Here Is a Human Being (39 page)

After three years, I had done it: While I’d hardly conquered it, I had come and seen my genome, or at least some tiny fraction of it. I was glad to have cracked open my own cells. But of course I ignored most of their contents. Not because they were toxic, but because in the end, this journey of self-exploration had turned out to be more of a speculative intellectual exercise than a life-changing clinical one. I had arrived at the theater early enough to grab a good seat, but the carpenters were still building the sets. Or maybe they were done—maybe the show had started but we were still in the first scene in the first act and there was still no way to know whether the performance would be any good. Chances are some of it would, but the reviews would dribble out in the coming years.

The critics will be difficult to assuage. The genome has been the subject of as much hype as anything science has ever undertaken. “Personalized medicine,” “translational medicine,” and “genomic medicine” are the relentless catchphrases, the ubiquitous buzzwords, and all too often, the wishful thinking. Indeed I use them myself: on some level I suppose I have been part of the problem. It could be argued that the PGP, too, has had greater success in the media than it has in the laboratory.
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So far.

By the time you read this, the novelty and the price tag of a human DNA sequence will both have diminished significantly from when I wrote this, much as they’ve been doing for the last few years. In 2009, Illumina announced it would begin sequencing individuals’ whole genomes for $48,000,
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one-seventh the cost Knome announced it would charge when it launched its service in late 2007.
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Not long after, Knome itself dropped its price to $68,500.
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By September 2009, Kevin Shianna was sequencing human genomes for $23,000. By November, Complete Genomics had delivered a genome for $1,726 in reagent costs;
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in the coming months the company’s per-genome costs would shrink even further.
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In early 2010, Illumina unveiled the HiSeq 2000, a souped-up sequencer that could deliver 200 billion bases of DNA—two complete human genomes at thirty-fold coverage—in a single run at a cost of less than $10,000 per genome.
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At Marco Island that year, Jonathan Rothberg, the man who brought the first next-gen sequencer to market, unveiled a semiconductor-based machine costing $50,000 for decoding subsets of the genome for a few hundred bucks. And it was eminently portable: “You can sequence on the back of a donkey if you want to,” said Rothberg.
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Meanwhile, George had begun giving talks around the country: “The $0 Genome.”
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An affordable price tag was no longer in doubt. What it all meant still was. Maynard Olson, a gangly man with horn-rimmed glasses, one of the genomics pioneers in both yeast and human, told me that we should not expect much of anything from individual genomes before we had sequenced thousands upon thousands of them. Until then, each one might be a modest technical achievement depending upon how fast, how accurately, and at what cost it was decoded. But for its owner, any individual genome would not be much more than a “just so” story.
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It was a difficult argument to refute: our genomes may remain “just so” stories for several years. My own genome was no longer an abstraction for me, but neither was it an immediate revelation. My expectation is that the revelations will come, but their exact nature will continue to surprise us. In late 2009, deCODE scientists reported that in some common diseases, which parent the risk allele came from made a difference. In other words, an allele could predispose someone to type 2 diabetes when inherited from dad. But the same allele actually
protected against
type 2 diabetes when it was inherited from mom.
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Male and female genomes are chemically modified in different ways. Thus, personal genomics may depend upon having access to one’s parents’ DNA. One can imagine how this might complicate things in some families.

I suspect that genomes will be like savings bonds or annuities (insert Wall Street joke here): we have invested in them, but, if we are honest with ourselves, in most cases their abiding value to otherwise healthy people has yet to be demonstrated. Those of us who are impatient (I am looking in the mirror) will continue to try to force the issue and extract returns from those investments sooner rather than later.

But even if that takes a long time, I have no intention of boycotting DNA Day (April 25, the day Watson and Crick’s paper appeared in 1953— mark your calendar) just because the marketing of personal genomics has outpaced the science. Nor do I have plans to stop going to my daughters’ school with salt, liquid soap, and rubbing alcohol and showing the fourth graders how to use these simple things to extract their own DNA. Thinking DNA is cool, even in the face of its often-limited predictive value, hardly makes one a genetic determinist. Yes, we are fixated on genes in part because we find them to be seductive and reductive explanations for human traits and behavior. But we are also fixated upon them because, like the proverbial drunk looking for his keys under the lamppost, we
can
be: sequencing genomes is a helluva lot cheaper and easier than collecting detailed phenotypic data and probably always will be. In the next few years, a genome is likely to be a onetime test one gets at birth—hell, even Francis Collins says so!
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Meanwhile, stress tests, mammograms, and colonoscopies will probably always require repeat visits to the clinic throughout our adult lives.

When my kids ask me about pea plants and fertilization and Watson and Crick and Rosalind Franklin and SNPs, I will tell them what I can. But I will also remind them about
environment:
about the microbiome, about the air they breathe, about diet and exercise, and about how much their mother and I love them.

G
lenn Close has had her genome sequenced. So has Desmond Tutu. So have a few identifiable nuclear families.
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And at the beginning of 2010, the Personal Genome Project had 12,500 people in the queue waiting to be participants. Of those, more than a thousand had passed the exam with perfect scores and signed the scary consent form.
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All the PGP needed now was money.

Over lunch at the Prudential Mall in Boston between sessions of the first annual Consumer Genetics Conference in 2009, George, Jason, and the PGP’s pro bono lawyers from Charlotte, North Carolina, brain-stormed about how to keep the project afloat in the absence of much public funding and an unpredictable flow of corporate dollars. George—his usual glass-of-water lunch before him—admitted he worried about it a little bit, though clearly not as much as everyone else at the table did. “It’s

kind of like the skydiver without a parachute,” he said. “Halfway down he says, ‘So far so good.'”
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In April 2010, there would be a personalgenomes.org thousand-dollar-a-plate fund-raiser/conference featuring many if not most of the world’s identified full genomes. Thanks to David Goldstein and Kevin Shianna, I would not have to sneak in through the kitchen. There was some skepticism from the media, but the participants were fully engaged and mostly buoyant. One highlight was John Halamka, clad in a one-of-a-kind black Kevlar dress suit, asking guests to pour water on him only to have it roll right off his synthetic clothes.

Another strategy the PGP adopted was to ask would-be participants for a financial pledge, albeit with the understanding that one’s ability to pay would not have any bearing on whether she was accepted as a participant. George and Jason took pains to make sure that participants could not ever construe this arrangement as any sort of a quid pro quo. “A pledge-type arrangement may contribute toward mitigating the coercive lure of a free genome sequence,” reasoned Jason. “Recall that genome sequencing had a street value of $350,000 not so long ago. That’s a big lure.”
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I understood this argument, but was a $0 genome going to be a lure? Also, I couldn’t help but worry that asking for money would create expectations. If I give my local NPR station $100, I expect a coffee mug or a tote bag. If I give it $10,000, then I expect Brooke Gladstone to bring me breakfast in bed, read me the news in a throaty whisper, and pick out my socks.

The heat on the personal genomics companies had been turned down, at least for a moment. In 2009 a paper appeared in Jim Evans’s journal
Genetics in Medicine
that included both academics and company officials as coauthors. It laid out a framework for how genetic tests should be evaluated and even paid obeisance to the idea of “personal utility” as put forth by Robert Green.
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At first glance this publication seemed like a “Kumbaya moment.” If nothing else, it was a clarion call for more research monies and “independent panels” to study the positive and negative effects of

consumer genomics. At the end of the paper was a list of the commercial coauthors’ conflicts of interest. I found it curious, though not terribly surprising, that while none of the academic physicians and scientists who stood to benefit from an influx of research dollars had any qualms about citing their private-sector colleagues’ conflicts of interest, they never felt conflicted enough to include their own names on the list.

At least two of the seminal figures in commercial personal genomics would be witnessing this new era of public-private cooperation from different vantage points. Linda Avey left 23andMe in 2009 to start a nonprofit foundation devoted to research in Alzheimer’s disease, which claimed her father-in-law.
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It was not clear to me whether she jumped or was pushed, though I have my suspicions. And Navigenics cofounder Dietrich Stephan opted to step away from an operational role in the company. Once Navigenics moved out of the “invention” stage and became a more conventional business trying to move spit kits, Dietrich was ready to return to academia. Indeed, as early as the SoHo launch party, he seemed to me to be tired, beaten down by his company’s legions of critics: medical geneticists, regulators, ethicists, genetic counselors. “I went from being a respected academic researcher who got grants like nobody’s business,” he said, “to landing in a world that was totally foreign to me and having my scientific credibility called into question. It was like getting kicked in the stomach every day.”
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“There’s something about this field,” agreed Linda. “People love to shoot arrows at us.”
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Dietrich started a research institute in the D.C. area, the Ignite Institute,
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which immediately jumped into the fray and ordered a hundred of the latest SOLiD sequencers.
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He had no regrets about the arrows or the blows to the stomach. “I think history will look back kindly on us: Navigenics launched direct-to-consumer genomics for chronic disease in a goldstandard way. deCODE has done a great job on the science… . I just wish they were nicer. Kari’s sharp elbows are unnecessary. I think 23andMe’s greatest skill has been in listening and iterating: they find out what regulators and customers want, and they go back home and change things.”
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As I put this book to bed, it was still not clear what the fate of the Big Three would be. With the meltdown of the Icelandic economy and the company’s failure to develop any genome-based blockbusters, deCODE was in real trouble. In November 2009 it filed for bankruptcy, although the ever-pugnacious Kari Stefansson vowed to fight on.
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In early 2010, the company emerged as a “consulting” firm whose specialty was genome interpretation, while the fate of its personal genome scanning business remained uncertain.
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Meanwhile, 23andMe announced a series of layoffs.
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And the specter of harsh regulation was never far away.

Indeed, this was never clearer than when newcomer Pathway Genomics announced it would begin selling DNA spit kits at Walgreens drugstores in May 2010. The bioethics community had its usual conniption, and within a few days the FDA put the kibosh on the whole thing.
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Shortly thereafter Congress sent letters to Pathway, Navigenics, and 23andMe requesting all kinds of information.
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But neither was the news all bad. Right before Christmas, 23andMe announced that it had bagged another $14 million, bringing its 2009 total to nearly $28 million.
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In early 2010, I sat on a panel with Kari Stefansson and Dietrich Stephan. Kari had his new business partner in tow and his elbows seemed to me to be less sharp. Dietrich seemed relieved to be free of the day-to-day headaches of running Navigenics, though he joked that in his new role running an institute he had exchanged doing battle with regulators and academics for begging for money from hospital administrators.

In my view, the personal genomics companies’ success would ultimately hinge on doctor buy-in, more predictive science, and something that went beyond specific predictions: a cumulative sense that this information was useful in making decisions about one’s life and health. They would also need a deep well of creative and tireless people who have problems with authority; people like Dietrich Stephan, Kari Stefansson, and Linda Avey.

I was pretty sure that I would continue to pester PGP staffers about my latest data releases. Not to be a jerk, but because I actually wanted to have a