Friday, July 10, 2015
The Roving Reporter : Mixed up Brothers of Bogota -----#3
The Myth of Identical Twins
At the moment that a sperm penetrates an egg, that single-cell zygote is what is known as totipotent: It is pure potential. It has in it the makings of an eyebrow’s curve, a heart’s thick muscle, a neuron’s electrochemical power; it has in it the finicky instructional manual that will direct the building of the body’s every fiber and the regulation of those fibers. But that one cell splits into two, and instantly, lights begin to go out, potential dims. In order for that one cell to become a tiny bit of flesh in a heart, and not the hair of an eyebrow, one or more of its genetic signaling pathways must shut down. The result is differentiation, a steady process of elimination that allows complex biological universes to be built. Every time a group of cells divides, each one becomes more like one thing, less like another.
By the time that embryo is five or six days old, which is when a majority of fateful twin splits occur, some of those cells, by chance, go to one twin and some to the other. This means that the expression of some genes in one of those future twins is already, in subtle ways, likely to be different from the expression of genes in the other future twin, theorizes Harvey Kliman, the director of the reproductive and placental research unit at the Yale School of Medicine. From the moment that most identical twins separate, they may well have different epigenetics, a term that refers to the way genes are read and expressed, depending on environment. They are already different products of their environment, the environment being whatever uterine conditions rendered them separate beings in the first place.
The casual observer is fascinated by how similar identical twins are, but some geneticists are more interested in identifying all the reasons they might differ, sometimes in significant ways. Why might one identical twin be gay or transgender and not the other? Why do identical twins, born with the same DNA, sometimes die of different diseases at different times in their lives? Their environments must be different, but which aspect of their environment is the one that took their biology in a different direction? Smoking, stress, obesity — those are some of the factors that researchers have been able to link to specific changes in the expression of specific genes. They expect, in time, to find hundreds, possibly thousands, of others.
The meta-analysis published this spring in Nature Genetics, which examined 50 years of studies of twins, arrived at a conclusion about the impact of heredity and environment on human beings’ lives. On average, the researchers found, any particular trait or disease in an individual is about 50 percent influenced by environment and 50 percent influenced by genes. But that simple ratio does not capture our complicated systems of genetic circuitry, the way our genes steadily interact with the environment, switching on, switching off, depending on the stimulus, sometimes with lasting results that will continue on in our genome, passed to the next generation. How an individual’s genes respond to that environment — how they are expressed — creates what scientists call an epigenetic profile.
Before she left for Bogotá, Segal contacted Jeffrey Craig, who studies epigenetics at Murdoch Childrens Research Institute in Australia, to ask if he would analyze the epigenetics of Carlos, Jorge, Wilber and William, using saliva swabs she would obtain while she was there.
Craig has analyzed the epigenetic profiles of 34 identical and fraternal twins at birth, collecting swabs from their inner cheeks. To Craig, it was noteworthy that in some cases — not many, but some — the epigenetic profile of one newborn twin was more similar to an unrelated baby than to the identical twin with whom that baby shared a womb. Structural differences in the womb could possibly account for it, Craig says — a thicker umbilical cord for one than the other (there are, in fact, two cords) or an awkward site of connection for the umbilical cord on the placenta. But he recognizes that there could be additional factors still in the realm of guesswork. Perhaps one twin is farther from the sound of the mother’s heart, its reassuring steady beat, sending that child on a slightly different life course.
Segal and Craig were eager to see the epigenetic results for the Colombian twins. Whose epigenetic profile, they wondered, would look more alike? The biologically unrelated twins who shared an environment — Segal calls them virtual twins — or the ones whose DNA was the same?
A sample of four subjects could only raise questions, not answer them. But epigenetic testing on larger samples of twins reared apart could one day provide a valuable resource for epigenetic science, says Kelly Klump, who is the co-director of the Michigan State University Twin Registry. ‘‘You can’t look at how the environment will change the function of the genome without holding constant the genome,’’ she says. ‘‘Identical twins allow you to do that.’’ Given how hard it is to find identical twins raised apart, twins researchers working in epigenetics have mostly been focusing on the identical twins who show difference. Tim Spector, a professor of genetic epidemiology at King’s College London, is generating a huge global registry for identical twins in which only one twin has, for example, diabetes or autism.
Bouchard was influential in convincing his fellow researchers, as well as the public, that some significant part of who we are is influenced by DNA, which was hardly a given when he started his work. Spector and Craig, by contrast, are trying to identify how, exactly, we change in response to the environment. Their essential question is different: How can science identify genes that have been flicked on or off, with potentially harmful results, so they can be switched back the other way? Traditional twin studies were perceived to be seeking the immutable; epigenetic twin studies try to clarify what, in us, is subject to change — and more specifically, what mechanisms make that change happen.
Falling Into a Hole
A local politician had accompanied the group on the hike to Santander. Along the way, he tried to persuade the group to visit a nearby attraction: the second-biggest hole in Colombia, a cavernous pit 500 feet wide and 600 feet deep. Locals like to get on their bellies, inch their way up to its rim and peer down into the abyss.
The second-biggest hole became a recurring joke among the brothers, but for Yesika Montoya, the Colombian psychologist, it also became something of a metaphor for the young men’s experience. She was trying to get them to identify their feelings about all they had gone through, partly by recalling the physical sensations that they felt at various stages. ‘‘It was vertigo,’’ Jorge told her, as he described waiting for William the first time they met. ‘‘I felt a pressure. Like when you go on the roller coaster and you’re falling.’’
Montoya imagined that feeling to be like ‘‘going down a hole and not being able to feel the bottom.’’ She added: ‘‘It never stops. And just when you have put a foot here or there, you keep going down.’’
The process of spending time with Segal and Montoya and sharing their life histories necessarily changed the young men’s experience of their reunion. Carlos seemed surprised at one point when Segal asked him to describe the ways in which he and Wilber differed. ‘‘Well, the thing is, we’ve always focused on what our similarities are,’’ Carlos said. ‘‘We haven’t actually talked about our differences.’’ He seemed pleased, at last, to be given the opportunity.
At the time, Carlos pointed out that he liked older women, while Wilber liked younger ones. But the answer was, of course, far more complicated. Carlos was like Wilber in large, sweeping ways, and unlike him in infinite small ways: the expressions that darted across his and his face alone, the thoughts and worries that filled his mind. Carlos was, for better or for worse, more cynical than Wilber, more suave; Wilber was more joyful around small children, quicker to laugh out loud.
Jorge and William, too, have obvious differences. Jorge is a dreamer, a restless traveler, an optimist who believes that ‘‘if you give your best to the world, it will give its best back.’’ William’s face, more narrow, more gaunt, reflects a far warier outlook. ‘‘Nothing in life is easy,’’ he remarked once, a sentiment that you could hardly imagine Jorge expressing.
Carlos could feel Jorge drifting toward his identical twin. It was making him feel lonelier than ever.
Was every one of these differences learned? Did some reflect different epigenetics? Perhaps there might be some extra biological protection built in for Wilber and Jorge, who, unlike Carlos and William, had been raised in their biological mothers’ arms. The mother who raised Carlos loved him, he knew. But he was also aware that a cousin had moved in with them when they were babies, expressly so that each child could be the beneficiary of the form of attachment parenting the hospital was encouraging at the time. Their mother wore Jorge in a sling; it was the cousin who wore Carlos.
In May, Carlos told Wilber that he wanted to visit his biological family, but without crowds of relatives or psychologists or camera crews. And Wilber passed that on to William. It was becoming easier for William to accept that Carlos’s reserve on those excursions to Santander was not so much in reaction to his new family as it was in response to the public nature of the outings. On a weekend in June when Wilber unfortunately had to work, William, Jorge and Carlos took a bus to see Carmelo and Ana for a relaxed, private visit.
Carlos sat next to William on the bus on their way up and listened as William, who had become something of a local celebrity in Santander, talked about his plans to run for City Council in La Paz. Carlos did not think much of Colombian politicians, but he was impressed by William’s ambition; he liked that William was taking a class to learn Microsoft Word. He had discovered, from the questions Segal and Montoya asked, that Wilber had no intention of returning to school. That disappointed him; he wanted to talk to Wilber about more than women. He wanted more for Wilber — wanted more from Wilber, but he was starting to think he might not get it.
Carlos knew Wilber wanted the two of them to spend more time together. But he also knew that Wilber, at some level, understood that Carlos was a solitary soul. Wilber, at any rate, had a life of his own and a new girlfriend, who had two young children whose photos he showed off, with admiration, to anyone who would look. The whole experience was less complicated for Wilber than for the other three brothers — simply because, as Wilber himself put it, he was not a very complicated person.
For Carlos, this fourth visit to Santander felt like a fresh start. The brothers arrived at Ana and Carmelo’s home early in the morning, after traveling through the night, but Carlos was enjoying the beauty of the countryside too much to go straight to sleep. Instead, he bathed in a water tank. He listened to the birds; he was a willing audience to the family parrot, Roberto, who had a talent for singing ranchera songs. Then, while his brothers dozed, he wandered into the kitchen, where Ana, a tiny woman — he had her giggle, he was told, although he never heard it that way himself — was cleaning a sheep’s head she would cook for dinner that night. He stood by the kitchen counter, keeping her company as she worked. He realized it was their first time alone.
They talked about her health, her aching joints, her back pain. ‘‘You know, you’ve worked so much your whole life,’’ Carlos told her. ‘‘It’s time for you to rest. Your children are so big already. Why do you work so hard for them?’’ The relationship with Ana felt more relaxed, but not necessarily closer. He told himself it would come in time. Jorge was always implying that there was something wrong with him for not feeling, instantly, that powerful, primal connection, that emotional force of biology and destiny, that William seemed to feel for the mother he never got to know. Carlos wondered whether he might have drawn closer to Ana had his own mother been alive to grant some kind of permission. But maybe it was simpler than that. Maybe he and William were just different that way.
Before starting her research, Segal would not have been surprised if each young man tested similarly to his identical twin, despite their different environments. But her preliminary results, she said, show that on a number of traits, the identical twins were less alike than she initially anticipated. ‘‘I came away with a real respect for the effect of an extremely different environment,’’ Segal said.
Perhaps the results merely indicate that people raised in deeply rural environments, with little education, take tests in a wholly different manner from those who attended a university. William, who managed a small business with competence, at times seemed overwhelmed by the test. But Segal considered the young men’s story a case history that might provoke further research, inspiring others to seek out more examples of twins reared apart with significantly different upbringings, whatever they were.
Over the course of the week that the young men spent on Segal’s questionnaires, they looked back at the past that helped make them who they were. How many books did they have in their childhood homes? Did they ever smoke? Did they grow up in families in which people kept their feelings to themselves? For one week, they stepped out of time to look backward. But the moment Segal would leave, they would continue on their usual paths, speeding forward toward some unknown future, colliding with chance. They sometimes talked about all living together; as four, William liked to think, they were at their strongest. Like members of any family, they might drift and then regroup, or find themselves falling back on the deep comfort of their particular bonds. It is rare to grow up as a twin at all, part of a primal pair; now each young man had a second, rare pairing, a second chance at an unusual kind of closeness. What did that kind of entanglement — a double-doubling — mean for whom they would each become or what they might achieve?
To celebrate the end of a week’s worth of research, Segal and Montoya decided to take the young men dancing one night at a popular Bogotá steak house with a big dance floor. Jorge and William took turns dancing with Segal; they smiled gamely and turned and twirled with only glancing attention to the rhythm. Carlos, in his element, showed Wilber a few steps; they danced in not-quite-synchrony, side by side, Carlos with sureness, Wilber staring down at his feet and concentrating. Occasionally he looked up, as if he was feeling it: He would get the hang of it soon enough, he knew. ‘‘Wilber has the goods,’’ Montoya said, watching from the table. ‘‘He just needs the experience.’’ When all the brothers stopped for more aguardiente, a sugar-cane based liqueur, and sat at the table, they took turns flirting with a young woman who had joined the party.
Here at the club, Carlos was assured, poised, smooth. As the evening wore on and he drank more aguardiente, his moves got bigger, more daring, until he was showing off a maneuver that he and a friend had made up one night, a pivot from the waist that had him leaning so far back that his spine was practically parallel with the floor, his knees bent and nearly buckling. Carlos called that move ‘‘the Matrix,’’ after a similar backward dodge that the movie’s star, Keanu Reeves, executes while evading bullets in a parallel universe. As he leaned all the way back, Carlos looked as if he might lose his balance altogether. Wilber, William and Jorge quickly surrounded him, still dancing, a mixture of emotions on their faces: amusement, irritation, concern. But Carlos was not falling. It only looked that way, and he managed to right himself.
The dancing went on as before. The four men seemed to bounce off one another in different pairs and groupings, splitting off in search of young women, returning to compare notes before heading out onto the floor again. They were one, they were two, they were four, merging, dividing and merging again as the music played, long into the evening.