Here Is a Human Being (2 page)

Now I wondered about Jesse. What if he carried one of the mutations I had identified ten years earlier?
¹⁹
What if my brother did? What if I did? And what
did
it mean?

God, I decided, was fucking with us.

I called my brother on the phone one day. He was tired and loopy after another night on the foldout chair in the hospital. “How’s it going?” I said. An absurd question and a pretty feeble conversation starter.

“Why,” my brother wanted to know, “couldn’t you have done your graduate work on the gene for large penises?”

I tell the Hirschsprung’s story not to elicit sympathy, though my brother and his wife surely deserve it in spades, as do all the parents who’ve ever had to watch their babies tethered to tubes in the PICU, terrified and uncertain about what the coming days might bring. Nor do I tell it because it strikes me as so metaphysically improbable, though, despite knowing better, I remain convinced that it is. I tell it because it points up the fact that all human genomics is personal—that is to say, it is finally about us. Mothers and fathers can negotiate almost anything: marriage, money, careers, sex, cooking, laundry, the Netflix queue, who gives the dog a bath. What they can’t negotiate are their own genomes (although with techniques such as preimplantation genetic diagnosis, a few are beginning to negotiate the genomes of their children). Occasional strange cases notwithstanding, every parent gives his or her biological child 50 percent of that child’s DNA. And every one of us, regardless of zip code, membership in an executive health program, or religious affiliation, carries at least a handful of harmful mutations that may or may not manifest in us or in our children, should they inherit them as part of that 50 percent. Yes, Jesse’s Hirschsprung’s disease was an unlikely event—on the order of one in five thousand. But unless we get hit by a bus or succumb to an infectious disease, eventually almost all of us are the numerator, the “one in” something—cancer, heart disease, diabetes, Alzheimer’s. Genes are rarely the final arbiter of these late-onset chronic conditions, our understanding of them remains woefully inadequate, and they probably don’t constitute the secrets of our being, but there’s no denying the importance heredity plays in them.

One of the promises of personal genomics is that it will tell us exactly what we are at risk of becoming the numerator for. One of the dangers is that it might also tell our insurers the same thing while not being actionable. It will provoke suspicions and perhaps ulcers and force us to think about our destinies in terms of probabilities, as though we are watching the tote board at a Las Vegas sports book a few minutes before kickoff.
How will I die?
It might also tell us something about various “positive” traits—intelligence, memory, musical aptitude, athletic ability—and how we measure up … or down. What will we do when our entire genomes are no longer abstractions, but palpable bits of information we carry in our pockets?

A growing number of people are opting to find out. With some trepidation, I became one of them.

L
ike a character on
Lost,
John Halamka has arrived from the future.

Wearing all black and brandishing his BlackBerry, he looks the part. And he lives it. As chief information officer at Harvard Medical School and CareGroup Healthcare System, he is responsible for the information needs of three thousand doctors and the health records of two million patients. He is conversant in twelve computer languages. He is a self-taught mycologist: if you find yourself in the ER after having ingested a wild mushroom, it is likely to be Halamka who gets called to figure out which of the twenty-five hundred North American mushroom species you ate and what to do about it.
¹

He is also apt to be mistaken for a shoplifter at Home Depot.

After the Food and Drug Administration approved the technology in 2004, Halamka had a bean-sized Radio Frequency Identification chip implanted in his right triceps. The RFID contains his medical record identifiers.

In part his interest was personal: An avid mountain and ice climber, Halamka was concerned that if he fell off a cliff and lost consciousness, his would-be rescuers would not be able to identify him. Now by scanning his arm they could. The downside is that the same ISO-standard 134.2 KHz RFID scanner at the mall may occasionally confuse him with a roll of duct tape or a garden hose.
²

Visit Halamka in his feng shui corner office on Harvard Medical School’s Longwood campus and chances are you’ll find him serenely clacking away at his computer, his desktop as clean as the day it left the office-furniture showroom. His lunch is all vegan, probably eaten with chopsticks and great dexterity. Send him an email and you’ll likely get a response within minutes, just like the hundreds of others who’ve emailed him that day, including the ER docs wondering whether the mushroom little Billy swallowed is going to be lethal, hallucinogenic, or merely vomit-inducing. Listen to Halamka talk in his calm, measured cadences and it’s not hard to imagine his flat Iowa accent booming out from your local public radio station.

When I visited, his office inside the Center for Educational Technology was emblematic of the rest of the medical school these days: an incongruous mix of Boston Brahmin stateliness and sleek hi-tech utility. Outside his door, banks of computers lined long tables in an otherwise open area, like a bullpen in a brokerage firm, only without the manic buying and selling, just the basal hum of conversation and the HVAC. Clad in his usual onyx ensemble (“At 3
AM
halfway around the world, you do not have to think about color matching”
³
), hands folded on his lap, Halamka emphasized that his participation in the RFID trial was about more than just preparing for some hypothetical mountaineering accident. He saw it as both part of his job description and a moral obligation. Having the chip implanted allowed him to answer questions that might someday be relevant to his patients: Does an RFID hurt? (No, but there is some discomfort upon implantation.) Would it lead to infection? (Not so far.) Would it place any limitations on his activities? (Other than getting rung up for $27.99 at big-box retailers, no.)

There was the stalker, however. “This guy thought that RFID tagging was the mark of the beast. He basically devoted his life to blogging about me.” Rather than antagonize his “fan,” Halamka began a dialogue with him. “He said his name was Bob, he lived in Kansas City, he was disabled, and that following me was going to be his daily activity.” After a while Bob went away.
⁴
Even the mark of the beast can get tedious.

Did the stalking episode dampen Halamka’s appetite for early adoption? Hardly. Stalking him is now an utterly trivial exercise on par with checking the weather forecast: He has an application on his BlackBerry that tracks him via GPS and produces Google maps of his whereabouts. Anyone with a username and password can locate him anywhere on the planet.

“I think somebody has to do these experiments,” he said of the Personal Genome Project. “We need to get a dataset and figure out what all the implications of this stuff could be.”
⁵

Halamka was probably destined to become Subject Number Two: like him, the PGP was another Harvard-based bit of self-experimentation and potential compromises in personal privacy. That’s not to equate the two. For all of their potential applications, in the early 2000s RFIDs and GPS devices were really nothing more than LoJack for human beings—fancy dog tags. But if Harvard geneticist George Church had his way, the Personal Genome Project would raise the stakes by making public thousands of identifiable human DNA sequences. Church came to Halamka’s attention several years ago after Church posted his own medical records online.
⁶

Researchers have long been interested in the relationship between genome and—in the trendy parlance—
phenome,
that is, how what’s encoded in our DNA interacts with the environment to give rise to traits ranging from height to athletic prowess to behavior to assorted health conditions, be they cancers or various forms of male-pattern baldness.
⁸
Datasets have gotten larger and the DNA sequencing industry has become a multibillion-dollar behemoth.
⁹

The Personal Genome Project’s initial goal was to recapitulate the Human Genome Project; the HGP was the effort by both government and private-sector scientists to decode the entire complement of human DNA. The PGP would sequence the DNA of ten individuals, that is, ten persons’ entire collection of 6 billion base pairs,
^*
a task that by 2009 would take any properly equipped and extremely well-funded molecular genetics lab no more than a few weeks and a few hundred thousand dollars.
¹⁰
But statistically speaking, ten people is not that much different from one person or even zero people, which is to say, it’s not much at all. Most if not all of the insights from those ten genomes would have to be replicated in a much larger sample, an undertaking that would not commence in earnest for a while yet. But in the early days when George Church discussed the PGP with me, he often began sentences with the phrase “When we get to a million.”
¹¹
Even though many of us rolled our eyes at that (and even its less ambitious interim successor, “When we get to a hundred thousand”), the premise was fundamentally correct: the real promise of genomics resides in large numbers. Only by studying thousands of people (and corralling a collection of supercharged computers and really smart people) can we begin to detect the subtle and meaningful DNA variants that affect complex and common traits like heart disease, arthritis, and diabetes. Those traits have been among us for millennia, but the technology capable of identifying their molecular underpinnings did not reach fruition until twenty-odd years ago. (Whether what we find will be at all helpful is another question entirely.)

Church, the PGP’s Grand Pooh-Bah, is a tall man in his early fifties often hunched over the tiny netbook he carries with him everywhere. With his thick beard and backswept hair he reminds one of a healthier, pre-Appomattox Robert E. Lee crossed with a younger incarnation of the Band’s keyboardist Garth Hudson, and perhaps a touch of Gandalf: a gnostic, gentle giant. He smiles and laughs easily. He is at peace with what he admits to be an idiosyncratic view of the world. When students and postdocs ask if they should share some juicy piece of data with other labs, his answer is almost invariably yes. His voice is a mellifluous baritone with a trace of twang; he has the air of a southern gentleman who’s amused and beguiled by most of what he sees. His bright green eyes do not betray madness exactly, but the mischievous twinkle is undeniable.

According to his official online PGP profile, he’s six feet four, 245 pounds. He takes statins (hyperlipidemia; his personal Web page cites a heart attack in 1994). He is narcoleptic. He has had squamous cell carcinoma. He takes vitamins.
¹²

Every morning George walks the 0.8 miles from his house in Brookline to his office and lab in the unimaginatively named New Research Building in the Longwood Medical Area, a sleek glass edifice that could work as a setting for a science fiction movie. It is clean and new. Security is tight: two guards sit at the entrance. They greet visitors and monitor the goings-on via sixteen digital cameras. The restrooms are “smart”: enter and the lights turn on. Upstairs they are identified by the male and female karyotypes: XY and XX chromosomes, respectively. George’s office is spacious but not ostentatious. It’s moderately bright: surrounded by glass on two sides, but nestled among tall buildings and parking garages. Children’s Hospital is visible at the end of the access street two blocks away. Immediately below the window is a small green space that was recently invaded by a phalanx of geese (“More geese poop!” said George
¹³
). A welder’s sparks tumbled from above—yet another parking garage was going up next door.

The culture of the Church lab is reminiscent of the best labs I worked in. It is characterized by an utter lack of pretentiousness. People wear jeans, T-shirts, and sandals or flip-flops along with their lab coats, goggles, and latex gloves. Elaborate drawings of molecular biology experiments appear on wipe boards next to cartoons of superheroes and deep-sea divers, and cutouts of rock stars. There is conversation, but mostly it is quiet. Everyone has his or her experiments to do. The British-born geneticist and Nobel laureate Oliver Smithies,
¹⁴
famous for discovering a bunch of things, including how to knock out single genes in mice in order to see what traits those genes control, continued—and for all I know, continues—to go to his lab at the University of North Carolina every day well into his eighties. When I asked him why, he likened the lab to a monastery and told me that good scientists more or less take a vow of poverty in order to do science: they must renounce most of the rest of their lives.
¹⁵
My sense is that George would never regard it as a solemn vow. Science is fun, so why not do it?

When George was born, his biological father, Henry Stewart McDonald III, was working as a clown. At various times he was a race car driver, actor, model, auto mechanic, aircraft pilot, movie producer, writer, TV commentator, and champion water-skier.
¹⁶
After a public address announcer introduced him as “Barefoot McDonald” because of his disdain for wearing shoes, the name stuck. The resistance to footwear, however, was not an act: A 1971
Sports Illustrated
profile described his infamous ejection from a Las Vegas casino under protest. “Whaddaya mean, bare
feet?
You’ve got broads in here wearing dresses without any backs. Some of the dresses don’t even have any fronts.”
¹⁷
In 1992, at the age of sixty-seven, McDonald was inducted into the Water Ski Hall of Fame.
¹⁸
Indeed, there is an adorable picture of seven-month-old George sitting on a tiny chair that has been fastened to a tabletop and is being pulled through the water by his father. “My mother was beside herself with terror,” George recalled. “My father was convinced I was enjoying it.”
¹⁹

When George was two, McDonald left his mother, Virginia Anne Strong, who went on to marry twice more. George’s wife Ting Wu attributed much of her husband’s success to his mother’s influence. “An amazing woman,” she said of Strong. “She was brilliant—a lawyer, a psychologist, and an artist. And like George she was extremely flexible and optimistic. I don’t think I ever heard her say a negative thing. I think George grew up knowing he could weather anything.”
²⁰

George lived in Tampa and Clearwater, Florida, until he was a teenager. His second stepfather, a doctor and Phillips Academy Andover alum, suggested George might like the prestigious boarding school. George excelled at Andover, both in academics and on the varsity track and wrestling teams. He applied to and was accepted at Harvard and Duke, went to Duke, and finished an undergraduate degree in zoology and chemistry in two years. He received a predoctoral fellowship from the National Science Foundation and dove into graduate work in microbiology.

Within a year he had flunked out.

To hear George tell it, microbiology was the wrong home for someone with a passion for biochemistry. And when he switched to biochemistry, he found that his new department was not terribly interested in him, either: the orphan narrative, it seemed, had followed him to the academy. And then there was the course work. George often read his assigned textbooks cover to cover by the first or second week of class. After that, there wasn’t much point in showing up; after all, he could be using that time to do actual hands-on research rather than simply read abstract accounts of what had already been done. He refused to take “baby science courses” just to fulfill curricular requirements. Recalling this, he gave a sheepish laugh and shrugged. “I guess I should’ve told them I wasn’t going to attend classes.”
²¹

His academic problems did not prevent him from beginning to get his name on papers, including a first-author publication in
Proceedings of the National Academy of Sciences
at the age of twenty-two.
²²
After Duke wished him luck elsewhere, he reapplied to Harvard, stated in his application he wanted to work with renowned molecular biologist Walter Gilbert on a new approach to decoding DNA, and was accepted. In an interview, Gilbert maintained that Harvard’s admissions policy at the time did not consider incoming students’ preferences for faculty, let alone require them. He was willing to believe, however, that George flunked out of Duke. “He always marched to his own drum.”
²³
George began his doctoral studies at Harvard in the fall of 1977, just a few months after Gilbert and graduate student Allan Maxam published a paper on how to sequence DNA,
²⁴
for which Gilbert would go on to share in the 1980 Nobel Prize.
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