A trip to Mars will cost the human body more than time. After the initial days of motion sickness, an out-of-this-world physiological transformation sets in. Without gravity’s downward pull, muscles atrophy. The heart shrinks. The skeleton weakens. The immune system falters. Blood and other bodily fluids slosh headward, pressing on the eyes and impairing vision. Ninety-minute days disrupt an astronaut’s circadian rhythm, as radiation scrambles their DNA.

“That’s the price you pay,” Canadian Space Agency astronaut David Saint-Jacques tells Nature Medicine. “It’s tough on your body.” As a medical professional and a space-farer, Saint-Jacques has to balance two competing priorities every time he leaves the stratosphere. “Going to space is fun,” he says. “But it’s very, very bad for you.”

Six months aboard the International Space Station (ISS)—the average mission length—takes an impressive toll. In that time frame, an astronaut’s bones lose density and their arteries thicken and stiffen the equivalent of a normal decade of terrestrial aging. Over a six-month period, an astronaut’s internal temperature can rise by 1 degree Celsius as they are exposed to the 375 chest X-rays’ worth of radiation and become more susceptible to kidney stones, allergies and infectious diseases.

Even an astronaut’s height changes in space, Emmanuel Urquieta, Chief Medical Officer at the Translational Research Institute for Space Health at Baylor College of Medicine, tells Nature Medicine. “We have been designed to live inside our bubble on Earth.” Once we leave that safe haven, “pretty much every organ system gets impacted and affected,” he says, “one way or another.”

As space agencies prepare for a return to the moon in the coming decade—and after that, travel to Mars—space-medicine research continues to be ambitious and boundary-pushing. “For an extreme environment, you need extreme approaches,” Urquieta says. “You need solutions that sound crazy.”

Earth dwellers should benefit from these innovations. “Yes, we’d like to go to Mars,” Farhan M. Asrar, a professor of medicine at the University of Toronto and Trillium Health Partners and a faculty member at International Space University in France, tells Nature Medicine. When it comes to the technical accomplishment that will get us there, he asks “How can we use those to benefit Earth and healthcare on Earth?” Already, technologies developed to help astronauts survive—including telehealthportable ultrasoundsair purifiers and gravity-compensating bodysuits, to name a few examples—have made their way down to terrestrial healthcare settings.

“Space exploration can be the perfect excuse to scratch our heads,” Saint-Jacques says, “and push medicine.”

A template for telehealth

Making humans a space-faring species has become a central challenge for space medicine, Thu Jennifer Ngo-Anh, research and payloads program coordinator for the European Space Agency, tells Nature Medicine. “It’s not enough to just bring them there and get them back in one piece,” Ngo-Anh says. Instead, researchers are investigating ways to equip astronauts so they can serve as their own medical providers: monitoring their own health, diagnosing any issues, and treating them with whatever is onboard.

The ISS is 240 miles above the Earth and has to serve as an all-in-one home, office, research laboratory, grocery store, pharmacy, gym and hospital. Regular supply flights from Earth bring food, experiments and medicines.

The further humans venture from Earth, the more challenging supply flights will be. In recent years, some researchers have focused on how to augment a spacecraft’s stores with a biological foundry for pharmaceuticals: plants. By using genetically modified plants as chemical factories, astronauts could someday grow the medicine they need in space.

Communications pose another problem for deep-space voyagers. On Mars, communication delays with Earth could be as much as 20 minutes — one way. That means astronauts will not be able to depend on guidance from medical professionals at mission control, or on resupplies of food or medicine across the multi-million-mile expanse. “They will need to diagnose and treat themselves without any reliance on Earth,” Urquieta says.

NASA astronaut Mark Vande Hei sets up an experiment inside the Microgravity Science Glovebox.
Canadian Space Agency astronaut David Saint- Jacques tries the Bio-Monitor, an innovative smart shirt designed to measure and record astronauts’ vital signs. Credit:Canadian Space Agency/NASA

Technology developed to help astronauts conduct basic medicine with limited tools and knowledge has already helped in the delivery of healthcare to remote places such as Antarctica, ships at sea or home care settings, which are hard to access and face a shortage of healthcare workers and supplies. “We’re all hungry for medicine to come to us,” Saint-Jacques says. Take, for example, a frail and home-bound elderly person. “They might as well be in space, they’re so hard to reach,” he says.

In September 2021, the all-civilian, four-person crew of SpaceX’s Inspiration4 mission tested out the Butterfly iQ, a handheld ultrasound, taking images of their hearts, lungs and urinary systems without any ground support. That same pocket-sized device has already been deployed in rural communities around the world where X-ray, CT and MRI machines are hours away. Other remote monitoring innovations such as miniature and body-worn scanning devices collect and track biomedical data from astronauts, such as breathing, heart rate, body temperature and blood oxygen levels.

This allows astronauts to identify health problems as soon as they arise. These same devices could autonomously monitor critically ill patients in the hospital around the clock. A portable, self-operable vision-testing tool developed for space could help astronauts deal with space-related changes in vision, as well as the billion-plus people worldwide who suffer from poor vision due to undetected and uncorrected eye problems.

Other breakthroughs have led to orbital lab testing systems that do not require an expert to operate. “They’re paving the way so you don’t have to go to a centralized laboratory or pull a whole vial of blood and wait a whole week for results.” Urquieta says. These tests could have a positive impact in rural or isolated communities.

The perfect guinea pigs

On 12 April 1961, Russian cosmonaut Yuri Gagarin’s 108-minute orbit of the planet marked the first episode in humanity’s short history in outer space. At the time, scientists had a sense that its physical environment—the weightlessness, radiation, extreme temperatures and vacuum conditions—would be hostile to the human body. But the exact physiological impact of space travel remained an open question.

“Before the Apollo missions flew, the engineering community developed 0.999 reliability figures for all of the parts of the spacecraft and launch vehicles. They wanted me to do the same for [humans],” US National Aeronautics and Space Administration (NASA) flight surgeon Charles Berry later recalled. “I had repeatedly said that I could not do that for astronauts.”

Fewer than 600 people have followed Gagarin into space, but the understanding of how to safeguard the human body from its perils has transformed dramatically. That is thanks in part to astronauts who have conducted research (an estimated 3,000-plus science experiments) aboard the ISS, or have participated in human experiments as test subjects.

Mark Shelhamer, a human spaceflight researcher at Johns Hopkins University School of Medicine and former chief scientist of the NASA Human Research Program, says it is much easier to control an experiment on astronauts. Variables such as exercise and social dynamics are “all almost impossible to measure in a cohesive manner on Earth,” Shelhamer says, but are easy to track in a spacecraft’s strict confines. “We know what they eat, how much they sleep, their workload.”

And whereas on Earth, researchers are resigned to hoping participants will be honest and follow a study’s rules, astronauts are duty-bound to carefully and precisely carry out directions, often for their own safety. “They are very, very good at following procedures. They follow it to the letter,” Urquieta says. “In a terrestrial trial you don’t have that luxury.” Saint-Jacques agrees, “We’re the perfect guinea pigs.”

Health research conducted in space has thus far been severely limited by small sample sizes, the impossibility of blinding, and its participants’ overwhelmingly white and male demographic. But some of those statistical and representation weaknesses could begin to improve as space travel becomes accessible to space tourists.

The Inspiration4 mission, for example, was led by the first Black woman to pilot a spacecraft, and it included a 29-year-old female survivor of cancer. During their three-day mission, crew members measured their heart activity, movement, sleep, blood oxygen saturation, and cognitive performance. They also took ultrasounds of their organs, collected and analyzed their blood, and tested their balance and perception.

Shelhamer will study the Inspiration4 data to understand how the vestibular system, which helps the body maintain balance, operates in a weightless environment and after return to Earth. The research could eventually help people on Earth with conditions such as vertigo and is one example, Shelhamer says, of how “space is an acute form of all the things we face on Earth.”

To Mars and back

A trip to Mars will require further medical advances so that astronauts can survive the journey there—and back again.

Researchers are exploring how to put astronauts in hibernation to reduce their metabolic rate, oxygen consumption, carbon dioxide production and caloric needs during the estimated three-year round trip to Mars. There is hope that this will inform terrestrial efforts to cryopreserve tissues and organs for transplantation. Instead of the current race to match donors with recipients in a limited window of time, cryopreservation could allow organs to be deposited in a frozen bank, to be withdrawn whenever needed.

A trip to Mars will also expose astronauts to years of cosmic-ray exposure, increasing their risk of cancer and damaging their cardiovascular and central nervous systems. “This kind of radiation is constant,” Urquieta says. “Low-dose, but chronic.” On Earth, exposure to radiation can be mitigated with lead aprons and thick slabs of concrete—solutions too heavy for space flight. Instead, researchers are exploring molecular methods of boosting cellular repair in astronauts, such as gene therapy with an adeno-associated virus vector, which could protect astronauts against radiation before they leave the ground. Viral gene therapy to protect astronauts against radiation could prevent the need for onboard pharmaceuticals and could have long-lasting protection of several years’ duration.

If successful, such viral gene therapy could have many applications on Earth, including helping to minimize the harmful effects of radiotherapy for patients with cancer by genetically shielding noncancerous cells from damage, leaving only the cancer exposed.

“Everything we do in space has a spin-off for Earth,” Urquieta says. “If not 100%, close to 100%.”

Merits of microgravity

One of the greatest challenges of living in space is the microgravity environment, but this provides benefits for research. “There are advantages to taking gravity out of the equation,” Bryan Dansberry, program scientist for NASA’s International Space Station Program Office, says, as it allows “stuff you can’t easily do when you have 1g pushing down on you.”

In microgravity, liquids do not need solid containers; they form floating spheres bound by surface tension. Fluid dynamics in microgravity are helping medical researchers study amyloid fibrils, the protein tangles that stubbornly accumulate in the brains of people with neurodegenerative diseases such as Alzheimer’s and Parkinson’s. On Earth, scientists struggle to grow amyloid fibrils in vitro, due to their physical, chemical and electrostatic properties. This is where microgravity can come in handy. Early research shows it may be possible to grow and study amyloid fibrils in self-contained liquid drops in the ISS’s microgravity environment. If amyloid can be grown, it can be understood, which could unlock understanding of the associated neurodegenerative diseases.

Microgravity slows the formation of crystals, so it is possible—and easier—to produce high-quality crystals in gravity’s absence. These high-quality crystals can be used for structural biology studies. In addition, pharmaceutical investigations are exploring how to transform intravenous liquid treatments into a uniform crystalline form in space, which could pave the way to more drugs that are cheap, pure, injectable, fast-acting and shelf-stable—useful for astronauts, but with plenty of applications on Earth.

Cell-biology experiments are altered in microgravity, with stem cells retaining their stemness for a longer duration. This could improve individualized stem-cell therapies that depend on large quantities of stem cells, which are difficult to grow in two-dimensional cell cultures. Researchers have already begun to test the feasibility of growing stem cells in space to harvest and use in clinics on Earth. Scientists will use the effects of microgravity to study how cancers grow, with experiments planned for China’s new Tiangong space station. The hope is that this increased understanding of cancer-cell biology, learned in microgravity, will lead to new treatments for cancer.

One field that is fairly advanced is the use of microgravity for engineering and materials science. Engineers are developing a system for manufacturing retinal implants, or artificial retinas, in space, where microgravity allows more-uniform layering. Earth-bound efforts to bioprint transplantable materials have been stymied by gravity, Dansberry says, which can collapse lace-like networks of veins and nerves. In the future, space might provide the exact right conditions for printing out those delicate tissues.

“It’s still sci-fi at this point,” Dansberry says, “but we’re taking first steps.”

This article is reproduced with permission and was first published on February 9 2022.