The sharp edge of a genetic legacy is a fatal Mendelian disease. But this is just one of the ways that genes affect our lives. There are recessive diseases and complex disorders whose frequency is affected by ancestry. There are traits that shape our appearance, which people react to, which then shapes our reactions, feelings, and behavior. Being a creature that is formed from the genomes of two other creatures via a lottery of bits has many consequences, none of which can be completely understood without taking into account our DNA.
DNA tells us that we are creatures of chance and fate and that no one has quite the same mix of the two in his or her life. We think of ourselves as essentially whole, but when we look at our genome, we see that we are composed of many fragments stuck together. Many of our bits have different histories, and they each bring different probabilities into our lives. “Nobody is going to have a complement of alleles that is totally perfect,” Jeff Carroll observed:
There is a particularly Western tendency to think that we’re pristine or untainted . . . that we can go off and do anything we want if we work hard enough and nothing can stop us except our own efforts. It’s a really, really excellent lie for us all to believe in. But we need to know it’s a lie. . . . There are those of us that have extreme cases . . . [but] even with one of these extreme cases you can still be a useful human being and do good work.
We are also creatures of changeless truths and of interesting possibilities. Once you are born, your spot in the tree of humanity is fixed. You will always have emerged out of everything that shaped the tree before you—the biology and the history. The millions of bits that initially made you—all the cultural bits and the genetic bits, each with its risk factors, predispositions, and probabilities—were shaped by that past.
As you develop and grow older in whatever world you live in, the calculations change. Your family, the history of your community, your government, and even your food alter them. You alter them. Why not find out what the calculations are? Doing so will not guarantee that you will learn what will happen, but it may help you to consider the possibilities. Your genome is just the first hand that life deals you. How you play it is up to you.
Epilogue
During the time I’ve been writing this book I’ve met many people who have lost someone, not in the poignant, fading way that older people eventually leave us but with a sense of sudden or unnatural separation. A friend came to stay with us and told us about his father, who was born in Taiwan. He was adopted as a young boy but only discovered that fact as an adult, when his wife-to-be’s family investigated his background. It fell to his wife to tell him that the people he thought were his parents were not. Later he searched for his parents and found a woman in a small village who claimed him as her own. He sent her money and kept her comfortable until she died. His son now suspects that she wasn’t a relation at all. Our friend recently sent his DNA to two genetic-genealogy companies, expecting to be told that his ancestry was entirely Chinese, but both reported that 7 percent of his DNA likely came from somewhere else. One of them suggested the mysterious 7 percent was Polynesian.
A woman who works in the same building as I do told me that her father was left as a baby on a doorstep in England. All she knew of his parents was the name of his mother. She started to dig through records, and they sent his DNA to a genetic-genealogy company. She found a handful of women with the same name, and she narrowed the candidates to one. Every time I see her, another small step has been taken.
I met a geneticist whose parents were particularly old, something he had noticed as a child but had never really thought about. Only as an adult did he discover that his “sister” was not in fact his sister but his mother. He was raised by his grandparents.
I haven’t yet found out much about my own paternal grandfather. Since I began this book, my parents and I have slowly begun to speak about genealogy, and while it has been hard for them they have supported my desire to know. The search goes on.
• • •
One of the most interesting findings of twenty-first-century genetics is that it is not as determinative as we feared. Increasingly, however, we find evidence that cultural history shapes us more than we knew. How long can we expect the effects of culture to persist? Karla Hoff, a senior research economist at the World Bank, provides insight through her examination of caste divisions and decision making in India.
The caste system is a form of social division that dates back thousands of years. While it is thought that historically there was some flexibility for individuals to change their caste, the system has been rigidly stratified since British rule in India. Higher castes have always had more freedom, greater status, and more rights. Typically, low castes were allowed to take only jobs that no one else wanted to do, like working with corpses or cleaning toilets. High castes called the lowest of the low “untouchables.”
Untouchability was outlawed fifty years ago, and today legal differences among castes have been eradicated. Many social differences have flattened out too. Just because someone belongs to a high caste doesn’t mean he is necessarily wealthy, highly educated, or connected to his local political scene. Nevertheless social boundaries among castes continue to be vigorously policed by the community. It’s not uncommon for married couples with one high-caste spouse and one low-caste spouse to be lynched, raped, or beaten. In April 2014 a seventeen-year-old Dalit boy was beaten and strangled by a group of high-caste men because they saw him sitting in a field with their sister. Discriminatory practices and caste-based violence are still reported in 80 percent of Indian villages.
Hoff investigated how modern-day levels of group solidarity have been shaped by the caste system. She set up a number of experiments in which three individuals from either high or low castes played a game that involved cheating and punishment. She found that people in low castes were disinclined to punish anyone, regardless of which caste the cheater belonged to. People in high castes, however, were happy to punish cheaters from other castes who hurt members of their own caste. Even when wealth, education level, and participation in politics were accounted for, the caste effect was the same: The already-privileged had one another’s backs.
Hoff believed that a culture of righteous punishment and a strong group identity were passed down in the high-caste families, helping them maintain their power. Recall that high castes have had power in India for an extraordinarily long period of time, so it’s likely that these attitudes have been passed down by thousands of family groups over many centuries.
The question for a development economist like Hoff is whether these incredibly ancient attitudes can be changed. She is hopeful and described a recent study that tracked social change in India after a 1993 constitutional amendment required that in one third of all villages, the position of village chief must be reserved for women. “What they found is that in the course of just seven years, being exposed to village leaders who were women eliminated the bias men had against women leaders in evaluating them,” Hoff said. “Men still didn’t like women leaders but they didn’t evaluate their performance as leaders unfairly. Parents’ aspirations for their daughters went up and the level of domestic violence that was reported went way up, even though the village leaders have no jurisdiction over the police. Even after the reservations ended, women ran for office and were more likely than before to win elections. The results suggest the possibility of a sea change in culture.”
“If you believe that culture was a set of rules of thumb—don’t trust a woman, don’t elect a woman, don’t educate a daughter—that were very resistant to change because it was passed down in your mother’s milk,” Hoff said, “then you couldn’t make sense of this.”
• • •
The tools we now have for making sense of cultural history and the personal past are nothing less than extraordinary. If everyone had his DNA analyzed, for example, and that information were linked to everyone’s historical information, it would be the nearest
thing to the book of humanity. But should we get our DNA analyzed? There are practical considerations and potentially negative consequences. There are insurance issues, privacy issues, health issues, and questions about how the whole industry will develop. Anyone who wants to have his DNA analyzed should consider all of these factors.
In 2010 I had my DNA analyzed by the Icelandic company de-CODEme. The organization was the first to offer an in-depth personal DNA analysis over the Web. Its parent company, deCODE, is a famous innovator in genomic research. In 2013 deCODE was taken over by one of the world’s biggest biopharmaceutical companies, which is publicly traded. Presumably the company that acquired this asset must answer to its investors about how to best profit from it. At the time deCODEme stopped taking new customers.
When the company was sold, I did not receive information about deCODEme’s suspension or deCODE’s new owners. As of May 2014 I was still able to log in to see my deCODEme analysis. But it does not appear to have been updated at all. What will happen in a few years, in ten years, in one hundred? It made me wonder about what policies companies like this would follow if they changed hands. Different companies make different commitments to their users, and it is sensible to read the fine print before sending in a sample. But also consider that no matter what is said now, while any company can be shut down, your DNA sample may live on and it will point to you forever.
George Church runs Harvard’s Personal Genome Project, the goal of which is to amass a collection of complete genomes and make them—and their owners—available to scientists for research. Now any individual may volunteer his own genome to the project, and if he is accepted, he will pay to have it sequenced. Each year many PGP members attend a special conference in Boston with scientists who are eager to explore their genomes and the traits they may underlie. At the 2013 conference I saw PGPers undergo smell tests, submit bacterial swabs, and guess at the identity of well-known people. Everyone seemed to be having a great time.
Church kicked off the project with just ten volunteers. Cognitive psychologist Steven Pinker was PGP number 6. His genome is now available on the Internet, along with his medical history. “With the genome no less than the Internet,” he wrote at the time, “information wants to be free.” In 2014, he described the FDA intervention in 23andMe as regulatory overreach. “No harm can come from people knowing more about their genomes, and it’s none of the government’s business if they want to do so,” he said. PGP pioneer number 4, Misha Angrist, a professor at Duke University, told me the sense of anticipation he had that sequencing his genome was going to change his perception of himself was much greater than the reality. Now Angrist checks his genome every few months. “One thing I notice is alleles that were identified as high risk have been downgraded,” he said. “That is to be expected. As we sequence more and more genomes, we start to see these mutations that we might have thought, Well, it looks like it really messes up a protein, and in fact there are thousands or millions of us walking around with them.” He added, “It’s a reminder of how naive we are, how simple our understanding of human biology is.”
When I met PGP contributor number 3, investor and technology commentator Esther Dyson, she told me that when she had chicken pox as a child she carefully counted the spots on her face every day. Even then, she said, she was curious about the “quantified self.” What had she learned about herself from her quantified genome? In fact, it was not a great deal, she said, and this was true for most people. “It’s like learning American history, you may not learn a lot about yourself individually but you learn a lot of context,” she explained. “To be an educated person, this is the sort of stuff you should know . . . You will understand things better.”
As an afterthought, she added, “Actually, I have one APOE4, so I have double the normal chance of getting Alzheimer’s. But honestly it hasn’t changed my life; it hasn’t changed how I think about things. I’m well aware I’m going to die someday, and everything else really is detail.”
Church told me that early in the development stage of the project it became clear that it would be impossible to guarantee the privacies that are traditionally given to experimental subjects. DNA is an inescapable identifier, and we live in an age when it is virtually impossible to retract information from the public domain once it has been shared. Indeed, a 2013 study showed that using DNA data from yet another database, the 1000 Genomes Project, along with the age and location data that the project made publicly available, researchers were able to use a genealogy Web site to identify by name five people they chose from the 1000 Genomes set. Because they found the individuals’ family trees, they found their families too.
Church’s approach has been to pioneer “open consent,” which means that there is no promise of anonymity. Volunteers are counseled and vetted; they must prove they understand what is at stake before they are allowed to join.
Many people I spoke to were worried that insurance companies might obtain their genetic data and, despite the fact that most DNA is not determinative, adjust their policies in light of it. There is cause for concern. Currently in the United States the Genetic Information Nondiscrimination Act prevents health insurers from forcing customers to share genetic information, although they may request that an individual take a particular test if there is a known risk. However GINA does not apply to life, disability, and long-term-care insurance. In Britain a moratorium on making the results of DNA tests available to insurers has been extended a number of times and is currently set to expire in 2017. British insurers, however, require that when a life insurance policy over £500,000 is issued, test results for Huntington’s disease be disclosed. In Australia individuals who have taken genetic tests may be forced to give the results to insurance companies. In 2013 one company even offered its customers a discounted genetic assay. The offer was pitched as a positive way to help people look after their health, but the fine print stated that people might have to disclose the test results. Currently many European countries ban genetic discrimination, although Canada has no law against it.
Now governments are carrying out large-scale genomewide association studies to investigate common diseases and rare mutations, and the biological networking of populations will only increase. In addition to projects in the United States, the United Kingdom, and many European countries, the government of the small Faroe Islands in the North Sea, settled by Vikings in the ninth century, is planning to offer sequencing to its entire population of fifty thousand people. There are extraordinary gains to be made, but if careful regulation is not put in place, one wonders how insurance and pharmaceutical companies will treat our grandchildren if they have genetic information about them, perhaps even before they are even conceived.
Insurance aside, in the coming years we will all be reading more stories about genetics and health as the gaps in missing heredity are filled in. It’s important to keep in mind that researchers should be able to account for socioeconomic effects as well as genetic ones. Even now a number of studies have shown that what appears to be a genetic predisposition to a disease—say, type 2 diabetes—in a certain population may actually be a result either of that group’s socioeconomic situation or of a combination of genetics and socioeconomics.
• • •
As researchers advance their understanding of culture and DNA, perhaps the most exciting prospect is a larger synthesized body of knowledge that explains the way that history affects DNA and the way that DNA affects history, with both together acting on some version of us, whether our private self, our family self, or our admixed self. A recent look at the folktales of Europe used the techniques of population genetics to study their distribution. The researchers found that stories cluster geographically in the way that genes do and that you can determine language and ethnic boundaries by the different versions of a tale. In fact, the effects of geography and language boundaries were stronger for stories than for genes, meaning that genes overlapped between groups in a more fine-g
rained way. As far as mixing goes, it looks as if it is typically easier for two people to mix their genes without many words in common than it is for a story to be passed through a language barrier. Or, as Razib Khan, a geneticist and science blogger, put it, culture is chunky, whereas genes are creamy.
Now that we can see so much more clearly what has been passed down to us, what will we choose to hold back, what will we send further down the line, and how will we pass that information on? We will do so in all the traditional ways, no doubt, but we also have one more method that is completely new. Noting that DNA is an extraordinary medium for the storage of high-density information, scientists have begun to explore its potential for use as a digital storage device. The first attempts to encode a trivial message with a few words in it took place at the end of the twentieth century; a decade later scientists were able to lay down complex stories in DNA, including Martin Luther King’s “I have a dream” speech, a scientific paper, and, of course, Shakespeare’s sonnets. Rather ingeniously this new technique may yet add more layers to the palimpsest of DNA.
ACKNOWLEDGMENTS
With admiration, thank you to Misha Angrist, Andrew Appleby, Tony Arthur, Gil Atzmon-Druze, Holly Choon Bachman, Barbara Barandun, Nola Beagley, Alan Bittles, Blaine Bettinger, Cinnamon Bloss, Sir Walter Bodmer, Baiying Borjigin, Jeff Carroll, Stanley Chang, George Church, Anna DiRienzo, Peter Donnelly, Eric Durand, Esther Dyson, Eran Elhaik, Eric Ehrenreich, Jim Ericson, Yaniv Erlich, Edward Farmer, Ellen Gunnarsdóttir, Marc Feldman, Cassandra Findlay, Jill Gaeiski, Ivy Getchell, Leanne Goss, Robert C. Green, Bennett Greenspan, Colin Groves, Helen Harris, John Hawks, Brenna Henn, Karla Hoff, Evan Imber-Black, Dan Jones, Turi King, Damian Labuda, David Allen Lambert, Andrei Lankov, Stephen Leslie, Donald MacLaren, Joe Mauch, Janet McCalman, Gavan McCarthy, Michael McCormick, Rhonda McClure, Glynis McHargue Patterson, Robert McLaren, Garry McLoughlin, Geoff Meyer, CeCe Moore, Joanna Mountain, David Murray, Leo Myers, Paul Nauta, David Noakes, Robert Noel, Nathan Nunn, Paul Nurse, Katy Oh, Peter Pan, Nick Patterson, Steven Pinker, Ugo Perego, Peter Ralph, David Reich, Mark Robinson, Thomas Robinson, Wendy Roth, Jacqueline Ross, Kevin Schurer, Richard Scott, Leonie Sheedy, Guido Tabellini, Shelly Tardashian, Jay Verkler, Nico Voightländer, Jennifer Wagner, Leonard Wantchekon, Bruce Whinney, Sloan Williams, Wayne Winkler, and Scott Woodward.
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