment generally brightens or dims the activity of only a few genes at a time.

Robinson, however, suspected that environment could spin the dials on “big sectors of genes, right across the genome”—and that an individual's social environment might exert a particularly powerful effect. Who you hung out with and how they behaved, in short, could dramatically affect which of your genes spoke up and which stayed quiet—and thus change who you were.

Robinson was already seeing this in his bees. The winter before, he had asked a new postdoc, Cédric Alaux, to look at the gene-expression patterns of honeybees that had been repeatedly exposed to a pheromone that signals alarm. (Any honeybee that detects a threat emits this pheromone. It happens to smell like bananas. Thus “it's not a good idea,” says Alaux, “to eat a banana next to a beehive.”)

To a bee, the pheromone makes a social statement:
Friends, you are in danger.
Robinson had long known that bees react to this cry by undergoing behavioral and neural changes: their brains fire up and they literally fly into action. He also knew that repeated alarms make African bees more and more hostile. When Alaux looked at the gene-expression profiles of the bees exposed again and again to the alarm pheromone, he and Robinson saw why: with repeated alarms, hundreds of genes—genes that previous studies had associated with aggression—grew progressively busier. The rise in gene expression neatly matched the rise in the aggressiveness of the bees' response to threats.

Robinson had not expected that. “The pheromone just lit up the gene expression, and it kept leaving it higher.” The reason soon became apparent: some of the genes affected were transcription factors—genes that regulate other genes. This created a cascading gene-expression response, with scores of genes responding.

This finding inspired Robinson's kidnapping-and-cross-fostering study. Would moving baby bees to wildly different social environments reshape the curves of their gene-expression responses? Down in Ixtapan, Robinson's collaborators suited up every five to ten days, opened the hives, found about a dozen foster bees in each one, and sucked them up with a special vacuum. The vacuum shot them into a chamber chilled with liquid nitrogen. The intense cold instantly froze the bees' every cell, preserving the state of their gene activity at that moment. At the end of six weeks, when the researchers had collected about 250 bees representing every stage of bee life, the team packed up the frozen bees and shipped them to Illinois.

There Robinson's staff removed the bees' sesame-seed-size brains, ground them up, and ran them through a DNA microarray machine. This identified which genes were busy in a bee's brain at the moment it met the bee-vac. When Robinson sorted his data by group—European bees raised in African hives, for instance, or African bees raised normally among their African kin—he could see how each group's genes reacted to their lives.

Robinson organized the data for each group onto a grid of red and green color-coded squares: each square represented a different gene, and its color represented the group's average rate of gene expression. Red squares represented genes that were especially active in most of the bees in that group; the brighter the red, the more bees in which that gene had been busy. Green squares represented genes that were silent or underactive in most of the group. The printout of each group's results looked like a sort of cubist Christmas card.

When he got the cards, says Robinson, “the results were stunning.” For the bees that had been kidnapped, life in a new home had indeed altered the activity of “whole sectors” of genes. When their gene-expression data was viewed on the cards alongside the data for groups of bees raised among their own kin, a mere glance showed the dramatic change. Hundreds of genes had flipped colors. The move between hives didn't just make the bees act differently. It made their genes work differently, and on a broad scale.

What's more, the cards for the adopted bees of both species came to ever more resemble, as they moved through life, the cards of the bees they moved in with. With every passing day their genes acted more like those of their new hive mates (and less like those of their genetic siblings back home). Many of the genes that switched on or off are known to affect behavior; several are associated with aggression. The bees also acted differently. Their dispositions changed to match that of their hive mates. It seemed the genome, without changing its code, could transform an animal into something very like a different subspecies.

These bees didn't just act like different bees. They had pretty much become different bees. To Robinson this spoke of a genome far more fluid—far more socially fluid—than previously conceived.

 

Robinson soon realized he was not alone in seeing this. At conferences and in the literature, he kept bumping into other researchers who saw gene networks responding fast and widely to social life. David Clayton, a neurobiologist also on the University of Illinois campus, found that if a male zebra finch heard another male zebra finch singing nearby, a particular gene in the bird's forebrain would fire up—and it would do so differently depending on whether the other finch was strange and threatening or familiar and safe.

Others found this same gene, dubbed zenk, ramping up in other species. In each case, the change in zenk's activity corresponded to some change in behavior: a bird might relax in response to a song or become vigilant and tense. Duke researchers, for instance, found that when female zebra finches listened to male zebra finches' songs, the females' zenk gene triggered massive gene-expression changes in their forebrains—a socially sensitive brain area in birds as well as humans. The changes differed depending on whether the song was a mating call or a territorial claim. And perhaps most remarkably, all of these changes happened incredibly fast—within a half hour, sometimes within just five minutes.

Zenk, it appeared, was a so-called immediate early gene, a type of regulatory gene that can cause whole networks of other genes to change activity. These sorts of regulatory gene-expression responses had already been identified in physiological systems such as digestion and immunity. Now they also seemed to drive quick responses to social conditions.

One of the most startling early demonstrations of such a response occurred in 2005 in the lab of the Stanford biologist Russell Fernald. For years Fernald had studied the African cichlid
Astatotilapia burtoni
, a freshwater fish about 2 inches long and dull pewter in color. By 2005 he had shown that among
burtoni
, the top male in any small population lives like some fishy pharaoh, getting far more food, territory, and sex than even the No. 2 male. This No. 1 male cichlid also sports a bigger and brighter body. And there is always only one No. 1.

I wonder, Fernald thought, what would happen if we just removed him?

So one day Fernald turned out the lights over one of his cichlid tanks, scooped out big flashy No. 1, and then, twelve hours later, flipped the lights back on. When the No. 2 cichlid saw that
he
was now No. 1, he responded quickly. He underwent massive surges in gene expression that immediately blinged up his pewter coloring with lurid red and blue streaks and, in a matter of hours, caused him to grow some 20 percent. It was as if Jason Schwartzman, coming to work one day and learning that the big office stud had quit, morphed into Arnold Schwarzenegger by close of business.

These studies, says Greg Wray, an evolutionary biologist at Duke who has focused on gene expression for over a decade, caused quite a stir. “You suddenly realize birds are hearing a song and having massive, widespread changes in gene expression in just fifteen minutes? Something big is going on.”

This big something, this startlingly quick gene-expression response to the social world, is a phenomenon we are just beginning to understand. The recent explosion of interest in “epigenetics”—a term literally meaning “around the gene” and referring to anything that changes a gene's effect without changing the actual DNA sequence—has tended to focus on the long game of gene-environment interactions: how famine among expectant mothers in the Netherlands during World War II, for instance, affected gene expression and behavior in their children; or how mother rats, by licking and grooming their pups more or less assiduously, can alter the wrappings around their offspring's DNA in ways that influence how anxious the pups will be for the rest of their lives. The idea that experience can echo in our genes across generations is certainly a powerful one. But to focus only on these narrow, long-reaching effects is to miss much of the action concerning epigenetic influence and gene activity. This fresh work by Robinson, Fernald, Clayton, and others—encompassing studies of multiple organisms, from bees and birds to monkeys and humans—suggests something more exciting: that our social lives can change our gene expression with a rapidity, breadth, and depth previously overlooked.

Why would we have evolved this way? The most probable answer is that an organism that responds quickly to fast-changing social environments will more likely survive them. That organism won't have to wait around, as it were, for better genes to evolve on the species level. Immunologists discovered something similar twenty-five years ago: adapting to new pathogens the old-fashioned way—waiting for natural selection to favor genes that create resistance to specific pathogens—would happen too slowly to counter the rapidly changing pathogen environment. Instead, the immune system uses networks of genes that can respond quickly and flexibly to new threats.