by Mark Bowden
Larry’s fascination is less with feces themselves than with the data they yield. He is not a doctor or a biochemist; he’s a computer scientist—one of the early architects of the Internet, in fact. Today he directs a world-class research center on two University of California campuses—San Diego and Irvine—called the California Institute for Telecommunications and Information Technology, or Calit2 (the 2 represents the repeated initial I and T). The future is arriving faster at Calit2 than it is in most places. Larry says his eyes are focused “ten years ahead,” which in computer terms is more like a century or two, given how rapidly the machines are transforming modern life. Intent on that technological horizon, Larry envisions a coming revolution in medicine, and he is bringing his intellect and his institute to bear on it.
At sixty-three, he is engaged in a computer-aided study of the human body—specifically, his body. It’s the start of a process that he believes will help lead, within ten years, to the development of “a distributed planetary computer of enormous power,” one that is composed of a billion processors and will enable scientists to create, among many other things, a working computational model of your body. Your particular body, mind you, not just some generalized atlas of the human frame, but a working model of your unique corpus, grounded in your own genome, and—using data collected by nanosensors and transmitted by smartphone—refreshed continually with measurements from your body’s in sides. This information stream will be collated with similar readings from millions of other similarly monitored bodies all over the planet. Mining this enormous database, software will produce detailed guidance about diet, supplements, exercise, medication, or treatment—guidance based not on the current practice of lumping symptoms together into broad categories of disorders, but on a precise reading of your own body’s peculiarities and its status in real time.
“And at that point,” says Larry, in a typically bold pronouncement that would startle generations of white-coated researchers, “you now have, for the first time in history, a scientific basis for medicine.”
When those who consulted the Delphic Oracle saw the inscription, “Know thyself,” they could not have imagined an acolyte so avid, or so literal, as Larry. You’ve heard of people who check their pulse every few minutes? Amateurs. When Larry works out, an armband records skin temperature, heat flux, galvanic skin response, and acceleration in three dimensions. When he sleeps, a headband monitors the patterns of his sleep every thirty seconds. He has his blood drawn as many as eight times a year, and regularly tracks a hundred separate markers. He is on a first-name basis with his ultrasound and MRI technicians, who provide him with 3-D images of his body, head to toe. Regular colonoscopies record the texture and color of his innards. And then there are the stool samples—last year Larry sent specimens to a lab for analysis nine times.
Larry is a mild, gentle soul, someone generally more interested in talking about you than about himself. He does not go out of his way to get your attention, and nothing about him is even remotely annoying or evangelical. But if you show an interest in his project and start asking questions—look out. Beneath the calm and the deference, Larry is an intellectual pitchman of the first order. In his quest to know, he burns with the pure intellectual passion of a precocious ten-year-old. He visibly shudders with pleasure at a good, hard question; his shoulders subtly rise and square, and his forehead leans into the task. Because Larry is on a mission. He’s out to change the world and, along the way, defeat at least one incurable disease: his own. (More on this in a moment.)
Larry is in the vanguard of what some call the “quantified life,” which envisions replacing the guesswork and supposition presently guiding individual health decisions with specific guidance tailored to the particular details of each person’s body. Because of his accomplishments and stature in his field, Larry cannot easily be dismissed as a kook. He believes in immersing himself in his work. Years ago, at the University of Illinois, when he was taking part in an experiment to unravel complex environmental systems with supercomputers, Larry installed a coral-reef aquarium in his home, complete with shrimp and sixteen phyla of other small marine critters. It was maddeningly fragile. The coral kept peeling off the rocks and dying. He eventually discovered that just five drops of molybdenum, a metallic element, in a 250-gallon tank once a week solved the problem. That such a tiny factor played so decisive a role helped him better grasp the complexity of the situation. And as he fought to sustain the delicate ecosystem in his tank, he developed a personal feel for the larger problem his team was trying to solve.
Today, he is preoccupied with his own ecosystem. The way a computer scientist tends to see it, a genome is a given individual’s basic program. Mapping one used to cost billions of dollars. Today it can be done for thousands, and soon the price will drop below $1,000. Once people know their genetic codes, and begin thoroughly monitoring their bodily systems, they will theoretically approach the point where computers can “know” a lot more about them than any doctor ever could. In such a world, people will spot disease long before they feel sick—as Larry did. They will regard the doctor as more consultant than oracle.
Not everyone sees this potential revolution as a good one. Do people really want or need to know this much about themselves? Is such a preoccupation with health even healthy? What if swimming in oceans of bio-data causes more harm than good?
“Frankly, I’d rather go river rafting,” says Dr. H. Gilbert Welch, a professor of medicine at the Dartmouth Institute for Health Policy and Clinical Practice, and the author of Overdiagnosed: Making People Sick in the Pursuit of Health. “Data are not information. Information is not knowledge. And knowledge is certainly not wisdom.” Welch believes that individuals who monitor themselves as closely as Larry does are pretty much guaranteed to find something “wrong.” Contradictory as it sounds, he says abnormality is normal.
“It brings to mind the fad a few years ago with getting full-body CT scans,” Welch says. “Something like 80 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, 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 led to 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 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 do 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 were 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 this to his colleagues, who were still working mostly with pencil 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 secret nuclear programs was set up in Munich, Larry started spending his summers there. “And in about 1982, 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 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 of the Internet) to link the centers, so that civilian researchers across the nation could use the fastest computers in America for basic research. The proposed linking 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, etc.—preferred a market model where 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 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 many 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 inflammation score on the blood test 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 he has things that are wrong with him 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 t
wenty-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 500,000 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 42 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 acute 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.