For 340 days, Scott Kelly circled the Earth aboard the International Space Station, gathering data about himself.
He drew blood from his arms. He saved his urine. He played computer games to test his memory and reaction speed. He measured the shape of his eyes.
Two hundred and forty miles below, Mark, the twin brother of Mr. Scott, who also served as an astronaut, performed identical tests. Now, a comparison of these two men has provided a unique opportunity to learn what happens to the human body in space, up to the molecular level.
On Thursday, just over three years after Mr. Kelly, 55, returned to Earth, researchers at the NASA Twins Study published the first results detailed in the journal Science.
The researchers found that Mr. Kelly's body experienced a lot of changes while in orbit. DNA mutated in some of its cells. His immune system produced a series of new signals. Your microbiome gained new species of bacteria.
Many of these biological changes seemed harmless, disappearing after he returned to Earth. But others, including the genetic mutations and, after their return, decrease in the scores of the tests of cognition, were not corrected, which raised concern among scientists.
Some considered the risks manageable, while others wondered if it would be safe for astronauts to make long trips to Mars or beyond. The final answers will depend on the studies of even more astronauts.
"I think it's the most complete evaluation of human beings to date," said Dr. Eric Topol, director of the Translational Research Institute at Scripps, who was not involved in the study. "I do not know that there was anything like this."
Even though astronauts have been brought along for almost six decades, there is much about life in space that scientists still do not understand. NASA would like to solve some of that mystery before sending astronauts on longer flights.
In 2012, NASA chose Mr. Kelly to join Russian cosmonaut Mikhail Kornienko aboard the space station for a year-long examination of the challenges of space travel, twice as many previous studies.
In the run-up to the mission announcement, Mr. Kelly asked the officials if they had any plans to compare him with his twin. "We have these two guys who are genetically identical," Mr. Kelly recalled as he told them. "They would do it for an interesting experiment."
The officials did not have such plans, but soon decided to accept the offer. Mark Kelly agreed, and the Twin Study of NASA was born. (Mark Kelly, who retired from NASA in 2011 and is the husband of former Representative Gabrielle Giffords, is running for the Senate seat of John McCain in Arizona).
By comparing the brothers, NASA hoped to better understand the changes that Scott Kelly experienced during his mission.
"The fact that they are twins actually reduces the alternatives," said Susan Bailey, a cancer biologist at Colorado State University and co-author of the new study. "We can say that, as far as possible, these changes are due to space flight."
Ten research teams designed experiments for the twins; They are likely to bring an avalanche of investigation. But for Mr. Kelly, the experience was not very different from previous missions.
Drawing his own blood in zero gravity, for example, was a familiar routine. "I've had a couple of spills in my time," Kelly said. "You just have to stretch out and grab the drops of blood."
According to the measurements that the scientists finally found, Mr. Kelly changed as much as the astronauts who remained on the space station for only six months. Finally, the pace of biological change slowed, suggesting that perhaps the human body reaches a new balance in space.
But Mr. Kelly's body was also altered in some surprising ways.
Dr. Bailey studied special sections of his DNA called telomeres, which are located at the end of chromosomes, protecting them from deterioration.
As people age, their telomeres tend to shorten. Stress, such as radiation or pollution, can accelerate aging by undoing telomeres even faster than usual.
Interestingly, the average length of Mr. Kelly's telomeres increased in space, instead of decreasing, as if his cells were becoming younger.
Regular exercise and a healthy diet can be part of the reason. But going into space could also have woken up a quiet population of stem cells in Mr. Kelly's body, said Dr. Bailey.
It is possible that your cells have not grown longer telomeres, in other words. Instead, maybe his body made a new supply of young cells with longer telomeres.
Going into space also seemed to cause a genetic change in Mr. Kelly. Thousands of genes that once were silent increased their activity, genes that remained silent in the body of Mark Kelly on Earth. The longer Scott Kelly stayed on high, the greater the number of genes that are activated.
It is known that some of the awakened genes encode proteins that help repair damaged DNA. That would make sense, since the radiation levels on the International Space Station are higher than on Earth.
Christopher Mason, a geneticist at Weill Cornell Medicine in New York, estimated that Mr. Kelly was exposed to 48 times more radiation than the average exposure on Earth over the course of a year. Your cells may have been busy repairing radiation injuries.
However, many other activated genes play a role in the immune system. What exactly triggers those changes is not clear.
It may be that the general stress of life in the space station elicits an immune response. But recent studies have also shown that latent viruses can awaken in astronauts.
Or maybe it's that the immune system, which never evolved To survive in space, it simply gets confused.
"Is it good or bad? We just know what's more," said Dr. Mason, co-author of the new study, on immune activity. "To be sure, we would need more astronauts."
The return of Mr. Kelly to Earth on March 1, 2016, proved to be one of the greatest moments, from the biological point of view, of the entire mission. His body showed signs of intense stress, and his immune system was underway.
Michael Snyder, a Stanford University geneticist and co-author of the research, cautioned that this response may not be typical. "Maybe he had a viral infection," he speculated. "That's why you want to see more people."
Despite that shock, Mr. Kelly's body returned to its pre-flight condition. Some species of bacteria that thrived in their entrails while in space, for example, were again rare in their landing.
The strange lengthening of Mr. Kelly's telomeres disappeared after less than 48 hours on Earth. In fact, Dr. Bailey and her colleagues began to find many cells with telomeres that were shorter than before Mr. Kelly went into space.
"People have asked me:" Well, will you space the fountain of youth? ", Said Dr. Bailey. "I do not believe it, if it's like that, you'll have to stay up forever."
"Fighting against quicksand"
Some aspects of Mr. Kelly's biology did not return to the prior verification standard.
Six months after he returned to Earth, 8.7 percent of his genes were still behaving in an altered way. Judging by the small size of this change, Dr. Snyder described the change as modest.
The researchers also found that Mr. Kelly did not perform as well on his cognitive tests. "It became slower and less accurate in virtually all tests," said Dr. Mathias Basner, a cognitive scientist at the University of Pennsylvania.
It is possible that some biological change is the culprit. But Dr. Basner noted that Mr. Kelly also faced many lawsuits on Earth, including a busy schedule of television interviews and public speaking.
And at an unconscious level, you may not have been pushing. "I mean, basically he retired the moment he hit the ground, and so maybe he just I was not so motivated anymore, "said Dr. Basner.
In his 2017 memoirs, "Resistance," Mr. Kelly describes how he struggled after his return with pain, trouble sleeping and other ills. One night he felt as if he was "struggling against quicksand," he wrote.
In a interview Last week, Mr. Kelly speculated that those difficulties could be to blame for his cognitive scores. "It's hard to concentrate when you're not feeling well," he said.
Another lasting change, the scientists found, was a collection of genetic mutations that Mr. Kelly obtained in space. "We see them appear in flight, and then they persisted," said Dr. Mason.
Sometimes, radiation triggers a type of mutation that causes cells to be prone to gain even more mutations as they divide. Over time, cells can begin to grow uncontrollably, "taking steps on the road to cancer," said Dr. Bailey.
Peter Campbell, a cancer biologist at the Wellcome Sanger Institute in Britain who was not involved in the new study, said scientists can not predict what additional mutations will mean for Mr. Kelly's health.
"It's hard to be sure, but I think that kind of numbers would be badociated with a moderate increase in cancer risk," he said.
These two lingering changes, in Mr. Kelly's cognition and DNA, left several experts concerned about the risks of a Trip to Mars, which could take a year.
Gary Strangman, a psychologist at Harvard Medical School, said a decrease in speed and accuracy "could have serious consequences for long-duration missions."
After a grueling trip to the red planet, the astronauts would probably need to take quick and precise actions when they landed.
"If you had a slower period of cognitive processing speed and difficulty with balance and coordination between the head and the eye, those behaviors would be at risk," said Rachael Seidler, a cognitive neuroscientist at the University of Florida.
A large load of genetic mutations would not present immediate dangers to astronauts in their missions, but could increase their cancer risks for life.
Dr. Mason estimated that a mission to Mars would expose an astronaut to eight times more radiation than Mr. Kelly experienced.
"Everything possible should be done to limit exposure to astronauts during periods of prolonged space travel," said Charles Swanton, a cancer biologist at the Francis Crick Institute in Britain who was not involved in the new study.
Dr. Topol, of the Scripps Institute, found the implications of Mr. Kelly's experience discouraging.
"The main conclusion I got from this document, based on all the objective data, is why would anyone want to go to Mars or be in space?" He said. "Because this is really scary."
Jerry Shay, a cell biologist at the Southwestern Medical Center at the University of Texas, was much more optimistic. He maintained the hope of countermeasures that protect the astronauts.
He and his colleagues, for example, are testing drugs to cause cells to repair DNA damaged by radiation. "I think all these problems are solvable," said Dr. Shay.
NASA has begun to review all of these results to help plan the next round of missions to the International Space Station.
"It will not be a replica of what you saw in the Twins Study," said Jennifer Fogarty, chief scientist of NASA's Human Research Program.
"We're going to learn from that and we're going to be smarter about the questions we ask, there's a lot of fascinating things to measure, it's just not clear what that means."
Dr. Bailey, meanwhile, plans to continue studying the bewildering telomeres of Mr. Kelly. Solving that mystery could shed light on common aging and the diseases it brings.
"When we discover how and why, it will be important for astronauts and for us simple earthlings," he said.