Endure. Alex Hutchinson

third child, the seizures returned, and over the next few years they got progressively worse. Working with neurologists at the University of Colorado, she eventually decided to have a partial right temporal lobectomy, to remove the portion of the brain where the seizures were originating. The surgery went well, and the seizures stopped—but not without a cost.

      Even before the surgery, Van Deren had found running therapeutic. When she felt an “aura”—the odd out-of-body sensation that, for her, signaled an impending seizure—she was often able to ward off the seizure by heading out the door and running, sometimes for hours. After the surgery, she kept running, and began venturing farther and farther into the trails near her home south of Denver. Soon she was covering distances that would have daunted even the fittest runners, and in 2002 she entered her first ultramarathon, a 50-mile trail run with only one other entrant. The 50-miler turned out to be just a stepping-stone to 100-milers, which in turn led to multi-day races like the Yukon Arctic Ultra and, eventually, the three-week assault on the Mountains-to-Sea Trail in North Carolina in 2012.

      In the final days of the record attempt, Van Deren’s feet were so beat up that she had to start each day by crawling along the trail until, thanks to the familiar numbing of endorphins, she could stand up and start putting weight on them. Then she would resume clicking off the miles, one by one. By 12:20 P.M. on the twentieth day of the run, she and Millsaps were still four miles away from the crucial 1 P.M. Okracoke ferry—so they accelerated. They caught the ferry with just minutes to spare, and the ferry operator solved the mystery of the “airplane” that had buzzed them earlier: “You must have just come through those tornadoes back there,” he marveled. Two days later, Van Deren climbed an 85-foot sand dune in Jockey’s Ridge State Park to complete the trail in a new record of 22 days, 5 hours, and 3 minutes. “That,” she told a small crowd of supporters, “is the hardest thing I have ever done.”

      In the Runner’s World profile, neuropsychologist Don Gerber, who worked with Van Deren at Craig Hospital in Denver, speculated that brain surgery might have made her a better runner. Thanks to the region of her brain that was damaged, he said, “Diane’s brain interprets pain differently than yours or mine does.”

      Van Deren, for her part, rejects this suggestion. “They all think, ‘Oh, great, you don’t feel pain,’” she argued in a subsequent profile. “Well, shit—I don’t feel pain? I feel pain. I just push through it.” And indeed, her suffering during the run in North Carolina was evident.

      Still, it’s hard to escape the sense that how Van Deren experiences a prolonged endurance challenge is inescapably different from how it is for most people. Unable to read maps or keep track of where she is on a course, she doesn’t focus on the challenge ahead of her. Hampered by poor short-term memory, she doesn’t dwell on the effort already expended, either. “I could be out running for two weeks, but if someone told me it was day one of a race,” she once joked, “I’d be like, ‘Great, let’s get started!’” Instead, she has no choice but to focus on the immediate task of forward motion, taking one more step, and then another. Semi-oblivious to the passage of time, she is also free of the cognitive challenge—the shackles, perhaps—of pacing herself. She is all hare and no tortoise—which, Aesopian morality aside, has its advantages.

      To get a visceral feel for the struggle between mind and muscle, there’s no better place to stand than at the finish line of the Comrades Marathon, the largest, oldest, and most prestigious ultra-race (that is, any race longer than the standard marathon distance of 26.2 miles) in the world, as the clock ticks down toward its rigid 12-hour cutoff. By the time the runners enter the cricket stadium in the coastal city of Durban, they’ve covered 56 miles of relentlessly undulating terrain, the downhills shredding their quads as mercilessly as the uphills burn their lungs, under the fierce South African sun. (In odd-numbered years, the course runs in the opposite direction, finishing in the inland city of Pietermaritzburg.)

      In 2010, I joined thousands of other spectators in the stadium counting down the final seconds as the race director assumed his position on the finish line, his back to the oncoming runners and his starter’s pistol pointed skyward. To be recorded as an official finisher of the race and receive a coveted finisher’s medal, you have to cross the line before the 12-hour gunshot is fired. Summoning their final reserves of willpower, the runners within striking distance began to urge their battered legs into a final, frantic sprint. As the gun cracked, one man staggered across the line in 11:59:59; mere strides behind him, another man bounced off the burly course marshals who had linked arms to barricade the finish chute, while vuvuzelas sounded a mocking raspberry of defeat.

      I had come to South Africa on assignment for Outside magazine, to write about Tim Noakes’s contrarian ideas about the brain. The hook for my story was the Comrades debut of American runner Josh Cox, who was fresh off an impressive American record of 2:47:17 over 50K. I figured that if he conquered the distance, he (and Noakes, who was also in Durban to watch the race) would be able to offer vivid insights into the nature of the limits he’d had to overcome—and if the distance conquered him, the story would be even better. “The one guarantee in an event like this is the pain,” Cox told me, all too prophetically, when we met for coffee the day before the race. “You have to welcome it—say ‘Here you are, my friend.’” But Cox’s hopes fizzled just a few miles into the race, thanks to recurring bouts of stomach cramping and diarrhea that slowed him to a walk. As familiar as this debacle might be to marathoners, these were not the limits I was hoping to write about. (The story was eventually killed.)

      Still, the race had given me a perfect excuse to make a pilgrimage to one of the temples of modern exercise physiology: the next day, I flew to the opposite end of the country to spend a week visiting Noakes’s lab at the University of Cape Town. At sixty, Noakes had graying temples, a near-permanent grin that expressed everything from disbelief to delight, and a habit of punctuating his sentences with the all-purpose interjection “ja.” His fourth-floor office had a postcard view of Table Mountain’s iconic ridgeline, and a museum’s worth of sports memorabilia—framed clippings, signed rugby shirts, battered old Onitsuka Tiger running shoes—covering the walls and filling a long trophy case. On my first day there, we talked almost nonstop for four hours (“I don’t normally have much lunch,” he said, a bit apologetically, when I proposed a break, “but you’re welcome to if you’d like”) as he recounted the origins of what has become known as the “central governor” theory.

      In his keynote lecture at the 1996 ACSM conference, Noakes had argued that A. V. Hill’s concept of VO₂max was fundamentally flawed: that physical exhaustion isn’t a consequence of the heart’s inability to pump enough oxygen to the muscles. Otherwise, he reasoned, the heart itself, and perhaps the brain, would also be starved of oxygen, with catastrophic results. He liked to point out a famous picture of South African marathoner Josia Thugwane, moments after winning the 1996 Olympic marathon, jogging around the track with silver medalist Lee Bong-Ju, whom he had outsprinted by just three seconds. “Do you notice he’s not dead?” he’d say, pointing at Lee. “What does that tell you? It means he could have run faster.”

      But if Hill’s ideas about oxygen were wrong, what was the alternative? Noakes felt the brain had to be involved, and in a 1998 paper he coined the term “central governor,” borrowing terminology that A. V. Hill himself had used seventy years earlier. But the details remained unclear. Over the next decade, working with collaborators such as Alan St. Clair Gibson, then at the University of Cape Town, Frank Marino, of Charles Sturt University in Australia, and a succession of other students and postdoctoral researchers in his own lab, he began to assemble a coherent picture with two key planks. First, the limits we encounter during exercise aren’t a consequence of failing muscles; they’re imposed in advance by the brain to ensure that we never reach true failure. And second, the brain imposes these limits by controlling how much muscle is recruited at a given effort level (an idea we’ll explore in detail in Chapter 6).

      The first point—the concept of “anticipatory regulation,” as Noakes and his colleagues refer to it—is subtle, so it’s worth pausing to unpack it. Long before Noakes, researchers had theorized that the brain might sense distress signals from elsewhere in the body and shut things down when the warnings exceeded a critical level. Exercise in the heat is a classic example: if you run