Here Is a Human Being (26 page)

And she was living the life of any other happy five-year-old. She had started to read and learn math. She attended science camp with her older brother Mac and came home ebullient about the experiments they’d done; one sensed the pride in her hypothesis-generating old man. Maybe she would make it to Hopkins as a student one day instead of a patient.

Meanwhile, Bea and Mac had become close: Mac treated her like a peer, teased her as only a big brother can, and stuck up for her when necessary. “Bea’s not above kicking a boy in the
cojones,”
reported Hugh. “She got into a fight the other day at camp with a boy who was much stronger than she is. Macky had to step in and defend her. She’s got to learn to take what she dishes out. But … chivalry is good, too, I suppose.”
⁸⁷

Hugh had gotten off Highway 101, the perpetually clogged artery in and out of Silicon Valley, and we began saying our good-byes. Where was he headed?

“My ambition is to eat lunch. After all,” he said, “you gotta have ambition.”
⁸⁸

T
he first PGP-10 meeting was both baby shower and brainstorming session. George expressed his gratitude to us. The other seven of us who could attend sat around a table and made speeches, wish lists, and plans for our genomes. Filmmaker Marilyn Ness was there to capture it, having scraped together enough money to shoot documentary footage of us for a few hours. After a day of offering paeans to George and getting to know one another, fanciful musings, and gentle arguments, five of us adjourned to George and Ting’s unassuming Brookline house with the pond in the back for food and drink. The next day we scattered, full of ambition and hope for the project.

The second annual gathering was intended to be both a bigger deal and more substantive: PGP-10ers would see their data fresh from the Polonator, they would consult with a clinical geneticist about it, and they would make decisions about how much of it they were willing to share going forward. The press would be invited to learn about the PGP, its participants, and how genetic information need not be toxic.

It was just after 5
a.m.
on Sunday. I sat in the Raleigh-Durham airport anticipating a nap as I waited to board an American Eagle flight to Boston. It was hard to believe that the last two years of running around the country had brought me to this, the presumptive crucible of my entire personal genomics experience. Amy Harmon, the Pulitzer Prize–winning
New York Times
reporter who covers “The DNA Age” for the paper, had called me nearly every day for the last week to ask me questions for a story that would coincide with the Big Event: Why did you do this? What do you hope to learn? What does your family think? What would you redact? I danced around, but I didn’t really have any hard-and-fast answers for her. To my own surprise, I was torn. Should I let it all hang out, as I had said I would over and over with studied insouciance, and thereby demonstrate my solidarity with the other nine and my loyalty to the open-consent ethos? Or should I heed my colleague Bob Cook-Deegan and all the other cautious pre-Facebook, pre-Twitter people I knew and opt for the old privacy norms?

At the beginning of my involvement with the PGP, I had longed for my genome to be something more than someone else’s lab experiment, more than a set of anonymous data, more than an
abstraction.
The lesson I failed to heed, of course, is to be careful what you wish for. But before revisiting that theme, a little concrete backstory.

In 1976, at age forty-two, after months of denying the existence of the growing mass in her chest, my mother was diagnosed with breast cancer. I was twelve and don’t remember it well, perhaps because I was such a burgeoning pothead at that age. I do recall fidgeting in the backseat of my parents’ Plymouth Valiant and listening to my older brother, whom I idolized, trying to impress upon me the gravity of the situation: “Mom could
die.”
For once I knew he had to be wrong.

My mother opted for a radical mastectomy. Twelve years later, after her doctor found a thickening of cells in her remaining breast, she went back to the hospital for another one. Years later, when I asked her about this decision, she smiled and said, “I already had one breast gone, so I figured why not make it even. If you don’t have breasts, you can’t get breast cancer.”
¹
When it comes to her own health, she has always been a practical woman (less so when it comes to her children’s and grandchildren’s health).

Given her young age at diagnosis and her heritage, there’s a decent chance my mother carries a mutation in either the BRCA1 or BRCA2 gene. Five to 10 percent of breast cancers in white women are due to aberrant versions of one of these genes. In Ashkenazi Jewish women with hereditary breast cancer, three mutations in particular account for as much as 90 percent of the disease burden, perhaps more. Females with one of these mutations have an 80 percent lifetime risk of developing breast cancer.
²
The chances of me or my brothers developing breast cancer were fairly remote: about 1 percent of U.S. breast cancers occur in males. We are “hormonally hostile” to breast tumors.
³
But these genes are not on the sex chromosomes; thus, men can
transmit
BRCA mutations to their offspring just as well as women. I could have passed it to either or both of my two daughters, who turned seven and ten in 2009.

At the dinner banquet that closed the first annual Cold Spring Harbor Personal Genomes Meeting, I sat next to the doyenne of breast cancer genetics herself, Mary-Claire King. She was and is a brilliant thinker and tough-minded professor at the University of Washington. She gives off maternal charm and empathy. She is a tireless crusader for human rights; in the 1980s, her lab used molecular genetics to prove kinship among Argentine families in which the parents had been imprisoned by the military dictatorship and the “orphan” children were being adopted out surreptitiously.
⁴
In 1994, King lost the race for the two major breast cancer genes with such grace and humility that her already-stellar aura only grew.
⁵
Years later she would find dozens of novel mutations in those two genes, mutations that Myriad Genetics, the company with a monopoly on genetic testing for breast cancer, had missed.
⁶
I told Mary-Claire my story and asked for an on-the-record interview with her, but she quickly recognized that, with the PGP meeting less than two weeks away, what I really wanted was genetic counseling. And she was happy to give it. She suggested that I redact several million base pairs around BRCA1 and BRCA2 before going public; if my BRCA carrier status weren’t public then I would not have to lie to my daughters. If I didn’t have a mutation, then no harm, no foul. If I did, then Ann and I could talk to the girls when they were older. It all sounded so simple.
⁷

Ann and I agreed that at the very least, I should find out whether I carried a breast cancer mutation before putting my entire genome on the Web. If one or both girls were at high risk for developing breast cancer later in their lives, we wanted them to hear it from their parents when they were ready, and not from some intrepid blogger while they were still in elementary school. I had already discussed my risk with Elissa Levin at Navigenics, but her company was not offering BRCA mutation results—she could only quote me risks based on my family history. Thus I hoped the next PGP trip to Boston would bring some clarity to the whole business.

But without sequence data neither this nor any of the other promised moments of genomic truth could happen at the October gathering, and back in Polonatorville, all was not well. At the end of 2007, the machine was reportedly ready to ship. By the time of the Marco Island meeting the following February it had become a source of conversation, fascination, and maybe even buzz: an open-source sequencer from George Church’s lab that was one-third the cost of the next cheapest commercial competitor! But the truth was, at that time the Polonator was more about promise than it was decoding actual nucleotides from people’s genomes. It was a good-looking, well-engineered box that didn’t have working software: Mr. Spock without a brain.

Rich Terry, a boyish, thirty-four-year-old engineer from Boston, and grad student Greg Porreca—short, close-cropped hair, New Jersey accent—had devoted much of the previous year working seven days a week trying to breathe life into the Polonator. Terry spent his days tweaking design problems, thinking about microfluidics (extremely tiny channels that carried chemicals in and out of the machine), and, together with Porreca, writing code that would get the moving parts to go where they needed to be at each step. Had Terry known that this is what his life was going to be like, I wondered, would he still have taken the job toiling in the Church lab? He paused … and then he groaned … and then he laughed. “Noooooo!” he said. “I don’t know … Last summer was tough. I like to ski, though, so I don’t mind being indoors in the summer.”
⁸

I asked him and Porreca about other next-gen sequencing technologies. They handicapped the field and more or less stuck to the conventional wisdom of the day: Illumina/Solexa was the tentative front-runner, 454 Life Sciences had squandered its early lead by being too expensive to run, and Helicos charged too much for its instrument and was late to the party. Both also said that ABI’s SOLiD platform was essentially an earlier version of the Polonator—the primitive tangle of wires hooked to a microscope, named after Simpsons characters, and known as the D.05—in a box.
⁹
“It’s very similar,” agreed George.
¹⁰
In one sense, this was true: in the early 2000s, Agencourt Personal Genomics licensed the key Church-lab patent that described the nuts and bolts of polony sequencing, which meant sequencing short stretches of DNA in massively parallel fashion using the enzyme ligase, whose raison d'être is to stitch together DNA fragments.
¹¹
ABI, the dominant purveyor of the Sanger sequencing technology that had conquered the Human Genome Project a few years earlier, was in danger of falling behind up-and-comers 454 and Illumina; it had to make a move. After evaluating more than forty next-generation sequencing technologies, the company in 2006 settled on George’s sequencing-by-ligation; it bought Agencourt for $120 million.
¹²
Kevin McKernan, who was CEO of Agencourt and subsequently became senior director of scientific operations at ABI
¹³
(which itself merged with Invitrogen in 2008
¹⁴
), said it was a logical choice given the promise of the method and its source. “George’s mind is always in a lot of different fields at once. He pulls from nanofabrication, microfabrication, and computer technologies. He often has very simple ideas, but they are fundamentally different from the way other people are thinking about things. And his lab got the proof-of-principle done.” McKernan conceded the Polonator machine was similar to the SOLiD instrument, but emphasized that the “chemistry is very different.”
¹⁵

When I put the same question to Chad Nusbaum, he laughed. “Is SOLiD a D.05 in a box? No! But I can understand why George’s people would say that: they have a slightly biased position. There are similarities, but SOLiD’s molecular biology is much different. I told George I wanted to call his machine Ligation-Inspired QUery into DNA, or LIQUiD. He said, ‘Well, it’s open-source. It can have as many names as you want.’ He was neither particularly amused nor especially annoyed by my joke.”
¹⁶

But George was annoyed about something else. In his mind the Polonator’s open-source status remained its most defining feature. And through Agencourt’s dealings with his lab, George felt that the company had revealed its true mercenary stripes. “Before they licensed our technology, they said, ‘Oh yeah, we like this whole Red Hat–Linux thing: let’s go with it.’ And almost the instant they got the license from Harvard, they started saying, ‘Well, maybe we’re not so keen on this open-source stuff.’ And after they were purchased by ABI, it was like, ‘We’re definitely
not
interested in open source.’ And they dropped our license just like that. I think they didn’t like the ‘open’ part and they’re hoping we’ll go away.”
¹⁷

The Polonator couldn’t go away, however, if it never arrived. The Max Planck Institute in Berlin had one. Jeremy Edwards, a former Church trainee, had one at the University of New Mexico. Another lab at Harvard took a flyer and committed the requisite $150,000+ to buying one.
¹⁸
In early 2009, George said that “it’s not going fast but it’s going okay,”
¹⁹
which I took as a fairly sober assessment from its co-inventor and tireless booster. Meanwhile, despite the arrival of newfangled software courtesy of Porreca and Terry, and despite the impassioned insistence of a number of genomics movers and shakers that an open-source sequencer was a good thing to have in NHGRI’s portfolio and that the Polonator should be taken seriously (see chapter 8), Nusbaum admitted over lunch in 2009 that his team had still not done much with it. The Broad already had a cavernous building full of Illumina and SOLiD machines plus a Helicos unit fresh from the factory floor down the street. “It’s a good machine,” Nusbaum said of the Polonator. “But I have no ambitions for it at the moment. It’s not obvious to me what I’d use it for right now… . I think that would be an awkward conversation to have with George.” He looked sheepishly at his soup. “I have to prepare myself that it will eventually happen.”
²⁰