Here Is a Human Being (6 page)

One difference between Project Jim and the PGP was that the former was not originally conceived of as research at all. Rather, it was an agreement between a company, 454, and a private individual, Watson. When in early 2007 Baylor medico-legal scholar Amy McGuire was brought in to address the ethical aspects of Project Jim, the first thing she did was push to restructure it as a research protocol. This meant drafting a more rigorous consent and getting the Baylor IRB involved. She and I talked at Cold Spring Harbor—if she had any concerns about Watson’s persona or that the sequencing of his genome might be perceived as self-serving, she did not betray them.

“I think this is a really unique opportunity,” she told me. “He is someone who has extraordinary knowledge and expertise on all of these issues, one of which is: How do we get people to understand the meaning of the data that we’re generating? That is a tremendous challenge, especially when we don’t understand much of it ourselves. If anybody’s going to understand it, it’s him. At the same time we could think about the future when these special circumstances are not going to be present. With him we didn’t have to worry about the vulnerability aspects.”

She was hopeful that Watson and his ilk would allow the bioethics issues surrounding personal genomics to be dealt with beforehand (again, this was before Watson’s public meltdown). “I don’t like being reactive—it’s not fun when the shit hits the fan. It only takes one example to set us back so far—look at the Jesse Gelsinger case.”
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I told her she sounded like George.

National Human Genome Research Institute director Francis Collins was at the meeting. I braced myself for the party line about traditional modes of informed consent, and genomics as the fountain of youth and proof of God’s egalitarian plan for humanity. (Collins was a born-again evangelical Christian and prone to invoke religious imagery in his pronouncements about the human genome. In 2009, shortly before he was nominated to the directorship of the NIH, he launched the BioLogos Foundation,
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which “promotes the search for truth in both the natural and spiritual realms, and seeks to harmonize these different perspectives.”)
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At Cold Spring Harbor, Collins moderated an evening panel on the discovery of genes that appeared to have been selected for in humans during the course of evolution.
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It was and is a topic raising all of the usual bugaboos about race and ethnicity in genetic and genomic research (and the very topic that would get Watson in deep doo-doo a few months later). Have some human traits been selected for in specific human populations but not others? And the uncomfortable corollary: Are some ethnic groups stronger, faster, smarter than others? It is a rich, controversial, and fascinating question similar to the most provocative ones raised by the PGP: At the biological level,
what are we?
And what do our differences mean?

Despite his casual dress—jeans and blue-striped golf shirt—Collins appeared to be a bit ill at ease. He spoke without identifying specific researchers: “There was a paper published in a very prominent journal suggesting a signature of selection… .”

The paper he referred to made claims that a particular gene had been favored over the course of evolution by playing a role in brain size and therefore, it implied, intelligence.
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Scientifically it was a real stretch, but
Science
ate it up, no doubt because it was such a sexy and controversial story. I listened as Collins went on to exult in the fact that subsequent work showed the connection between this particular gene and intelligence not to be real. Others on the panel chimed in on the paper in question and the delicate business of doing this kind of research. Collins seemed relieved when the subject was changed. At one point during the Q&A he said, “I won’t go to IQ because that’s probably the most explosive, but let’s talk about athletic performance.” It seemed to me something of an Orwellian moment: the world’s most visible genome scientist felt the need to censor himself in public. He was, in many ways, the anti-Watson.

The next day, between talks I was stalking another übergeneticist when I practically bumped into Collins, who towered over me. I introduced myself and made a lame, passive-aggressive joke about not being able to get through his human firewall of an assistant. I told him I was hanging around George Church, documenting what the PGP was doing. (Was I committing some ethical breach by not disclosing my status as a PGP subject? Probably.) I asked if he would say something on the record about personal genomics. He would not.

I asked him about 454 sequencing Watson, the biotech company Illumina sequencing a Yoruba man, Craig Venter sequencing himself, and George launching the PGP. He was dismissive of all of it. He thought it unfortunate that this was what I was focusing on. He gave me the impression that he thought these high-profile white-guy sequencing efforts were guided by Narcissus. He hoped that this would be a brief, transient chapter in the history of our field. The public, he suggested, would not understand these efforts and would be turned off by them.

When I told him I couldn’t speak to what the others were doing but that I believed George’s goal was to scale up to thousands or even millions of people and to have the first few people sequenced be those who could sustain any unintended consequences as a means to that end, Collins was unpersuaded. He intimated that it was a self-interested, “look at me” approach to genomics. His bottom line seemed to be that this was an elitist approach, a step in the wrong direction.

The conversation was over.

In the bar/café I saw a man in a kelly green sweater and porkpie hat buying an iced coffee and a huge Danish. Still reeling from my encounter with Collins, I approached feebly and told him I was writing a book on personal genomics and asked him if he would speak to me. “Sure, but I don’t have much time,” said Watson.

Like Collins, Watson didn’t want me to record him, though his demurral was somewhat gentler. He mentioned a magazine article in which he was portrayed as anti-Semitic, which he assured me he was not. In fact, he told me that his father admired the Jews because “they don’t believe in God—they use reason.” And so he therefore considered himself to be “culturally Jewish.” Oy.

We moved to the veranda. Watson leaned against the railing, his face framed by a swaying stand of trees and the harbor in the background. This brought to mind the famous 1953 photograph of Watson and Crick standing with obvious pride in front of their model of DNA. Crick—all sideburns, ears, nose, and especially eyebrows—is standing on the platform upon which the giant helix is fixed, his left hand on his knee, his right gently resting on the sugar-phosphate backbone of the molecule, a small ruler between his fingers. Watson—rumpled shirt, skinny tie, and unruly pompadour—is looking not at the model or Crick or the camera. Rather, his attention is to something somewhere offstage, his smile at once knowing and mischievous. His face appears to be saying, “I can’t believe this! And I’ve only just turned twenty-five!” Standing on the sun-dappled deck with him fifty-four years later, I could have sworn he was wearing the same expression.

When 454 approached him about Project Jim, did he have any hesitation? “Oh no. I never thought twice about it.”

When I asked about his reluctance to know his APOE status he said simply that his grandmother died of Alzheimer’s at eighty-three and he didn’t want to spend the rest of his life worrying that any lapse in memory he might experience would be the onset of dementia. So was he nervous about discovering anything else that might lurk in his genome? “Not at all,” he said.

What did he say to Francis Collins about all of this? “I told him how much more reassured I was having had my genome sequenced. And he looked uncomfortable.” He laughed, eyes wide.

I asked about the value of sequenced human genomes. “I think we will have a more compassionate, better society because of them,” he said. “They will be useful to explain why people are the way they are, why some people don’t fit in. My son has schizophrenia, for example. He never wanted to go to work or to school because he couldn’t fit in. Maybe genomics can explain that. We are all different. We all have different abilities. Some people can’t sing or dance. Why should we make them go out on the dance floor? I think it’s better to understand people’s limitations. If we understand the biological basis of those limitations, then I believe we will treat people better.”

Did he get permission from his children? “No,” he said. “They might have said no.”
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He laughed again. I recalled George’s lament that because of Watson’s bull-in-a-china-shop approach, perhaps Watson was not a good choice to start with for personal genomics.
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I asked about the concerns some people had about informed consent and individual whole-genome sequences. He was unmoved. “If we get ourselves wrapped up in this, then no information will
ever
be released.” And what about charges of elitism? “It’s crap! Not everyone can afford an automobile. Does that mean the rest of us shouldn’t be allowed to drive? People who want these types of restrictions on genetics
don’t like genetics.
They see genetic determinism everywhere and they think it’s an evil worse than fascism. No competent geneticist can believe in genetic determinism.”
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I regretted not asking him why, then, if he were not a genetic determinist, he would be so discomfited by knowing his status for APOE, which, after all, is only a susceptibility gene. While it alters one’s risk for Alzheimer’s, in its worst guise it is still well short of a guaranteed death sentence. (Persons carrying two copies of the APOE4 allele have a fifteen-fold increased risk for developing Alzheimer’s.)

Every time Watson flitted away and I thought the discussion was over, he drifted back with an addendum. The conversation caromed from Michael Crichton (“He told me he was on his fifth wife—I thought that explained a lot”) to religion (“I don’t hate God the way Francis Crick did”) to psychiatrists (“They don’t know very much”).

Finally he signaled he was really leaving, but not before imparting some literary advice. “I wouldn’t spend more than twenty-five pages of your book on George Church,” he said. “He’s not that interesting … though he’s very tall. He can be one character … but you need more. You need a villain if you’re going to compete with the Michael Crichtons of the world. Who’s your villain?”

I hesitated. “Gosh, I don’t know,” I said.

“You
have
to have a villain,” he insisted.

“Well … right now I suppose it’s Francis,” I said without much conviction.

“Aha! That’s good. So now you’ve got at least two thousand readers.”
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I looked around nervously—there were chortles of affirmation from some of the other folks who’d gathered on the veranda and were eavesdropping if only to hear what outrageous thing Watson might say next. One scientist assured me that if Francis Collins were indeed my bad guy then she would be among the two thousand. I started to talk with her; when I looked up Watson was gone.

Later that afternoon, the organizers of the meeting grudgingly gave him a forum to talk about his genome. The feeling seemed to be that this was a nonevent, though I wasn’t quite sure why. Maybe because human genomes were still not taken seriously—they weren’t “real” science; rather, they were thought of as tiny blips of data that added up to nothing. Maybe because Watson was likely to say something outrageous (a pretty safe bet). Maybe because it had simply become too much work for the veterans of these meetings to manage and minister to him. A longtime CSHL denizen had seen this tug-of-war before and offered a note of sympathy for Watson. “It’s hard being ex-emperor when people have been saying yes to you for sixty years.”

Watson made it clear that his genome—and all human genomes—should be cause for celebration. Having them would make us better, healthier people. “If there had been a genetic diagnosis for my son Rufus,” Watson told the audience, “we would have raised him differently and not expected him to go to Exeter… . I’m not hesitant to say we’re playing God. Someone should.”
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Ting Wu gave a congenial laugh at the notion of her husband as an elitist. “I think when people get to know him that thought will vanish. He’s very modest. People won’t be able to miss it.”
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When I raised the issue with George, he patiently explained—again—that we ten were not really important. We would be among the first, sure, but he reminded me that his premium was on scalability, that is, getting to a million. Thus he opted to sequence only our protein-coding 1 percent, our exomes—at least for now. “If you give me a hundred million dollars,” he told me, “I would rather spend it on ten thousand or one hundred thousand exomes than on one hundred complete genomes.”
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In other words, he would rather have 1 percent of the genome from one hundred thousand people than 100 percent of the genome from a hundred people. To paraphrase
The Incredibles,
once everyone’s genome was super, then no one’s would be.

But to scale up meant moving beyond the limited pool of master’s-level geneticists willing to share their genomic information (there are only a few hundred board-certified medical geneticists in the United States and only about 2,500 master’s-level genetic counselors).
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George therefore wanted to replace the credential requirement with an exam that all PGP subjects from any walk of life would have to pass before being allowed to enroll. “A test could help prove they know what they’re doing and might even have a psychosocial component to make sure they’re not pathologically exhibitionistic or likely to react in a depressed way to news about, say, Huntington’s disease.” What else would it cover? “Interactions with insurance companies. Things like ‘Do we think having reporters in our living room is a good thing or a bad thing?’ And ‘How much do we think our cells are worth?'”
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