From his eyes to his immune system, astronaut Scott Kelly's body sometimes reacted strangely to nearly a year in orbit, at least compared to his Earth-bound identical twin - but newly published research shows nothing that would cancel even longer space treks, like to Mars.
The good news: Kelly largely bounced back after returning home, say scientists who released final results from NASA's "twins study," a never-before opportunity to track the biological consequences of spaceflight in genetic doubles.
It marks "the dawn of human genomics in space," said Dr Andrew Feinberg of Johns Hopkins University. He led one of 10 teams of researchers that scrutinized the twins' health down to the molecular level before, during and after Kelly's 340-day stay at the International Space Station.
More importantly, the study "represents more than one small step for mankind" by pointing out potential risks of longer-duration spaceflight that need study in more astronauts, said Markus Lobrich of Germany's Darmstadt University and Penny Jeggo of the University of Sussex, who weren't involved in the work.
The findings were published in Friday's edition of the journal Science, on some notable space anniversaries - when Soviet cosmonaut Yuri Gagarin became the first person in space in 1961, and the first launch of the space shuttle in 1981.
NASA already knew some of the toll of space travel, such as bone loss that requires exercise to counter. This time, NASA-funded scientists looked for a gamut of physiologic and genomic changes that Scott Kelly experienced in space, comparing them to his DNA double on the ground, former astronaut Mark Kelly. Some results had been reported in February.
Possibly the weirdest finding had to do with something called telomeres, the protective ends of chromosomes. Those tips gradually shorten as we get older, and are thought to be linked to age-related diseases including some cancers.
But in space, Scott Kelly's telomeres got longer. "We were surprised," said Colorado State University telomere expert Susan Bailey. She can't explain it although it doesn't mean Kelly got younger. Back on Earth, his telomeres mostly returned to preflight average although he did have more short telomeres than before.
Next, Kelly's DNA wasn't mutated in space but the activity of many of his genes - how they switch on and off - did change, especially in the last half of the voyage, which ended in March 2016.
Immune system genes especially were affected, putting it "almost on high alert as a way to try and understand this new environment", said study co-author Christopher Mason, a Weill Cornell Medicine geneticist in New York.
Again, most gene expression returned to normal back home, but some of the immune-related genes were hyperactive six months later.
- Some changes in the structure of Kelly's eye and thickening of his retina suggested that, like about 40% of astronauts, he experienced symptoms of "spaceflight-associated neuro-ocular syndrome." It may be caused by fluids shifting in the absence of gravity.
- He experienced some chromosomal instability that might reflect radiation exposure in space.
- A flu shot given in space worked as well as one on Earth.
- Kelly aced cognitive tests in space but slowed down after his return, maybe as more things competed for his attention.
Ultra long-distance testing
Researchers needed months' worth of blood, urine and fecal samples, along with cognitive and physical tests and ultrasound scans.
That meant getting creative: Some blood samples required analysis so rapidly that Kelly would time collection so the blood could travel on Russian Soyuz capsules carrying other astronauts back to Earth.
That wouldn't be an option on a three-year trip to Mars. One of the study's technological advances: Portable DNA-sequencing equipment that will let astronauts run some of their own genomic analyses on future missions, said Weill Cornell's Mason.
Studying one pair of twins can't prove risks of spaceflight, researchers cautioned. And longer missions, to the moon or Mars, will mean greater stress and radiation exposure.
Colorado State's Bailey plans to study 10 additional astronauts on year-long missions, using the twin findings as a road map.
"We need to get outside of low-Earth orbit and we need for the astronauts to spend longer periods of time to really evaluate some of these health effects," she said.