Here Is a Human Being Read online

  But of course, they could be monks with a thousand kids. And if tradition holds, Kirk admitted, most of those kids would be sired by lean monks over six feet tall. But he rejected the notion that this amounted to eugenics. “Eugenics is state-sponsored. This is what everyone is allowed to practice: PERSONAL eugenics. And only the mothers are allowed to choose. They get to pick the traits and the person whose genes they will help carry into the next generation.”52

  I could hear my ethicist and social-scientist colleagues groaning and gnashing their teeth. But in George’s eyes, Maxey’s travails were neither a deterrent nor a source of shame; on the contrary, “Kirk didn’t ask to have four hundred kids. He has seen a worst-case scenario. He might not be perfectly innocent in all of this, but he has seen, firsthand, genetics gone awry. I think having people who’ve lived through failure is very important for the early stages of this project.”53

  “Since I’m pretty famous, I’d rather keep my name and email address private to all but the PGP researchers for now,” read the email.54

  For more than a year, none of us other than George, Jason, and the IRB knew who PGP Participant #6 was. In mid-2007, I asked George exactly what the deal was with Mr./Ms. X. “He/she doesn’t want to participate in any of our discussions or with any of the press,” he said.55

  “Did you have any qualms about this person’s reticence?” I asked.

  “I wasn’t wild about it, but … we should expect this to happen. Now I think it’s great,” he said.56 As usual, the Churchian view was sunny. But he was not completely convincing.

  I pressed him on #6's identity. Based on his/her anonymous responses to the initial questionnaire George had sent around, I was sure s/he was a woman, though I couldn’t say why.

  “It’s a man,” said George. “Just don’t ask me his zip code.”57

  I wondered why this guy would want to participate in such a public project and still remain anonymous. How could he expect to have his cake and eat it, too?

  “He has dealt with the press quite a bit—he’s been there and done that. It’s not exciting to him and he doesn’t want to spend any more time on it, especially since this isn’t really his party. But he’s certainly interested in this topic.”58

  I thought this playing hard to get was maybe a bit pretentious, but it also lent the proceedings an air of mystery. I was intrigued. Who was this famous man who, according to his email, was a Harvard professor, hated chocolate, and didn’t really want to meet the rest of us?59

  “I’ve got it!” I said to George one day. “It’s Alan Dershowitz!”60 I had been thinking this for a while and was hoping it wasn’t true: I found Dershowitz to be an insufferable gasbag—even in those instances when I agreed with him—and not someone I wanted to represent the PGP. It was bad enough when he was asked to speak for the Jews. Now he would be holding forth on genetics?

  George laughed. “Well, I suppose it could have been him, since I know Alan fairly well. Good guess … but no.”

  And then he told me who it was. A few months after that, I met Professor Chocolate Hater himself. Steven Pinker has a lion’s mane of hair (a self-described member of the “Luxuriant Flowing Hair Club For Scientists”61), a wide jaw, and a small, shallow cleft in his chin. He is short and thin. He wears stylish boots. He speaks in a quiet, measured, slightly nasal voice with a noticeable Anglo-Canadian accent. And he has piercing, iridescent blue eyes. In 2004 he engaged in a conversation on consciousness, morality, Gödel, and objective reality (among other subjects) in SEED magazine with the novelist and philosopher Rebecca Goldstein;62 not long after that the two were married.63 He is a prolific writer on the subjects of language, evolutionary psychology, and cognition. He is the Johnstone Professor of Psychology at Harvard. The novelist Ian McEwan said of him, “I sometimes follow up, when Steve has been in public debates, transcripts of things said on the wing. And I’m always struck by the extraordinary wit and articulacy—even though he is not at his word processor—just defending his position or indeed attacking a point.”64

  One that caught my eye was in his and Goldstein’s 2007 joint interview with Salon. “[T]he reason I’m not a neurobiologist but a cognitive psychologist is that I think looking at brain tissue is often the wrong level of analysis. You have to look at a higher level of organization … a movie critic doesn’t focus a magnifying glass on the little microscopic pits in a DVD… . I think there’s a lot of insight that you’ll gain about the human mind by looking at the whole human behaving, thinking and reporting on his own consciousness… . It may be that the historian, the cognitive psychologist and the biographer working together will give us more insight than someone looking at neurons and brain chemistry.”65

  He was, it seemed to me, a contradiction: a cognitive scientist interested in the granular power of biology; an evolutionary scientist and Richard Dawkins (The Selfish Gene) aficionado who did not seem prepared to concede the Dawkinsian primacy of the gene. He was a reductionist interested in holistic analyses.

  And a guy who couldn’t recall wanting to be anonymous. “Maybe it was a misunderstanding,” he told me. “Or I didn’t have enough information. But I don’t have any clear memory of choosing anonymity.”66

  Okay, whatever. At our gathering in October 2008 he was the life of the party, asking questions of the speakers and telling jokes at the press conference about his genetic predisposition to irregular menstrual periods. And he brought his usual sharp rhetorical powers and vivid prose to bear on personal genomics in a piece for the New York Times Magazine in 2009:

  Assessing risks from genomic data is not like using a pregnancy-test kit with its bright blue line. It’s more like writing a term paper on a topic with a huge and chaotic research literature. You are whipsawed by contradictory studies with different sample sizes, ages, sexes, ethnicities, selection criteria and levels of statistical significance. Geneticists working for 23andMe sift through the journals and make their best judgments of which associations are solid. But these judgments are necessarily subjective, and they can quickly become obsolete now that cheap genotyping techniques have opened the floodgates to new studies.67

  For all of his caveats about personal genomics, Steve, like Jim Watson, chose not to know his APOE status. When I asked him about it, he downplayed the decision. “I know that even if I found out I wouldn’t jump off a bridge. Looking at the risks, I decided I have enough existential anxieties. I know I could deal with another one, but given the choice, who needs it?”68

  Ironically, Steve’s genome did indeed turn out to be a source of existential anxiety, but APOE was not the culprit. I didn’t know for a while because I didn’t find out about the mutation from Steve; I learned about it from an abstract of a paper that was to be submitted by George’s lab describing the sequencing of the ten of us. I didn’t know if I was supposed to see it or not. But I couldn’t avert my eyes. And besides, the PGP was all about transparency, right? Wouldn’t this all wind up on the Web in a few days anyway? The paper called Steve’s mutation “the most significant finding” of the project thus far (see chapter 12). Secrets, especially when freighted with life-threatening significance, really were hard to keep.

  The first time I met him, Keith Batchelder posed a riddle. “Who is the biggest single commercial user of Affymetrix GeneChips?”

  I had no idea. “Quest Diagnostics? LabCorp?” He shook his head and smiled, knowing the answer would surprise. “Nope. Canyon Ranch!” he said. “What’s that?” I asked. “You know: Canyon Ranch! The spa!”69 I wondered where he got that tidbit from and promptly filed it away, fairly convinced it was bullshit. But some time later, Linda Avey of 23andMe told me that this had been one of her initial ideas for personal genomics in the pre-23andMe days (see chapter 5): spas were going medical and hiring doctors. People who went to spas had disposable incomes and were interested in their health … and their genes.

  I soon learned that Keith, five feet eleven and 180 according to his public profile,70 trafficked in factoids and observatio
ns like this. “Do you know what the most common indication for a genetic test being ordered today in a hospital is? The patient asking for it.”71 He had tiny glasses that sat on the end of his nose, a receding hairline, and a voice that occasionally cracked when he was excited or making a point. He smiled and laughed easily, even as he told me what a cynic he was. “Life is hard and then you die.” He was also a bit of a restless soul: he had been a dentist, a physician, an entrepreneur, and a research scientist. What led to this trajectory? Medicine, he told me, was just a more complex version of dentistry. Once he got his M.D., he became interested in how drugs were approved and did a stint at the FDA. From there it was biomarkers and predictive medicine. When I met him he was in entrepreneurial mode, running his own consulting business in Boston, Genomic Healthcare Strategies. This seemed to fit: he had genuine zeal for talking about genes, phenotypes, drugs, business models, commercial partnerships, and PR firms.72

  Like several other industry players I spoke with, Keith stressed how disruptive personal genomics was and would continue to be. “When I as a patient can know a significant amount of information about my health, manage that myself, and have access to other information via the Internet, then that’s a revolution.”73

  But for all of his free-market preoccupations, Keith was not espousing a laissez-faire approach. When the eight of us met for the first time, he was the one who brought up the idea of a Good Housekeeping Seal of Approval for personal genomes.74 He was prescient: New York and California would soon crack down on personal genomics companies out of fears that patients would be harmed by receiving genetic information in an unmediated way. In the wake of these enforcement actions, talk about industry standards began to percolate. “Wouldn’t you like to know whether this stuff was good or bad?” Keith said. “What agency or organization will be able to tell you this? For all of its trying, I’m not sure the federal government can react fast enough. You get toothpaste with the American Dental Association symbol on it. The ADA is not a federal agency, but an organization that has managed to create a brand and a sense of confidence. It doesn’t say that if you use an approved toothpaste you’re guaranteed never to get cavities. But you can assume that if you use the toothpaste it meets some set of criteria—it’s not gonna kill you and the quality is at some minimal level.”75

  We talked about warfarin, the anticoagulant that millions of people with blood clots, including my nephew, most often took. Warfarin interacts with a slew of other common drugs, from aspirin to statins to Prilosec. And its therapeutic window is narrow: if the dose is too high, the patient can bleed to death (it was originally marketed as a rat poison). If the dose is too low, then the clots remain unresolved. Since the mid-1960s, we’ve known that different people are genetically predisposed to respond to warfarin differently—these responses can vary dramatically. People with certain versions of two genes, called CYP2C9 and VKORC1, are highly sensitive to warfarin and at risk of overdosing.76 Keith hoped that the time to make testing of these genes standard practice in patients who needed blood thinners was nearly at hand. “We know we can predict whether you’re a fast or slow metabolizer of warfarin. Warfarin is a pill that patients take themselves. Diabetes patients have glucometers and do their own insulin. They don’t call up their doctors and say, ‘What dose should I have today?’ They may consult with a physician, they may get a prescription filled, but they manage themselves on a day-to-day basis. Wouldn’t it be cool to have a diagnostic tool that would help you manage your warfarin dosing without having to go to a coagulation clinic?”77

  It would be, but it appeared that it wasn’t time yet: Even as this book went to press, warfarin dosing based on genotype was still undergoing randomized clinical trials. Most of the literature I read emphasized caution. But not all: surprisingly, one of the voices that advocated moving forward came from Larry Lesko, head of the Office of Clinical Pharmacology in the FDA’s Center for Drug Evaluation and Research:

  The question about warfarin pharmacogenetics before us now is not “is it ready for prime time?” The more important question is, while more and more studies are being planned and/or conducted, should we accept and use our current knowledge about genetic factors to improve the quality of warfarin initial dosing and anticoagulation in our patients. The benefits and risks of pharmacogenetics, in my view, favor pharmacogenetics.78

  Lesko’s paper closed with the famous quote from Voltaire: “Le mieux est l’ennemi du bien.” The perfect is the enemy of the good.79

  Reading this reminded me of Keith. He engaged a medical information firm to set up his own personal, portable electronic health record. He would send around electronic articles about personalized health and ask you what you were reading and would you send him a PDF. He said he knew a radiologist who would scan PGP participants for free. He asked questions about the current state of the art in genomic interpretation. He suggested the PGP talk to Procter & Gamble or Johnson & Johnson because these companies would know how much it costs to reach consumers efficiently and systematically. They would already know, he said, how many people were willing to pay right now and how much they’d be willing to pay in a year for a predictive genetic test. Again, he was prescient.

  “People are saying that the future of the genome is twenty years from now,” he told me at George’s kitchen table, eyes widening. “But look at what Medco’s doing: they have grabbed onto pharmacogenomics* in a big way. They have gone as far as trademarking ‘genetics for generics’ (can you hear branded pharma groaning?) And look at what employers are doing … they are looking at ways to save money with this kind of information. I say this is happening now.”80

  Participant #8 we’ve already met: he is Stan Lapidus, founder of Helicos BioSciences, which had waded into the next-generation sequencing market unabashed, despite being late to the party with its machine and, in a show of both up-front engineering costs and unmitigated chutzpah, began by charging more than twice as much as its competitors were for their instruments. At fifty-nine, Stan was the oldest of the PGP-10. He wore a bow tie and a faded green sweater. We sat in his nondescript office at Helicos headquarters in Cambridge’s Kendall Square. When I asked Stan about whether George’s plan to market a low-cost sequencer was a factor in his decision to become a PGPer, he said no. “What George is doing doesn’t matter. There’s no doubt in my mind that his technology won’t be the one that will go the distance.” He paused and reconsidered. “But what do I know? I’m just another guy.”81

  What did matter to him was genomic privacy. He believed that the PGP would be “at the vanguard of this debate.” Stan told me that an individual had two rights with respect to his or her DNA. One was a right to know the content of one’s genome; he described this as a “natural right” that regulators had no business in curtailing. The other was the right to genomic privacy. The second one, however, he was not prepared to grant unconditionally. “If you were an airline pilot and you were susceptible to hypertrophic cardiomyopathy, I wouldn’t want you to be an airline pilot,” he said. “Pilots are given stress tests every six months because a lot is riding on their health. Is it fair and appropriate to step into the realm of genetic testing for people whose genetic differences can affect the lives of others? It’s a complex question.”82

  Stan had googled me and read an article I cowrote with Bob Cook-Deegan about gene patenting. The subject, it turned out, was another of his fixations: genes were discoveries, he said, not inventions, and therefore should not be protected by intellectual property rights. Worse, gene patents would stand between the citizenry and their natural right to know their genome sequence. “Patenting discoveries makes no sense at all. I never understood it. So 23andMe can sequence this and that but it can’t sequence your breast cancer genes because they’re patented?* It’s crazy!”83

  Stan was on the back nine of a long career as a biotech entrepreneur: he founded two companies prior to Helicos and nurtured thirty-one-year-old wunderkind and Knome CEO Jorge Conde,84 among others. He told me about be
ing at Columbia University during the Vietnam War and having a physics professor who had played a cameo role in the Manhattan Project. In the mid-1940s, Stan explained, the thinking of Robert Oppenheimer and the rest of “the atom-bomb boys” never went beyond the notion that we were at war and the fear that Germany was developing a bomb; that we had to develop one first seemed obvious. But thirty years later, Stan’s professor had palpable regrets about how he had spent the war. Stan had a deep-seated desire to avoid the same fate. He described a scenario in which a Slobodan Milosevic could use genetics to carry out ethnic cleansing with “pinpoint precision.” He imagined Iraqis sorting Shiites from Sunnis, and the stern rabbis of his childhood using genetics as the final arbiter in deciding who was a Jew.85

  None of this is to say that Stan was against wielding the power of genetics and genomics to bring about social change. Like Kirk Maxey, under certain circumstances he was all for it. He offered another vignette. “Suppose I were single and wanted to meet women who were college-educated, interested in the sports I’m interested in, interested in philanthropy and the humanities, scientifically accomplished, and who didn’t carry the same recessive diseases as me. Well, the last one can be done. Doing the matching can occur semi-anonymously and in such a way that you simply won’t meet the woman that you ‘shouldn’t’ meet so she won’t break your heart. This would be useful for things like Facebook and Yahoo! Dating.”86 (Indeed, another PGP-10er, Steven Pinker, had helped found a company aimed at young couples based on broad carrier screening for dozens of genetic diseases.)87