Here Is a Human Being Read online

  But on this night in SoHo, the sisters were doing it for themselves. During the Q&A the indignation that had been building found its voice. “First of all this is a class issue,” said one counselor from an Alzheimer’s clinic, presumably referring to the company’s $2,500 price tag and how it would put Navigenics’ service beyond the reach of many. “Secondly, this runs counter to everything we are taught as genetics people. Family history is the gold standard… . And finally, I don’t see how [Alzheimer’s] is preventable … How does this particular disease fit into your criteria?”

  The cognitive dissonance between the newfangled personal genomics model and old-school genetics continued to reverberate among the counselors as I drifted through the crowd and eavesdropped:

  "What happened to the standards we were taught in school? Sensitivity, specificity, positive predictive value, having an intervention?”

  "They’re clinically applying this information that’s not been replicated, the studies are underpowered … I just don’t get it.”

  "It’s cutting edge and exciting … but I feel like it’s premature.”

  “What’s everybody reading in the [New York Times] Science Times every Tuesday?” said Deb McDermott, a counselor based at Weill Cornell Medical College in New York. “They’re worried about cancer, Alzheimer’s, heart attack. We still don’t know why eighty-five percent of women with BRCA mutations get breast cancer and fifteen percent don’t. Did they eat an apple every day? Did they smoke or not smoke? Did they take oral contraceptives? No one can tell me because no one’s done the studies. So it’s bullshit to think that testing a sixty-five-year-old Wall Street banker, who can afford this test, who can start going to his personal trainer and going to a nutritionist, will prevent him from getting, say, prostate cancer. It’s bullshit!”

  “Would you feel differently if it were fifty bucks?” I asked.

  “No. [This company is] not in Indianapolis or Columbus. They’re in New York for a reason. It’s all about money. We’re a couple of subway stops up from Wall Street.”

  “And if I came to you with these results,” I said, “and they showed I had an elevated risk of heart attack, what would you do?”

  “I would throw the test results out and say, ‘Let’s look at you and how you’ve lived your life. Let’s look at your family history. And I’m sorry you didn’t spend that twenty-five hundred bucks on a trip to Jamaica.’ These are population data they’re trying to apply to single individuals—it just doesn’t work.”34

  A few months earlier a scientist friend who didn’t want her name used said almost the same thing verbatim. “Dietrich is a nice guy. The 23andMe people are nice ladies. But I don’t know what this is going to do for anybody. It’s a waste of time and money.”

  The next day I met with Dietrich in the cavernous basement of the loft, which resembled a theatrical costume studio crossed with a junk shop. He and I sat in a set of mod 1960s chairs beneath the winding staircase. Dietrich had a cold and sniffled throughout our conversation; he had been in New York for two weeks and looked as though he hadn’t slept since arriving. Was he put off by the counselors’ hostility? I asked. Had he expected it?

  “I didn’t expect it. But I was more concerned that some genetic counselors didn’t seem to understand that family history is really just a surrogate for exact testing of the genetics of a person. Once you have the ability to extract all of the genetic information using a sequence, the need for a family history will go away, I would think.”

  He thought that perhaps the counselors felt threatened but said that they needn’t have: traditional counseling for single-gene disorders would always be around. But we were now in a position to get access to our complex, common genetic risk factors, not just rare genetic disorders controlled by a single strong (“highly penetrant”) gene. “I think the counselors will have to learn that those are two different things.”

  He was equally sanguine about criticism of Navigenics’ pricing. “I’m not worried about that at all. There’s not much we can do about it. It is what it is. This is a market-driven economy. If you don’t like that, go move to a communist country.”35

  These words appear much harsher on the page than they sounded in person. Dietrich may not have shared much in common with George Church, but he was at least as comfortable in his own skin. He never raised his voice and was a consummate diplomat, someone who could tell you to go to hell (or to a communist country) and somehow you would find yourself looking forward to the journey. Despite his illness and exhaustion, despite the undisguised unfriendliness of the medical establishment toward Navigenics and its competitors, he seemed genuinely happy with the events of the previous ten days. Yes, it was a pure and shameless marketing ploy: go to the heart of hipster country and throw a lavish party. But in Dietrich’s view it had succeeded—the tone of the lay press had turned positive, and a few days earlier even stodgy old Nature had thrown personal genomics companies an editorial bouquet:

  … to advocate relatively light regulation does not mean turning a blind eye to the risks of such a strategy. It means taking seriously the presumption that people should be free to inform themselves and make their own choices, and that by doing so they may benefit not just themselves but also the overall pace of innovation.36

  And no, Dietrich admitted, downtown New York City was not an accidental choice for a launch site; it was market research at work. “In coming to understand our demographic, it was clear that these were forty-to sixty-year-olds, high income, mostly urban, early adopters, fifty-two percent male,” Dietrich said. “Where’s the epicenter of our customer base? Well, New York is the capital of the world! In SoHo we have our demographic walking down the streets every day.”37

  There was only one problem. Navigenics was forbidden to peddle its product in New York State.

  A few days after the SoHo shindig came to an end, the New York State Department of Health sent a hangover in the form of a warning letter to the company and twenty-two others telling them that they needed a permit before they could offer their tests and services.38 Stephan was unruffled—he told me that it was a matter of submitting applications and paperwork and that he had been to Albany a couple of weeks earlier to meet with Department of Health officials. “Their biggest thing is they want this information to be used in conjunction with a physician. That’s totally reasonable. We will probably need to modify the business model a little bit in New York State. We’re working through that, but we’re good to go everywhere else.”39

  Or so he thought. In June 2008, California followed New York’s lead and sent cease-and-desist letters to thirteen companies, including the Big Three (Navigenics, 23andMe, and deCODEme), some of which claimed to be in compliance with state law, while others stopped offering their services in the state, at least temporarily.40 The California Department of Public Health complained that 1) the clinical labs used by the companies to perform the genotyping were not appropriately certified; and 2) as in New York, the companies could not offer their tests directly to consumers in California without a physician’s order. These companies were, according to California officials, “scaring a lot of people to death.”41

  That summer the Secretary’s Advisory Committee on Genetics, Health, and Society convened its biannual meeting. SACGHS was formed in 2002 (an outgrowth of an earlier committee on genetic testing) by then-HHS secretary Tommy Thompson, and asked to consider the impact of genetic technologies on American society.42 The meetings took place in the Hubert H. Humphrey Building, a singularly ugly 1970s edifice that serves as the headquarters of the Department of Health and Human Services and lives in the shadow of the Capitol. Day one of the meeting was as boring and Kafkaesque a gathering as I’d ever attended, devoted to a dissection of the process by which the committee would decide what its priorities were; I thought I’d stumbled into a scene from the film Brazil. Two hours into the session my posterior was numb and I could feel my eyes rolling back in my head. Worst of all, the building didn’t seem to have wireless
Internet available to civilians; I made a mental note to bring an Ethernet cable, some sudoku, or something to read next time.

  Day two, unassumingly titled “Session on Personal Genome Services,” was the antithesis of the previous day’s sleepy proceedings. On three sides of the rectangular assemblage of tables sat committee members—academic physicians, geneticists, biotech executives, law professors, theologians, social scientists, and assorted bureaucrats. At the head of the room were empty chairs reserved for the leading lights of the new wave of personal genomics: Dietrich Stephan (Navigenics), Linda Avey (23andMe), Jeff Gulcher (deCODEme), Ryan Phelan (DNA Direct), and George Church (Personal Genome Project; Knome [about which more later]). There was a cacophony of excited chatter beforehand. By the time the chairman asked people to take their seats it was standing room only.

  At this stage of the game, eight months since the launch of the first commercial “Saliva Diviners,” the blogosphere had, for the most part, warmed to personal genomics.* Customers were comparing results from different companies;43 some were writing their own software to interpret it.44 But the folks in white coats remained unimpressed: the backlash against the companies by the medical establishment was almost immediate. Not only are these companies doing more than dispensing “information,” the critics said, they are practicing medicine, and indeed, they are practicing—in the immortal words of Bon Jovi—bad medicine. These tests are inaccurate, they don’t measure what they are supposed to measure, they are not actionable, they will lead to the “wrong” actions, they will lead to unnecessary anxiety, they will rob medicine of valuable resources, physicians will not be able to handle the data deluge, and they are frivolous manifestations of important science.45 (Perhaps the unkindest cut was “recreational genomics,”46 a label Navigenics gave to 23andMe and one that, much to Linda Avey’s chagrin, had stuck.)47 When it threw down the gauntlet in January 2008, the New England Journal of Medicine encouraged doctors to tell patients that the information derived from these services was essentially useless and that patients should “ask again in a few years.”48

  One of the authors of that editorial was Muin Khoury, director of the National Office of Public Health Genomics at the Centers for Disease Control and Prevention. He was also on the Secretary’s Advisory Committee and expected to be a sharp interlocutor at the July meeting. He didn’t disappoint.

  “Where is the balance between waiting and validation?” he wanted to know. The development of valid cholesterol testing, he pointed out, took many years. “What is the value added by genes versus pure family history and traditional risk factors?” Later, he answered his own questions with a sharp rhetorical flourish: “This information is not ready for prime time. Replication is not clinical validity. When you [panelists] talk about value to consumers and clinical utility, I talk about balance of harms and benefits. The problem is lost in translation.”49

  The companies had also appeared a couple of months earlier at the Cold Spring Harbor meeting. There, at a session moderated by Francis Collins on commercial personal genomics, Dietrich, Linda, and deCODE’s Kari Stefansson were downright deferential to the assemblage of scientists. They wanted to know how they could work with scientists. They acted not like competitors, but like colleagues—even deCODE’s notoriously cantankerous Stefansson made nice.50 At the SACGHS meeting two months later, the companies were still “on message”: they were doing everything they could to cooperate with the state health departments in New York and California, they were going to meet to hammer out standards, and they were actively soliciting advice from all of the stakeholders in personal genomics.51

  If there was a panelist who exuded above-the-fray gravitas at the SACGHS gathering (as opposed to Gulcher’s slight hostility and George’s phlegmatic indifference), it was DNA Direct CEO Ryan Phelan. Like Linda Avey, she was a Silicon Valley veteran. She was married to Whole Earth Catalog author and counterculture/cyberculture icon Stewart Brand; the pair lived on a tiny tugboat in Sausalito.52 Phelan came to genetics well into her career. But DNA Direct preceded and was wholly distinct from the Big Three and other personal genomics SNP-chip companies; it was in essence a clearinghouse for traditional, one-disease-at-a-time genetic testing. When I met her for lunch in San Francisco not long after the 23andMe and deCODEme launches, Phelan had already sussed out what the new companies would mean for her business. “Both 23andMe and deCODEme are drawing a line and saying, ‘We’re just health information. We’re going to give you some interpretation but not a whole lot. And we’re also going to tell you that what we do is not a medical diagnostic. So if you really think you’re at risk for something [like breast cancer], you need a follow-on DNA diagnostic.’ DNA Direct can be a service to those customers.”53

  Looking ahead, Phelan saw an opportunity in the arrival of whole-genome sequencing: interpretation. “The core competency I want to add is helping people to utilize this cool new technology.”54

  After the regulatory crackdown, the DNA Direct website included a statement from Phelan:

  “DNA Direct has not received a cease & desist letter from the California State Department of Health. And DNA Direct has no reason to expect to receive any such letter. Our company fully complies with all applicable state and national regulations for genetic information services, including facilitating genetic test requests.”55 Clearly the company was not in the crosshairs of regulators the way the genome scanning firms were.

  Kevin FitzGerald, a SACGHS committee member and perhaps the only person in the world who was both a trained molecular biologist and an ordained Jesuit priest, asked the assembled purveyors of personal genomics, “Would you sacrifice your bottom line for the sake of health care?” Phelan didn’t hesitate: “From an investor’s perspective, we have always sacrificed the bottom line.”56

  Linda Avey chimed in that while 23andMe was a business, it also had a social mission. Jeff Gulcher said deCODEme was genotyping some people at cost. Dietrich seemed piqued by the question. “Implementing genotyping as a service doesn’t fit as a not-for-profit model. What portion of medical infrastructure operates as not-for-profit?”57

  It’s doubtful the meeting changed any minds. During a break I heard geneticist Jim Evans, who had earlier compared personal genomics to astrology, say to some attendees, “I don’t care if they want to make a buck. They just shouldn’t pretend like they’re doing something else.”58

  But even if there had been an understanding between personal genomics companies and the feds on that day in July, political reality made it extremely unlikely that anything meaningful would happen before President Bush left office six months hence. Because everyone knew that, much of the day’s later proceedings had a relaxed, valedictory feel. Not only did Francis Collins make his last appearance as an ex officio committee member before stepping down as director of the National Human Genome Research Institute in August 2008, but HHS secretary Mike Leavitt himself turned up unannounced (it was his committee, after all). And like any capable politician, Leavitt managed to make people feel good while saying absolutely nothing of substance. When asked how he thought we might move ahead with direct-to-consumer genetic testing, he said that he would not weigh in on either side but that the matter represented “a positive struggle.” When asked politely by Collins when reimbursement for preventive health-care measures would be implemented, Leavitt admitted that it was indeed a pressing issue. But, he said, “It’s not likely to happen in the next one hundred and ninety-seven days.”59

  A month earlier, molecular biologist Steve Brenner of the University of California at Berkeley organized a dinner at a swanky San Francisco hotel aimed at helping to realize his vision of a “Genome Commons.” Brenner’s idea arose from the need to “specifically address the incredible difficulty of integrating and interpreting multiple variants in an individual, each associated with a given trait.”60 In other words, we will soon have tens of thousands of genomes … how in the hell will we even begin to interpret them? As an example of what not to do, he pointed to
the 2007 paper announcing the completion of Craig Venter’s genome,61 and especially the “inscrutable” table therein that was meant to relate his genotypes to his traits, but contained only a smattering of random phenotypes and susceptibilities (for example, “evening preference,” “novelty seeking,” “tobacco addiction,” “Alzheimer’s”), a sort of 23andMe lite. “What did we learn [about Craig Venter’s phenotype from that paper]?” said Brenner. “Nothing that was worth even reporting correctly.”62

  Among others at the dinner were the Big Three: Gulcher from deCODEme, Avey from 23andMe, and Stephan from Navigenics. At that time it seemed that wherever one was, you could find the other two. Geneticist Hugh Rienhoff (whom we will meet again later) opined that most of the variants the companies were reporting to customers didn’t pass the “so what” test. A variant that raised one’s risk for any given disease from one in a thousand to one and a half in a thousand, for example, was not clinically meaningful. And even when changes in risk were large, physicians still weren’t getting the message, said Rienhoff; in fact, they probably didn’t care.

  “I find every paper that’s published in the New England Journal about [genetic] association studies to be almost completely useless for the reader,” said Rienhoff. “And the [intended] reader is the clinician! But he doesn’t understand the statistics, he doesn’t understand the technology, and it won’t make any difference for ten years.”

  “But that’s what the missing piece is,” Avey shot back. “We don’t have a way to translate this into the clinic.”

  “Well,” said Rienhoff, “I think it’s premature, to be honest with you.”

  “It’s premature,” echoed Avey. “But when is it mature?”63