Caitlin Compton Gregg has never met a sport she didn’t like.
Her parents met at a bike shop and Gregg was riding through her neighborhood in New York City not long after she began to walk. Gregg and her family frequently spent weekends skiing in the mountains of Vermont, and it wasn’t long before she showed significant promise as a downhill skier.
When the ground wasn’t blanketed in white, Gregg would spend her days running and cycling. As a teen, Gregg signed up for a mountain run, which is precisely what it sounds like: You run all the way up the mountain and then all the way back down. Not only did Gregg find she liked it, she also found that she was good at it. Really good.
So Gregg began doing more endurance sports, trading downhill skiing for cross country. It was this latter sport that Gregg saw the chance to do something she had always wanted for as long as she could remember.
“Even as a little girl, I wanted to be an Olympian,” Gregg said. In college at Northern Michigan University, Gregg excelled at both cross-country skiing and cross-country running. After graduation, she joined a professional cross country skiing team and began training year-round. She qualified for the 2010 Olympics, and has been on four world championship teams. Gregg spends up to four to five hours training each day in Minneapolis, combining weight training, running, and skiing. It’s a grueling routine, but it has resulted in Gregg being super-fit.
Scientists love to study athletes, and have focused much effort in helping them train to be at their peak. No doubt important work that has allowed athletes to continually break world records in their efforts to go faster. But geneticist Euan Ashley at Stanford University and an international team of researchers, including Swedish exercise physiologist Mikael Mattsson, think that super athletes like Gregg can tell us more than the best way to train. They think the genomes of Gregg and others might just hold the secret to better health for everyone.
Medicine has had a long history of identifying the cause of diseases by studying people who are sick. Studying large families in which multiple people have the same condition, such as cystic fibrosis, phenylketonuria, or amyotrophic lateral sclerosis (ALS), scientists have been able to pin down some of the genetic causes of these conditions. These mutations have also helped identify potential treatments. Knowing that phenylketonuria was caused by an inability to break down the amino acid phenylalanine, which then built up to toxic levels in the body, allowed physicians to create a special phenylalanine-free diet that prevented the onset of symptoms.
Discoveries about other diseases operated similarly. If an illness was caused by having too much of a certain enzyme, scientists could design a drug that lowered the production of that protein. If it was the lack of a functional protein, there were drugs that could take its place. You couldn’t gain these insights simply by studying people who were well. To paraphrase Tolstoy, healthy people are all alike; every sick person is sick in their own way.
Except maybe healthy people aren’t all alike. Ashley and Mattsson realized this as they worked with people across the full range of cardiac function. Ashley had spent his career studying individuals with cardiac failure, and the gene mutations that may have caused their hearts to stop functioning. At the other end, Mattsson worked with people like Gregg, super athletes who would compete at peak performance for hours at a time. This meant their hearts could pump more blood for longer periods, giving their bodies the ability to get the most out of every oxygen molecule they breathed. The pair realized that, just as some of Ashley’s heart failure patients had genetic mutations that made them sick, some of the athletes Mattsson worked with might have genetic mutations that made them unusually healthy.
“We wanted to find the genes that might drive people towards health instead of disease,” Mattsson said. “And it might be possible to find medication based on these variants.”
The project initially started with just a handful of athletes, but the researchers soon realized that to determine anything definitive, they would need a larger sample of around 1,000 elite athletes. To qualify, athletes had to have an unusually efficient measure of oxygen usage, measured as VO2 Max. Men needed a VO2 Max of more than 75 milliliters per kilogram per minute, while women like Gregg needed a VO2 Max greater than 63. (For reference, healthy untrained males and females have VO2 Max levels around 37 and 30 mL/kg/min, respectively). Gregg passed the test with flying colors.
“I was used to being a guinea pig in everyday life with my training, because there’s no magic formula for training and there’s no magic formula for optimum health,” Gregg said. “It was fascinating to be able to see how these two might connect somehow.”
The researchers have just started sequencing some of the genes of the initial batch of athletes, so they don’t have any results yet, but they remain hopeful. Mattsson points to the previous discovery of a mutation in a gene called PCSK9, which was discovered by Helen Hobbs and Jonathan Cohen at the University of Texas Southwestern. The pair made the discovery when they found a San Antonio-area woman who had an LDL cholesterol (aka “bad” cholesterol) level of just 14 milligrams per deciliter. Current medical recommendations advise maintaining an LDL level below 100 mg/dL.
After extensive medical testing to determine that this PCSK9 variant didn’t cause any other health problems—it didn’t—the research community began work on a cholesterol-lowering drug that would give the millions of people around the world with high cholesterol the benefits of this mutation. Although the drug isn’t currently ready for the market, experts say that it is poised to be one of the next big blockbuster drugs.
Whether Gregg and other super athletes will provide the same kind of breakthrough remains to be seen, but Mattsson and Ashley remain confident that their approach may just change the way we look at health—a disease.