Here Is a Human Being (22 page)

“Why not return all of the variants or even all of the sequence data back to participants who want it?” I asked.

“I’m not interested in the genome as entertainment,” he said.
¹⁸

When I got back to my car, I noticed a sign on the top floor of the parking garage.
ATTENTION: OVERHEAD LEAKS OR BIRD DROPPINGS MAY STAIN CAR FINISHES. PARK AT YOUR OWN RISK.

In my twenty-five years of parking I had never seen such a sign. I imagined it was dreamt up by a government lawyer somewhere as some form of preemptive legal strike against angry drivers. But maybe that was too cynical—maybe it was just full disclosure: “Here are the possible consequences of parking here. If you park here then you consent to the possibility of bird shit on your car.” Okay, good to know—two cheers for NIH. But bird droppings or unspecified overhead leaks were not in the same league as genomic information. Given the gauntlet one had to traverse just to pay a visit to NIH, it was easy to understand why the institutes appeared to have zero interest in health information altruism or open consent. Openness implied risk. In acknowledging how little we know about what any of the information written in our genomes means, Amy McGuire once said we must learn to consent to uncertainty.
¹⁹
But bird poop notwithstanding, that was a lesson our government seemed unlikely to assimilate anytime soon. Uncertainty was still Kryptonite.

While fighting for NIH acceptance, George continued to pursue private funding sources. Although George would not discuss it, others familiar with the PGP told me that at one point Google was poised to infuse tens of millions of dollars into the PGP to help develop sequencing technology and use the project as a showcase for Google Health, the company’s new Web-based platform for central storage and management of all of one’s health information. Before pulling the trigger, however, Google higherups wanted to solicit the opinions of other thought leaders. What effect would public disclosure of DNA and trait data have on the public’s view of a company whose unofficial motto was “Don’t Be Evil"? The PGP brain trust had a sit-down with NHGRI leadership, a few bioethicists, and a couple of senior Googlers. According to a PGP affiliate who was there, “It was clear we were walking into a hornets’ nest.” After the meeting, sources told me, NHGRI leadership followed up with an email to someone on Google’s board of directors saying that if Google went ahead with the PGP it could set personal genomics back twenty years. At that point the collaboration was all but dead.

George was distraught. He had imagined Google Genomes taking its place alongside Google Books, Google News, and Google Maps. Admittedly, the PGP still had a million bucks from the company. But that is all it would get for the foreseeable future.

“For one brief shining moment,” said Ting, “it was Camelot. George had gotten to be good friends with the Googlers. It had become kind of an extended lab situation. So when it ended it was hard.”
²⁰

All of this pushback made the inclusion of the PGP in George’s grant renewal proposal a piping hot potato. George still desperately wanted NIH’s approval for the project, but after four years of supplication, argumentation, butting of heads, and politicking, he was no longer sure how to get it.

Enter Robert Green. In preparation for the site visit, he began meeting with George and Jason Bobe several times a week. If this proposal were to succeed, he told George, the PGP would have to be scaled down by at least two orders of magnitude. He laid out some ground rules:

• No use of the phrase “100,000 people” (500 max, or better yet, 250)
  

• No discussion of asking participants to pay their own way
  

• No insistence on a total lack of privacy for participants
  

• Come up with a very modest plan to collect trait information
  

• Rehearse your PowerPoint presentations ad nauseam
  

“If George’s goal is to get NIH funding for a portion of the PGP,” Green said, “there really isn’t any choice. You have to play this game. One has to abide by the standards of scientific proposals that have become the norm at NIH.”
²¹

Under Green’s tutelage, the Church team fell into line. Everyone dutifully made slides and practiced their talks while Green sat in the audience and played the role of hostile questioner. But the dry runs seemingly paid off: the new, scaled-down incarnation of the proposal—now with the even more unwieldy moniker, “The Human Gene/Environment/Trait Technology Center” (HGETTC)—was ready. Two days prior to the site visit, Jason was giddy. “This is going to be like Gettysburg,” he said, invoking a George metaphor.

“You mean a bloodbath?” I teased him.

“No,” he laughed. “A turning point!”
²²

• • •

Gail Henderson had never heard of George Church. And even after reviewing the materials that had been sent to her, she still didn’t know quite what to make of the Personal Genome Project. But since she was the member of the site-visit team responsible for ethical, legal, and social-issues (ELSI), all eyes were on her. Henderson was professor of social medicine at the University of North Carolina Chapel Hill, about ten miles from where I work. “Durham is a full day’s journey from Chapel Hill,” she told me half jokingly over beers, referring (I think) to both the cultural divide between Duke and UNC and the increasingly snarled traffic on the highway connecting the two cities.
²³

Henderson may have been new to the PGP, but you would have been hard-pressed to find anyone who knew more about ethics and biomedical research. She had long studied how scientists, patients, and ordinary people perceive genetic research and genetic medicine. And now, as director of UNC’s Center for Genomics and Society (an ethics center funded by NHGRI), she had turned her attention to ethical and regulatory issues posed by new genomic technologies and the big science that came with them. The PGP was right in her wheelhouse. “Our center’s theme is about exactly this: What are the ethical, legal, and social issues when you start to scale up?”
²⁴

The night before the site visit, Henderson caught a plane from Raleigh to Boston. When she arrived she felt tired, out of breath. Her heart raced whenever she stood up. She thought she was exhausted from traveling and stress: after the site visit she had a meeting in D.C. and from there was scheduled to go to China, where she was to continue her studies of the Chinese health-care system. She reached the Best Western near Harvard Medical School and went straight to the restaurant—maybe she just needed to eat something. She sat down … and promptly passed out and fell to the floor. When she came to, two strangers were kneeling over her. They called an ambulance, which didn’t take long. “If you’re gonna pass out,” Henderson said, “the place to do it is directly across from Brigham and Women’s and Beth Israel Deaconess hospitals, right?”
²⁵

She was experiencing a slow but massive gastrointestinal bleed, though she did not fully apprehend its severity at the time. “I had this idea that this was nothing,” she said. “I talked to the NIH and said I’m
sure
I’ll be out of here soon; put me on the agenda for tomorrow afternoon.”
²⁶

Once word spread that Henderson was in the hospital, there was concern on both sides, not only for her health, but for what this would mean for the site visit. The Broad Institute’s Chad Nusbaum, a member of the NHGRI team whose job was to evaluate the sequencing technology, was worried that he would be called upon to have “intelligent opinions on ELSI matters.”
²⁷
Jeantine Lunshof, the philosopher/bioethicist who had helped George articulate the rationale for open consent, fretted over the prospect of not having a fellow ethicist in the room.
²⁸
And Jason Bobe feared the worst. “I thought this was a sign that NHGRI wanted to bump this part of the proposal altogether.”
²⁹

Robert Green sensed the apprehension and decided to act. “It’s always good to meet people face-to-face,” he said. “The value of the site visit was that we were going to be able to talk person to person. It was not a calculation, but an instinct. I went to her hospital room and found her fully lucid and ready to talk. We started to go through the slides, but she stopped me and said, ‘Why don’t you just tell me about this?’ And that turned into a conversation that went on for over an hour.”
³⁰

By the time Henderson was piped into the meeting by phone, most of her reservations about the PGP seemed to have been assuaged. “[When she addressed the meeting], she ended on this enormously positive note,” said George. “The impression I got from NHGRI was that they thought we were really doing our homework on the ELSI.”
³¹

What about everything else George wanted to accomplish? What about the RNA, immunogenetics, the microbiome—i.e., the collective genomes of the thousands of microorganisms that live inside of us? What about adult stem cells? “They said we were being too ambitious,” remembered James Sherley, who, in addition to being one of the PGP-10, was collaborating with George on the adult stem cell project. “This is the weakness of NIH and I think even NIH itself recognizes it. It’s been designed to support work that has a high probability of success. That makes it hard to support things that are truly visionary.”
³²

Without exception, everyone I spoke to thought the site visit went extremely well. The dress rehearsal had gone off without a hitch. But that was in front of a small crowd in an advisory role.

Now the real critics would see the real performance with $24 million at stake.

After the site visit, the key was to incorporate NHGRI’s feedback into the final proposal before the May deadline, about seven weeks hence. A few months after that, George and a couple of colleagues would travel to Bethesda to answer questions on NIH’s turf: a reverse site visit. “A reverse site visit is the weirdest, most unfulfilling experience,” said Chad Nusbaum. “You go down there, you put on a show, and then you wait. You don’t know how you did. You’re on the plane ride home and you don’t know if you’ve won the World Series or not.”
³³

George certainly had no idea what the outcome would be, but as he left Maryland, he thought the proceedings felt rushed. An important reviewer had not been in the room and two co-investigators from the PGP team were absent as well.
³⁴

After discussing an NIH application, reviewers were given the task of assigning it a number from 100 to 500, where 100 was best.
^*
Priority scores of 100 to 150 were most likely to be funded; 150 to 200 might be funded; and proposals with scores greater than 200 had almost zero chance.
³⁵
In mid-December 2008, in the middle of the worst economic crisis since the Great Depression, George sent me an email: “to add to our 1929-style holiday cheer, we just got a 265 score on our renewal.”
³⁶

Team Church had lost the World Series, and its defeat apparently had nothing to do with open consent. More likely it had to do with open source.

“It does not seem likely that the scale of effort described in this proposal would keep pace with ongoing development efforts by the commercial suppliers,” said one review. Elsewhere it called the Polonator “homemade.”
³⁷

George was exasperated and crestfallen. After all the work to make the proposal palatable to NIH and after the triumph of “Gettysburg” nine months earlier, to be called an amateur by his peers was, in the immortal words of Sting, “a humiliating kick in the crotch.”
³⁸
George speculated that one of the reviewers, a venture capitalist and former commercial sequencing heavyweight, saw the Polonator as a potential competitor to private-sector sequencing companies just beginning to gain a foothold in the marketplace, to say nothing of those that were still in the development stage. He wondered if the reviewers knew that he was on the scientific advisory board of nearly every single next-generation sequencing company in existence; but how could they not?
³⁹
“The point of the Polonator is not to compete with them,” he wrote by way of rebuttal, “but to provide an open and common ground to help as many of them as possible. What we are doing is innovation that companies and academics typically don’t do (for example, open source). How do we know if open, platform-independent genomics will continue to lead in cost-effectiveness if we don’t fund the experiment? It is clear that it doesn’t take a monopoly to create a market environment of fixed high prices and ‘proprietary’ (that is, secret) components marked up by 80x (Agilent) or 1000x (Illumina) without the community knowing it. It would be rather convenient for the companies to eliminate the main voice for open-source sequencing (and set an example for other would-be open-source grantees).”
⁴⁰

He decided to call in one of the big guns, someone the genomics community was not inclined to ignore. This person wrote a stern missive to NHGRI on George’s behalf, pointing out that not only was George’s team responsible for the only open-source sequencer in the world, but that it had been the driving intellectual force behind two of the current commercial platforms. The email called on NHGRI to grant George’s request for interim funding;
⁴¹
George wound up submitting a request for some of Obama’s stimulus money to tide the PGP over. And he submitted another renewal proposal in 2009. In both cases NHGRI helped guide George through the process.
⁴²

I recalled a conversation with George in the summer of 2008, not long after Navigenics entered the market and things began to heat up; George was “invited” to Washington by the Secretary’s Advisory Committee on Genetics, Health, and Society (see chapter 4) to defend the personal genomics company he founded, Knome. Representatives of deCODEme, Navigenics, DNA Direct, and 23andMe were there as well.
⁴³
The meeting was civil but pointed. New York and California had already come down on the companies, and some committee members were clearly underwhelmed by what the companies were offering to a naïve public and the idea that they had the temerity to charge money for it. In George’s eyes, this skepticism was reminiscent of his dealings with NIH.