The Sports Gene: Inside the Science of Extraordinary Athletic Performance (12 page)

Cuban runner Alberto Juantorena, who in 1976 became the only athlete ever to win gold medals in both the 400- and 800-meters, had been an aspiring basketball player in 1971 when the national team basketball coach suggested he switch to running. “Thanks for the offer, but no, I’d rather not,” Juantorena insisted. “You know basketball is my life.” To which the coach responded: “We’re sorry, but it’s already been decided that you will change sports. Starting tomorrow, you are a runner, not a basketball player.” Juantorena made the Munich Olympics the very next year.

But it could also be that some naturally fit people are not like Wellington or Wheating, but are instead like the low responders in the HERITAGE study, in which case they would not improve rapidly with training. (Bouchard’s research group also has DNA from three hundred endurance athletes with very high VO
₂
max scores. Based on their gene variants, unsurprisingly, none of them is predicted to be at
the low end of the responder spectrum.) Based on his data, Bouchard estimates that between one in ten and one in twenty people start with elevated aerobic capacity—though not nearly as high as the naturally fit six—and between one in ten and one in fifty people are high aerobic responders. “The probability that a person will be highly endowed and highly trainable is the product of those two probabilities,” Bouchard says. “It’s not pretty. It’s between one in one hundred and one in one thousand.”

The ultimate combination, of course, would be a person who starts with a highly elevated aerobic capacity and has a rapid training response. It is very difficult to identify those people before they start training, as athletes are not normally subjected to lab tests until they have already accomplished something. Science is far better at looking at an elite athlete and retrospectively suggesting why that individual is succeeding than in finding someone who might succeed before he or she has started practicing—and had a chance to respond to training—and then following them.

But there was a bit of unique and relevant science done by Dr. Jack Daniels, an exercise physiologist, former U.S. Olympic pentathlete, and one of the world’s most well-respected endurance coaches. Decades ago, Daniels tracked one Olympic runner over the course of five years, testing him on all manner of biological traits at least every six months. When fully trained, the runner had a VO
₂
max about double that of an average, untrained but healthy man. The third year of the study, however, brought an unexpected research problem: the athlete got sick of competing. The pressure of expectations and the ceaseless slog and drudgery of interval training got to him. The runner was less than halfway through a race at the national championship when he simply stepped off the track and refused to run another step for an entire year. More than a year and a half passed before he really got serious about racing again.

Instead of giving up on his research, Daniels tested the athlete during his year of lazing around. An athlete who stops training can within
weeks lose more than 15 percent of the VO
₂
max he built up. The runner’s VO
₂
max had fallen 20 percent by the time Daniels tested him. In the absence of training, the Olympian’s aerobic capacity lined up exactly with the naturally fit six from the York University study. (Decades later, this would become a familiar pattern to Daniels. In 1968, for his Ph.D. dissertation, Daniels tested twenty-six elite runners, fifteen of whom went on to the Olympics. When he retested them in 1993, even those who had stopped running many years earlier and were overweight maintained a VO
₂
max much higher than normal men. Said Daniels, in an interview with
Flotrack
: “Even the ones who hadn’t [continued to] run pretty well proved the genetic characteristics.”)

After a year of mental convalescence, the runner started jogging with his wife. And with the Olympics approaching, his fire for full-time training was reignited. As the runner gradually increased his training intensity, he quickly regained, essentially precisely, the 20 percent of his aerobic capacity that he had lost during his fallow period.

From a physiological standpoint, what Daniels chronicled over five years was in line with the results of a seven-year study of male, junior Japanese distance runners. The boys were selected for the study because each had won a middle- or long-distance event at the Japan Junior Championship. The study then followed the boys as they trained assiduously from the ages of fourteen to twenty-one for two hours each day, five or six days a week. Their aerobic capacities started at almost the identical level as Daniels’s Olympian during his period without training—around the same level as the naturally fit six. Over the course of their years of training, the boys all improved, but naturally divided into two groups: study group I, which saw an average aerobic capacity increase of 13 percent; and study group II, with boys who hit a plateau of 9 percent aerobic improvement—as well as a plateau in race time improvement—by age seventeen. Each of the boys in the latter group, having ceased to improve, quit running altogether after age seventeen. There may have been, in effect, a form of natural self-selection that left in the competitive population (and working toward their 10,000 hours)
only those boys who continued to improve. That is not to say the boys who continued competing were just lucky. The study suggests that the more potential to improve the boys had, the longer and harder they had to work to reach it. But the ability to improve may have kept them in the sport and dedicated to training.

So the group I Japanese boys appeared, like Daniels’s Olympian, to have a high baseline aerobic capacity as well as the ability to improve more than their peers. But Daniels’s Olympian improved even more, while some of his peers, like the group II Japanese boys, flat-lined and went off to follow other interests. From the looks of it, Daniels’s Olympian both had a naturally high aerobic fitness and was a high responder to training.

Incidentally, the Olympian was Jim Ryun.

Superbaby, Bully Whippets, and the Trainability of Muscle

T
he baby boy was born around the turn of the millennium, and it was the twitching that grabbed the nurse’s eye. Sure, the boy was slightly on the heavy side, but nothing jaw-dropping for the nursery at Charité hospital in Berlin. But those jitters. The little ticks and shudders that started just a couple of hours after he was born. The doctors worried that he might have epilepsy, so they sent him to the neonatal ward. That’s where Markus Schuelke, a pediatric neurologist, noticed his pipes.

The newborn had slightly bulging biceps, as if he had been hitting the womb weight room. His calves were chiseled, and the skin over his quads was stretched a bit too taut. Soft as a baby’s bottom? Not this baby. You could bounce a nickel off these glutes. Ultrasound examination of his lower body showed that the boy was beyond the top of the baby charts in the amount of muscle he had, and beneath the low end of the charts in terms of fat.

The boy was otherwise normal. The functioning of his heart was ordinary, and the jitters subsided after two months.
Perhaps the baby was the Benjamin Button of bodybuilding, and would gradually lose muscle.
Not quite. By the age of four, he had no trouble holding 6.6-pound dumbbells suspended horizontally at arm’s length. (Imagine toddler-proofing that household.)

Monstrous strength ran in the family. The boy’s mother was strong, as were her brother and father. But her grandfather—he was acclaimed on his construction crew for unloading 330-pound curbstones from truck beds with his bare hands.

Fully clothed, the boy did not stand out from his peers. You wouldn’t ogle his puerile pecs if you passed him in the street. But the muscles in his upper arms and legs were roughly twice the size of other boys his age.
Double muscle
. It reminded Schuelke of something.

•

In the early 1990s, Johns Hopkins geneticist Se-Jin Lee had begun searching for muscle in his lab on North Wolfe Street in Baltimore. Not the finished muscle tissue itself, but the protein scaffolding that builds it. The purpose of the search was to find treatments for muscle-wasting diseases, like muscular dystrophy. Lee and a group of colleagues targeted a family of proteins known as transforming growth factor-ß. They cloned genes that coded for the proteins and then set off like kids with new toys, trying to figure out what the heck each gene did.

They gave the genes prosaic names—growth differentiation factor 1 through 15—and then bred mice that lacked working copies of each gene, one at a time, so they could see what would happen and thereby deduce each gene’s function. The mice without GDF-1 had their organs on the wrong side. They didn’t survive long. The mice without GDF-11 had thirty-six ribs. They, too, died quickly. But the mice without GDF-8 survived. They were freak show rodents of a different kind. They had
double muscle
.

In 1997, Lee’s group named GDF-8, a gene on chromosome two, and its protein “myostatin.” The Latin
myo
-, meaning muscle, and -
statin
, to halt. Something that myostatin does signals muscles to cease growing. They had discovered the genetic version of a muscle stop sign. In the absence of myostatin, muscle growth explodes. At least it did in the lab mice.

Lee wondered whether the gene might have the same effect in other species. He contacted Dee Garrels, owner of the Lakeview Belgian Blue Ranch in Stockton, Missouri. Belgian Blue cattle are the result of post–World War II breeding that sought more meat to accommodate the increased demand of Europe’s postbellum economy. Breeders in Belgium crossed Friesian dairy cows with stocky Durham shorthorns and got cattle with heaps of muscle. Double muscle, to be precise. Belgian Blues look as if somebody unzipped them and tucked bowling balls inside their skin. “Hotline,” Garrels’s 2,500-pound prize Belgian Blue bull, once ripped a steel restraining gate off its hinges and flicked it aside en route to a cow in heat.

Lee asked Garrels for blood samples from her double-muscled cattle. Sure enough, the Belgian Blues were missing eleven of the DNA base pairs—out of more than six thousand—from the myostatin gene. It left them without a stop sign for their muscles. Another breed of double-muscled cattle, Piedmontese, also had a genetic mutation that resulted in no functional myostatin.

So Lee went hunting for human subjects. First stop: the grocery store, where he loaded his cart with muscle mags, the kind with cover photos of bulging-veined men in itty-bitty skivvies. Lee has jokingly been called “the skinniest man in the world” by a colleague, and he still remembers the sideways look from the cashier. Nonetheless, he placed an ad in
Muscle and Fitness
and was immediately swamped with willing volunteers, many of whom mailed him photos of themselves flexing and scantily clad, or not clad at all. He took samples from 150 muscular men, but found no myostatin mutants.

He put the work aside until 2003, when Markus Schuelke called to talk about the bulging baby boy who was born at Charité hospital three years earlier and whose development he was monitoring. The following year, Schuelke, Lee, and a group of scientists published a paper that would introduce the world to the “Superbaby,” as the media would name him. The German boy, whose identity has been carefully guarded, was the human version of a Belgian Blue. Mutations on
both of his myostatin genes left him with no detectable myostatin in his blood. Even more provocatively, Superbaby’s mother had one typical myostatin gene and one mutant myostatin gene, leaving her with more myostatin than her son but less than the average person. She was the only adult with a documented myostatin mutation, and she was a professional sprinter.

•

Double muscle might seem like an unconditional blessing, but myostatin exists for a reason. It is, in evolutionary terms, “highly conserved.” The gene serves the same function in mice, rats, pigs, fish, turkeys, chickens, cows, sheep, and people. This is probably because muscle is costly. Muscle requires calories and specifically protein to sustain it, and having massive muscles can be a massive problem for organisms—like ancestral humans—that don’t have steady access to the protein necessary to feed the organs. But that is a diminishing concern in modern society.

In Superbaby’s case, doctors initially worried that the boy’s lack of myostatin might cause his heart to grow out of control. So far, though, no major health concerns have been reported in him or his mother.
*
Thus, it seems unlikely that an individual with a myostatin mutation would ever even think to get tested. The result is that nobody has any idea just how rare the myostatin mutation is, other than that most people (and animals) don’t have it. But the facts that the one boy with two of the rare myostatin gene variants has exceptional strength, and that his mother had exceptional speed, are no coincidence. Superbaby and his mother fall precisely in line with racing whippets.

Since the late nineteenth century, speed-seeking whippet breeders unknowingly created dogs that, like Superbaby’s mother, have single myostatin mutations and that are lightning fast. In the highest level of
whippet competition—racing grade A—where dogs hit a top speed of thirty-five miles per hour, more than 40 percent of the dogs have what is normally an exceedingly rare myostatin mutation. In racing grade B only about 14 percent have it. In grade C, it all but disappears.

Even in racing grade A, the myostatin mutation is not a prerequisite, but it is clearly beneficial. The drawback in the whippet breeding system is that some dogs end up with too much muscle.

Every whippet puppy inherits one copy of its myostatin gene from each parent. If two sprinter whippets—dogs that each have one copy of the myostatin mutation—have four puppies, this is the likely scenario: one puppy will have zero copies of the mutation and be normal; two puppies will have one copy of the mutation, like Superbaby’s mother, and be sprinters; the fourth puppy will have two copies of the mutation, like Superbaby, which make for a double-muscled “bully” whippet. Bully whippets are cartoonishly buff. A bully whippet looks like a shrink-wrapped rock pile stuck to a cuddly face. Bully whippets are too bulky to sprint, so breeders often put them down.

The more scientists look, the more species they find that hold with the pattern of myostatin gene mutations and speed. In early 2010, two separate studies independently found that variations in the myostatin genes of Thoroughbred racehorses were powerful predictors of whether the horses were sprinters or distance runners. And horses with a so-called C version of the myostatin gene—a variant that results in less myostatin and more muscle—earned five and a half times more money in purses than did their counterparts that carried two T versions and were flush with myostatin.

The scientists who discovered this have, not surprisingly, started genetic testing companies for Thoroughbred breeders.

•

As soon as Lee published his first mighty mice results in 1997, he was inundated with messages from parents of children with muscular dystrophy (no surprise), and also from athletes (surprise!) ready and
willing to offer themselves for genetic experimentation. Some of the athletes hardly knew what they were talking about. They asked Lee where they could purchase myostatin, not realizing that it is the absence of myostatin that leads to muscle growth.

Lee himself is a huge sports fan. He can recite the last forty-five NCAA basketball champions and he reverse-engineers the memory of a two-decades-old date with his wife by first thinking of who the St. Louis Cardinals’ pitcher was that day. But he has been reticent to talk with sportswriters about his work. He is troubled by the apparent willingness of athletes to abuse technology that isn’t even technology yet, and that is meant for patients with no other options. He hopes that any future myostatin-based treatments won’t be stigmatized the way steroids have been because of their role in sports scandals.

The occasional keyhole view into the genetic cutting edge has proven understandably tantalizing for athletes. After myostatin, Lee moved on to mice in which he both blocked myostatin and altered another protein involved in muscle growth, follistatin. The result:
quadruple muscle.
In collaboration with researchers at the pharmaceutical company Wyeth, Lee then developed a molecule that was shown to bind to and inhibit myostatin and with just two injections increased mouse muscle 60 percent in two weeks. A subsequent trial by the pharmaceutical company Acceleron reported in 2012 that a single dose of that same molecule boosted muscle mass in postmenopausal women. Several companies now have myostatin inhibitor drugs in clinical trials.

For pharmaceutical companies, this is the search not simply for a cure for muscle-wasting diseases, but for the all-time pharma pot of gold: a cure for the normal muscular decline of aging. And myostatin is not the only gene that has emerged in the quest for explosive muscle growth.

The year after Lee’s mighty mice made headlines, H. Lee Sweeney, a physiology professor at the University of Pennsylvania, introduced the world to his own ripped rodents, made by injecting them with a
transgene—a gene engineered in a lab—to produce the muscle-building insulin-like growth factor, or IGF-1. Like Lee, Sweeney was flooded with calls. A high school wrestling coach and a high school football coach both offered up their teams as genetic guinea pigs. (Of course, the offers were rejected.)

The gene-doping era may even already be here. In 2006, during the trial of German track coach Thomas Springstein on charges of providing performance-enhancing drugs to minors, evidence emerged that the coach had been seeking Repoxygen, an anemia drug that delivers a transgene that prompts the body to produce red blood cells.

Before I traveled to the Beijing Olympics in 2008, a former world powerlifting champion gave me the name of a Chinese company that he said bodybuilders were using for gene therapy techniques. Once in China, I contacted the company, and a representative did respond to discuss potential genetic technologies. But I suspect it was just a strategy to tantalize patients, and that the company was not actually performing gene therapy.

Still, Sweeney says that one method of delivering transgenes, simply pouring them into the bloodstream, is not necessarily safe but is simple enough that it could be accomplished by a sharp undergrad studying molecular biology. Sweeney has helped World Anti-Doping Agency officials prepare to fight gene doping, but if gene therapy is proven completely safe, he says, his impetus for keeping it out of sports disappears.
*

But perhaps the most interesting question is whether common DNA sequence variations in genes like IGF-1 and myostatin, as opposed to rare mutations, help to determine whether one gym-goer will pack on muscle faster than her spotting buddy. Comparisons of common variants of the human myostatin gene in both weight lifting
and sedentary subjects have had less than eye-popping results. Some studies have found slight differences and some none at all. Other genes involved in the process of muscle building, though, are emerging as critically important to understanding why some people get sculpted when they pump iron while others struggle toward buffness in vain.

•

Muscles are pieces of meat made of millions of tightly packed threads, or fibers, each a few millimeters long and so thin as to be barely visible on the end of a needle. Along each fiber are a number of command centers, or myonuclei, that control muscle function in the area. Each command center presides over its fiber fiefdom.

Outside of the fibers hover satellite cells. These are stem cells that wait quietly, until muscle is damaged—as happens when one lifts weights—and then they swoop in to patch and build the muscle, bigger and better.

For the most part, as we gain strength we do not gain new muscle fibers but simply enlarge the ones we already have. As a fiber grows, each myonuclei command center governs a larger area, until the point when the fiber gets big enough that the command center needs backup. Satellite cells then form new command centers so the muscle can continue to grow. A series of studies in 2007 and 2008 at the University of Alabama–Birmingham’s Core Muscle Research Laboratory and the Veterans Affairs Medical Center in Birmingham showed that individual differences in gene and satellite cell activity are critical to differentiating how people respond to weight training.