Here Is a Human Being (38 page)

But involved in what exactly? How did genetic ancestry testing come to be and where is it going?

The consensus—both from fossils and genetic variation studies—is that modern humans originated in Eastern Africa 160,000 to 200,000 years ago.
²⁶
Some of us left Africa for Eurasia, Oceania, and the Americas 60,000 to 100,000 years ago. If you look at the millions of human SNPs that have been characterized, Africa is the most genetically diverse place on the planet. All human genetic variation is a subset of what’s in Africa. As a general rule, the farther you get from Africa, the less genetic diversity you see. Genetic differences between human populations are small; however, they are undeniably real. The more markers you look at, the easier it is to distinguish an “Asian” genome from an “African” or “European” one.
²⁷
As scientists identified more markers and typed increasing numbers of individuals from different populations, the prospect of spitting in a tube and learning about one’s genetic ancestry became less of a dowsing rod and more of a bona fide science.

Traditionally, genetic ancestry testing was based on Y-chromosome and mitochondrial DNA (mtDNA) markers. The Y chromosome is passed only from father to son. Mitochondrial DNA resides in the mitochondria, the “cellular power plants” that are thought to have evolved from bacteria. Part of this evolutionary artifact is a small circular genome that codes for just a handful of genes. It is passed only from mother to child: the spermatozoa jettison their mitochondria and therefore males do not transmit mitochondrial DNA. Y-chromosome and mtDNA markers are called lineage markers. When sperm meets egg, they do not get shuffled (recombine) the way other chromosomes do because eggs don’t have Y chromosomes and sperm don’t have mitochondria with which to pair up and exchange parts. Thus they make it easy to reconstruct maternal (mtDNA) and paternal (Y) lineages. They can provide regionally specific information: your paternal line may have roots in Native American populations, let’s say. Your maternal line may suggest a Northern European origin. The problem with these markers is they can paint a skewed picture: together mtDNA and the Y chromosome account for less than 1 percent of the human genome. And they are, by definition, linear: they follow a
single
line backward. But of course our family trees only get wider as we move back in time: we have four grandparents, eight great-grandparents, sixteen great-great-grandparents, and so on. At ten generations, we have 1,024 ancestors. A Y-chromosome or mtDNA test will take us directly back to only one of them.
²⁸

More recently, with the advent of millions of SNPs scattered across the genome and better computer algorithms, genetic genealogists have availed themselves of
autosomal
markers, that is, DNA markers on chromosomes 1 through 22 that travel in pairs and that do get shuffled at every conception. These tests incorporate information from the full range of one’s ancestors, not just those in the direct maternal or paternal lines. They suggest, for example, that my recent genetic ancestry is 99 percent European—that is, boring.

In 2009, 23andMe began beta testing of Relative Finder, a program that compared customers’ DNA with each other.
²⁹
When two people shared identical segments of DNA, this indicated that they shared a recent common ancestor. The length and number of these identical segments were used to predict the relationship between any two people. As I wrote this, there were fifty other 23andMe users who were predicted to be my third cousins. Did that mean we actually shared great-great-grandparents? Absolutely not. But we were the functional equivalent of third cousins: we shared the same amount of DNA
as if
we had the same great-great-grandparents.

Skip Gates had similar analyses done for himself and his
Faces of America
participants by scientists at the Broad Institute. He was an unabashed fan of this approach. “It’s the emotional high point of the series,” he said. If you tell somebody, ‘You [and this other person] are descended from a common ancestor twenty thousand years ago,’ they’ll go, ‘Oh yeah. Wow. Big deal.’ But if you tell them they descended from a common ancestor since the time of Columbus and maybe as recently as two hundred and fifty years ago, that’s heavy, even if they don’t look alike. They share an
actual human being
in the recent past.”
³⁰

Many of his colleagues (and, I should say, some of mine) in the humanities and social sciences did not share his enthusiasm for genetic ancestry testing, or even constructing family trees. In a blistering takedown in the journal
PMLA,
the University of Virginia’s Eric Lott wrote:

Less frothily, other folks worried that commercial genetic ancestry testing promoted the fallacious idea that “race” is rooted in our DNA.
³²

Gates was, to say the least, unbowed. Yes, he worried about DNA testing being used to justify the creation of a genetic underclass. But he clearly saw it as a potential for empowerment as well. “There’s nothing that can disappoint me in any genetic or genealogical analysis of my ancestry. It provides relief, it provides
answers.
Identity commences as a question. Our genealogical identity and our genetic identity are subsets of one large question:
Who am I?
And each bit of data uncovered by your genealogy, your genetic analysis, provides another small answer to this larger conundrum. So there can be no bad or troubling news. Medically yes, these tests could be very troubling, but not in terms of ancestry. I’ve been black for fifty-nine years, and other than some radical black nationalists, nobody I’ve met minds having white ancestry. People just want to know who they were. They’d like to know the circumstances. African Americans want to find out
more
about their complex ancestry, not less.

“You can’t be a Luddite. You can’t stop it. You have to try to understand it. A lot of humanists and social scientists are like this,” he said, putting hands over his ears, closing his eyes, and singing loudly. “'La la la la la la la la la la!!!’ I say to them, you people need to read a genetics book!
The geneticists are not making this up.
We’re in the era of the recuperation of biology. We have to become scientifically literate so that we can learn how to
intelligently
challenge the potential abuses. And I’m eternally grateful to Rick Kittles for introducing me to genetics and also to its dangers, perils, and limitations. I’ve learned a new field to some extent.” He paused. “I also know I don’t have APOE4.”
³³

Gates and his father, Henry Louis Gates, Sr., were among the first four to be fully sequenced by Illumina’s $48,000 service.
³⁴
They were the first African Americans and the first identifiable father and son to have their complete genomes done. Gates learned that he had six hundred thousand SNPs that had never been seen before.
^*
“Six hundred thousand,” he marveled. “I’m the Skip Chip!”
³⁵

Gates, his father, and his brother also became PGPers, which made them outliers among African Americans. When asked by George to be among the first ten, Rick Kittles declined. “I think the PGP is wonderful,” he told me, “but I can’t be that ambassador or take that responsibility on behalf of other African Americans. We’re still in the enlightenment phase. This sort of information … once it’s out, it’s out. There are downstream effects I’m not sure I can control.”
³⁶
Harvard anthropologist Duana Fullwiley, who was studying the PGP, said blacks’ reticence about public genomics should not be a surprise. “The real issue is how this information might be used against African Americans. That comes from knowing the history and how certain groups really do get short shrift.” She mentioned DNA dragnets and forensic databases. She was sympathetic to Kittles. “When it is in the public realm it can be utilized in all kinds of ways.”
³⁷

So would Skip go public? His ninety-six-year-old father had already said he would. But Gates
Fils
hedged. I thought maybe he was still smarting from the death threats he received and the paparazzi chasing him after his arrest. But it wasn’t that. “I have two daughters,” he said. “I have all the information about my genome, but they don’t. They would be affected by my decision. If one daughter says no, then that’s it. It’s gotta be unanimous. It can’t be undertaken cavalierly. I will probably make it public unless my daughters have strong objections. The advantage of me making mine public is that it would let people study this relationship between father and son. And particularly with the father pushing a hundred.”
³⁸

He called me into the dining room and sat down at his computer. He called up a lavish PowerPoint series that a scientist at Knome had made for him. Colorful graphics of the two Henry Louis Gateses’ genomes came up with their photographs superimposed. And then, shockingly, his mother’s picture appeared superimposed upon
her
genome. Given the availability of Skip’s full DNA sequence and his father’s, it became a trivial exercise to reconstruct half of his mother’s genome (she died in 1987). “Seeing this was so moving,” he said softly. “The irony was I did it to immortalize my father, and it resurrected my mother.”
³⁹

Having one’s genome sequenced, it seemed to me, included both aspects of a trip to the South Pole. First, with some exceptions, a genome contains a lot of information that simply can’t be gotten anywhere else. Someone at risk for Huntington’s disease could know decades in advance whether he would suffer a slow, downward spiral in middle age or not. An oncologist could learn whether a cancer patient was likely to respond to a particular drug; a neurologist could anticipate whether someone in pain would be helped by codeine. A person with HIV might learn what to expect regarding the course of his illness. An Orthodox Jewish couple could learn whether they were both carriers of mutations that put their offspring at risk for Tay-Sachs disease, the heartbreaking disorder that kills children before age four. An orphan, adoptee, or donor-conceived child could learn about all kinds of hereditary health risks, carrier states, and likely drug responses that, in the absence of information from her biological parents, she could not find from any other source unless she already exhibited the phenotype.

At the other end of the spectrum was curiosity for curiosity’s sake. Skip Gates could get a pretty good idea as to his continental ancestry. Others of us were interested in traits, some of them whimsical or at least not likely to have a profound impact on our lives. Some of us might be able to roll our tongues, taste bitter foods differently from others, or drink coffee to excess with no ill effects. We may have blue eyes or brown eyes, curly hair or no hair, freckles or not. We may flush when we drink alcohol, or not. And because high school science classes somehow failed to kill our interest in genetics completely, we would like to know why. Even if genes can give only a woefully incomplete explanation or one that’s subject to radical revision, we would simply like to learn about our own human heritable traits—not at a population level, but at a
micro
level, one that pertains directly to us and, to some extent, our family members. This is personal genomics.

The argument that we’d be better off exercising, losing weight, and quitting smoking than learning about our genomes was a nonstarter with me. Indeed, it’s a non sequitur. Of course we’d be better off doing those things! And that would be true whether we knew our APOE genotypes or not, and it would probably be true even when we knew what the vast uncharted regions of our genomes meant, whether we were on the cosmological timescale or the nanosecond DNA sequencing one. And anyway, going to the gym and scrutinizing genomes were hardly mutually exclusive. I suppose what bugged me most was the genetic-determinist assumption behind this charge: that if we paid attention to our genes then we were doing so at the expense of everything else. Is this what happened with cholesterol? What about prostate-specific antigen (PSA) and mammography?

Jamie Heywood, founder of PatientsLikeMe.com, whose brother succumbed to ALS at the age of thirty-seven, said, “Genetics today is a very low-resolution picture, but the only way to get started is to get started.”
⁴⁰
For all of the dead ends, the technical hurdles, the possibilities of unpleasant discoveries, and the deep chasms of uncertainty, I am excited. Not by the prospect of digging into my data every day, but by the collective aggregation of genomes and traits and the years of code-breaking we have ahead of us.

I still see my genome as the least of my problems and I believe that that’s true for most of us. Certainly, given our tragic history of eugenic behavior, to recoil at the Awesome Power of Genetics is an understandable reflex. But I don’t see willful ignorance as much of a solution. I don’t like the idea, for example, that GINA may preclude employee wellness programs from collecting family history information because it amounts to private and dangerous genetic information.
⁴¹
This was how we were going to enable prevention?

I believe it is possible to demystify the genome while remaining in awe of it. I want to hitch up my thermal underwear, zip up my parka, don my mittens and snowshoes, and go to the coldest, driest, windiest place on earth. And if it turns out that it’s not such an extreme experience after all, then so be it—I am convinced that I will still be smarter because of it. And I will try again tomorrow … or in ten minutes. Meanwhile I want anyone else who cares or can make use of the contents of my chromosomes in some constructive way to have at it.