Blood Matters

by Masha Gessen

  The relationship between genes and behavior is probably equally complex in simpler creatures, such as mice, but researchers who study rodents do not have to fear offending their subjects when describing their findings. What Popova observed was that the male mice with the MAOA gene knocked out were more likely to attack other male mice; that they responded less actively to stress than normal mice; and that they had an increased tolerance for alcohol. They were not merely aggressive but aggressively antisocial. “If we put strangers in a cage together,” explained Popova, “we are collecting dead bodies every day. That is unusual for animals in general: Normally the purpose of a fight is to establish dominance, not to kill.”

  Human males with the less-active-than-normal MAOA gene tend to be both antisocial and alcohol-dependent. In the dozen years after the original Dutch discovery, the gene was studied extensively in different populations, including Germans, Brazilians, and Han Chinese. Most researchers found an association between the mutation, aggression, and alcoholism, and most leaned toward the theory that antisocial behavior, not substance abuse, was the primary factor. On the subject of how the mutation might influence or shape behavior and alcohol consumption, the scientists tried to tread most carefully.

  Genes, it seemed clear, do not regulate behavior directly: The brain does. But genes may determine or influence the amounts of different neurotransmitters in the brain, thereby regulating both behavior and emotions. In the case of “the aggression gene,” the neurotransmitter serotonin, implicated in regulating mood, sleep, sexuality, and appetite, among other things, emerged as the primary suspect. A genetic variant may interfere with serotonin processing in one of three ways: by lowering serotonin synthesis or making its breakdown less efficient; by disabling the reuptake system, through which we recycle neurotransmitters; and by reducing the sensitivity or the density of serotonin receptors. The MAOA gene appeared to regulate the amount of enzyme required to process serotonin, and that, the researchers believed, was why serotonin levels in both mice and men were higher than normal, which may have made them act similarly antisocial, impulsive, and aggressive.

  After three decades of researching mice, Popova decided to venture into studying the brains and genes of humans. Her staff traveled to regions of the Russian North where various indigenous populations continued to enjoy a fair amount of isolation and looked for inroads into studying their serotonin systems. Preliminary research on a Khant family that seemed to have suicide running through it suggested that its members might have a gene variant that lowered the level of serotonin transporters, the ones responsible for sending the neurotransmitters on their way again once they had reached a receptor.

  Popova was both eager and reluctant to talk about her human research. Her results were strictly preliminary, she stressed, and we had so much more to learn still about the ways humans work. And then maybe one day we would learn not only why men in a particular Khant kindred often committed suicide but also why Russians—regardless, it seemed, of the ethnic group to which they belonged—drank so much.

  ***

  On June 2, 2006, I looked out the window of my Moscow apartment as Vova, my eight-year-old son, went out to walk the dog. I watched as he sauntered past a playground, empty at the early hour, and stopped in a small grove at the far end of the building’s courtyard. A man was standing in the grove already, watching over his own dog. Vova stood, very adultlike, and chatted with his fellow dog-walker. I took pleasure in watching them: Vova, very small for his age (I bought him clothes for six-year-olds), proudly holding our medium-sized mutt, and the man, tall and scrawny, walking a dachshund, of all things. Vova said something to the man, the man extended his arm, with a beer bottle in it, and I watched Vova take a sip.

  Russia is a nation of drinkers. Sipping a morning-after beer out in the courtyard while walking his nice purebred dog marked the man as perhaps a well-behaved, domesticated alcoholic, or even just a man who had hosted a party the night before. But what was my eight-year-old doing? I asked him when he came back in.

  “I was just socializing,” he said. My son was giving me a preview of himself as a teenager.

  “That’s nice,” I said. “What was with the bottle?”

  “He had some nonalcoholic beer with him, and he offered me a sip.”

  I decided to ignore the doubtful alcohol-content assertion and focus instead on the germs that Vova had clearly risked getting by engaging in risky behavior. I chose my words carefully, and I had the distinct sense that I was speaking to an alcoholic in training. I had some experience in speaking to alcoholics about drinking: My partner, Svenya, and I had just separated as she entered rehab for drugs and alcohol. Svenya had been using mind-altering substances for sixteen years—half of her life. Now I wondered whether I was seeing the consequences of her drinking: Our son had emulated her by drinking nonalcoholic beer (a popular beverage in Russia, and apparently harmless from a purely biochemical standpoint). Then again, I could be seeing the evidence of Vova’s genetic heritage.

  Vova was born in Kaliningrad, Russia, to a twenty-year-old woman who was HIV-positive. Statistically speaking, that meant she was probably a drug user: At that point nearly all HIV-positive people in Russia were injection drug users. My memory helpfully produced episodes demonstrating that Vova had inherited a predilection to chemical dependency. At the age of four he had swallowed an infant’s daily dose of phenobarbital, which had been prescribed for my two-month-old daughter, Yael, who had been having non-fever-related seizures. Two years later, at Svenya’s and my wedding, a Jewish ceremony in Massachusetts, each of our children was given a sip of white wine under the chuppah. Both scrunched up their faces in disgust, but then Vova said, “Can I have some more?”

  So if Vova went on to develop a drug or alcohol problem, I would have my pick of people to blame: Vova’s biological mother, for having saddled him with a genetic predisposition to addiction, or Svenya, for having taught him the behavior by example. The question was, with this frightening confluence of genes and environment, was there anything I could do about it now that he was almost nine and sharing a beer with a stranger in the courtyard?

  ***

  A particular problem in our family was that I myself could not understand addiction. I was the sort of infuriating person who could—and did—smoke two to three cigarettes a day for nearly twenty years, and then stop without a second thought. When Svenya and I were first together, I drank heavily alongside her: We were young, childless, and in love, and I could still get up for work the next morning. Then the children came, and I stopped drinking heavily, expecting Svenya to do the same. It took me years to understand that she could not stop. But even now, as I write this, I cannot imagine what it is like to be unable to stop doing something that you know is ruining your health and your family.

  A few months into our separation and her sobriety, Svenya became an exemplary recovering substance abuser. She talked to me about codependency, family dynamics, and vicious cycles. I talked to her about genes and neurotransmitters and the substance-abusing brain. Sometimes, our understandings collided. It was easier for me to come around to her view of the forces that shaped us: There was a huge arsenal of tools on her side, created over decades of understanding human behavior through psychology and, at least in the United States, through psychoanalysis. Psychobabble was so common, it felt like plain English.

  But this was about to change. In fact, our understanding of human behavior was already changing, in ways perhaps more dynamic and more profound than our understanding of race and ethnicity. Physiology was starting to make common sense. The names of various neurotransmitters could be dropped into conversation without explanation. And everyone knew that the genome offered the ultimate map of the human being. I could imagine that a new language—let us call it biobabble—would start insinuating itself into the meetings of Alcoholics Anonymous, where people would talk about their family’s drinking in terms of heredity, and into, say, the dating scene, where well-educated midcareer professiona
ls would start explaining to potential partners that they had never formed an intimate relationship because of this or that polymorphism.

  By the time this book comes out, one or more U.S. companies will likely start offering commercial testing for genes associated with behavior. These are likely to be the same companies that already offer commercial ethnicity and paternity testing—they are the ones with the technology and the expertise—but they will likely do it in the guise of new companies, to separate their behavior-gene testing from their established ethnicity-gene testing. They will be aware they are treading on thin ice. They will risk looking like charlatans. But they will do it anyway: They will offer the testing, because we really want them to. In the era of the genome, we all want a printout of who we really are.

  ***

  I certainly did. Which is why a late-spring afternoon found me in the basement of a mental health facility in Jerusalem, gargling. The geneticist Richard Ebstein and his team used this ingenious method for collecting DNA: Instead of finger pricks or cheek swabs, they gave their patients a cap of regular mouthwash. One swished it around in one’s mouth, then spat into a plastic tube. Ebstein was not happy with my first tube: The liquid was too clear. I had gargled instead of swishing. My second plastic tube was half filled with satisfyingly murky liquid. This meant my DNA sample had been collected.

  Brooklyn-born and Yale-educated, Ebstein had moved to Israel with his American wife in the 1960s, for fear of the American draft. He chuckled when he told me this. I wanted to ask him more about this oddly courageous choice of haven, but he was not particularly good at answering questions about himself and his motivations: He was, he explained to me, fairly autistic, in the way of many scientists. And he had made a reputation out of such well-founded generalizations.

  A biochemist by training, he made his first genetics headlines in the early 1990s, when he claimed to have identified a “novelty-seeking gene.” A particular polymorphism of a dopamine receptor gene, found in a sizable minority of people, seemed to make them more likely to try new things and take concomitant risks. Using a captive population of Hebrew University students in Jerusalem, over the years Ebstein continued to administer psychological questionnaires and look for correlations in the genome. He got a fair amount of mileage out of the dopamine receptor gene: The same polymorphism, it seemed, was responsible for conferring on a minority of people a highly active sex drive, but worked against one of the most mysterious human traits—altruism. The propensity to help others at one’s own expense, and sometimes even at one’s own risk and peril, had long fascinated researchers. Some have argued that altruism as nature intended it extends only to kin. Others have argued that altruism does not contradict what we know about evolution because it is geared toward the survival of the species, if not the individual. Ebstein contributed to the debate by suggesting that altruism is hardwired: The most common polymorphism of exon 3 of the DRD4 dopamine receptor gene, a combination of two alleles of equal length—four base pairs—seemed correlated with a propensity for helping others. It also worked against both novelty-seeking and heightened sex drive: The sexy, risk-taking few were marked with one seven-pair allele. The purported altruism polymorphism also looked like it might raise one’s risk of depression—although, being very common, it seemed an unlikely suspect for causing a disorder. Then again, depression is very common, too.

  I was fairly certain of my pending test results. I was a novelty-seeking, sex-crazed, egomaniacal optimist, a preternaturally hard worker who was always basically happy. Most of my friends thought this too. Most of the people who could say this sort of thing to me would claim they tolerated my inattention to others in order to feed off my boundless energy. So I was caught off guard when one of Ebstein’s coauthors, a talkative Russian Israeli named Inga Gritsenko, informed me I was a common four-four. She refused to interpret my test results for me, but I knew what the implications were: The survey of my genes showed that I had a lowered sex drive and did not possess the novelty-seeking gene but was an altruist at risk for depression. This was pure silliness. I had the evidence: the time I was sentenced to death by Kosovar guerrilla fighters after I dragged a photographer and two interpreters into the mountains to look for action (if that was not novelty-seeking, what was?); the rather significant number of sexual partners and romantic involvements of both sexes accumulated over the years; my ability to bounce back from all sorts of trying experiences while maintaining an even demeanor. I had indeed had two bouts of depression at the classic junctures—as a college freshman and postpartum—but I hardly thought of these miserable periods as my defining moments. I had never been treated for depression.

  Feeling slightly offended, I continued combing through Ebstein’s published papers. He had studied the dopamine receptor gene in women with fibromyalgia, a common but mysterious illness that hits people—many more women than men—in midlife, causing sleep disturbance and painful tenderness all over. Women with fibromyalgia were said to have a particular personality, to be more prone to anxiety and depression. They also turned out to have a disproportionate number of four-four repeats, the kind I have. Blogs and alternative medicine sites told me that fibromyalgia sufferers tended to be hard-driven overachievers. Psychobabble would tell us their bodies were telling them to stop. Biobabble would tell us what Ebstein wrote: that with the unusual personality profile, it was no surprise that there seemed to be a link between the disease and a gene associated with behavior.

  Inga also informed me that I was homozygous for the short form of a serotonin transporter gene, which itself is linked to harm avoidance and neuroticism and anxiety. But not all studies confirmed these findings, so Ebstein and his team decided to study neonates—eighty-one two-week-old babies, male and female, healthy babies of healthy mothers. Babies with my variant of DRD4 scored lowest on orientation, motor organization, range of state (just what it sounds like—a measure of how aroused a baby can become) and second lowest on regulation of state (the baby’s ability to calm down, essentially). Babies with my variant of the serotonin transporter scored lowest on regulation of state. I actually felt embarrassed: All these people in Ebstein’s lab had seen my results. Of course, I was no longer two weeks old, but I did have certain lifelong problems with regulation of state, and anyway, I would feel embarrassed, with my tendency toward anxiety and neuroticism. They observed that, overall, babies tended to want to engage in interactive behavior—with the exception of those who, like me, had both short DRD4 alleles and were homozygous for the short serotonin-transporter allele. In other words, I thought they might note, the fact that I can pick up a phone and call someone—even if it did take me years to learn to—was an impressive achievement. At the end of this paper, there was a long passage outlining all the problems with corroborating the findings in other ethnic populations, but this did not help me: All the babies were Jewish, twenty of them Ashkenazi.

  Another experiment concerned second graders. The researchers looked at shyness. I know shyness. And I know that shyness is inherited. I got mine from my mother. My mother’s shyness was what scientists would have called “totally inhibiting social phobia.” She was terrified of strangers, even in her own home. When I was a child, what should have been routine socializing had the spirit, if not the trappings, of a major event: a function, I realized later, of my mother’s fear and a reflection of the effort she had to make to overcome it. Still, her social circle was largely limited to members of our extended family and others she had known for a very long time. When I was in my late teens and early twenties, my own brand of shyness would render me essentially speechless. Entire dinner parties would go by without my uttering a word; or I might be producing words, but I was basically inaudible. When I was able to overcome this, which was not always, I might find myself yelling, which embarrassed me further.

  When I was twenty-four, at the end of my first major relationship—which suffered unduly from my shyness; I basked in the luxury of human contact while making others uncomfortable—I was offere
d a job in California, a place where no one knew how shy I was. I decided to pretend I was not shy. For the most part, it worked. In the fifteen years since, I have made friends, had relationships, changed jobs, interviewed hundreds of people—all with only occasional cold sweats and mere minutes spent paralyzed, staring at the telephone pad. Here was a clear example of environment—one I created myself—beating genetics. But I would find no affirmation in Ebstein’s study: He found a significant correlation between shyness and the long serotonin-transporter allele, which I did not have.

  They seemed to find that the long allele of the serotonin transporter was far more common among smokers: ever-smokers (those who have ever smoked in their lives), past smokers, and current smokers. I was never really a smoker, which is why I quit so easily. “You are what the literature calls ‘a tripper,’” said Ebstein, sounding slightly amused. “There are some people who never go over two or three cigarettes a day, or a few cigarettes a week. Very unusual.” I had a slight suspicion that he was trying to comfort me for having the most common dopamine-receptor gene variant: at least I had an unusual relationship to smoking. He acknowledged that my short-short serotonin may have had something to do with my failure to become a smoker—and the lack of the “novelty-seeking” dopamine-receptor variant helped to avoid pushing me in that direction: Novelty-seeking and risk-taking seemed to be associated with smoking, at least in the Israeli population. The “novelty-seeking” allele was also found to be a risk factor for opioid dependence, when Ebstein looked at Israeli heroin addicts. My own relationship with opiates was marked by revulsion: I had undergone enough surgeries to try a variety of opiate painkillers, and I consistently chose pain over the loss of control and brain fog. Now here was an explanation: I did not have the dopamine receptor-related polymorphism that would predispose me to opioid addiction, and I had the serotonin-transporter polymorphism that predisposed me to anxiety, which made me a downer-averse control freak. This, in turn, created significant stores of Percocet and Tylenol-3 with codeine in our medicine cabinet, laying the environmental foundation of Svenya’s easily triggered heroin addiction.