During the Olympics we all gather around our television sets to watch the best athletes in the world compete against each other and we wonder how it is that they can humanly perform at such a high level?
This feature story about Stanford HCM Clinic’s Dr. Euan Ashley provides us with an interesting overview of the research Dr. Ashley is doing on high performance elite athletes with the hope that their genes may provide clues that will one day help to help treat those of us with HCM and other genetic heart conditions.
The Superhero Genes
One scientist is on a quest to find the genetic mutations that make athletes elite — which may lead to new treatments for the rest of us.
Today, Gregg, a compact, Nordic-looking 35-year-old, is a four-time NCAAAll-American in running, an Olympian, and a 2015 world-championship bronze medalist in cross-country skiing. It turns out she has something the vast majority of us, even those who are athletically able, do not: a biological advantage that has allowed her to become one of the world’s most elite athletes.
In the lab, I watched as Kyle Peter, who is widely considered among the best ultra-endurance adventure racers in the U.S., prepared to test his VO2max. Peter, who has won two adventure-racing world cups in the past year with only a few weeks’ break in between, is a three-time national champion and currently heads the third-highest-ranked ultra-endurance team in the world. He can race two days without sleep and has been known to machete for 20 hours through Brazilian wetland to complete a course.
Peter, a stocky, self-effacing, bearded 31-year-old, was dressed in running shorts and a very loose T-shirt: He explained that during his most recent race in Belize, he had acquired a jungle rash that reacts whenever his body heats up, as it would on the treadmill that day. The pacing of the test was calibrated to Peter’s last 10K running time of 37:30 minutes. The test would last between six and ten minutes. The goal is for the athlete to go until he feels he cannot possibly go any farther, speeding up until the pace is unsustainable.
Peter started at a jog. Soon, as he sped up, his face changed from relaxed to determined to altogether grim. When he finally grabbed the handlebars and collapsed on a chair, he was unable to speak for several minutes. His VO2max for the test: 60.6. Not close to qualification. To put the cutoff in perspective, the 11-time Olympic medalist and multiple-record-holding swimmer Ryan Lochte reportedly comes in at 70 milliliters per minute, meaning he is out of contention. “We’re starting at the top,” Ashley said. “Getting the most elite first.” To optimize the chance of finding true genetic markers of performance outliers, you need to set incredibly high limits.
The results were astounding, and so Ashley ran some genetic tests. He looked at a gene related to cardiac function — the angiotensin-converting enzyme, or ACE, which is involved in increasing blood pressure. What he found was that a tiny polymorphism in the gene could predict the extent to which heart function would decline — or remain stable. In that finding, something seemed to click: ACE had previously been linked to an increased rate of heart attacks. Could the same gene, in different manifestations, cause disease and lead to superior performance?
The question itself wasn’t new, but the lens of extreme athletes was, and there were other examples that bolstered Ashley’s idea. Consider Eero Mäntyranta. The champion Finnish skier won seven medals over four Olympic games — three gold, two silver, two bronze. At the time, it was an unparalleled feat. So unparalleled, in fact, that he was accused of blood doping. Testing seemed to provide confirmation: The percentage of his blood made up of red blood cells, which carry oxygen to the muscles, was multiple deviations away from the average range. It would soon turn out, however, that the accusations were false. The skier was clean. He simply had a mutation in a receptor that controls how many red blood cells are produced and allowed to remain in the blood. In Mäntyranta’s case, a tiny change had hugely shifted the balance. The same mutation was eventually found in his extended family. “It was as if he had an accelerator down on his red-blood-cell-manufacturing plant permanently,” Ashley said. “He was a genetic superhero.”
Mäntyranta’s mutation, however, can also cause polycythemia, a red blood cell disease. (Mäntyranta actually had polycythemia, though it didn’t manifest with negative symptoms.) Understanding the performance-enhancing change, Ashley thought, could lead to treatments for people with cardiovascular problems. “You can short-circuit normal drug discovery,” Ashley said, “by creating a drug that mimics that.”
It’s a transition in thinking that has begun to crop up in other treatments. Sharlayne Tracy, an aerobics instructor in Texas, became medically famous for her impossibly low levels of cholesterol, ones that exercise and diet could not explain. Healthy levels of cholesterol are usually less than 100. Below 50 is considered exceptional. Tracy’s was 14. When Tracy’s genome was sequenced, geneticists found a mutation in a gene that is a sort of cholesterol trash collector: It tells the body when to remove excess cholesterol from the blood and when to go home for the night and let the trash pile up. Tracy’s mutation, Ashley explained, was the equivalent of giving a sedation shot to the head of the trash-collection agency. He’s knocked out cold, so he never tells his team to go home. They stay out all day collecting that trash — and cholesterol levels remain abnormally low. The finding has led to two new drugs for treating high cholesterol.
“We learn a lot of things by looking at extremes,” Ashley told me. “The fittest and the most failing in the world — the power of the genome speaks to more than one system.” This is the logic that governs his work: He’s on a quest to use the healthiest people in the world to help the least healthy, and, perhaps, those of us who fall somewhere in between.
Another intriguing variant found in several athletes is RUNX3 — though, as with all of these mutations, the data are quite preliminary and any conclusions likewise so. Originally, the gene came to light in cancer research. Normally, it suppresses tumors, but in mutated form the suppression function is lost and increased cellular growth ensues. If you’re an athlete, cellular growth can be good: The better your muscles and heart grow, the more quickly you respond to training. The mutation, however, can also lead to tumors. There’s a finely calibrated and fungible line between overperforming and underperforming, between what makes us healthier and what puts us at risk.
It’s tempting to see Ashley’s work and imagine a Gattaca-like future in which the revelations of the genome help not just the diseased, but those of us who are average — a time when this information could take all of us from normal to elite. That has worrying implications: not only the fears that accompany any genetic interference, but a further fear, of health ramifications. As the RUNX3variant suggests, playing with these genes is a hazard the healthy probably won’t want to risk, since tweaking the genome could take us from benefit to harm in an instant. Even maximizing our abilities could give us more than we bargained for. You would think that the fittest people on Earth would also be the healthiest; you would be wrong. If you compare Olympic athletes with the average human, you would indeed find that they live longer and are healthier. But when compared with people who are generally fit, who exercise at levels that are more recreational and don’t push their bodies to extremes, research has found that Olympians die at a younger age. Being elite is an honor, but it may be a complicated one.
MARIA KONNIKOVA is a contributing writer for The New Yorker. Her book The Confidence Gamewas released in January.
NILS ERICSON is a photographer living in Brooklyn. His work will be on view at the Institute of Contemporary Art at Maine College of Art in November 2016.