Over the past five decades, under 700 humans have flown in space. Nearly every one of those humans were professionally trained astronauts and in similar peak physical condition. And most of those astronauts were men. But in 2021, the first space mission with four civilian astronauts — meaning, not government agency astronauts — flew. It opened a new path for the scientists who study the effects of spaceflight on human biology.
On June 11, 2024, more than 200 of those researchers published a suite of 44 papers across multiple Nature journals. These papers are helping to build a foundation, a baseline of sorts, to understand not just how being in space affects the human body but how scientists can mitigate those effects.
Humanity is a long way from being an interplanetary species, but this is “the very first step on what will be many steps to prepare for the Moon and Mars,” says Weill Cornell Medicine’s Christopher Mason, the biophysicist and physician who led the data accumulation and analysis behind the papers.
These data are also showing scientists how the human body reacts under extreme stress, both physically and cognitive. “We really need to know how the human condition reacts” to the radiation and the extreme acceleration forces, in addition to changes in the body’s circadian rhythm, or sleep cycle, says Stanford geneticist Michael Snyder who was not involved in these recent papers.
These varied studies show that just a few days in space affects biology in ways that don’t seem to reverse. And they’re starting to hint at differences between females and males.
Studying the body in space
When human space missions took flight in the 1960s, space health investigations began. Apollo astronauts wore biosensor harnesses to monitor the heart and lungs and underwent thorough physical exams and tests preflight and postflight. The astronauts experienced back pain from microgravity, flashes of light from radiation, and other health changes. But this was just the start.
Over the past two decades, the International Space Station (ISS) has served as an orbiting biological laboratory to investigate everything from bacterial changes to bone loss to brain deformation. Then in 2015, biologists had the unique opportunity to better understand how the environment of space environment affects biology at the smallest scales. In an experiment NASA called the Twins Study, one astronaut, Scott Kelly, boarded the ISS for a year and his identical twin, Mark Kelly, who was also an astronaut, stayed on the ground.
By directly comparing identical twins, biologists could study the genetic effects of space. When Scott returned to Earth, his telomeres, the ends of chromosomes that act to protect genetic material, had lengthened. (Read more about NASA’s Twins Study.)
But Scott Kelly was a sample size of only one space traveler. In addition, most astronauts in the decades of previous scientific studies were U.S. or Russian men who had trained for years to make the trip to space.
A 2021 SpaceX mission, Inspiration4, presented researchers with an opportunity to study space health in more varied space travelers. The mission, called Inspiration4, would have four private astronauts, who collectively cover a wider variety of ages, ancestries, and biomedical backgrounds. “They are representative of a broader swath of humanity,” says Mason.
Mason and many of his colleagues on the new collection of papers had also worked on the Twins Study. The team already had a suite of experiments that had flown in space and that “had been validated up the wazoo, in astronauts” says Mathias Basner of the University of Pennsylvania School of Medicine who studies human behavior and cognition. The researchers would develop those tests further for the Inspiration4 mission, to study a broader collection of the human biological system.
The team examined blood, urine, stool, saliva, and sweat samples, in addition to skin biopsies. They also included behavior and cognitive set of tests, and sleep data. These tests were performed before flight, during flight, and post-flight. And all those data were inputted into a growing biometric database, known as the Space Omics and Medical Atlas (SOMA), organized and maintained by Mason and his colleagues.
The catalog, published in June, includes detailed data collected over the past decade from dozens of NASA and Japanese Space Agency astronauts, 12 private space farers (where four were on the Inspiration4 mission), and a control group of 10 people who climbed Mount Everest. Researchers also used animal data from experiments aboard the ISS to better understand the effects of space on the body.
“We’re now starting to get the sketches of what our baseline measurements, for bloodwork, for radiation, for what happens in genes and your immune system,” in spaceflight, says Mason.
Even short trips alter biology
On September 15, 2021, just after 8pm EDT, the Inspiration4 mission launched with four civilian astronauts. Roughly three days later, the capsule and its crew splashed down in the Atlantic Ocean off the coast of Florida.
Upon analyzing the data, one of the most surprising results, says Mason, was that “we saw a lot of the same signatures of spaceflight that we saw on longer missions.” That indicates there’s a “dosage” of spaceflight, that you can start to see in the body, he adds.
Like in the Twins Study, telomeres lengthened, he says. The elongated telomeres (likely a result of radiation exposure, say the researchers) and related genes’ activation may help protect DNA from harmful radiation.
Many changes didn’t revert after returning to Earth’s surface even multiple months after they came back. “You’d think people would bounce back faster than they did,” says Snyder.
The Inspiration4 astronauts’ microbiomes also changed over only those few days. “It’s intriguing to see how quickly their skin becomes like each other and the spacecraft,” says Mason. While the crew’s skin microbes grew more similar, and their mouth microbes changed, the researchers didn’t see the same changes to their intestines.
While gene expression and microbiome changes are some of the microscopic scale effects of space, there are also macroscopic effects, including cognition and behavior. To test behavior and cognitive ability during flight, researchers looked at 10 intellectual and mental domains, says Basner, like memory, attention, abstraction, risk decision making, emotion recognition. “Our behavior is like a combination of all of these, but we try to disentangle that,” he says, to see if one of those domains are more effective than others.
The Inspiration4 crew exhibited cognitive decline early into flight, and the average was driven mostly by one crew member, says Basner. Cognition leveled out during the rest of the flight and returned to normal once the crew returned to ground. Behavior-wise, the crew was a more positive post-flight, he adds. “But that just hinted to the fact that they were happy that they made it,” back to the ground safely.
How females compare to males
The SOMA database is open access, publicly available to biologists for their own research. “Everyone comes with their own perspective,” says Mason. “They see the biology through their own lens, and then see the questions with their own perspective.”
That’s how Begum Mathyk, a doctor of obstetrics and gynecology at the University of South Florida, became involved. “It’s not much difference for me to, you know, advocate for women’s health on Earth or beyond,” she says.
Mathyk and her colleagues’ analysis of the Inspiration4 blood and urine samples showed changes to genes associated with the hormone estrogen, which is involved in the reproductive system but also in muscles, the brain, and other bodily systems. They found genetic changes to the way the estrogen-related reactions work in space, with more changes in the females’ B cells than in males. B cells are related to autoimmune diseases, which tend to affect women more than men. These hormone changes also affect the body’s responses to infections, says Mathyk.
Genes associated with how insulin regulates blood sugar also changed during those few days in space. “These changes suggest that spaceflight may impair metabolism and the immune system,” adds Mathyk. They noted other changes to immune cells, as well, and these changes took longer to return to normal in the males than in the females after the flight ended. These cells relate to how the body reacts to inflammation and some also relate to blood clotting.
While the microbiology showed slight differences between males and females, there were no behavior or cognitive sex differences, says Basner.
Radiation can have negative effects on the ovaries and uterus, and maintaining sleep cycles in space is important for a functioning reproductive system, Mathyk and her colleagues stressed in a review paper looking at data from Inspiration4 crew, JAXA astronauts, and animals. Studies of mice and their embryos suggest space is an “unfavorable environment” for reproduction, she says. “But it’s not easy to conclude or project all the data to the human, because we are more complex,” adds Mathyk.
Researchers will have more data soon. Mathyk is part of a proposal to fly a handheld ultrasound device on an upcoming SpaceX mission to image female reproductive organs, including the uterus and ovaries. And additional private and government missions are incorporating these tests.
Plus, the SOMA database is already growing. It now holds biological information from the private flights Axiom-2 and the pre-flight samples for Polaris Dawn, which is scheduled for launch this summer. Researchers will also add Axiom-3 data later this summer, says Mason.
Beyond simply understanding the biology of the human body in space, the atlas and the work that results could lead to ways to counteract these effects, including custom tailoring specific medications to someone’s genetic background. “There’s a lot more coming,” says Mason.
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