by Deborah Blum
But this was a study of just fourteen people. Cole needed more.
Over the next several years, he got them. He found similarly unbalanced gene-expression or immune-response profiles in groups including poor children, depressed people with cancer, and people caring for spouses dying of cancer. He topped his efforts off with a study in which social stress levels in young women predicted changes in their gene activity six months later. Cole and his collaborators on that study, psychologists Gregory Miller and Nicolas Rohleder of the University of British Columbia, interviewed 103 healthy Vancouver-area women aged fifteen to nineteen about their social lives, drew blood, and ran gene-expression profiles, and after half a year drew blood and ran profiles again. Some of the women reported at the time of the initial interview that they were having trouble with their love lives, their families, or their friends. Over the next six months, these socially troubled subjects took on the sort of imbalanced gene-expression profile Cole found in his other isolation studies: busy attack dogs and broken leashes. Except here, in a prospective study, he saw the attack dog breaking free of its restraints: social stress changed these young women’s gene-expression patterns before his eyes.
In early 2009, Cole sat down to make sense of all this in a review paper that he would publish later that year in Current Directions in Psychological Science. Two years later we sat in his spare, rather small office at UCLA and discussed what he’d found. Cole, trimly built but close to 6 feet tall, speaks in a reedy voice that is slightly higher than his frame might lead you to expect. Sometimes, when he’s grabbing for a new thought or trying to emphasize a point, it jumps a register. He is often asked to give talks about his work, and it’s easy to see why: relaxed but animated, he speaks in such an organized manner that you can almost see the paragraphs form in the air between you. He spends much of his time on the road. Thus the half-unpacked office, he said, gesturing around him. His lab, down the hall, “is essentially one really good lab manager”—Jesusa M. Arevalo, whom he frequently lists on his papers—“and a bunch of robots,” the machines that run the assays.
“We typically think of stress as being a risk factor for disease,” said Cole. “And it is, somewhat. But if you actually measure stress, using our best available instruments, it can’t hold a candle to social isolation. Social isolation is the best-established, most robust social or psychological risk factor for disease out there. Nothing can compete.”
This helps explain, for instance, why many people who work in high-stress but rewarding jobs don’t seem to suffer ill effects, while others, particularly those isolated and in poverty, wind up accruing lists of stress-related diagnoses—obesity, type 2 diabetes, hypertension, atherosclerosis, heart failure, stroke.
Despite these well-known effects, Cole said he was amazed when he started finding that social connectivity wrought such powerful effects on gene expression.
“Or not that we found it,” he corrected, “but that we’re seeing it with such consistency. Science is noisy. I would’ve bet my eyeteeth that we’d get a lot of noisy results that are inconsistent from one realm to another. And at the level of individual genes that’s kind of true—there is some noise there.” But the kinds of genes that get dialed up or down in response to social experience, he said, and the gene networks and gene-expression cascades that they set off, “are surprisingly consistent—from monkeys to people, from five-year-old kids to adults, from Vancouver teenagers to sixty-year-olds living in Chicago.”
Cole’s work carries all kinds of implications—some weighty and practical, some heady and philosophical. It may, for instance, help explain the health problems that so often haunt the poor. Poverty savages the body. Hundreds of studies over the past few decades have tied low income to higher rates of asthma, flu, heart attacks, cancer, and everything in between. Poverty itself starts to look like a disease. Yet an empty wallet can’t make you sick. And we all know people who escape poverty’s dangers. So what is it about a life of poverty that makes us ill?
Cole asked essentially this question in a 2008 study he conducted with Gregory Miller and Edith Chen, another social psychologist then at the University of British Columbia. The paper appeared in an odd forum: Thorax, a journal about medical problems in the chest. The researchers gathered and ran gene-expression profiles on thirty-one kids, ranging from nine to eighteen years old, who had asthma; sixteen were poor, fifteen well-off. As Cole expected, the group of well-off kids showed a healthy immune response, with elevated activity among genes that control pulmonary inflammation. The poorer kids showed busier inflammatory genes, sluggishness in the gene networks that control inflammation, and—in their health histories—more asthma attacks and other health problems. Poverty seemed to be mucking up their immune systems.
Cole, Chen, and Miller, however, suspected something else was at work—something that often came with poverty but was not the same thing. So along with drawing the kids’ blood and gathering their socioeconomic information, they showed them films of ambiguous or awkward social situations, then asked them how threatening they found them.
The poorer kids perceived more threat; the well-off perceived less. This difference in what psychologists call “cognitive framing” surprised no one. Many prior studies had shown that poverty and poor neighborhoods, understandably, tend to make people more sensitive to threats in ambiguous social situations. Chen in particular had spent years studying this sort of effect.
But in this study, Chen, Cole, and Miller wanted to see if they could tease apart the effect of cognitive framing from the effects of income disparity. It turned out they could, because some of the kids in each income group broke type. A few of the poor kids saw very little menace in the ambiguous situations, and a few well-off kids saw a lot. When the researchers separated those perceptions from the socioeconomic scores and laid them over the gene-expression scores, they found that it was really the kids’ framing, not their income levels, that accounted for most of the difference in gene expression. To put it another way: when the researchers controlled for variations in threat perception, poverty’s influence almost vanished. The main thing driving screwy immune responses appeared to be not poverty, but whether the child saw the social world as scary.
But where did that come from? Did the kids see the world as frightening because they had been taught to, or because they felt alone in facing it? The study design couldn’t answer that. But Cole believes isolation plays a key role. This notion gets startling support from a 2004 study of fifty-seven school-age children who were so badly abused that state social workers had removed them from their homes. The study, often just called “the Kaufman study,” after its author, the Yale psychiatrist Joan Kaufman, challenges a number of assumptions about what shapes responses to trauma or stress.
The Kaufman study at first looks like a classic investigation into the so-called depression-risk gene—the serotonin transporter gene, or SERT—which comes in both long and short forms. Any single gene’s impact on mood or behavior is limited, of course, and these single-gene or “candidate gene” studies must be viewed with that in mind. Yet many studies have found that SERT’s short form seems to render many people (and rhesus monkeys) more sensitive to environment; according to those studies, people who carry the short SERT are more likely to become depressed or anxious if faced with stress or trauma.
Kaufman looked first to see whether the kids’ mental health tracked their SERT variants. It did: the kids with the short variant suffered twice as many mental-health problems as those with the long variant. The double whammy of abuse plus short SERT seemed to be too much.
Then Kaufman laid both the kids’ depression scores and their SERT variants across the kids’ levels of “social support.” In this case, Kaufman narrowly defined social support as contact at least monthly with a trusted adult figure outside the home. Extraordinarily, for the kids who had it, this single, modest, closely defined social connection erased about 80 percent of the combined risk of the short SERT variant and the abuse. It came close to inocu
lating kids against both an established genetic vulnerability and horrid abuse.
Or, to phrase it as Cole might, the lack of a reliable connection harmed the kids almost as much as abuse did. Their isolation wielded enough power to raise the question of what’s really most toxic in such situations. Most of the psychiatric literature essentially views bad experiences—extreme stress, abuse, violence—as toxins, and “risk genes” as quasi-immunological weaknesses that let the toxins poison us. And abuse is clearly toxic. Yet if social connection can almost completely protect us against the well-known effects of severe abuse, isn’t the isolation almost as toxic as the beatings and neglect?
The Kaufman study also challenges much conventional Western thinking about the state of the individual. To use the language of the study, we sometimes conceive of “social support” as a sort of add-on, something extra that might somehow fortify us. Yet this view assumes that humanity’s default state is solitude. It’s not. Our default state is connection. We are social creatures, and have been for eons. As Cole’s colleague John Cacioppo puts it in his book Loneliness, Hobbes had it wrong when he wrote that human life without civilization was “solitary, poor, nasty, brutish, and short.” It may be poor, nasty, brutish, and short. But seldom has it been solitary.
Toward the end of the dinner I shared with Cole, after the waiter took away the empty platters and we sat talking over green tea, I asked him if there was anything I should have asked but had not. He’d been talking most of three hours. Some people run dry. Cole does not. He spoke about how we are permeable fluid beings instead of stable unitary isolates; about recursive reconstruction of the self; about an engagement with the world that constantly creates a new you, only you don’t know it, because you’re not the person you would have been otherwise—you’re a one-person experiment that has lost its control.
He wanted to add one more thing: he didn’t see any of this as deterministic.
We were obviously moving away from what he could prove at this point, perhaps from what is testable. We were in fact skirting the rabbit hole that is the free-will debate. Yet he wanted to make it clear he does not see us as slaves to either environment or genes.
“You can’t change your genes. But if we’re even half right about all this, you can change the way your genes behave—which is almost the same thing. By adjusting your environment you can adjust your gene activity. That’s what we’re doing as we move through life. We’re constantly trying to hunt down that sweet spot between too much challenge and too little.
“That’s a really important part of this: to an extent that immunologists and psychologists rarely appreciate, we are architects of our own experience. Your subjective experience carries more power than your objective situation. If you feel like you’re alone even when you’re in a room filled with the people closest to you, you’re going to have problems. If you feel like you’re well supported even though there’s nobody else in sight; if you carry relationships in your head; if you come at the world with a sense that people care about you, that you’re valuable, that you’re okay; then your body is going to act as if you’re okay—even if you’re wrong about all that.”
Cole was channeling John Milton: “The mind is its own place, and in itself can make a heaven of hell, a hell of heaven.”
Of course I did not realize that at the moment. My reaction was more prosaic.
“So environment and experience aren’t the same,” I offered.
“Exactly. Two people may share the same environment but not the same experience. The experience is what you make of the environment. It appears you and I are both enjoying ourselves here, for instance, and I think we are. But if one of us didn’t like being one-on-one at a table for three hours, that person could get quite stressed out. We might have much different experiences. And you can shape all this by how you frame things. You can shape both your environment and yourself by how you act. It’s really an opportunity.”
Cole often puts it differently at the end of his talks about this line of work. “Your experiences today will influence the molecular composition of your body for the next two to three months,” he tells his audience, “or, perhaps, for the rest of your life. Plan your day accordingly.”
PIPPA GOLDSCHMIDT
What Our Telescopes Couldn’t See
FROM The New York Times
EDINBURGH—To avoid light pollution and bad weather, professional astronomers have to be prepared to travel long distances to use telescopes on mountaintops far away from towns or cities. Astronomers from Britain, which is not generally well known for its clear skies, are particularly used to traveling. When I was an astronomer in the 1990s, working at the Royal Observatory in Edinburgh and at Imperial College London, I made regular trips to observatories around the world, especially in Chile.
Back home all I could usually see were a few lonely stars fighting against the clouds lit up by a flat dull wash of reflected streetlight. Looking up from the Andes was a fundamentally different experience—the sky was so bright with stars that there were scarcely any dark gaps between them. To make the experience even more striking, in the Southern Hemisphere you can see phenomena like the Magellanic Clouds, the crowded heart of the Milky Way, and the jewel-like constellation of the Southern Cross.
I was studying quasars, some of the most distant known objects in the universe, which are understood to be the bright centers of galaxies containing supermassive black holes. At a superficial glance, quasars don’t look particularly interesting. All you can see is a starlike point of light, because the extraordinarily bright center dwarfs the rest of the galaxy. But detailed measurements of quasars reveal their vast distances and the amazingly high speeds of the gases that spin around the invisible black holes.
When I first went to Chile’s Atacama Desert in 1990—the year Augusto Pinochet finally stepped down after nearly sixteen years in power—I found that the terrestrial landscape was almost as extraordinary as the objects I studied in the sky. In some parts of the desert it rains only once every few years. During the day there is nothing to see but rocks and sand and the dazzling sunlight reflected from distant telescope domes at the other observatories around the mountains.
At this time, astronomy was on the cusp of changing technologies. I was accustomed to using old-fashioned glass photographic plates—13 inches across and thin enough to be curved into the focal plane of the telescope. The light of stars was caught in the photographic emulsion on the plates, and the resulting complicated shapes of galaxies reminded me of insects preserved in amber.
But this sort of photography was dying out and being superseded by CCDs—electronic devices that created virtual images of the sky, and the precursors of today’s digital cameras.
So instead of fitting the plates into the telescope by hand while gazing out at the sky, observing in Chile meant sitting in a control room and operating the telescope remotely. Resulting images were displayed on computer screens. We saw the telescope only at the beginning of the night, when we were setting up, and at the end, when we shut everything down as the sun rose. During the night we didn’t even see the sky, because the control room—with its banks of computers that made it look like a low-rent starship Enterprise—had no windows.
After a few nights of this work, everything, not just my quasars, started to feel remote. The objects on the screen reminded me of ghosts, with no substance to them. Going outside helped somewhat—the stars looked so large and real I felt I could reach out and grab them—but in contrast the landscape was so empty I might as well have been on the moon. There was nothing to pull me back to earth.
I used to remind myself that I was there to work and nothing more. But I would long for the complexities of life, tedious British rain, and the screech of seagulls, even traffic jams started to have a certain nostalgic charm. As I sat in the control room, I would reread old newspapers, trying to keep faith with the world.
But at that I did not succeed. I know now that the desert wasn’t empty, that it had a t
errible secret; farther north from the observatory, in an even more remote part of the Andes, was an abandoned prison camp set up during the Pinochet regime, called Chacabuco. This was a place where political opponents of the regime were sent in the 1970s. Sometimes they died there. As the celebrated 2010 Chilean documentary Nostalgia for the Light shows, their relatives are still searching the desert for their remains.
Our telescopes had the power to detect candle flames many miles away, not to mention galaxies billions of light-years away. And yet they never turned toward the camp. They weren’t built to do that sort of observation.
Nor were we. The observatory that I visited in Chile is part of the European Southern Observatory. It’s one of the largest in the world and was first conceived of not long after World War II, partly as a way of bringing together former enemies and encouraging peaceful scientific endeavors. But our only political contribution was neutrality: we were supposed to keep our heads down and get on with our work. When I arrived, we were advised not to talk about politics with people in Chile.
I left the world of professional astronomy some time ago. In the years since, I have often thought of how astronomy is seen as a benign, unbiased science. Its sole function is to increase our understanding of how the universe works: astronomers receive and record, but they do not experiment or perturb. They are not tainted by any application to, say, energy development or military technologies. Astronomy is, essentially, a passive science.
I remember realizing when I was a student that I could make a measurement of an object in the sky, and how extraordinary that felt to me, as if it were a way of reaching out and connecting with something so far away. But maybe I found distant galaxies easier to understand than the people around me, and I wonder if my work became a substitute for any true connection. I still look to the edge of the universe, but I try to remember always to keep one eye focused here on earth.
