On the short list of people who’ve been into space, two are identical twins. Scott and Mark Kelly, whose parents were police officers, are both NASA astronauts; they’re about to become subjects in a unique and groundbreaking study. In March, Scott—a former International Space Station commander and veteran of the space program—departs on a one-year mission to the ISS, alongside Russian cosmonaut Mikhail Kornienko. Meanwhile, Mark, who is now retired from NASA, will stay on the ground, at home in Arizona. A group of researchers will track Scott in space, and his genetic doppelgänger on Earth, to get a fuller picture of the myriad effects of long-term space travel—crucial information if we hope to send astronauts to Mars and beyond.
The twins study brings NASA into a new realm of science, what Craig Kundrot, at NASA’s human research program, calls “21st-century omics research.” This includes genomics (the study of the Kellys’ DNA), metabolomics (their metabolism), microbiomics (the bacteria in their guts), and more. “The twin study is really a baptism for us,” says Kundrot, who’s based at the Johnson Space Center in Houston. But there’s another reason NASA has largely avoided this type of research, until now. “NASA has never been in the genetics game for one simple reason,” says Fred Turek of Northwestern University, one of the investigators on the twin study. “Astronauts have only one fear in life: that some scientist is going to find something wrong with them.”
Some wonder if this could mark the beginning of genetic testing for astronauts. “The last thing [astronauts] want is for you to genotype them, and say they’re five times more likely to have a kidney stone, so we won’t send you to Mars,” Turek says. A manned mission to Mars could take around three years, and cost billions. If anything went wrong, it would be much harder to help the crew, or bring them home. If we’re going to send astronauts there or farther, some form of genetic testing might be unavoidable.
Scott Kelly will be living on the Space Station for a full year, a first for any American astronaut. (The record still belongs to cosmonaut Valeri Polyakov, who spent 437 days aboard Russian space station Mir two decades ago.) Living in space affects virtually every system in the human body. Without gravity’s downward pull, “the body deconditions,” says Canadian astronaut Robert Thirsk, and loses muscle mass, and bone. Even after five decades of space flight, we still don’t understand its full effects. “It seems that every time we do something different, a new problem crops up,” Thirsk says. In 2009, he lived aboard the ISS for six months, the first Canadian to do a long-duration mission. During that time, he and a U.S. astronaut started having vision problems. Ultrasounds revealed their eyeballs had become squished: the back end was “flattened, pushed in,” and Thirsk became temporarily farsighted. This was a new problem, but since then, some other astronauts have reported the same thing. Space agencies are still trying to understand why.
Twin studies are a favourite method to separate out the impact of environment from genes, and flying Scott Kelly, who has an identical twin on the ground—another trained astronaut, no less—is a one-in-a-million opportunity. Even so, it came about almost by accident. Shortly after Kelly was named to the one-year mission, in 2012, he was meeting with NASA officials “and asked if any studies would involve his brother,” Kundrot says. “The initial response was—we hadn’t thought about this, because he was just named—that there was nothing in the pipeline.” NASA put out a call to researchers, ultimately picking 10 investigations, all U.S.-based.
Scott Smith, who runs NASA’s nutritional biochemistry laboratory at Johnson, is leading one of the investigations. He’s been collecting blood and urine samples to build what he calls an astronaut’s “biochemical profile”—one that tracks levels of vitamins, minerals, proteins, hormones, immune markers, and much more, during space flight. (He’ll be doing the same with Scott and Mark Kelly.)
Already, Smith’s research has turned up some clues on the troubling question of why some, like Thirsk, have a shift in vision: he’s found that those who do have higher levels of homocysteine, an amino acid that’s often a marker of cardiovascular disease. We don’t know why, “but there may be a predisposition,” he says. “When you fly two astronauts, and one gets vision issues and the other doesn’t, there’s a very clear possibility that genetic differences are contributing.”
Susan Bailey at Colorado State University will be studying the Kellys’ telomeres—tiny caps at the ends of our chromosomes, which offer a rough marker of biological age. Telomeres shorten as we grow older, but certain factors, like stress, seem to speed up the process. And people with longer telomeres appear to be at lower risk of age-related illness, including heart disease and cancer. We have no idea how telomeres respond to life in space. “That’s where my project starts,” says Bailey, who hypothesizes that Scott’s telomeres will shorten over the course of his mission, compared with Mark’s. She’ll be collecting blood samples from both before the launch, during the flight, and when Scott returns. “It could become a very important biomarker of how time in space has affected you, and whether it accelerated aging,” Bailey predicts. “Are you at higher risk for cancer or cardiovascular disease, for example? Telomere length can give you a clue.”
Turek, at Northwestern, is overseeing a study that looks at communities of bacteria living in the astronauts’ guts. His samples will be swabbed from what’s collected in the Space Station toilet, then frozen, a simpler process than an on-orbit blood draw. Emerging research shows just how much the human microbiome—bacteria that live in, on, and around us, outnumbering our human cells by 10 to one—intimately affects all aspects of our health, including risk for conditions as diverse as cancer, colitis, and asthma. We know next to nothing about what happens to these bacteria in space, or on the Space Station, which is kept ultra-sterile by design. On Earth, “we’re encountering more people, touching more surfaces, and using different utensils [than on the Station],” Kundrot adds. “What’s coming into the big bioreactor in our gut is different than for Scott.” How space travel affects Scott’s immune system is the focus of another investigation, by Emmanuel Mignot at Stanford University. Kundrot says he’ll give the Kellys three separate flu vaccinations (before, during, and after the flight) to observe their immune response.
While his brother’s in space, Mark won’t mimic Scott’s on-orbit activities; he’ll live his regular, earthbound life. (Mark, who is married to Gabrielle Giffords, the U.S. congresswoman who survived a 2011 shooting attack, has joked he’d rather not eat “crappy Space Station food.”)
As these and other scientists track the twins, they’ll share reams of data through the person Kundrot calls “the master integrator”: Stanford geneticist Michael Snyder. Snyder is perfect for the job. For the last 4½ years, he’s been performing a similarly detailed study—on himself.
In a paper published in the journal Cell in 2012, Snyder described how he created his own “personal omics profile,” analyzing his blood to observe the inner workings of his immune system, gene activity, metabolism and more. He’s kept it up since, and plans to continue tracking himself for the rest of his life. “When we sequenced my DNA [for the Cell paper], I was predicted to be at risk for Type 2 diabetes,” he says. Over the course of that 14-month study, a doctor did diagnose him with diabetes; with interventions like diet and exercise, he managed to curb it. “My prediction was accurate,” Snyder says. Imagine the benefits of having such detailed data on a crew of astronauts as they travel through space, allowing for tailor-made interventions even before problems arise.
One can question the scientific value of a study of a single person, whether it’s Snyder or the Kelly twins. Snyder counters that this type of work is increasingly important. “It’s what personalized medicine is all about,” he says. “At the end of the day, I want to know what’s going on with me, not 500 other people.” The twin study’s incredibly small sample size also raises ethical questions for NASA. In anything that’s published, Scott and Mark Kelly will be instantly recognizable. What if scientists discover that one or both have a genetic predisposition to Alzheimer’s, for example? Both men, who are receiving genetic counselling, will have a final say over what gets published, and what doesn’t.
Bailey admits this clause presents a challenge, from a researcher’s perspective. “I’m used to working with cell lines, and they don’t care. The jury’s still out on how it’s going to go, but at the end of the day, it will be [the Kellys’] choice.” According to Kundrot, all researchers have been informed that, for now, NASA’s policy is to “err on the side of conservatism, and they haven’t balked.”
The most important question remains how genetic testing will impact the astronaut corps. Smith, the NASA nutritionist, is emphatic that it won’t be used to bar anyone from a mission. “It’s illegal to job discriminate based on genetics.” The trick, he believes, will be using this data to tailor new ways to counteract the risks of space flight. Still, it’s a murky area: astronauts can already be disqualified for health problems, and of course, many of these have a genetic component. In his autobiography, An Astronaut’s Guide to Life on Earth, Canadian Chris Hadﬁeld described how ofﬁcials almost blocked him from his history-making turn at the helm of the ISS, over their concerns about an intestinal issue. (Hadfield ultimately had to have an ultrasound exam, which he passed.) It’s new territory for NASA—and Scott Kelly’s mission hasn’t even begun. “As much as we’re trying to probe the great beyond,” Snyder says, in poring over the inner workings of this astronaut and his identical earthbound twin, he and other scientists are on a parallel quest: to explore “the great within.”