What’s Different About Astronaut DNA?

Three researchers describe their findings in NASA’s study of identical twin brothers, one in space and one on Earth.

Chris Mason has never met Scott Kelly, but he knows all about his DNA.

Mason, a geneticist at Weill Cornell Medicine in New York City, is one of the researchers participating in NASA’s twins study, an investigation of the effects of space travel on the human body. In 2015, Scott launched to the International Space Station for a 340-day stay while his identical brother Mark Kelly, also an astronaut, went about his life on Earth. For months, the brothers rolled up their sleeves for regular blood draws. Some samples beat Scott back to Earth, hitching a ride with other astronauts on their return trip on the Russian Soyuz.

“I’d go to bed at night and check Twitter and see he’d posted another amazing, beautiful view of Earth from space, and was smiling thinking of his DNA comfortably and securely sitting in my freezer,” Mason said.

The Kellys actually came up with the idea for a study themselves, pointing out to NASA that, hey, they’re identical twins, and maybe there’s some science to be done when one is on a planet and the other’s not. The space agency agreed and put out a call for research proposals. In 2014, NASA picked 10 teams and gave them a combined $1.5 million over three years. Scott returned last March, and researchers have been pouring over the samples since, looking for evidence of genetic changes in Scott that potentially could be attributed to living and working in the extreme environment of space.

There is, however, one glaring caveat in this investigation. The study is an n-of-1 trial, a case study of a single patient, Scott. Any detectable changes could be the result of random chance, or they could be the product of differences in experience. Whatever results emerge from this work, they cannot be generalized to the astronaut population, let alone the human population.

The results are preliminary so far, and the 10 teams will spend the next few months analyzing and comparing their respective data sets; some, like Mason and Feinberg, are studying gene activity, while others are examining vision or immune-system responses. The twins get briefed on findings by genetic counselors, and reserve the right to withhold any information from being published. DNA, after all, is about as personal as it gets.

One surprising finding from the study had nothing to do with space travel. The Kellys thought they fully came of Irish descent, but genome sequencing revealed they have roots in England, too.

The rest of the findings have researchers puzzled. Mason, whose team is in charge of sequencing the Kellys’ genomes, anticipated microgravity would induce some molecular changes in gene-expression signatures, the “on” and “off” switches that tell genes what to do. That happens all the time to Earth-bound humans, thanks to shifts in sleep, stress, and diet. What was unexpected, he said, was how many of these changes were recorded. Mason and his team are currently comparing the data from Scott’s RNA sequencing to similar, publicly available data to determine whether all these changes have been recorded before. The goal, he said, is to spot evidence of a “space gene,” a stretch of DNA that may become activated only when humans are plopped into microgravity.

Susan Bailey, another investigator, is studying the brothers’ telomeres, the protective caps on the ends of chromosomes that help ensure chromosomes get replicated properly when cells divide. Going into the study, Bailey, a radiation cytogeneticist and Colorado State University professor, thought long-term exposure to radiation, microgravity, and other space-related stressors would cause Scott’s telomeres to shorten. On Earth, telomere loss is a natural symptom of aging, and can be accelerated by stress. Being in space puts plenty of stressors on people: without the pull of gravity, bones lose density, eyesight worsens, heads get clogged up as bodily fluids float upward. Spaceflight, Bailey thought, would cause Scott’s telomeres to shrink from the stress.

That didn’t happen. Instead of shortening, the telomeres actually got longer. Within a few months after his return, the telomeres bounced back to pre-flight levels.

“Could this be real? I think that’s the first thing that pops into your mind,” Bailey said, laughing now about her initial hypothesis.

Bailey doesn’t know why Scott’s telomeres seemed to defy logic. Separate data on the telomeres of 10 other NASA astronauts showed a similar effect. Perhaps short telomeres in some cells, sensitive to the environment of space, disappeared altogether, making the count of longer telomeres appear higher. Or maybe microgravity caused the enzyme telomerase, to spring into action, adding more of the nucleotides that create telomeres to the ends of chromosomes. That’s the controversial bit, Bailey said. Telomere length can certainly be maintained with the help of healthy life choices, like good diet and exercise. But the lengthening of telomeres has never been convincingly shown in humans.

Longer telomeres are a sign of longevity—until they’re not. “You might at first think, ‘Oh, this is great. He’s going to live longer,’” Bailey said. “But the opposite side of that coin is always that it also increases cancer risk, because one of the very first things cancers do is turn telomerase on to maintain telomere length so they can essentially be immortal.”

More mysteries abound for Andy Feinberg’s team, which studied the brothers’ DNA methylation, the mechanism by which cells control gene expression. The Kellys had normal and similar levels of DNA methylation before Scott blasted off to space. But while Scott was in space, his average level of methylation decreased across his genome, while Mark’s rose. Both returned to baseline levels post-flight. Feinberg, a geneticist at Johns Hopkins University in Maryland who applied to be an astronaut himself in 1979, doesn’t yet know what this means. Various factors, like nutrition and exposure to radiation or toxins, and influence DNA methylation, but the bottom line is you want the “right” level for a specific gene, whether it’s in the cells of your eyeballs or your gut.

Mason, Bailey, and Feinberg were all careful to note that the results of their work can’t be extrapolated to the general population, nor may they be entirely explainable. There are too many factors at play. “How do you know whether it’s space, microgravity, being inside of a box for a year, having altered sleep, eating freeze-dried food?” Feinberg said.

Still, the study was the first of its kind, with special hurdles not found inside an average laboratory. Delivering equipment for sample collection, for example, was a lot more expensive, since it costs thousands of dollars per pound to send cargo to the International Space Station. There are no medical professionals to do the blood draws on the station, just Scott and his fellow astronauts. And the last thing they’d want is to take too much blood and make him feel woozy in an environment where he can’t sit down. In June 2015, SpaceX’s Falcon 9 rocket exploded minutes after takeoff, destroying a giant payload of supplies that included Mason’s and Feinberg’s equipment. There is one perk: Once samples returned on a Soyuz rocket, they were quickly loaded onto a government plane and flown from Kazakhstan to Houston, with no stops through customs. “We got the blood faster from space than we can often get it from some lab somewhere else in the United States,” Feinberg said.

As with any research NASA conducts or oversees into astronauts’ health, there’s an endgame. Scientists must understand how human bodies react to long-duration spaceflight before governments send them on a mission to Mars or beyond. If scientists figure out what’s causing epigenetic changes—changes in genes brought on by external factors—maybe they could stop or reverse them.

“If there’s going to be a Mark Watney marooned on Mars,” Feinberg said. “He’s probably going to need a sequencer if he needs to grow something new to eat, or if he’s growing some infection that could kill him.”