The Sports Gene: Inside the Science of Extraordinary Athletic Performance (26 page)

Or Herschel Walker, best known as the 1982 Heisman Trophy–winning running back and twelve-year NFL veteran. Now fifty-one, Walker is 2-0 as a professional mixed martial artist. Walker has trained in ballet, taekwondo (he’s a fifth-degree black belt), and, in 1992, was an Olympic bobsled pusher. Most indicative of Walker’s drive to be active, though, is the workout regimen he started at age twelve, before he was involved in organized sports, and which he has continued every day since. “I would start doing sit-ups and push-ups at seven
P.M
.,” he says, “and go until eleven. It was every night, on the floor. It was about five thousand sit-ups and push-ups.” These days, Walker says he “only” does 1,500 push-ups and 3,500 sit-ups a day—in sets of 50 to 75
push-ups and 300 to 500 sit-ups or crunches—but he also has his martial arts training.

Walker says the push-ups and sit-ups routine will remain, even after he stops competing. “It has nothing to do with my competitions,” he says. “It becomes a drug, or a medicine. Even if I’m sick, I do it. It’s like there’s something saying, ‘Herschel, you gotta get up. You gotta do it.’”

•

Variations in the brain’s dopamine system make certain individuals more likely to feel reward when using particular drugs, and they are more likely to become addicted. Is it possible that, like sled dogs and lab mice, some people are biologically predisposed to get an outsized sense of reward or pleasure from being constantly in motion?
*
All sixteen human studies conducted as of this writing have found a large contribution of heredity to the amount of voluntary physical activity that people undertake.

A 2006 Swedish study of 13,000 pairs of fraternal and identical twins—fraternal twins share half their genes on average, while identical twins essentially share them all—reported that the physical activity levels of identical twins were twice as likely to be similar as those of fraternal twins. That study used a survey to measure physical activity, though, and people chronically overestimate their own physical activity levels. But another, smaller study of twin pairs that used accelerometers to measure physical activity directly found the same difference between fraternal and identical twin pairs. The largest study, of 37,051 twin pairs from six European countries and Australia, concluded that about half to three quarters of the variation in the amount of exercise
people undertook was attributable to their genetic inheritance, while unique environmental factors, like access to a health club, had a comparatively puny influence.

It is entirely clear that the dopamine system
responds
to physical activity. This is one reason that exercise can be used as part of treatment for depression and as a method to slow the progression of Parkinson’s disease, an illness that involves the destruction of brain cells that make dopamine. And there is evidence that the reverse is true as well, that physical activity levels respond to the dopamine system. Several lines of scientific evidence have begun to implicate genes that control dopamine.

Particular versions of dopamine receptor genes have been associated with higher physical activity and lower body mass index.
Multiple studies—including a meta-analysis of all published studies—have also replicated the finding that one of those variants, the 7R version of the DRD4 gene, increases an individual’s risk for attention deficit hyperactivity disorder, or ADHD. Tim Lightfoot, director of the Sydney and J. L. Huffines Institute for Sports Medicine and Human Performance at Texas A&M, has authored papers on voluntary physical activity in rodents and humans, and he sees a connection between ADHD, exercise, and dopamine genes. “The high active mice we bred in the lab,” Lightfoot says, “they mimic ADHD kids, at least as far as the dopamine system goes. . . . They’re low on [a particular kind of] dopamine receptors, and if you can drive the amount of dopamine up, their physical activity decreases.”

Ritalin drives dopamine up in hyperactive children, and their activity decreases. Obviously, this is a good thing for a child who is having difficulty sitting still in school. But, Lightfoot suggests, it might have unintended consequences. “These may be kids that have a very strong drive to be active, and maybe we’re blunting it with medications.”

“Our society is so scared right now of kids being fat,” Lightfoot
continues. “Well, what if we’re putting some of these kids on drugs that actually may be contributing to this by driving their activity levels down?” In any case, that’s exactly what happened in Lightfoot’s mice.

A set of scientists have proposed the controversial idea that hyperactivity and impulsivity may have had advantages in the ancestral state of man in nature, leading to the preservation of genes that increase ADHD risk. Interestingly, the 7R variant of the DRD4 gene is more common in populations that have migrated long distances, as well as those that are nomadic, compared with settled populations.

In 2008, a team of anthropologists genetically tested Ariaal tribesmen in northern Kenya, some of whom are nomadic and some recently settled. In the nomadic group—and only in the nomadic group—those with the 7R version of the DRD4 gene were less likely to be undernourished. One of several hypotheses the researchers offered: “It might also be that higher activity levels in [the 7R] nomads are translated into increased food production.” In other words, it could be that carriers of that version of the gene are harder workers when it comes to physical activities.

“One of the issues with our field is when we’ve looked at activity, and what controls activity, we’ve forgotten that we know very clearly there are biological mechanisms that actually influence people to be active or not,” Lightfoot says. “You
can
have a predisposition to be a couch potato.”

Quite obviously, as is the case with Kenyan children, the necessity of transportation by foot and the aspiration for a better life can have profound influences on physical activity levels. But those environmental factors do not exclude the significant contribution of genetics that has shown up in every study ever conducted on the heritability of voluntary physical activity.

Those consistent findings are reminiscent of a famous quote by Wayne Gretzky, the greatest hockey player in history: “Maybe it wasn’t talent the Lord gave me, maybe it was the passion.”

Or maybe the two are inextricable.

—

Even as it has been demonstrated in study after study that genetic inheritance influences physical activity, scientists are only beginning to discern the specific biological processes that play a role. Plus, every scientist knows full well that extreme environments can dramatically alter how much an individual trains. While dopamine plays a role in the drive to be in motion, there are certain, more obvious enticements.

When Floyd Mayweather Jr., renowned for his furious training, dropped by the
Sports Illustrated
office in 2007, fresh off his victory over Oscar De La Hoya, he described an unhappy period in his past when he was constantly concerned about money. “But I’m happy now,” he said with a mile-wide smile, referring to the $25 million he made for the fight.

All told, the tangle of nature and nurture is so complex as to prompt the question: can there possibly be any practical use at all for genetic testing in sports right now, in the present day?

The answer, despite all the complexity: absolutely.

The Heartbreak Gene

Death, Injury, and Pain on the Field

I
wasn’t there that day, February 12, 2000, in the desiccated winter air at the indoor track at Evanston Township High School. I had graduated and was off running at college. But my brother was a freshman on the team and my father was there too, videotaping. He was among the spectators in the aluminum bleachers standing up for a better look when my friend and former training partner, Kevin Richards, went down.

It was not unusual for a bone-tired runner to crumple to the ground after a hard race. But it had never happened to Kevin before. His teammates knew him to address his aches in silence, and always standing up. He embraced the pain of a race, and scorned the practice of lying down in exhaustion. “I love being sore,” he once said. “It feels like you did something.”

Normally, a fallen runner draws only slight curiosity from a track-savvy crowd. But Kevin was a state champion, and the dusty, green rubber floor of the track was no place for a state champion to be lying on his back, shuddering.

Kevin’s mother, Gwendolyn, had sensed something was wrong with him that morning when he overslept. He never overslept on race day. She thought he must be getting sick, so she asked him not to go. But Dan Glaz of Amos Alonzo Stagg High School was in town to race the
mile. Glaz was one of the best runners in Illinois. He would become a state champion and earn a scholarship to Ohio State.

Kevin was a junior, and he was getting recruiting packets too. In addition to being one of the top half-milers in Illinois, Kevin was an honors student, and would be the first in his family of Jamaican immigrants to attend college. He had told me—often while I was struggling to breathe on our runs—that he wanted to be a video game designer, and Indiana University was atop his college wish list. On this day, he wasn’t about to miss a chance to run against Glaz, a potential future Big Ten rival.

Gwendolyn, who worked at a nursing home, had been reluctant to bank on Kevin’s speed, so she attended financial aid seminars to figure out how to pay for college, until Kevin told her to stop. “You aren’t paying a penny for me,” he said, and then turned his back and walked away.

Moments before he crumpled to the floor, Kevin had been flying through the final surge, in pursuit of Glaz. There were other runners in the race, but it had become a duel between Kevin and Glaz. The duo had already lapped the field. With two laps to go, Glaz opened a gap, but as the bell clanged hollowly, signaling the final lap, Kevin reached down. He came steaming back around the final curve, swallowing ground and slicing into Glaz’s lead with each gaping stride. He ran out of room, just barely, and finished on Glaz’s shoulder, in second place.

Kevin walked a few exhausted steps past the finish line. As coach David Phillips came to lend a supporting arm, Kevin slipped through his grasp to the floor and started to shake.

Bruce Romain, the head athletic trainer, had seen nearly one hundred seizures in his career. He knelt beside Kevin and took his pulse. It was racing. He squeezed Kevin’s hand. Kevin did not squeeze back, but continued, like a fish washed ashore, to quake and heave and force air out of his mouth. Bits of saliva frothed over his lower lip with each labored breath.

A fireman among the spectators called the paramedics. Within minutes of Kevin’s collapse, emergency medical technicians raced
into the field house to help Romain give him mouth-to-mouth resuscitation. Kevin gave a mighty suck, and then exhaled a long, lackadaisical sigh. He stopped breathing.

Romain looked across Kevin’s body at a medic. The eyes of the two professional rescuers locked. “Oh, shit,” Romain blurted, as Kevin’s pulse disappeared. A medic rushed back to the rig for defibrillator paddles. Romain and the other medic continued furiously to give Kevin CPR. One of them acted as Kevin’s lungs, blowing oxygen-rich air into his mouth. The other was his heart, pushing down on his chest to force the oxygenated blood to flow through his body. But CPR could only buy some time. It could not make Kevin’s heart beat again. Like a car in need of a jump start, only a machine could save him now.

Somewhere on that last lap, the electrical signals that cued Kevin’s heart to pump had begun to misfire horribly. Rather than contracting and relaxing rhythmically, Kevin’s heart trembled, like Jell-O on a shaken tray. His left ventricle, the chamber that takes oxygenated blood from the lungs and squeezes forcefully, sending it hurtling through the body, had malfunctioned, causing a circulatory traffic jam. Blood backed up in the capillaries in his lungs—vessels so narrow that red blood cells have to move through them in single file—while the water in Kevin’s bloodstream pushed through the capillary walls and seeped into the tiny air sacs in his lungs. Water occupied the space where oxygen should have been. Kevin began drowning in his own body’s water.

The medic returned with the defibrillator paddles. They would try to jolt Kevin’s heart back into a normal rhythm by jarring it with electricity. They meant to shock him back to life, and they hoped they could do it sooner rather than later. Of all the times Kevin had been measured by the clock, these next few minutes on the track would be the most critical of his life. In the time it took him to run a mile, Kevin’s brain cells would begin to die in droves, in the poisonous, oxygenless environment of his own head.

One of Kevin’s teammates paced back and forth near the finish
line murmuring, “No way. He’s too strong.” Romain backed away, stunned. He told one of the assistant coaches to call Gwendolyn at her work. By the time she arrived, her son was being loaded into an ambulance. She forced her way into the passenger seat. A medic pulled down a shade so she could not see her son being worked on in the back.

When they arrived at Evanston Hospital, Gwendolyn sat in the waiting room, passing the longest minutes of her life. Then a chaplain came to meet her. “I know he’s dead! Just tell me he’s dead!” she screamed. Then she fainted.

Kevin was dead. He had died at the track.

•

Somewhere amid the three billion base pairs—the chemical compounds that form the rungs of the twisting DNA ladder—Kevin had a single misspelling in his genetic code. That’s like a single typo in a string of letters vast enough to fill thirteen complete sets of the
Encyclopaedia Britannica
.

Kevin’s genetic mutation could have been in any one of billions of locations. One particular spot would have caused him to have muscular dystrophy, while another would have left him colorblind. Many, many other locations would have had no discernible impact at all, as is the case with most of the mutations that each one of us carries around every day. But Kevin’s mutation occurred at the precise rung of the DNA ladder to draft the biological blueprint for a broken heart.

Kevin had hypertrophic cardiomyopathy, or HCM, a genetic disease that causes the walls of the left ventricle to thicken, such that it does not relax completely between beats and can impede blood flow into the heart itself. About one in every five hundred Americans has HCM, though many will never exhibit serious symptoms. According to Barry Maron, director of the Hypertrophic Cardiomyopathy Center at the Minneapolis Heart Institute Foundation, HCM is the most common cause of natural sudden death in young people. And it’s easily the most common cause of sudden death in young athletes.

According to statistics that Maron has compiled, at least one high school, college, or pro athlete with HCM will drop dead somewhere in the United States every other week. Some of them will be famous, like Atlanta Hawks center Jason Collier, or San Francisco 49ers offensive lineman Thomas Herrion, or Cameroonian soccer pro Marc-Vivien Foé. Most, though, will be like Kevin Richards—teenagers, just on the verge of becoming.

In those people, the muscle cells of the left ventricle are not stacked neatly like bricks in a wall, as they should be, but are all askew, as if the bricks had instead been dumped in a pile. When the electrical signal that cues the heart to flex travels across the cells, it is liable to bounce around erratically. Intense athletic activity can trigger this short-circuit, which is especially dangerous during competition, when an athlete straining his body will not respond to the early signs of danger.

For the nation’s most pressing health problems—diabetes, hypertension, coronary artery disease—exercise is a miraculous medicine. But people with HCM can be at increased risk of dropping dead precisely
because
they exercise.

Eileen Kogut, for example, had long known that something dangerous ran in her family. When Kogut was twenty-one, in 1978, her fifteen-year-old brother, Joe, was playfully roughhousing with their brother Mark at the dinner table when Joe dropped dead. The autopsy report listed the cause of death as “idiopathic hypertrophic subaortic stenosis”—essentially, a heart that is enlarged for unknown reasons. “Joe was the youngest of seven siblings,” Eileen says. “His death was incredibly devastating to our family.” So Mark, who carried the memory of his little brother dying right in front of him, started working out every day, just in case he had a faulty heart, like Joe. Mark was on a treadmill at the YMCA in Lansdowne, Pennsylvania, in 1998, when he collapsed and died. The cause of death, again: an enlarged heart of unknown cause. Mark was thirty-seven. He left behind a wife and three young sons.

HCM is passed down in what’s called “autosomal dominant”
fashion, which simply means that there is a 50-50 chance—a coin flip—that a parent with the culprit gene will pass it to a child.

Eileen Kogut eventually learned that HCM was what took her brothers, and in 2008 she decided to look into her own DNA.

•

Just across the Charles River from Boston’s Fenway Park is another structure of brick and steel. But rather than flags commemorating World Series wins, snaking down three stories of the exterior of this building are two winding metal ribbons, an artistic depiction of the DNA double helix.

Inside the building—the Harvard-affiliated Partners HealthCare Center for Personalized Genetic Medicine—geneticist Heidi Rehm directs the Laboratory for Molecular Medicine. Rehm and her lab staff identify new HCM mutations by the week. In the early 1990s, it was thought that HCM came from any one of seven different mutations on a single gene, the MYH7 gene, which codes for a protein found in heart muscle. By the time I visited Rehm’s lab in 2012, there was a database that included 18 different genes and 1,452 different mutations (and counting), any one of which can cause HCM. Most of the mutations are in genes that code for proteins found in heart muscle, and around 70 percent of people with HCM have a mutation on just one of two specific genes. (To make matters extremely complicated, though, two thirds of the different HCM mutations are “private mutations.” That is, each one has only been identified in a single family.) The most common cause of HCM is a DNA spelling error known as a “missense” mutation. A missense mutation occurs when a single letter is swapped in the DNA code, but in such an important place that it changes the amino acid that goes into making the resulting protein.

HCM mutations can occur randomly in someone with no family history of the disease, but most HCM gene variants are passed from parents to children. Some, however, don’t make it down family lines. One particularly dangerous HCM gene variant only ever appears as a
spontaneous mutation in a single individual in a family. “That’s because it’s reproductive lethal,” Rehm says. “No one ever survives to an age to reproduce and pass it on.”

Other mutations can be so mild as to go entirely unnoticed over a lifetime, like the “Trp-792 frameshift,” which sounds like it’s out of an NFL playbook, but is actually a mutation found specifically in Mennonite people.

In most instances, though, it’s difficult to tell whether a particular mutation puts an HCM patient at risk of sudden death. In Kevin’s case, the disease was only diagnosed after he died and his heart was examined. Kevin’s autopsy showed that his heart was a gargantuan 554 grams. An average adult male heart is around 300 grams. Kevin had no obvious signs of disease, other than that he had once been told he had a heart murmur. But so had I, and so have hordes of athletes who have been at the flat end of a stethoscope. As with any muscle, the heart gets stronger with exercise, and athletes often have nondangerous heart murmurs that go away when they’re out of shape.
*

Given her family history, Eileen Kogut had all her children’s hearts checked regularly from the time they were little. Her son Jimmy, who played basketball and lifted weights, had occasionally complained of shortness of breath. He was told he had asthma, a common but dangerous misdiagnosis for someone with HCM, because asthma inhalers can prompt lethal heart rhythms in HCM patients. In 2007, as he was getting set to start junior year at the University of Pittsburgh, Jimmy had a genetic test and learned that he has one of the most common HCM mutations, on a gene that helps to regulate heart contraction. Like his hazel eyes and freckles, he got it from Eileen. With the family mutation identified, Eileen decided to have her other children,
Kyle, then eighteen, Connor, then sixteen, and Kathleen, then twelve, tested, even though they weren’t showing symptoms. In March 2008, she took the kids for genetic screening and prayed that she hadn’t passed the mutation to any more of her children.

But the tidings were bad. Connor and Kathleen both came up positive. “I was devastated,” Eileen says. “I don’t know what I expected. I expected to hear good news. It was not an easy pill to swallow . . . I was angry at the lab. I was not coping well. I just thought, ‘Why did I ever do this? They’re young, what was I thinking? It’s going to ruin their childhood.’”

Cardiologists who study HCM recommend that people with the disease abstain from extremely rigorous activity, because the increase in adrenaline may spark a deadly heart rhythm. After the diagnosis, Jimmy underwent surgery to have a defibrillator implanted in his chest. About the size of a matchbox, the tiny device has wires that reach into the heart and stand guard, waiting for an abnormal heart rhythm. If one is detected, the defibrillator automatically fires an electrical shock to jolt the heart back to a normal pattern. Jimmy returned to college life as usual, minus the basketball. And weight lifting was restricted to nothing overhead or that could stress his left side so much that it might damage the defibrillator wires.