DNA USA

by Bryan Sykes

  Over the weekend, true to her word, Joanna Mountain had contacted a small selection of friends who had already seen their chromosome portraits, so Ulla and I set about meeting as many as possible. On Monday we were heading down 101 again toward Palo Alto and the hallowed halls of Stanford University. One reason for 23andMe to be located in Mountain View was its proximity to Stanford and the genetics powerhouse it had become under the leadership of one of the true Olympians of genetics, Luca Cavalli-Sforza. It was he who had carried the torch for population genetics from the time of the blood-groupers in the 1950s right through to the modern DNA era. Although I had not always agreed with his conclusions, there was no doubting his pioneering contribution both in research and in writing some of the most influential textbooks. Two of these were my introduction to the field of population genetics and have pride of place on my bookshelf. Practically everyone in the field had been through Cavalli-Sforza’s laboratory at one time or another, including Joanna Mountain and my appointment that day, Dr. Roy King.

  We drove through the neat main street of Palo Alto and under the arch that joins it to the Stanford campus. This was not a crowded campus of the sort that are all too familiar in England, with buildings tacked on one by one as dictated by the ebb and flow of funding but without any sense of architectural continuity. This was a Tuscan town transplanted from Italy and then nourished in the warmth and prosperity of California. Piazzas flanked by round-arched colonnades, with palm trees shading students reading and talking on the grass. No wonder Luca Cavalli-Sforza, who was born in Genoa in northern Italy, felt so much at home at Stanford.

  Ulla and I made our way to the Psychiatry and Behavioral Sciences Building for our meeting with Dr. King, a psychiatry professor there. If I had been a patient suffering from depression, King’s specialty, the mere encounter would have taken me halfway to a cure. He was fast-talking, his sentences peppered with bouts of infectious laughter, as he led us to his office on the first floor. King is an African American with short grizzled hair and beard and laughing eyes behind steel-rimmed glasses. Once inside his office he explained that he was from Nashville, Tennessee, where his mother had been teaching biostatistics at Meharry Medical College. Meharry is one of several institutes for higher education founded by religious groups from the North after the Civil War to encourage the enrollment of former black slaves. It still has a largely African American faculty and student body, and is one of the major educators of black physicians in the United States. There she met King’s father who had recently returned from fighting in World War II and was enrolled as a medical student. King’s grandfather, his mother’s father, had been a math professor at Fisk University, also in Nashville, and another of the institutions founded during the Reconstruction era to cater for African Americans. His father, King’s great-grandfather, had been a poet, one of the very first to write in the vernacular, and his father, King’s great-great-grandfather, had written a diary during the Reconstruction period that was now lodged in the Library of Congress. So on King’s mother’s side there was a direct line back to the South and the difficult years that followed the abolition of slavery.

  In complete contrast, his father had been born in New York and been adopted by the King family. Nothing was known about his father’s family until, much later, King and his mother traveled to New York and traced his father’s birth certificate. The certificate showed that his mother was an African American with the surname Coleman. Unusually for a couple who were not married, the certificate also named his grandfather. To King’s complete surprise his grandfather’s name was Maurice Ginsberg, almost certainly a surname with an Ashkenazi Jewish origin. This was the first sign of an ancestry about which King knew nothing. Growing up in Pennsylvania during the late 1960s, when there was still plenty of discrimination, King recalled that he had many Jewish friends. He played golf with some of them at the few courses that allowed blacks and Jews to play. So, before he had his chromosome portrait painted, he knew that at least a quarter of his ancestry was European through his grandfather Maurice Ginsburg. But when he pulled the portrait onto his computer screen, the full complexity of his ancestry was there in green, blue, and orange. Other than demonstration portraits that MacPherson had showed me, this was the first time I had been able to look in close detail at the chromosome portrait of an African American.

  My first impression was that it was very colorful, and a lot more interesting than my own almost completely monochrome equivalent. There was about as much blue as green, but with a good sprinkling of orange as well. In fact there was slightly more blue, which indicated that Roy had more European ancestors than he did African. This was considerably more than the 25 percent coming directly from his Ashkenazi Jewish grandfather and, when Roy first saw it, had taken him completely by surprise. I asked how it got there, and he acknowledged that one reason was that, in the late nineteenth century, one of his black ancestors on his mother’s side was raped by a drunken white man when she was thirteen or fourteen and became pregnant as a result. This was the first time I had come across this explanation for the European component of African American DNA, but it was not to be the last.

  I hesitated to ask King a more difficult question, but then I thought, He’s a psychiatrist. He can take it. I wanted to know whether his chromosome portrait, particularly the higher-than-expected European ancestry it had revealed, had influenced how he thought about himself. Sure enough he was not fazed at all, and had already thought about this. He explained that he had grown up at a time when “embracing your African roots” was becoming publicly acknowledged, a time when African American youths did not want to learn anything about European history or culture. He just did not think it had anything to do with him. He only really woke up to his European heritage when he found out that his grandfather was Jewish. His Y chromosome is typical of Ashkenazi Jews, and, like Bennett Greenspan’s customers from Family Tree DNA, King has since become interested in Judaism and Jewish culture.

  Though he trained as a physician, King had always been fascinated by archaeology and was able to indulge this interest when he took a temporary teaching position at Stanford’s outpost in Florence, Italy, for a year. His wife, an art historian, was especially interested in the female figurines of the Neolithic period that are to be found all over Italy and Sardinia. Oddly enough it was this that later drew his attention to genetics, when he read a paper in Science about the geographical spread of Y chromosomes in Europe and thought he could see a congruence with one particular haplogroup, J, and the figurines. When he read the long list of authors he realized that some of them worked less than a mile away in Cavalli-Sforza’s laboratory on the same Stanford campus. He was at the point in his long career in psychiatry when he wanted to add something else, and genetics became that other dimension. Before long he was working with Peter Underhill, the Stanford scientist who has done so much to discover the genetic markers along the Y chromosome, and publishing on the genetics of the eastern Mediterranean. Only when he tested his own Y chromosome did he realize that it had come from that part of the world through his Jewish grandfather. Was this a coincidence, I wanted to ask, or was it his DNA that had somehow drawn King to feel an affinity for that region? Now we were entering the realm of the Jungian collective unconscious, but I thought once again, He’s a psychiatrist. He can take it. “Mmm, it’s possible, I suppose,” came the noncommittal reply.

  While King might have been feeling the homing instinct of his Y chromosome, he certainly agreed that his mitochondrial DNA was pulling him toward West Africa. Like many African Americans, he is a member of the Lingaire clan (L3D), which is found predominantly close to the Atlantic coast of Africa around Senegal. Even before he knew that, he had discovered an affinity with African art, but just not any African art, only art from that region. While he was an avid collector of the colorful abstract paintings from far West Africa, and with examples on the walls of his office, he had no interest at all in pieces from Central or Southwest Africa. Was this just chance or an
unconscious affinity passed on through his DNA?

  There was time for one final coincidence before it was time for us to go. King had used publicly accessible DNA databases to discover an exact mitochondrial match with a man from Togo, which is farther around the Gulf of Guinea from Senegal. He had an unusual surname, Agboto, and when Roy Googled the name he found only one match for it in the entire United States. It was a professor from Togo who was teaching biostatistics at Meharry Medical School, just as his mother had done fifty years previously. “Spooky” said King and, with that, our time was up.

  The next day, leaving our sanctuary of the airport hotel, Ulla and I joined the 101 once again, but this time heading north toward San Francisco. Our destination was San Francisco General Hospital, where we were to meet with another of Joanna Mountain’s nominees, Esteban Burchard. Like Stanford, the original style of the hospital was Italianate, with several handsome five-story buildings of multicolored brickwork topped by blind arches. More Venice than Tuscany. But that was where the similarity ended. There were no lazy palm-fringed piazzas here. We were in a poor neighborhood and since it was a public hospital, the patient base was largely made up of Americans without health insurance. As we pushed our way through the crowded lobby, the patients queuing for attention were mainly black or Latino. San Francisco General had been the first to treat AIDS patients in the early 1980s. This was well before the disease was understood, and it was the first hospital to witness the epidemic of rare skin tumors, Kaposi’s sarcoma, and the unusual lung infections that were the first signs of the immunodeficiency that marked the insidious advance of the retrovirus that caused it. As Burchard explained as he showed us the very ward that took in the first patients, being in a public hospital, the physicians give their time for no financial reward, supporting themselves instead by research grants through UCSF, the University of California, San Francisco, where he also teaches.

  Esteban is a pulmonary physician and an expert on asthma. Mountain had recommended that we meet because in his research Burchard had been using the chromosome paintings to try to understand the very different frequencies of asthma in blacks and Latinos. In fact, his interest in the way gene pools blended went much further back, and he had been a principal author on several important scientific papers on the impact of race and ethnicity in clinical practice that I had read. He had experienced more than his fair share of adverse reaction to his claim that there were genetic differences between races, something that professional geneticists had tried to play down for fear of being condemned as eugenicists. I have said, and written, in the past that my research with mitochondrial DNA showed that race has no genetic basis, but now I think that was an oversimplification. Researching DNA USA has given me the opportunity to consider far more closely what this statement means, as I will explain later.

  Of all my meetings this one was going to be the most directly related to my old life in medical genetics, and there was a pleasurable familiarity when Esteban began to tell me about his work on asthma. For a start he knew Bill Cookson, a colleague from Oxford, the irrepressible Australian scientist and author of The Gene Hunters, who had been searching for “the asthma gene” for as long as I can remember. Both Burchard and Cookson had begun their hunt in the days when, inspired by the triumphs of single-gene disorders, scientists thought there was bound to be only one asthma gene, only to find that their holy grail was a mirage, a goal always just over the horizon. The frustrating truth is that, like so many of the common diseases with a genetic component, there are many genes involved in asthma, with no single one of them having an overwhelming effect. There are many ways to look for asthma genes, and Burchard chose to approach the task by trying to understand the reasons why the incidence varied so much between different populations in America. Asthma is far more frequent in Puerto Ricans than in Mexicans, and reasoning that this difference has something to do with their gene pools, he began to look in detail at the genetic structure of both populations. That is how he came to work with Joanna Mountain and to admire her chromosome portraits, although he had already done a great deal with the AIMs we have already mentioned.

  It wasn’t long before we were sitting at his computer to have a look at his own chromosome portrait. Like Roy King’s, it was a colorful mosaic of the three principal colors—green, orange and blue. But the overall color scheme was very different. Instead of King’s mixture of African and European with a bit of Native American thrown in, Burchard’s portrait was predominantly Native American and European, with a touch of African. Although Esteban had been born and brought up in San Francisco, both of his parents are Mexican, which explains the orange segments in his chromosome portrait. Like Native North Americans, Mexicans are also descended from the first people who crossed into America from Asia. Burchard had already known that his DNA was a mixture of all three from his AIMs work, although the precise proportions were slightly different from those revealed by his chromosome portrait. Like me, he really liked the visual impact of the portraits and, also like me, saw how they dissolved the anxieties associated with the brutal arithmetic of the AIMs evaluations. AIMs were fine for the kind of large-scale studies that Burchard had carried out in Puerto Rico and Mexico where he was after averages, but far less appropriate for individuals.

  I asked what the effect of seeing his own chromosome portrait had been. He was slightly surprised by the amount of European DNA he was carrying, about 40 percent, and assumed, with no obvious disappointment, that his distinctly European Y chromosome had originally come from Spain. This is a common finding among Mexicans, where mitochondrial DNA usually reveals a descent from one of the Native American clans, while among Mexican men more than half carry a European Y chromosome. This is yet another example of the disproportionate genetic input of European men, this time stemming from the Spanish colonisations beginning in the sixteenth century. What meant most to Burchard was the 7 percent of his DNA that was African. Having done a lot of his asthma work work among African American communities in Puerto Rico and Boston, he now felt far more closely connected to them and to their struggles against the discrimination they faced. He reflected that had he lived a few generations before, during the days of the Jim Crow “one-drop” rule, where even the tiniest fraction of African ancestry meant you were relegated to a life outside the Caucasian mainstream, his life would have been utterly different as a result of the smudges of green in his genetic portrait. As it was, he now felt much more at home with his African American asthma patients. Their response to his newly revealed African ancestry was one of two alternatives: “No wonder we liked you” or “No, you’re not.”

  There were a few more people that I wanted to see in the Bay Area, but they would not be available for another week, which meant a bit of rescheduling. The original plan, such as it was, had been to make the return journey to the East Coast by train from Los Angeles to New Orleans, then to Washington after a few days in Atlanta, Georgia, which I had wanted to visit to get a flavor of the South. If we were going to stick to that itinerary, we could not wait another week in San Francisco. Ulla and I went down to the hotel lobby once more to think about it. As well as hosting the normal tourist guests, the hotel was also a thriving conference venue with labeled delegates arriving from all over the United States. One day it was a big travel company, the next it was the sales force from Victoria’s Secret. That day it was the turn of a well-known pharmaceutical company. We were seated at a table on a sofa with another one at right angles and, presently, two young women, both African American, sat down next to us. They were laughing and joking and, quite soon, Ulla slipped herself effortlessly into the conversation. I sat there smiling mildly in a professorial sort of way until the usual “Where are you guys from?” routine was over. I didn’t usually listen to the opening moves, but this time I could not help overhearing that the pair was from Atlanta. By the time I was properly introduced, they were eager to know more about the research—and I was eager to oblige—especially given where they were from. So that is how we
encountered “Mildred Pierce” and “Ned Land.” (By now I was running low on available and gender-appropriate Hollywood pseudonyms for my volunteers, and women were having to adopt masculine monikers.)

  “Mildred” and “Ned,” it transpired, were both colleagues and friends. “Mildred” was a production manager, while “Ned” was a corporate lawyer in the legal department. The conference was over, so they were relaxing before their flight back to Atlanta the following morning. Both had been born and brought up in the South, and both, as far as they were aware, had only African American ancestors. They knew that their ancestors had worked on the plantations and had no idea where in Africa they might have come from. They were glad to have a DNA test, so we withdrew to one of the booths, and moments later the samples were taken and soon on their way to the lab. Meeting “Mildred” and “Ned” had been a delight, but it also meant that we would not miss out completely if our new schedule left no time for a visit to Georgia. If we could not get to Atlanta, then in a way Atlanta had already come to us. This also gave us enough time to meet everyone Mountain had suggested and fit in a side trip to Houston to visit Bennett Greenspan, the founder of Family Tree DNA.