For almost one year, NASA astronaut Scott Kelly circled the planet on the International Space Station, completing three spacewalks, conducting experiments on plants and playing ping-pong with a ball of water. His earthbound twin, Mark, lobbied for stronger gun laws, played golf and drank an occasional beer. Together, the genetically identical subjects constituted the starkest nature-versus-nurture study in history.
By comparing blood samples from the twins before, during and after the mission, researchers found that Scott’s gene expression was exceedingly altered after spending a year in space, and that his DNA suffered “gross, large-scale damage,” probably as a result of radiation exposure.
Scott’s body exhibited a sharp uptick in biological markers of inflammation, changes in eyeball shape and a glaring deterioration of cognitive function. But six months after his return to Earth, the experiment revealed no significant differences in the twins’ overall health.
The results, published Thursday in a suite of studies in the journal Science, bolster NASA’s plans to embark on a more arduous human endeavor to Mars in the next decade.
“Having spent a year in microgravity, I can tell you that Mars is definitely doable,” Scott Kelly said in an interview. “The degree of plasticity in the human body is extraordinary. Will we be able to adapt? I think so.”
More than 550 people — including the Kelly twins — have traveled to space on short-term missions, so some biological stressors are well known. Exposure to radiation and microgravity can deteriorate bones; restricted diets and limited exercise decrease muscle mass; disrupted sleep cycles cause fatigue and even dangerous flight errors.
But only eight astronauts have stayed in space for more than 10 months, so the effects of extended journeys are still a mystery.
Under the direction of NASA’s Human Research Program, about 84 researchers at 12 institutions analyzed thousands of biochemical measurements of the twins over the course of 25 months. They began six months before Scott took off for the space station in late March 2015 and ended nine months after his return in early March 2016.
Indeed, the world’s only genetically identical astronauts may have been studied with greater depth than any other humans, said Christopher Mason, a biophysics professor at Weill Cornell Medical College, who led genetic investigations for the study.
Preparations were intense. Scientists spent a week testing blood-sampling protocols on the so-called Vomit Comet, an aircraft chamber that simulates weightlessness. (Researchers confirmed that the Vomit Comet abundantly lived up to its name.) Thanks to surface tension in microgravity, pipette work proved easier in a near-weightless environment — “except when the pipette tips float away,” said Dr. Andrew Feinberg, a scientist at Johns Hopkins University who studied how the space environment influenced the activity of Scott’s genes.
During Scott’s mission, when resupply shipments arrived at the space station on Russian Soyuz spacecraft, his biological samples were quickly loaded onto the vehicles and shipped back to Earth to be processed within 48 hours.
Throughout the Twins Study, the scientists used Mark Kelly’s biological samples as a control to test whether changes seen in Scott could be chalked up to living in space. In most cases, the researchers determined that it was.
Space travel did not alter Scott’s genetic code containing instructions for maintaining the human body. But researchers noticed a slew of changes in gene expression — the way the instructions are read and carried out.
These changes were most apparent in genes related to stress and immune response, as Scott’s body went on “high alert” to understand its new environment, Mason said. Researchers believe the ongoing radiation exposure and reduced gravity influenced the way Scott’s cells produced valuable components, like proteins used to repair tissue.
Strangely, in the second half of Scott’s mission, there were six times as many genes changing as there were in the first half, Mason said.
“Astronauts’ bodies typically show some biological sentiment of, ‘Holy crap, I’m in space,’ and then over time, the stress markers flatline,” he said. “But as Scott approached months five, six, seven, the genetic changes just ramped up.”
Then, within six months of returning to Earth, about 90% of Scott’s affected genes returned to their normal expression levels.
It is unclear whether changes to gene function would continue to climb during a two- or three-year mission to Mars, Mason said.
Telomeres typically become shorter over the course of a lifetime, increasing the risk for age-related conditions like cardiovascular disease and some kinds of cancer. But within weeks of Scott’s arrival in space, the telomeres in his white blood cell samples were longer. Scientists were shocked.
“I have never seen any elongation among any of us mere earthlings,” said Susan Bailey, a Twins Study principal investigator who studies telomeres at Colorado State University. “I won’t go so far as to say that space is a fountain of youth — but on Earth, this isn’t in the literature.”
Bailey said she suspects Scott’s body had launched a wound-healing response to chronic radiation by mobilizing stem cells, which typically have long telomeres. The discovery could help researchers design medical countermeasures to the stressors of space travel, she said. One day, it may even lead to methods for extending lifespans on Earth.
Other notable changes in space included weight loss, a reshuffling of the microbes in Scott’s gut, and increased thickness of the carotid artery that carries blood to the head and neck, which can increase the risk of cardiovascular disease and stroke.
The thickness of Scott’s retinal nerve also increased, as did the folds in the choroid layer that surrounds the eye, which can affect vision clarity, according to Feinberg. Those eyeball changes have been seen in other male astronauts, but not in females.
“In some respects, it looks like women are biologically better suited for long-term spaceflight,” Feinberg said.
If living in space was hard for Scott, returning to Earth was harder. His stress-related cytokines skyrocketed upon landing, and his C-reactive protein — a marker of inflammation — increased by about 3,000%, according to Mason.
“Scott felt physically like he needed to go to the ER, and we could see why,” he said. “I’ve never seen stress biomarkers so high. Ever.”
Within 48 hours of being on the ground, Scott’s telomeres rapidly shortened, and tests indicate they are now shorter than they were before his 340-day space mission. That could put him at higher risk for accelerated aging and the diseases that come with it.
The twins’ speed and accuracy on a battery of cognitive function tests were comparable before the mission, but Scott’s declined significantly for at least six months after it. Researchers said Scott’s results could have been affected by various factors unrelated to space travel, such as mental exhaustion or indifference.
You may not have to go to space to profit from the findings of the Twins Study. If doctors had a better understanding of gene expression under extreme stress, perhaps they could design personalized treatment plans for patients undergoing aggressive radiation therapy.
And the portable DNA-sequencing technology that emerged from the study has already been deployed to help control Ebola and Zika outbreaks in West Africa and Brazil. In the future, astronauts will use the sequencing devices to read their own DNA from space.
Despite its Space Age nature, the study had an obvious limitation: its small sample size.
The Kellys are “an n of one,” the world’s only identical-twin astronauts. So in order to corroborate the findings, Bailey plans to study 30 more astronauts — 10 on yearlong expeditions, 10 on six-month missions, and 10 on two- to three-month trips — and compare them to unrelated people who live together on Earth for same length of time. The people in that “control” group would be isolated from the world at large to simulate conditions on a spacecraft, she said.
Clifford Tabin, a geneticist at Harvard Medical School who wasn’t involved in the Twins Study, agreed that researchers will need to study more astronauts before drawing any definitive conclusions about the health effects of living in space. But he said the work on the Kelly twins is a strong start.
“This analysis allows us to start to think rationally about the biological risks that future space travelers face and the steps one might take as countermeasures to protect them,” he said.
For now, Scott said the most significant long-term consequence of his time in space is not biological but psychological. It’s something called the overview effect: the view of Earth “without its political borders,” which he said deepened his sympathy for the human condition.
Compared to that, the health risks associated with broken chromosomes and short telomeres don’t faze him.
“Besides,” Scott added, “Mark is running for a U.S. Senate seat. I’m sure his telomeres will shorten soon enough.”