The implications of an affordable exome and/or genome left him both excited and unsettled. And he wasn’t the only one. He forged ahead with the PGP, but was forced to use private money. He believed the National Institutes of Health (NIH) was balking at paying for the project (despite having approved it and every other aspect of his $10 million genome technology grant) because he refused to do it under the standard ethical paradigm set forth by the agency, that is, one in which subjects give informed consent and in return are promised, more or less, privacy and confidentiality.36 “I just feel uncomfortable signing up people under the supposition of anonymity if that’s not something that can be assured.”37
Why couldn’t it be assured? On his website, George offered a laundry list of real-life scenarios where presumptively anonymous subjects were reidentified without their consent.38 Some of these became infamous stories. In the 1990s, for example, then-MIT grad student Latanya Sweeney used publicly available voter records and a public, anonymized database of state employees to identify the medical records of Massachusetts governor William Weld. She was also able to identify the five African-American women living in the predominantly gay enclave of Provincetown, Massachusetts, purely on the basis of public data.39 Another example: a few years ago, a fifteen-year-old boy used a combination of a commercial DNA test of his Y chromosome, genealogical records, and Internet searches to locate his “anonymous” sperm donor father.40
In George’s eyes, these types of privacy-hacker stories would only become more common as genomic data proliferated. DNA is the ultimate digital identifier, after all—a social security number is only nine digits, while a genome is three billion. Not that anywhere near that number would even be necessary to hack one’s identity: a paper in Science suggested that as few as eight genetic markers could be considered a risk for reidentifying humans.41 Twenty-five such markers would likely be fully identifying, akin to the thirteen forensic DNA markers typically typed from crime scene samples.* And in 2008, researchers from the Translational Genomics Research Institute and University of California at Los Angeles were able to identify individual DNA samples from a complex mixture of samples from as many as two hundred people, even if a particular individual’s sample accounted for only one-tenth of 1 percent of the total DNA mixture.42 In response the NIH immediately backpedaled on its promise to facilitate widespread sharing of human DNA samples among the studies it funded.43 George saw this coming. Given the technical realities, he said, to promise privacy and confidentiality would be disingenuous at best.44
And there’s another reason not to do it, he said: it makes for bad, or at least limited, science. Ensuring anonymity, assuming it can be done at all, means restricting the use of any phenotypic information that could be used to reidentify a subject. But it is exactly those sorts of unique bits of data on human traits—hair color, eye color, facial features, cognitive measures—that George saw as necessary to fully leverage whole genomes and really begin to understand the human gestalt. “Some people look at a person’s face and think they can tell everything about his past, present and future,” he said. “That’s not true, of course. But when you ask who you are, a huge fraction is what your face is. So take the face plus the genome, plus metabolites, plus proteomics, and then you’re starting to get something that is without parallel in current practice.”45 Giving broad access can have practical benefits, too. One of George’s favorite stories—recounted on his website, naturally46—is from 2004. He was preparing to give a lecture in Seattle at the University of Washington Medical School when a hematologist in the audience raised his hand and said, “You really ought to get your cholesterol checked.” He had looked at George’s personal medical records Web page and seen that his total cholesterol was 288 mg/dL (the normal level is less than 200). The 288 measurement was more than a year old and George had not been back to his doctor to see if the statin he was taking was having the desired effect. It turned out it was not. His doctor doubled the dose and George went back to a strict vegan diet. In six weeks his cholesterol had fallen to 156 mg/dL. What struck George was that this interaction with a total stranger had had a tangible positive effect on his health. “That total-stranger expert will eventually be replaced by software,” he predicted.47
For that to happen and for it to be of practical value will require both genetic data and health records. George’s Harvard colleague, pediatrician, and champion of electronic health records Isaac “Zak” Kohane told me essentially the same thing as every other genome scientist I spoke to. “Without the phenotype, the genome is just not that useful.”48 But even ambitious genome sequencing efforts such as the internationally sponsored “1000 Genomes Project” were not prepared to collect detailed trait data on their subjects, preferring instead to use “old” DNA samples from “anonymized” subjects who had consented years ago.49 Collecting trait data is hard, it’s time-consuming, it’s expensive, and yes, it makes the subjects that much easier to identify.
For the last problem, George’s solution was “open consent.” Why not, he asked, recruit subjects willing to forgo guarantees of privacy and confidentiality—that is to say, people like him? This is why he became Subject Number One in the PGP.50
Of the first two prominent public genomes, Craig Venter has been open about his sequence, even though it told him that he is at increased risk for Alzheimer’s and macular degeneration.51 James Watson’s DNA now resides in a public DNA database.52 Watson’s son Rufus has schizophrenia.53 When I asked Watson if he consulted with his family members before making his genome public, he shook his head and smiled. “They might have said no.”54 Indeed, one sometimes wonders what might ultimately be found in Watson’s DNA. The same week in which he publicly implied that Africans were less intelligent than whites and lost his job because of it,55 he suggested that crystallographer and onetime rival the late Rosalind Franklin had been partially autistic.56 One wants to kick him under the table or pull him aside and say, “Dude. Stop.” When I asked George about Watson being one of the first complete and public genomes, he gave a less than ringing endorsement. “I don’t think it was an ideal choice. If you’re gonna put all your eggs in one basket, he doesn’t seem like the obvious first basket.”57
In 2005, the Harvard Medical School Institutional Review Board approved the Personal Genome Project, but only after lengthy discussion.* Initially, according to rabbi and IRB member Terry Bard, a longtime lecturer on pastoral counseling in psychiatry at Harvard, the Harvard IRB was not even sure the PGP was in its bailiwick. “Everyone, including me,” said Bard, “was scratching their heads and saying, ‘Why is this here?’ A number of members were not convinced—and maybe remain unconvinced—that, as presented, this was actually a research study. Did it meet the basic scientific criteria for research?” George appeared before the IRB twice to convince members that it was indeed research and to seek IRB guidance as to what to include in the protocol and the consent form.58
Initially, George was asked to limit the initial subject total to one: himself. Bard shepherded him through the consent process. Since George was putting both his genotype and phenotype on the Web and therefore making it available for public scrutiny, Bard said the IRB wanted to gauge the initial experience first. “We wanted to know how it would play in Peoria, so to speak,” said Bard. “Dr. Church made monthly reports back to us on how his decision was being received and what kinds of interactions he had had.”59
Bard is a short man who, when I met with him in his softly lit office at Beth Israel Deaconess Medical Center, wore a white hospital coat. As a perpetually confused Jew, I was anxious to avail myself of his other skill set. So at the end of our hour-long conversation, I asked him what the halachic view of the PGP might be—how would it be perceived through the lens of Jewish law? He said he’d never really thought about it. “Are you exposing yourself or others to irrevocable harm that can be avoided? If that’s the case, then in the Jewish tradition that’s not permissible. But on the other hand, you know the joke from Rabbi Akiva:
‘All is foreseen and free will is given.’ I don’t have an answer. You’re never gonna find anything that two Jews agree upon except that some third person should give to charity.”60
Eventually the IRB agreed to consent to admit two more people but still wanted to proceed with extreme caution. Each of the first ten participants would have to have a master’s degree in genetics or equivalent. Presumably those people could be expected to understand the risks of open consent. Or to put it more bluntly, as one bioethicist familiar with the PGP said to me, “If we have highly educated ‘altruists’ willing to take a hit and potentially go through life without insurance, then we should explore the unintended consequences with them because at least they could afford it.”61
In May 2006 the National Human Genome Research Institute asked for a “single coherent document” that would put forward a scholarly presentation of the PGP and address the attendant ethical, legal, and social issues (“ELSI”).62 George assembled a virtual collection of seventeen bioethics and legal experts (including, I should say, one of my colleagues at Duke, Bob Cook-Deegan, and me). With Dutch doctoral candidate Jeantine Lunshof and Harvard Law student Dan Vorhaus (both have since graduated), George drafted a white paper that tried to make the two cases I articulated above, namely 1) promising genomic privacy is dangerous and unrealistic, and 2) the only way to fully exploit genomic data is by integrating it with other biological and phenotypic data, some of which are intrinsically identifying (faces, for example).
By way of comparison, the white paper discussed—and took a couple of shots at—the consent used in a large-scale global genotyping project of a few years ago, the HapMap, which amounted to a survey of genotypes from four different populations and is widely acknowledged as a very useful resource to researchers who troll through the whole genome in order to find disease genes.63 The HapMap consent included this passage, which was singled out by George and company:
Because the database will be public, people who do identity testing, such as for paternity testing or law enforcement, may also use the samples, the database, and the HapMap, to do general research. However, it will be very hard for anyone to learn anything about you personally from any of this research because none of the samples, the database, or the HapMap will include your name or any other information that could identify you or your family.64 [Emphasis in original]
George’s original form, on the other hand, said the following:
You should also be aware of the ways in which knowledge of your genotype and phenotype might be used. For example, anyone with sufficient knowledge could take your genome and/or posted medical information and use them to (1) infer paternity or other features of your genealogy, (2) claim statistical evidence that could affect your employment or insurance, (3) claim your relatedness to infamous villains, (4) make synthetic DNA and plant it at a crime scene, (5) reveal the possibility of a disease or unknown propensity for a disease.65
It read like a list of potential plotlines for the Lifetime Movie Network (which, in 2007, ran a recurring feature titled “'Can You Handle The Truth’ Thursday”). The first two scenarios struck me as the most worrisome. Genetic discrimination was an obvious possibility for which we think we have the beginnings of a legal solution. Nonpaternity has been going on since Adam and Eve; we just haven’t had a way to confirm it until recently. If you give the same single-gene genetic test to parents (or even one parent) and their/his/her children, and the results don’t jibe, there are three possibilities: 1) a new mutation in the child, 2) laboratory error, or 3) nonpaternity. Of the three, assuming one is dealing with a reputable lab, the last is by far the most likely: 10 percent of the time, on average, the nominal father is not the biological father.66 When I was a genetic-counselor-in-training, we were told never to disclose nonpaternity to anyone but the mother—it was none of our business, it was not why families came to us, and really, who wants to deal with the headaches and heartaches living inside other people’s closets. But just as the teenage boy found his biological father in a few short steps, personal genomics has already made it that much simpler for children to find out whether the titular dad sitting at the dinner table shares half—or none—of their genomes. In conducting research for this book, I heard stories of personal genomics companies awkwardly having to negotiate the discovery of nonpaternity.
Public outing of people’s genomes is something Boston University’s genetic legal scholars Winnie Roche and George Annas have thought about for decades. In the 1980s they agitated for something that goes well beyond the Genetic Information Nondiscrimination Act, which collected dust in Congress for twelve years before becoming law in 2008. They would like to see a statute explicitly guaranteeing genetic privacy.67 But if there was no sense of urgency to pass GINA, which as I’ve noted is designed to prevent discrimination only in employment and in health (but not life) insurance, then what is the case for a more far-reaching law?
“Let me just give you a stupid example,” said Annas, a short man with glasses and a thick beard who’s known for his acid pen. “Let’s say you have this technology to do ten genomes a week [cheaply]. That’d become a major part of physicals for political candidates. It would get nasty! Each candidate would want to pull out the genomes of the other candidates and disclose every possible predisposition they have. ‘He’s got a pedophilia gene!’ ‘He’s gonna get Alzheimer’s!’ ‘Oh yeah, well, he’s probably got Alzheimer’s already!’ [But] you could certainly draft a criminal statute that says you can’t do that.”68 In the wake of the bitter 2008 presidential election, Annas and Boston University neurologist Robert Green wrote a cautionary piece in the New England Journal of Medicine citing the possibility of misleading results, false positives, and “genetic McCarthyism” that could result if the electorate started demanding genome scans from presidential candidates.69
While George Church included these sorts of caveats in his consent form, it’s unlikely he’s ever lost a moment’s sleep over them. His own behavior has been nothing if not consistent with an unflagging belief in openness. His website offers the best examples of this. To the uninitiated much of it is fairly dry biomedical science stuff: his lab, his funded projects, his publications, his scientific advisory roles.70 But its many tentacles include pages devoted to him that are not all that different from what a particularly guileless and nerdy college student might post on Facebook or MySpace. His main personal page, for example, features rotating pictures of himself at various ages, describes his upbringing, lists his hobbies (waterskiing [like father like son], aerobatics, turtle breeding, etc.) and charts his development as a scientific thinker from childhood on (“First independent chemistry experiments, Spring 1972. Organic synthesis of cyclohexanone as well as qualitative analysis & IR spectroscopy of various organic compounds”). But it also lets his demographic information all hang out: it includes links to a map of his Brookline neighborhood with an arrow pointing to his house, his signature, his diet and health records, his mother’s maiden name, and, until a few years ago, his Social Security number.71 Even his wife Ting, an otherwise unabashed supporter of her husband, recalled a moment of shock at the latter. “You have your Social Security number open to the public?” she said to him. George told her that it didn’t matter—if someone wanted it badly enough, they could get it anyway. “Well,” she said, “you don’t have to make it that easy.” Down it came.72
George’s high-profile and sometimes slightly off-the-reservation Web presence, his articles touting the PGP in the media, his rosy predictions about personal genomics on a large scale made to anyone who will listen, and especially his public embrace of the open-source ethos, all served as fodder for those who would characterize him, the way someone did to me with what sounded a lot like suspicion and contempt, as “that guy who wants to put everyone’s DNA up on the Internet.”
But George has always denied being a dogmatist. The motivation behind his recruitment of a seventeen-strong ethics contingent, he told me, was not to enlist them as a rubber stamp.
Rather, he said he did it because he really didn’t know exactly what the right thing to do was with respect to subjects’ data. (An aside: with all due respect to my social science colleagues, assembling seventeen bioethicists hardly seems like a recipe for consensus.) “We want to stay nimble,” George told me not long after we met for the first time. “We are listening and learning.”73
I asked him how the PGP would handle the discovery of bad news lurking in a subject’s genome. What if someone turned out to be at high risk for some catastrophic condition like Huntington’s or Lou Gehrig’s disease? George said that that person would have the option of not knowing.*
“Then you’re confident you can keep the data private,” I said.
“We’re not actually confident,” he said. “But we are going to try as hard or harder than previous human genetics studies. We’re pretty good at computational security and we will try, but we’re not promising that. It could become public immediately.”74
At a genomics meeting I met Margret Hoehe, a raven-haired and outspoken M.D.-Ph.D. who is a group leader at the Max Planck Institute for Molecular Genetics in Berlin. She recalled getting roundly mocked by colleagues for having the audacity to suggest we begin to sequence humans for medical purposes. This was in 1990. Now in her fifties, she seemed to be no more aligned with the German genetics community—one, admittedly, still wrestling with the colossal eugenic shadow cast by World War II—than she was in her youth. In 2009, the German government passed one of the stricter laws regulating genetic testing in history: all tests must be ordered by a physician, no anonymous paternity testing, no paternity tests during pregnancy except in cases of rape, etc.75 Wholegenome sequencing of healthy Germans seemed an unlikely prospect. “I’m always twenty years too early,” Hoehe said, laughing. She still had big plans for experiments she wanted to carry out, but was not optimistic that she could get sufficient buy-in to land the funding. She described herself as having the soul of an American but having the misfortune of being born German. Without question, she said, the most extraordinary period in her scientific career was her two years in the Church lab in the early 1990s. She stirred her drink and smiled at the memory.
Here Is a Human Being Page 3