Here Is a Human Being Page 7
Crenson used to be a science reporter for the Associated Press. Given the downward trajectory of the newspaper business, he seemed genuinely happy to land on his feet at 23andMe as “Content Manager,” the guy responsible for editing everything the customer read. This particular morning, however, the customer account he tried to show me, belonging to the whimsically named “Greg Mendel,”* wasn’t working. After some tinkering and technical help from a young guy dressed in black, we finally got to meet Greg Mendel’s genome. Matt walked me through it and pointed out various risk alleles for prostate cancer. “This one raises his risk to 1.29, but this one has only been studied in African Americans. There’s a lot of uncertainty now about how much ethnicity affects the results.”†
Crenson explained the company’s criteria for including a trait among the company’s officially sanctioned list, what it called the “Gene Journal.” To make the Gene Journal, a trait had to have been studied in a thousand people or more, been independently replicated in another study, and been reported in a reputable, peer-reviewed journal. “Not the Albanian Journal of Medical Genetics and Dentistry,” Crenson assured me.1 In December 2007 the company featured eighteen traits in the Gene Journal, from earwax consistency to restless legs syndrome to Crohn’s disease. Within a few months there would be a total of seventy-eight traits. Soon it was no longer called the Gene Journal, but simply “Health and Traits.”2 By 2010 the company was reporting risk estimates on forty-seven “clinical” traits that it considered to be fully vetted (including twenty-one recessive diseases for which one might be a carrier), and eighty-seven additional “research” traits for which either there was insufficient data (in 23and-Me’s eyes) or the traits did not affect disease risk (for example, “food preference,” “hair color”).3
From the beginning 23andMe offered customers information about their ancestry using mitochondrial DNA (passed on only by mothers) and Y-chromosome markers (passed on only by fathers); eventually it began including markers from the other twenty-three chromosomes (1 through 22 plus X). Crenson took me back in time through “Mendel’s” genealogy and the groups of markers that had been transmitted down through his family. A few months after my first visit, 23andMe would incorporate social networking based on genomic characteristics into its menu: a Facebook for the genome-savvy set. At the Global Economic Forum in Davos, Switzerland, company executives passed out spit kits to the glitterati, an apparent strategy to help brand personal genomics as hip.4 Bono was tested. Jimmy Buffett and Warren Buffett were tested: no relation, they learned!5 Peter Gabriel was tested.6 In 2009, 23andMe launched an online community of pregnant “mommy bloggers”: “Explore the genetic legacy your child will inherit from you and your partner.”7
23andMe was cofounded by Anne Wojcicki, the wife of Google zillionaire Sergey Brin, and Linda Avey, formerly of biotech behemoth Affymetrix and its now-defunct human genomics spinoff, Perlegen. On the day I visited, true to 23andMe’s start-up mojo, both women were running around with great urgency, putting out fires and hurrying to and from meetings and conference calls. They apologized and asked if I could come back later. That afternoon, Avey, a striking blonde in her late forties who grew up in South Dakota, finally sat down to talk about the origins of the company.
When Avey was at Perlegen, her mission was to convince pharmaceutical companies to use the Affymetrix GeneChip technology—the small glass wafers used to type some of the millions of SNPs in human and other genomes—to begin to go after genes that cause specific diseases. But in those days the genome was terra that was even more incognita than it is now—relatively few SNPs had been characterized. Thus Perlegen couldn’t begin gene discovery without first embarking on an expedition to isolate more markers that would allow it to sharpen the cartography of the genome. That meant a $100 million commitment to sequence bits and pieces of fifty human genomes, however crudely.8 This was an arduous slog, but it paid off: the company managed to identify 1.7 million SNPs, an unprecedented treasure trove in 2003.9 (For comparison, when I began graduate school in the early 1990s we knew about no more than a few hundred polymorphic DNA markers across the entire human genome.)
Perlegen was now in a position to design a DNA chip with several hundred thousand markers and begin to do genome-wide association studies (GWAS). These are essentially very dense case-control studies designed to find DNA markers important in disease. By typing the same set of markers in large numbers of cases and controls, it becomes a brute-force statistical matter of finding markers that pop up more frequently in sick people than in healthy ones. Those markers are very likely to be in or near genes that play a role in disease.10
GWAS studies have since become ho-hum.* But only a few years ago, they were the new new thing. So new, in fact, that NIH and industry were reluctant to fund them. By 2005, Perlegen had designed a chip with 250,000 markers, identified cohorts with diseases such as Parkinson’s, but could get neither corporate backing nor public funding to move ahead with GWAS.11
“You might identify a group of two thousand samples,” Avey said, “but the NIH funding mechanisms were stuck in their old paradigm—they had cutoffs. People would look at their sample sets and say, ‘Okay, [given my funding] I can only afford to do a certain number.’ And then it would sort of defeat the purpose because you wouldn’t have the statistical power to really find what you were looking for. The whole vicious cycle was infuriating after a while. A lot of people at Perlegen and Affy were frustrated. This technology was just sitting there and being under-utilized.”12
It was this frustration, Avey told me, that planted the seed for a freestanding personal genomics company. “What if,” she thought, “we just shifted this paradigm and opened up the ability for people to pay their own way and gave them access to their own genetic information?”13
Her first idea was spas. Spas, she reasoned, had become more clinically oriented while doctors’ offices had become increasingly more spalike. “You had this weird convergence happening. People at spas have got disposable income and they are very interested in their health. Some of the high-end spas had changed their image to become ‘wellness centers.'”14
Avey took the concept to some of the Affy VPs with whom she went on six-mile runs in the morning. “Talk to Steve,” they told her. According to Avey, Affy CEO Steve Fodor was enthusiastic and told Avey she had to do it … but not at Affy. It was, he told her, beyond the firm’s core mission as a research tool provider.
At a meeting where Perlegen was presenting data on the company’s efforts in Parkinson’s disease, Avey met Google mogul Sergey Brin, whose mother suffered from Parkinson’s.15 Brin began asking Avey detailed questions about Perlegen and its analytic approach. Hopeful that she could persuade Google to back her new venture, Avey began trying to set up meetings with Brin, but found it difficult.
“He always wanted to have his girlfriend there with him. And I thought, you know, who is this girlfriend?”16
Anne Wojcicki had been investing in health care and was herself frustrated at the sector’s lack of progress and poor return on investment. She and Avey came together at the annual Technology, Entertainment and Design meeting in Monterey and agreed to move ahead with what they called—aptly if unimaginatively—"Newco.” Google would kick in $3.9 million and Newco would eventually become 23andMe. Wojcicki told Fast Company that she was in her kitchen reading Wikipedia, saw a picture of the twenty-three pairs of chromosomes, and started singing the words, “Twenty-three and me.” Newco had a new name.17
Where 23andMe went for playful, its Silicon Valley neighbor, Navigenics, opted for serious. Serious as a heart attack, one might say. Whereas the 2009 iteration of the 23andMe Web presence was all light and shiny and iPod nano–ish, the Navigenics website felt more like a doctor’s office, full of pastel and sepia tones, handsome and mature couples, all sun-swept and looking extremely healthy—one half expected a medical history questionnaire and six-month-old magazines to materialize on one’s screen. The original video I saw describing the comp
any’s Health Compass service was presented by cofounder and chief scientific officer Dietrich Stephan, a short, amiable, and balding man in his early forties. In the video he appeared to me to be somewhat uncomfortable and constricted; in person he reminded me of a gentler, more garrulous, and perhaps more rumpled version of the great B-movie actor John Saxon. When I first met him at company headquarters he wore baggy pants and layers—shirt, red fleece, and brown cotton jacket. He spoke softly and with a faint Pittsburgh accent; he laughed easily, even when talking about the minutiae of FDA regulations.
He began plodding along from square one, giving me a rudimentary history of the Human Genome Project and Craig Venter. I tried not to make my impatience too obvious but rather to politely move him beyond the scripted VC speech. When I asked him about the impetus for starting Navigenics, he became animated, just as Linda Avey did when talking about the birth of 23andMe. Stephan was, he told me, toiling away at a large genomics research shop in Arizona, the Translational Genomics Research Institute (TGen), finding disease susceptibility genes and watching his discoveries go … nowhere. “I started getting frustrated that people weren’t applying this to understanding individual risk profiles. I tried desperately to get things placed into molecular diagnostic facilities, but they didn’t understand how to interpret that information and give it back to physicians or genetic counselors. They would say, ‘This is not a binary diagnostic.’ That’s what all of these folks are used to: you have two copies of a cystic fibrosis mutation and you’re going to have cystic fibrosis. Or you have one copy and you’re a carrier. Or you have zero copies [and you’re neither].”18
The diseases Navigenics focused on initially—type 2 diabetes, Crohn’s disease, heart disease, multiple sclerosis, obesity, rheumatoid arthritis, and a dozen others—rarely played by Mendel’s simple rules of genetics, that is, one gene = one trait. One can carry half a dozen versions (risk alleles) from six different genes that predispose to a common disease and still be at average or even below average risk for developing that disease. Stephan immediately recognized the challenges Navigenics would face. “How do you put that information in context and how do you communicate risk to people?”19
When describing the field, he used the word nuanced several times. He spoke about educating physicians and genetic counselors and developing a gold standard. “We want to set the bar high. We’re going to come at this from a hard-core medicine and science perspective, put all of the spokes of this wheel in place and then roll it out.”20
One of the early criticisms of companies like Navigenics was that they were giving information about diseases for which nothing could be done. I asked Stephan for an example of a condition that was both multigenic and “actionable.” Without hesitation he said, “Alzheimer’s.”
“It’s all about finding people four or five decades before they show the first symptoms, lowering their cholesterol, making sure they live an active physical and mental lifestyle, and taking advantage of some of the early screening programs. And if you do that, you’ve decreased the incidence by fifty percent and you’ve prevented ten million people from getting Alzheimer’s disease.”21
From many scientists this type of talk might have sounded like blather—hubris mixed with naïveté. Even though what we know about the biology of Alzheimer’s could fill volumes, preventing millions from succumbing to the disease seemed quixotic at best, a delusional and destructive fairy tale at worst. Did Stephan have a messiah complex? He went on about how this model could be applied to other common chronic diseases, such as cancer. The money we would save would help solve the U.S. health-care crisis. He believed it. And so did the investment community. In eighteen months Navigenics had enlisted VC big boys Kleiner Perkins and Sequoia Capital to the tune of $25 million,22 a tidy sum in a tough market, especially for a company that was not making widgets, but trafficking purely in information.
Stephan brought me into a room full of geneticists, their desks lining the perimeter of an office that looked out onto a man-made lagoon. They were young and enthusiastic, if a bit stressed—good old-fashioned dotcom-style fatigue. “We should have bars on the windows,” Dietrich said.23
He introduced me to Eran Halperin, a friendly Israeli and at the time the company’s head of genetic research; unshaven, he looked tired. A computational guy by training, he had been working hard on finding statistical ways to infer people’s genotypes at places where the million markers they used failed to provide information—the genes of interest had slipped through the cracks and were in places in the genome that were not represented by any of these markers. But because chunks of chromosomes tend to travel together as they’re passed from parent to child, it was possible to play a kind of probabilistic guessing game known as imputation that could often fill in the gaps between the mile markers represented by the SNPs.24 Halperin’s unofficial title was the Imputator.
Across the room sat Elissa Levin, an attractive, kinky-haired, and gregarious genetic counselor. She directed the Navigenics Genetic Counseling Program and I could recognize her genetic counselor persona—both warm and direct. Part of “getting it right,” Stephan had told me, would be providing customers with phone counseling after they received their results. But why? Weren’t most of these folks going to be highly motivated early adopters anyway?
“This is a lot of information,” said Levin. “We’re doing everything we can to try to present it in an eloquent visual and written way. But we understand that it’s also critical for someone to be able to pick up the phone. It’s not just calling your doctor, who might not be familiar with it. It’s having somebody on the other end of the line who can actually review your results with you and understand the context.”25
In the coming months, deCODEme would make referrals to genetic counselors part of its services.26 23andMe included a pointer to the American College of Medical Genetics on its website.27 DNA Direct, which served as a clearinghouse for traditional single-gene disease testing, employed several genetic counselors,28 as did genome scanning latecomer Pathway Genomics.29 But in the early days, Navigenics remained the lone consumer genome-scanning company with genetic counselors on staff that included counseling in its fee.
The company hosted a two-week launch party in New York, at a loft in SoHo. Outside flew a Navigenics flag. In the windows were blowups of the same people I’d seen on the website: the healthy-and-happy-but-serious people of different races and genders and sexual preferences. No fat people, though. Inside there were high ceilings and hardwood floors and generous bags of swag. There was an open bar serving, among other things, a delectable concoction that looked exactly like Hawaiian Punch called a Navatini. Venture capitalists know how to throw a party.
Beautiful people abounded. Al Gore, his climate-change star still at its apex, held forth at the initial reception. “This is a great firm,” he said. “On all these new genetic breakthroughs, there is always some resistance culturally, and then, when there’s an evaluation of the inherent value, if the ethics are right, if the surrounding culture is right, then it just breaks through… . I think this company has the culture right … and I think it’s going to be a fantastic success.”30
The buzz was palpable. The New York Times style section had a splashy feature.31 At the loft each day, the Navatini-induced revelry was mixed with gravitas as panels of mostly hot-shit scientists convened to discuss Important Topics relating to genomics and health care. An old friend from graduate school, Tara Matise, a statistical geneticist at Rutgers, had emailed me weeks earlier asking about 23andMe on behalf of her father, who was interested in his risks for Alzheimer’s. I mentioned Navigenics and, after catching wind of the party, she agreed to meet me there. “It’s possible it’s a little on the early side,” she said. “I think people like me are curious but they’re concerned [that it’s not ready].”32
We witnessed those concerns firsthand. Any notions that this would be a Tax-Day Love Fest were dispelled by the session innocuously titled “Genomic Testing and Your Pract
ice.” It featured Elissa, Dietrich, and two other genetic counselors on a makeshift white stage with an embedded video screen in the back room of the SoHo space. The audience was primarily genetic counselors, all women, and from the beginning their collective stance was skeptical … to say the least.
As I’ve said, in the late 1980s I was a board-eligible genetic counselor. I was never very good at delivering bad news and the moment I fell in love—or at least lust—with lab-based genetic research, I gave up most of my thoughts of working in a genetics clinic and promptly bluffed my way into a Ph.D. program. But I have retained a soft spot for genetic counseling as a profession and genetic counselors as people. Like nurses, I think they have chosen a fascinating and invaluable but quite impossible and largely thankless profession. They have to deal with stressed-out and/or grieving patients on the one hand and often overbearing and capricious doctors on the other. Because with few exceptions they have only master’s degrees, they are regularly dismissed and patronized by physicians, especially those physicians who aren’t geneticists and therefore don’t—or can’t—appreciate what counselors do. I’ve had more than one M.D. geneticist tell me that counselors are no more than “physician extenders.” Would they call them that, I wondered, if their ranks were 94 percent men instead of 94 percent women?33 Genetic counselors were underpaid, despite a common refrain that there weren’t enough of them to go around. Like nurses, they lacked autonomy. For decades they were told to be “nondirective” lest they unwittingly let slip their views about matters such as abortion with their patients. Have doctors ever been subjected to such rules?