My Beautiful Genome

by Lone Frank

  This sort of thinking stands in stark contrast to the current view that is expressed in all the stories about DNA piracy. In fact, as Vorhaus and I are standing here, debating visions of the future, a relevant case is being hotly discussed in the media. It involves a group of Native Americans in Arizona, the Havasupai tribe, which has received handsome compensation for the use researchers made of tribal members’ DNA, without their clear consent.

  In 1990, a number of Havasupai voluntarily donated their DNA to researchers at Arizona State University, who were looking for genetic causes for the tribe’s vastly increased risk of diabetes. The scientists found no diabetes genes. However, the donated material was later used for other projects. More than a dozen scientific articles, on topics ranging from the genetic causes of schizophrenia to the descent of Native American populations, were published. It was the latter studies that, many years later, the Havasupai especially resented. Genetic analyses show that the tribe, like many other Native Americans, originally migrated from Central Asia. But this was an affront to the Havasupai’s creation myths, which state they originate from the area, at the bottom of the Grand Canyon, where they still live today. The genetic data didn’t just rock their spiritual identity; the Havasupai also depend on revenue from tourists who visit the canyon and buy souvenirs tied to the tribe’s origins.

  In newspapers and blogs, the sympathy is for the Havasupai. And it’s spelled out in capital letters that researchers may not touch a DNA sequence without getting the donor’s informed consent for every thread of research they pursue with it. But apart from the fact that this is not practical from the point of view of science, in which a study may ask one question yet find an answer to another, is this a reasonable starting point? Is anyone’s DNA, in this sense, his or her own? Couldn’t you argue with just as much right that the information in the double helix belongs to the larger common human heritage? And that no individual has a right to stop it from helping others?

  “You should think of your genome like it was a cell phone,” George Church says suddenly. He has been casting longing looks toward the buffet but decides to add his two cents to the conversation. “Imagine that everyone bought a cell phone and just walked around looking at the shiny thing but never gave their number to anybody, because they were afraid of getting unpleasant calls,” he continues. “It doesn’t work, right? Telephones, fax machines, e-mail, and that sort of thing are only useful if you share the information, and the same holds true for genetic information. Ideally, everyone should be a part of one genome project or another.”

  Before sheer enthusiasm gets the upper hand, I recall that the interest is still quite limited out there among “everyone.” The publicity juggernaut 23andMe has thirty thousand customers, George Church’s Personal Genome Project has fifteen thousand people in line, and deCODEme boasts fewer than ten thousand clients. In other words, we are far from anything that resembles the market for mobile phones or e-mail.

  “I think we will see a turning point when it suddenly becomes popular and catches on,” says Church, who seems to be considering when this point might come.

  “Everything that is not about disease can make the difference. If there is anything people are seriously interested in, it is behavior, personality, and brain function. These are things that the Personal Genome Project will make it possible to delve into. The participants will soon undergo tests of cognition and social function,” Church relates, reaching for a mini croissant after all.

  I am inclined to believe that he has a point. Until now, personal genetics has largely been sold and served up as something that concerns health. Of course, health is important, but when it comes down to it, our diseases and infirmities are not really the most interesting thing there is about being human. All the physical stuff is rather a base. It needs to be in order, but you don’t really get turned on by that.

  Where it really gets exciting is at the intersection between the shell of a physical being and the person we recognize as human. How do we get from genes to what we call, for lack of a more scientific term, the soul?

  5

  Down in the brain

  Whenever you can, count.

  FRANCIS GALTON

  WHAT IS THE most interesting subject in the world? For all of us, it’s the same thing – ourselves. Me. And one of the most tantalizing questions is: How did I become who I am? Its answer is naturally linked to genetics, to the biological heritage that shapes our psyche, mindset, and, ultimately, our life. Is life’s trajectory plotted out on a predetermined course, or do we have the capacity to direct it in accordance with our iron will?

  “My temperament, my view of life, my personality – genes can’t possibly be involved in all that. It’s just not true!” Thus spake a female artist I met in Los Angeles. Her eyes widened behind a pair of trendy, heavy-framed glasses. She simply couldn’t reconcile herself to the idea that she herself was not the absolute sovereign of who she was; she felt in her soul that she was completely free to choose. That one’s ethereal psyche was not shaped by wet, sloppy biology but by education, experience, environment – not nature, in other words, but nurture. “It’s about who I am – it’s not something physical,” she said.

  Yet the thing is we are physical. We do not experience the world as it is but as it appears after being filtered through hundreds of billions of cells in our brains. The way these cells communicate with each other and thus react to external stimuli is, in part, determined by genetic specifications. Admittedly, the brain is so complex that its structure is not merely determined by our genes; we can see this in studies of identical twins, who are usually genetic clones but do not have completely identical brains. Regardless, genes help define the development and function of the brain, cell by cell, throughout your life. Busy receptors pass on a steady stream of nerve signals; growth factors govern the ongoing reconstruction of the brain’s architecture; enzymes take care of metabolism. The availability and efficiency of all the brain’s leading actors are specified by genetic information.

  “That genes strongly influence how we act is beyond question,” an article in Science states, before rolling out a history of the genes that have been closely studied for behaviors ranging from aggression and depression to infidelity and lousy love lives. To judge from the coverage in the major scientific journals, the field of behavioral genetics is the place to be.

  This has not always been the case. Exploring the genetic basis for how people think, feel, and behave was unpopular for quite a long time. For decades, the discipline was connected with a queasy-making stretch of science’s history. The stench of eugenics and genocide clung to behavioral genetics like cigarette smoke to a wool sweater.

  It all started with Darwin’s cousin. The British anthropologist and all-around intellectual Sir Francis Galton read Charles Darwin’s works on the evolution of species with enthusiasm and immediately called his kin’s attention to his belief that human mental faculties must be subject to the same laws as their physical characteristics. Intelligence and character must be heritable. To explore this intuition, Galton investigated the traits of many of the relatives and descendants of Victorian Britain’s most prominent and highly gifted men. By tracing family trees, he observed that there were many more “eminent relatives” in the families of geniuses than in the general population, but that the number of highly gifted people fell the further away in relationship you moved from the genius himself. Heritability jumped out at him, an indisputable fact.

  Galton described his observations in his book Hereditary Genius, published in 1869, a mere decade after Darwin’s foundational On the Origin of Species. In the following years, Galton pondered how his insight could be put to use. In 1883, he found his solution: the concept of eugenics. In his Inquiries into Human Faculty and Its Development, he proposed that British society get its act together and find some incentives to encourage the especially gifted to have more children and, thus, spread their desirable qualities among the population.

  An intelle
ctual heir to Galton was the American biologist Charles Davenport, who in 1910 founded the Eugenics Record Office at the nascent Cold Spring Harbor Laboratory. The early twentieth century saw research on heredity begin to blossom, through experiments with fruit flies and other similarly amenable animal subjects. Inspired by his experiences in the lab, Davenport turned Galton’s idea on its head, so to speak: instead of encouraging the breeding of more good qualities into the population he advocated preventing the spread of bad ones. Davenport was worried about society’s general welfare, and he especially wanted to cure the ills that came in the wake of caring for the mentally retarded, the psychotic, and the addicted. Such individuals must harbor “bad” traits and if they could be prevented from passing them on, they would disappear from the population.

  Davenport’s program was immediately and eagerly implemented throughout the civilized world. In the United States, “inferior” ethnic groups were precluded from immigration for eugenic reasons, and in many European countries, so-called “cretins” were forcibly sterilized. The movement reached its grotesque crescendo with the Nazi extermination of Jews, Gypsies, homosexual men, the mentally ill, the mentally handicapped, and other “asocial elements.” It was this catastrophe that, after World War II, relegated genetic tinkering to the graveyard of ideologies.

  But out in the trenches of research, a more vibrant and enlightened understanding of the interplay between nature and nurture gradually arose and, after the discovery of the structure of DNA, studies based on a scientific approach and method flourished. Inspired by Galton’s original work, people began to investigate the question of the heritability of mental traits and psychiatric illnesses by studying twins. Since then, twin studies have become a fundamental tool of quantitative genetics, a branch of genetics focused on establishing whether a trait has a genetic component and, if it does, how great that component is.

  Heredity, or rather the degree of heritability, can be difficult to pin down. It is not a number that applies to an individual but to an average in the population. If you can ascertain, for example, that height is ninety percent determined by heredity, this does not mean that ninety percent of my five foot eight-inch frame is determined by my genes and the rest by my diet and general state of health. On the other hand, it does mean that ninety percent of the variation in height you see in the entire population is due to the genetic variation found between individuals in the population.

  In mathematical terms, the heritability of a trait is the part of the variance in the trait under investigation that can be ascribed to genes. Twin studies try to estimate this component in various ways. One is to compare a given trait in identical twins who have been separated since birth and so have identical genes but carry the baggage of completely different environmental influences. If the trait varies, it cannot be explained by genes alone. Using statistical methods, scientists can deduce how much influence is due to environment and genetics respectively. Another approach is to compare a trait in identical twins, on one hand, and fraternal twins (who only share half their genes), on the other. Again, the difference between the two groups can be used to calculate a measure for the heritability of a trait.

  Twin studies are not without their critics, particularly because the precise methods and mathematics behind them are always under development and up for discussion. Can you allow yourself, for example, to assume that the environment of twins is identical just because they are born at the same time and grow up in the same place? Depending on which mathematical trick you use to correct for that sort of question, you have to face the fact that studies of the same trait may provide different numbers for heritability. Still, this does not alter the fact that the method is an excellent tool for assessing heritability.

  If you look at schizophrenia, for instance, you can determine how frequently twins, whether identical or fraternal, are struck by the illness. If there is a genetic component to schizophrenia, you would assume that more often both identical twins would be affected than would fraternal twins. And indeed, the statistics reveal quite plainly that if you have an identical twin who is schizophrenic, your risk of getting the disease is fifty times higher than the general population’s. If you have a fraternal twin or another sibling with schizophrenia, your risk is five times the general population’s. When these numbers are translated into the equations of quantitative genetics, scientists are able to conclude that schizophrenia is up to eighty percent determined by genes.

  The idea that diseases have something to do with “faulty” genes is quite digestible for most of us, but many people have difficulty in accepting that their own, quite normal psychological traits also draw directly upon their DNA. Nevertheless, this seems to be true. Over the decades, again and again, twin studies have indicated that there is some degree of heritability in pretty much every psychological or mental trait and in every possible type of behavior. Even in cases you might not at first believe have anything to do with DNA. The American psychologist, Eric Turkheimer, of the University of Virginia, has therefore proposed what he calls the first law of behavioral genetics: that “all human behavioral traits are heritable.”

  Take intelligence, one of the most intensely studied phenomena. We are infinitely fascinated with this trait: how we measure it; how we compare to one another in intelligence; whether we excel in one sort of intelligence rather than another. People have fought about and scrutinized the very meaning of “intelligence” for centuries. As it turns out, intelligence, as codified in the standardized test for IQ, appears to be one of the most heritable of normal traits. It looks as though eighty percent of the variant in IQ among adults may be ascribed to genetics. Another mental faculty, memory, is also partially inheritable, but here the rate slides down to around twenty percent.

  WELL, YOU MIGHT be thinking, in these instances we’re talking about mental ability – that is, a quality that can, to a degree, be traced back to the mechanics of the brain and how well it functions: it is almost too obvious that mental ability must be partly physical. But even particularly complex behaviors, and other “soft” characteristics we often chalk up to psychology or sociology, also display a surprising degree of heritability.

  Consider, for example, “compulsive hoarding.” The need to fill your house with Christmas elves, vintage comic books, or beer labels is, apparently, distinctly genetic – at least, that is, in women. In 2009, a major study involving over four thousand female twins came to the conclusion that the heritability was nearly fifty percent. Having a hard time understanding the collector’s itch? Well, the degree of empathy you are capable of has been shown, in scores of twin studies, to have a heritability of between thirty and fifty percent. And your level of religiosity is not simply foisted on you through parental preaching and regular churchgoing. In a major comparative study of a number of populations published in 2005, researchers at the University of Minnesota concluded that your tendency to be religious or spiritual is over forty percent heritable.

  In the political sphere, a small group of social scientists, many based in the United States, has turned to genetics to expand their explanatory models, since humans are biological beings, after all. Among the pioneers are “the two Johns,” John Alford of Rice University in Texas and John Hibbing of the University of Nebraska-Lincoln, who in 2005 found evidence of heritability in our fundamental political attitudes. Whether you are conservative or liberal is not just a question of parental influence and environment but also genetics. The researchers asked American and Australian twins a battery of questions about the extent to which they were for or against hot-button political issues such as gay rights, the death penalty, and school prayer. They found identical twins had a far higher rate of replying identically than did fraternal twins – so much so that it appears holding liberal or conservative values is forty percent heritable.

  Alford and Hibbings’ study was controversial, a call to arms for a new area of research carrying the unattractive name of genopolitics. For the past few years, the field has been le
d by the young and ambitious James Fowler of the University of California, San Diego, who advocates an amalgamation of sociology and genetics into a “new science of human nature.” As a result, he has been bestowed with superlatives such as “most original thinker of the year.” In 2008, two studies of voting behavior, made on the basis of the voter registration records of eight hundred sets of American twins, found that heredity played up to a sixty percent role in whether people went to the voting booth or stayed on the sofa. A year later, Fowler showed that genetics also plays a role in whether you are a loyal adherent of a political party, independent of which party.

  Some observers balk at such findings, wondering how genes can possibly have any significant influence on a behavior that is a modern invention and not the least bit “natural.” Nonsense, Fowler replies. If you peel away all the trappings of political slogans, polling booths, and the like, political behavior is about our attitudes toward cooperation and social exchange – human inclinations that were very relevant to our survival in the Stone Age. Fowler imagines the genes that play a role in politics are the genes that have long regulated our social behavior and taste for working in groups.

  Fowler admits that tying a gene to a prehistoric behavior involves a lot of assumptions. For that reason, he is not satisfied with the sorts of details that can be gleaned from twin studies. In a way, twin studies correspond to flying around at thirty thousand feet observing the landscape. You can see something is growing in the fields below and register that it is green, but there is no way to tell whether it is wheat or barley. Similarly, the fact that there is something hereditary at play does not tell you what is hereditary, that is, what biological mechanisms are involved.