The Best American Science and Nature Writing 2013

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The Best American Science and Nature Writing 2013 Page 39

by Siddhartha Mukherjee


  “It brings to mind the fad a few years ago with getting full-body CT scans,” Welch says. “Something like eighty percent of those who did it found something abnormal about themselves. The essence of life is variability. Constant monitoring is a recipe for all of us to be judged ‘sick.’ Judging ourselves sick, we seek intervention.” And intervention, usually with drugs or surgery, he warns, is never risk-free. Humbler medical practitioners, aware of the sordid history of some medical practices (see: bloodletting, lobotomy, trepanning), weigh the consequences of intervention carefully. Doing no harm often demands doing nothing. The human body is, after all, remarkably sturdy and self-healing. As Welch sees it, “Arming ourselves with more data is guaranteed to unleash a lot of intervention” on people who are basically healthy.

  Not to mention creating an epidemic of anxiety. In other words, the “quantified life” might itself belong to the catalog of affliction, filed under Looking too closely, hazards of.

  In that sense, the story of Larry Smarr might be less a pioneering saga than a cautionary tale.

  Larry’s journey started with that most American of preoccupations, losing weight. Larry doesn’t update the photo each time he renews his California driver’s license, preferring to keep, as a reminder, the one taken soon after his arrival at UCSD twelve years ago with his wife, Janet. It shows a fifty-one-year-old Larry, one with more and longer hair, a wide, round face, and an ample second chin. Call him Jolly Larry. He had just arrived from Illinois, a place he now refers to as “the epicenter of the obesity epidemic,” and he had a girth to match his oversize professional reputation. (Deep-fried, sugarcoated pastries were a particular favorite of his back then.) Arriving in La Jolla, Jolly Larry found himself surrounded by jogging, hiking, biking, surfing, organic-vegetable-eating superhumans. It was enough to shame him into action. If he was going to fit in on this sunny new campus, he would have to shape up.

  So Jolly Larry started working out, reading diet books, and stepping on the scale every day. At first his charts were disappointing. Like countless strivers before him, he dropped some weight, but not much, and it kept wanting to come back. Three or four popular books on weight loss left him mostly confused, but they did convey a central truth: losing weight was only 20 percent about exercise. The other 80 percent was about what he put in his mouth. What triggered his breakthrough was the advice of Barry Sears, the biochemist who created the Zone Diet, which pressed Larry’s buttons precisely. Sears proposed that to diet more effectively, one needed to know more. Larry decided to study up on his body chemistry.

  Few people in history have been better positioned to act on such advice. Larry had begun his professional life as an astrophysicist, trying to unravel the core puzzles of the universe. In 1975, when he was working toward his doctorate at the University of Texas, one of his advisers suggested that he get a top-secret government security clearance: behind the walls of America’s nuclear weapons program were not only some of the nation’s premier physicists, but also the world’s first supercomputers, hundreds of times faster than anything available on any college campus. Larry got his clearance, and in the following years, while working as a fellow at Princeton and at Harvard, he would disappear during summers behind the classified walls of the Lawrence Livermore National Laboratory, in the San Francisco Bay Area. There he would work sixteen-hour shifts on some of the most difficult problems in his field—but with a crucial difference. Working with a computer at one of his universities, Larry might set it a task to compute overnight. He would go home, and when he returned the next morning, the task would be nearing completion. Working with the new Cray supercomputer at Livermore, he could get the same result in a minute and a half.

  When he’d return to his university posts in the fall and rejoin his colleagues working at a comparative snail’s pace, he’d tell them, “You know, guys, we could be using supercomputers to solve the laws of physics instead of trying to do these closed-form static solutions that you do.” They would look at him as if he was crazy. “What are you talking about?” they’d ask. “That can’t be done.” To them, it seemed impossible. The supercomputer enabled not just faster work but a different style and language of experimentation. But when he tried to explain it to his colleagues, who were still working mostly with pencils and paper, they scratched their heads. “It was like I was living in two different worlds,” Larry says.

  When one of the first Cray computers outside of secret nuclear programs was set up in Munich, Larry started spending his summers there. “And in about eighty-two, we were at a beer garden and it was probably my second glass of beer, and I was being hosted by a German astrophysicist, world-class,” Larry recalls. “He asks, ‘Tell me something. My father helped build the trains Germany relied on during the war. And here in our occupied country, you guys, you Americans, come over here and mooch off of our supercomputers because you don’t have the wit to put them in your universities where people can get access to them. Have I got that right?’ And I said, ‘Pretty much.’ And he asks, ‘How did you guys win the war?’”

  Larry brought that question home with him to his perch at the University of Illinois. There, in 1983, he helped draft “The Black Proposal,” an unusually concise recommendation (in a black cover) for a $55 million National Science Foundation supercomputer center. When it was funded, along with four other NSF centers, Larry and others argued for using the protocols of the military’s ARPANET (the precursor to the Internet) to link the centers, so that civilian researchers across the nation could use the fastest computers in America for basic research. The linking proposal was controversial, not only because it took on the cult of secrecy surrounding the most advanced computers in America, but because it specifically recommended that the NSF include only computer networks using TCP/IP, a universal computer protocol designed to facilitate not secrecy but collaboration. TCP/IP allowed different kinds of computers to exchange data seamlessly. At the time, the large computer companies—DEC, IBM, General Electric, and so on—preferred a market model in which manufacturers competed to create large fiefdoms, networks that used only their own machines. By adopting Larry’s proposal, the NSF enabled computer networks to plug into the system, a critical step toward today’s Internet.

  By the time, years later, that Larry heeded Barry Sears’s suggestion to learn more about his body’s chemistry, Larry had at his disposal at UCSD a supercomputer with a capacity many times greater than that of any he’d worked on at Livermore. His research interests had shifted from astrophysics to the impact computers were having on all kinds of fields, including medicine. Calit2 already had numerous grants to study “digitally enabled genomic medicine,” so in 2010 Larry signed himself up as a test subject. As his personal quest to lose weight evolved into an effort to understand human biochemistry, his own body became the equivalent of the coral-reef tank he’d once kept in his living room.

  Larry had already radically changed his diet, breaking his intake into subcategories, aiming for a caloric split of 40 percent low-glycemic carbohydrates, 30 percent lean protein, and 30 percent omega 3–enriched fat. His meal portions were about half of ordinary restaurant portions. Following what was essentially Barry Sears’s Zone Diet, Larry had lost a pound every ten weeks, dropping twenty pounds in four years.

  Most people would have been happy with that. But his dieting taught Larry something. If he wanted good health, he could not simply trust how he felt and wing it. If he wanted to understand what was happening in his body, he had to examine the data. And despite his weight loss, the data were now telling him something that didn’t seem to make sense. By his calculations, the pounds should still have been falling off, but they weren’t.

  According to his measurements, he had doubled his strength and tripled the number of steps he took each day. His REM periods, the most valuable periods of sleep, accounted for more than half the time he spent in the sack—twice the typical proportion for a man of his age. His weight was steady. But Larry wanted to know more. He had been getting
blood tests once or twice a year as part of his normal health maintenance, but by the end of 2010 he was sending off blood samples more often and graphing dozens of markers, which enabled him to at least better define the mystery. The Zone Diet is designed to reduce inflammation, and because he followed it faithfully, Larry expected his blood-test inflammation score to be low. But the C-reactive protein (CRP), which rises in response to inflammation, was high.

  “I had discovered that my body is chronically inflamed—just the opposite of what I expected!” he wrote in an account of his project published last year in a special issue of Strategic News Service, a computer/telecommunications newsletter. (The article was prefaced by an enthusiastic note from the publisher, Mark R. Anderson, who said that it “may be the most important Special Letter we have ever published. For many of you reading it, it may also save your lives, or extend them.”) Larry wrote: “Even more intriguing: after I had been tracking my CRP for two years, I noticed that it had suddenly more than doubled in less than a year. Troubled, I showed my graphs to my doctors and suggested that something bad was about to happen.”

  Here you should try to imagine the average physician’s reaction when a patient, outwardly healthy, arrives with detailed graphs of his body chemistry, concerned that something evil is stalking his insides.

  “Do you have a symptom?” Larry was asked.

  “No,” he answered. “I feel fine.”

  He was assured that charts like his were “academic” and not useful for clinical practice. The doctors told him to come back if and when he found something actually wrong with him, as opposed to finding anomalies in his charts.

  I ask Larry a question his doctors might have been too polite to ask: “Are you a hypochondriac?”

  “A hypochondriac is someone who imagines that they have things that are wrong with them and worries about that,” he says. “I am the opposite of a hypochondriac. I don’t make any assumptions about what might be right or wrong with me, and I don’t imagine it. I measure it.”

  Larry was beginning to have serious doubts about the way medicine is practiced in this country. “Here’s the way I look at it; the average American has something like two twenty-minute visits a year with a doctor,” he explains. “So you have forty minutes a year that that doctor is going to help you make good decisions. You have five hundred thousand minutes a year on your own, and every one of those, you are making decisions. So we’re already in a situation where you are in charge of your ship—your body—and you are making a lot of pretty horrible decisions, or else two-thirds of the United States’ citizens wouldn’t be overweight or obese. You wouldn’t have the CDC saying that forty-two percent of Americans may be obese by 2030, and a third of all Americans may develop diabetes by 2050. That’s the result of a lot of bad decisions that people are individually making on their own.”

  A few weeks after his doctors dismissed his graphs as “academic,” Larry felt a severe pain in the left side of his abdomen. At his doctor’s office, he was diagnosed with an acute bout of diverticulitis, an intestinal disease caused by inflammation. He was put on a ten-day antibiotic program to treat the ailment. To Larry, this perfectly illustrated the problem. Doctors were ready, eager, and well equipped to address a clinical symptom but unwilling to wade with him into his charts, which, although undeniably abstract, had foretold the problem! It was at this point that Larry decided to take over his own health care.

  He asked to see the written report from his last colonoscopy and underwent another. He began testing his stool, recognizing that all of us are, in fact, “superorganisms,” that our gastrointestinal, or GI, tracts are a collaboration between human digestive cells and the trillions of bacteria that line our intestines. The stool samples provided detailed charts of the workings of these microorganisms, which is what Larry means when he calls his poop “data-rich.” He was learning more about the biochemistry of his own body than any patient had ever known, and the numbers continued to add up in an alarming way. They suggested that he was suffering not from diverticulitis but from some kind of inflamed-bowel disease. He then went looking for an expert to help him interpret the data. He didn’t have to look far: Dr. William J. Sandborn had recently left the Mayo Clinic to take over the GI division of UCSD’s School of Medicine.

  “I think he felt like he wasn’t really being taken seriously,” says Sandborn. “So he came over and we looked, and we ended up finding some degree of inflammation that was pointing in the direction of Crohn’s disease, but he wasn’t really having many symptoms. So the question then became: Is this some kind of early subclinical Crohn’s disease? Should we even go as far as treating it, or just wait?”

  Larry’s impressive quest to fine-tune his body had led him to this: an early diagnosis of Crohn’s disease, an incurable condition. It isn’t fatal, but it has a long list of uncomfortable and sometimes painful symptoms that tend to flare up from time to time; they center around the GI tract but may include eye inflammation, swollen joints, fever, fatigue, and others. Apart from that one episode of abdominal pain, Larry was still feeling fine. But the graphs showed, and his new doctor more or less confirmed, that he was sick.

  And that part about its being incurable? Let’s just say that in Larry, Crohn’s disease has encountered a very dedicated adversary.

  If past thinkers leaned heavily on the steam engine as an all-purpose analogy—for example, contents under pressure will explode (think Marx’s ideas on revolution or Freud’s about repressed desire)—today we prefer our metaphors to be electronic. We talk about neural “circuitry,” about “processing” information, or about how genes “encode” our physical essence. In this worldview, our bodies are computers, and DNA functions as our basic program, our “operating system.”

  This is certainly how Larry, the computer scientist, talks about the human body. In this context, all of human history can be seen as a progression from a world that was data-poor to one that is data-rich. Starting with those early summers working in secrecy at Livermore, Larry has witnessed firsthand the exponential progress of computing power posited by Moore’s Law, which states that the computer-chip transistor count should double roughly every two years. So when Larry talks about the potential for computers to help us understand our bodies, he isn’t talking about their showing us more isolated details about an unfathomably complex system; he’s talking about knowing everything.

  “We are going to know—once you know each of your cells’ six billion genome bases, with all the imaging down to the micron level, and when you know every damn gene and every bacterium—at a certain point, there is no more data to know,” he says. “So certainly by 2030, there is not going to be that much more to learn . . . I mean, you are going to get the wiring diagram, basically.” Once they are armed with the wiring diagram, Larry sees no reason why individuals cannot maintain their health the way modern car owners maintain their automobiles.

  Larry actually concedes the point made by Dartmouth’s Welch—that presented with enough data, pretty much everyone is going to find something wrong with them. He just disputes that this would be a bad thing. “All of us do have something beginning to go wrong, but then, so do our automobiles,” Larry says. “In today’s world of automobile preventive maintenance, we don’t wait for our cars to break down and then go to the ‘car doctor.’ Every ten thousand or twenty thousand miles, we go in and get an exhaustive look at all the key variables since the last check. If they find something wrong with my car—which will be different from what they find about yours—then they take appropriate action and I go back to driving a ‘healthy’ car. Occasionally, something is discovered that indicates a bunch of cars need to be called in and get a certain item replaced. I can imagine that occasionally, as a new DNA segment is related to some disease, people with that DNA signature will be called in for ‘preventive maintenance.’”

  If Larry is right, then our descendants may view early-twenty-first-century medical practices, which we consider a triumph of reason over supersti
tion, in the same way we now view eighteenth- and nineteenth-century folk remedies. A particularly likely candidate for scorn in an age of “quantified” health care is our one-pill-fits-all approach to prescription drugs. In his book The Creative Destruction of Medicine, the physician-author Eric Topol cites such dosing as an example of medicine that is “population-based” rather than “patient-centered.” He notes the widespread use of statins to lower LDL cholesterol, a factor in heart disease. Topol doesn’t deny the cholesterol-lowering effect of these drugs, but he argues that double-blind testing also shows that this effect benefits only a tiny fraction of those treated. One of the most effective statins, Crestor, has been found to reduce the incidence of stroke, heart attack, or death from 4 percent of patients in the placebo group to 2 percent of the group taking the statin. And yet these drugs are widely administered to patients considered at risk. Topol writes: “Instead of identifying the 1 person or 2 people out of every 100 who would benefit, the whole population with the criteria that were tested is deemed treatable . . . What constitutes evidence-based medicine today is what is good for a large population, not for any particular individual.”

  Pharmaceutical companies don’t mind. And as long as the harmful side effects are within acceptable limits, the Food and Drug Administration doesn’t mind, either. Some patients will be helped. All of them will be buying the pills, and all will be subjected to follow-up tests, some of them uncomfortable and most of them unnecessary. What if there were a way, Topol asks, of knowing, before prescribing the drug, which 2 percent would be most likely to benefit from it? In an observation that Larry wholeheartedly endorses, Topol writes: “Fortunately, our ability to get just that information is rapidly emerging, [and we are] beginning an era characterized by the right drug, the right dose, and the right screen for the right patients, with the right doctor, at the right cost.”

 

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