“He’s the only one who ever believed in my crazy ideas.”76
* Six billion base pairs = three billion paired nucleotides—the A’s, G’s, T’s, and C’s of the DNA alphabet—on one double helix times two sets of chromosomes, one from Mom and one from Dad.
* A draft version was first unveiled in 2000.
* Jim Watson received his genome sequence on a hard drive in an elaborate ceremony at Baylor College of Medicine on May 31, 2007, while Venter’s was published in the journal PLoS Biology in September 2007. But Venter, Watson’s once and future rival since the early days of the Human Genome Project, made sure to deposit his own sequence in GenBank, the public DNA database, before Watson deposited his. At the Baylor event, Watson recalled the race to sequence the human genome and said of Venter, “He was clearly so bad we couldn’t let him win.” A paper describing Watson’s sequence was published in Nature in 2008.
* Forensic DNA markers as used by the FBI tend to be highly variable (“polymorphic”); that is, they are present in many different versions in the human genome and therefore carry more information than standard markers used in genetic studies, which typically come in just one of two “flavors.”
* The Institutional Review Board is the ethical review board charged with approving, monitoring, and reviewing biomedical research on humans. Every hospital and academic medical center has one or more IRBs; I serve on Duke’s.
* Jim Watson, for example, indicated that he did not want to know which version (“allele”) of the APOE gene he carries, certain flavors of which could put him at risk for Alzheimer’s or heart disease; Craig Venter, on the other hand, is known to carry one high-risk version of APOE.
3 “Why Should We Make Them Go Out on the Dance Floor?”
“Why in God’s name would you want to do that?” a geneticist friend asked when I told him I wanted to be a PGP subject and make my genome public. The better question, it seemed to me, was why wouldn’t I?
At the risk of sounding Pollyannaish, I thought the PGP might actually help make a difference. True believers like Church, Halamka, and some of the other PGP subjects often said that personal genomics represented an opportunity to change health care. Physicians, they said, spend months and hundreds of thousands of dollars trying to find the right statin, the right blood thinner, or the right antidepressant for their patients, to say nothing of the right dose. Trial and error was still the MO. Genomics, they said, had the power to streamline that process: if we knew which genomic variants people carried and the way those influenced drug metabolism, we could prescribe medicines in a more rational way—this is the cornerstone of the burgeoning field of pharmacogenomics.1 If we knew the contents of folks’ genomes, we could avoid giving them the wrong drugs and in doing so save some lives (one study estimated that a hundred thousand people per year suffer fatal adverse drug reactions in hospitals2). Further afield, we could potentially use genomic medicine to avoid food allergies, curtail dangerous exercise regimens, and tell people how much sleep is too much … or not enough. Prior to the massive Obama healthcare overhaul, everyone I spoke to agreed that fundamental changes to health care were essential—in the United States we were spending more than 15 percent of gross domestic product on it and clearly getting ripped off. But should the necessary changes be more about quotidian details like reimbursement and incentives rather than newfangled technologies like supercheap DNA sequencing? Could the PGP help figure out what sorts of useful things one might do with 20,000+ genes appended to people’s health records?
I had more selfish hopes, too. I imagined the PGP would be an opportunity to walk in my former research subjects’ shoes, albeit with a twist. Scientists who do human subjects research spend so much time writing grants, crafting consent forms, collecting samples, experimenting on and analyzing those samples, and then looking for more, that most of us don’t have a clue as to how it feels on the other end of the phlebotomist’s needle, the graduate student’s personal questions, or the stethoscope. A few years ago I completed a yearlong exercise study, which was fun, got me in shape, and even helped me to drop a few pounds. It came with a few hundred bucks and ten months’ membership at a fitness club—a pretty good deal for doing something that I should have been doing anyway. As he biopsied my thigh muscle or pumped me full of glucose, the principal investigator, an amiable cardiologist, patiently answered all of my questions. But at the end of the day, he was not my doctor, he was a researcher—his team needed my data infinitely more than it needed what I needed, which was for my cholesterol numbers to improve. I was, finally, just another data point.
The uglier side of this equation can be found in bioethicist Carl Elliott’s brilliant and terrifying 2008 New Yorker article, “Guinea Pigging.”3 In it Elliott described a somewhat freaky underclass of people who eke out a living as research subjects in clinical drug trials. There were the subjects who had their recreational time cut short at the investigators’ whims, those in a Philadelphia-based study who were forbidden to leave their medical research facility on 9/11 (“No one’s going home! Everything’s fine!”), and most tragically, those in recklessly supervised psychiatric studies who took their own lives.
In part as a hedge against these sorts of outcomes, the initial PGP cohort of ten would be populated by people with biomedical backgrounds who actually read and understood the consent form and presumably knew what questions to ask of the principal investigator, who was himself a subject. The yawning chasm between scientist and subject would not be so wide. Or so we hoped.
And of course the PGP would also afford me the chance to have a look at my own genome. After all those years of graduate school and all those thousands of DNA samples I’d aliquotted into tiny polypropylene tubes, I might understand something about myself at the molecular level. Did I carry one or more Hirschsprung’s mutations as my nephew must? Were there some drugs I metabolized better than others? Was I at high risk for the same heart attacks that felled my paternal grandfather at age fifty and maternal grandmother at age sixty? Was I in the throes of a standard-issue midlife crisis or might there be a genetic basis to the anxiety and depression that had made me a regular on a therapist’s couch and at the drive-through pharmacy? Wouldn’t it be cool to know?
Accordingly, I sent my slightly alarmed but always practical wife an improvised email questionnaire. After mocking my formality, Ann responded in earnest (my questions in italics, her answers below them):
Hi:
Over the next few days, I’d like for you to think about these questions and respond in writing. I’m happy to discuss. Thanks—love you.
1) What are your overall feelings about the prospect of me getting my genome sequenced mainly for research purposes?
Overall I’m fine with it. I will feel better about it all if I know ahead of time what to expect (in terms of travel and medical interventions) so I can plan.
2) What if my sequence revealed that I’m at high risk for some devastating illness in the future?
Well, that would suck. Can’t make policy based on the worst-case scenario. I’m the optimistic type so we’ll just hope for the best.
3) What if that same information also suggested that one or both of our daughters are at higher risk for one or more diseases? How would you deal with that?
You mean how would we deal with that. I think we’d need to talk with folks about what we could do with this information. I’m thinking here about BRCA; I’m assuming you are, too. Would we have them tested, when would we tell them, etc.*
4) What if my genomic and health information were publicly available on the Web? Would you worry about some person or institution—my employer, an insurance company, a hacker—getting ahold of that information and harming me/us with it? Why or why not?
Again I need to know more to answer this question. What legal protections does an individual have regarding his/her own genetic material? I’m still unclear why, if this information is made public, that the media would need to know your identity. I’m not sure
why you cannot remain anonymous.
5) What if getting my genome sequenced meant a lot of press attention? How would you feel about frequent calls, emails and/or visits from reporters?
I’d rather they visit you at Duke. I don’t really want the girls involved.
My wife likes her privacy. Unlike her husband, she does not seek the spotlight. Indeed, despite the rise of reality TV and Facebook/Twitter exhibitionism, most Americans still treasure what Justice Louis Brandeis called “the right to be left alone.”4 Thus it was Ann’s response to question 4 that seemed to me to get at the core of why the PGP made some people—and the NIH—nervous. The truth of the matter was, outside of a patchwork of state nondiscrimination laws and the Genetic Information Nondiscrimination Act governing health insurance and employment, an individual had limited legal protections over his genome, especially with respect to the physical DNA itself. For most of the last thirty years the judicial system has been fairly consistent: once they leave your body, you do not own your tissue, organs, or bodily fluids or any of the revenue they might generate for a biotech company, a university, or anyone else.5
But why? And how did we get here? The issue has still not been completely settled and it’s one that continues to reverberate throughout the legal system. In 2003 urologist and prostate cancer researcher Bill Catalona moved from Washington University in St. Louis to Northwestern University after WU tried to assert control over the huge repository of patient samples he had collected. Catalona, a short man with white hair and a slightly gravelly voice, has performed thousands of prostate operations, those of St. Louis Cardinals greats Stan Musial and Joe Torre among them. He knows as much about the clinical genetics of the disease as anyone. Shortly after moving to Northwestern he asked ten thousand patients who were part of his studies to write letters to Washington University requesting that their samples be transferred to Northwestern; six thousand eventually complied.6 WU responded by filing suit against Catalona.7
The case rested on two competing interests: Missouri state property law and federal regulations meant to protect research participants. Catalona had prominent bioethicists and angry patients on his side. Eventually, the Office of Human Research Protections weighed in for Catalona, too. But the courts were having none of it. The Federal District Court ruled that under Missouri law, Washington University owned the samples—the patients had irrevocably “gifted” (such an awful transitive verb) them.8 If a patient withdrew from the study, it meant only that he needn’t donate any more samples in the future. Catalona’s attorneys argued that the federal regulations covering human subjects, known collectively as the “Common Rule,”* demanded that consent forms never include language that meant subjects had to waive their legal rights. But the Washington University consent forms did indeed include such exculpatory language, characterizing the transfer as a “free and voluntary gift.”9
The appellate court affirmed the district court’s ruling by virtue of what can only be called circular reasoning, saying essentially that federal regulations didn’t apply given that the patients, by signing the consent forms, had agreed to freely donate their samples without strings. The court noted that there was no mention of a right to “physically withdraw or request the return of biological samples,” nor was there any indication that subjects had a right to “direct the transfer of their samples to another entity for research purposes.” And because Catalona himself had routinely destroyed samples without consulting subjects, his legal team’s “right to opt out” argument was rejected.10
Predictably, Washington University crowed about the ruling. The dean of the medical school said it was “of great national importance… . This university and others may be unwilling to make those kinds of investments [in biorepositories] if we knew that at any time those collections could be removed.”11 Patients wanting out and asking that their samples be destroyed were told that their samples would instead be “anonymized” and therefore unidentifiable. Once that happened, they were no longer considered “human subjects” and therefore not protected by the Common Rule.
Genetics expert and law professor Lori Andrews of Chicago-Kent College of Law lamented this development and the ruling itself. “Anonymizing a sample … is not a satisfactory solution,” she told a newspaper in 2007. “Patients should have a right to decide what is done with their tissue. Otherwise it’s bait and switch.”12
Catalona’s final appeal—to the U.S. Supreme Court—was denied.
“I think it’s terrible,” he told me. He noted that anonymizing samples such that they could not be traced back to their donor could have grave clinical consequences. “Somebody may discover a genetic variant that will let us know whether someone in the family is going to get this disease or if his tumor is susceptible to a certain type of drug. And so if a man has prostate cancer and his son has it, it may be very important to compare those tumors to each other.”13
Catalona has continued to do clinical genetic research in Chicago and still performs three hundred radical prostatectomies a year. But while some patients discussed filing a class-action suit against Washington University, I reckoned that the years of litigation had taken a toll on their champion. “What came out of the case,” he said with resignation, “is that the patients could not depend on the court system to follow through on what had been guaranteed to them.”14 More than a year later he was still angry. “The courts have granted Washington University OWNERSHIP of the samples, provided by the patients specifically for prostate cancer research in my program and, as such, WU can now do with them whatever it wishes. My sense is that patients’ rights are continuing to erode. Many savvy ones are deciding that the safest strategy is simply not to provide a sample for research.”15
And what about the rest of us not even involved in research? What claims did anyone have on their own DNA or other body parts? I asked Stanford Law’s Hank Greely, who has been contemplating genetics’ relationship to the law for decades. A former clerk for Supreme Court Justice Potter Stewart, Greely is a rotund and friendly man with glasses, puffy cheeks, and slits for eyes; when he spoke he reminded me of my in-laws from Ohio (Greely grew up in Columbus), especially the way he pronounced the word potential with a long o.
“[You have rights to] things that are in you,” he explained, “not to things that have at one point been in you. You spit on a Kleenex and throw it away and, often, you lose. The courts have not yet confronted it, [but] it’s come up occasionally in criminal cases where cops follow a suspect around and find a Coke bottle or a beer bottle and get DNA from it for forensic purposes. The reaction has been to call it ‘abandoned property.’ When you put your trash on the street, the law’s clear: You don’t own it and anybody can come and get it.
“So you don’t have any property-like rights [to your DNA], but you might have a variety of rights to limit or control its use in ways that aren’t thought about as property. But all of those would be relatively novel. And they might come from treating it as health information that shouldn’t be released or disclosed.”16
Amy McGuire, a Baylor College of Medicine legal scholar who facilitated the public release of Jim Watson’s genome, agreed. “Property law was not designed to handle these kinds of issues.”17
Greely and I talked about the PGP and he gave it a weak endorsement. “I don’t think your position is irrational,” he said of my decision to have my genome sequenced and made public. “I’m not an anxious person, but I’d be a little concerned about my children. I have a sixteen-year-old and a nineteen-year-old, and in a sense [if I got sequenced] I’d be revealing half of their genomes. Although the fact we don’t know which half helps.”18
Throughout the writing of this book the subject of anonymity came up again and again. I thought about it often with respect to my daughters. Who did I think I was, taking liberties with their genetic information? At an NIH-sponsored Town Hall meeting in December 2006 to discuss how data for large human genomic studies should be handled, one person decried the George Church appro
ach for that very reason: to make one’s genome public would be to make family members’ genomes public, at least in part.19 Had I had sons, they would have inherited my Y chromosome almost unchanged (except for a small bit of the X, the Y lacks a dance partner with which to shuffle its genes). As it was, I would be exposing my brothers’ Y and my father’s Y and my paternal grandfather’s Y chromosomes to the world. (That said, the Y is a runt of a chromosome: it has just seventy-eight functional male-specific genes and very few of them are associated with disease.)20
But Ann’s question was a fair one: Why couldn’t I remain anonymous (other than to satisfy George’s desire for openness and altruism and my need for attention)? A few years ago the Wall Street Journal ran a frontpage article on a psychotherapy patient who was denied disability coverage for auto-accident-related injuries when her therapist turned over clinical notes to the insurance company. The therapist’s notes were mixed in with the patient’s general medical records and therefore denied any special protection.21 I suggested to George that this kind of story—"You can’t even trust your shrink to keep your secrets!"—would make “health-information altruism” a tough sell. He seemed to draw the exact opposite conclusion. “It might discourage people who wouldn’t or shouldn’t be involved anyway,” he said, “but it might also convince real altruists that we need to do something fast.”22
Here Is a Human Being Page 4
