NASA WANTS TO SEND astronauts to Mars by the 2030s. The private aerospace company SpaceX is even more ambitious, aiming for 2024, and on the engineering side, it’s possible that the necessary spacecraft, launch rockets and guidance systems could be good to go by then. Preparing a crew, however, may turn out to be more daunting. Although people have been going into space for more than half a century, the longest anyone has stayed away from Earth is about 438 days, and no one has ventured farther than the Moon, a mere 239,000 miles away. A crewed mission to Mars would be an exponential leap, especially for the human body.

The first visitors to Mars will most likely spend one year or so in microgravity, pummeled by levels of interstellar and solar radiation no previous humans have endured, while riding in a cramped metal craft to a destination some 140 million miles from Earth. Unlike previous astronauts, who have enjoyed real-time communication with Earth and could return relatively quickly if a medical emergency arose, a Mars crew will soon be too far away to do either of those things. A communication lag of up to 21 minutes each way will require crews to be medically self-reliant in emergency situations, and they’ll have to be able to diagnose and treat anything that comes up—physical problems such as broken bones and bacterial infections, but also depressed or delusional crewmates—without immediate guidance from the ground.

NASA’s Human Research Program (HRP) investigates risks to astronaut health and performance during space exploration, and is working to pinpoint the medical dangers of an interplanetary journey. The group’s latest “roadmap” for long-duration space exploration lists 34 health-related risks that include space-induced bone loss and vision problems, traumatic injuries and the potential for psychiatric disorders. “We look at a broad spectrum of conditions and take stock of our ability to manage them,” says chief HRP scientist Jennifer Fogarty, who works at the Johnson Space Center in Houston.

But NASA cannot hope to complete its mission without help. Contributing to this massive effort are thousands of researchers in medical schools and hospitals, government agencies and the military. Together, they are working on solutions to the problems of human bodies in outer space, which remain one of the most substantial barriers to exploring Mars and beyond.

ON THE GROUND, NO one thinks much about the Earth’s gravitational pull. But it actually plays a major part in many systems in the body, and living without it can cause a wide range of problems. Astronauts in low-gravity environments experience insomnia, motion sickness, back pain and nasal congestion as well as more serious neurological symptoms.

Without gravity’s resistance, muscles gradually lose strength and endurance, and cardiovascular fitness declines. To avoid those problems, crew members on the International Space Station (ISS)—the orbiting experimental facility that is a joint project of several national space agencies—work out for at least 12 hours a week on specially modified stationary bicycles and treadmills that simulate the effects of gravity. But that equipment weighs more than 4,000 pounds and takes up about 850 cubic feet. The Mars gym will have to be much more compact, and the four astronauts on NASA’s Exploration Mission-2—a three-week lunar “flyby” planned for 2023—will test a device called the ROCKY (for Resistive Overload Combined with Kinetic Yo-Yo) that is the size of a large shoe box, weighs 20 pounds and can be stowed in about 1 cubic foot. Crew members will use it like a rowing machine for aerobic exercise and to perform strength-training exercises with as much as 400 pounds of resistance.

Other teams are looking at drugs that might help astronauts keep their muscle tone. Recent studies on mice aboard the ISS tested a myostatin inhibitor made by Eli Lilly that could reduce atrophy in muscles, a treatment that was developed for patients on Earth with muscular dystrophy, ALS or other muscle-wasting diseases.

Astronauts in microgravity are also likely to lose bone mass, about 10 times as quickly as someone with osteoporosis, leading to an increased chance of fractures. In space, the thigh bone, for example, loses an average of about 1.5% of mass each month, adding up to a 10% loss during six months in space—and recovery on Earth can take three years or more. To counter that risk, preflight genetic testing might one day be used to reveal an inherited propensity to suffer bone loss, leading to extra preventive measures during interplanetary transit. Measuring bone density en route could flag crew members with higher rates of bone loss and help them take extra precautions. These travelers might get calcium and vitamin D supplements, perhaps coupled with bisphosphonate medications used on Earth for osteoporosis treatment.

Vision degradation is another peril of microgravity, and has affected six in 10 astronauts on long-duration missions on the ISS, according to a 2011 study published in the journal Ophthalmology. On Earth, intraocular pressure (fluid pressure inside the eyeball) and intracranial pressure (pressure within the skull) balance to make the eyeball round. But in microgravity, intracranial pressure increases, flattening the back of the eyeball and pressing on the optic nerve. This can cause distortions in vision, including farsightedness, among other problems, which can persist after return to Earth. “The eyes are essentially a pressure release valve for the head,” Fogarty says. “In microgravity, the whole system is thrown for a loop.”

One source of this problem is the roughly two liters of blood that shift from the legs toward the head during spaceflight, making the face look puffy and potentially adding to vision problems. Most interventions—including thigh bands, compression pants and a vacuum sleep sack—are designed to keep blood in an astronaut’s legs. But cerebrospinal fluid, a clear liquid in the brain and spinal column that buffers the brain from changes in pressure, also plays a role. A 2016 study by University of Miami researchers found that astronauts returning from months in orbit had significantly higher volumes of cerebrospinal fluid near the eyes.

Dozens of research groups are working on the space vision problem, testing eyes of mice in the ISS lab and of human volunteers under conditions approximating microgravity. Researchers need to parse multiple interrelated causes and effects, Fogarty says. “We might need four or five countermeasures, and if we interfere without completely understanding the problem, we could make a bad choice.”

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RADIATION, MEANWHILE, MAY POSE an even greater risk and limit the amount of time humans can safely spend in space. A 180-day flyby of Mars would expose astronauts to an average radiation dose of about 300 millisieverts, about 100 times the average exposure of a person in the United States during the same period of time—and more than 15 times the annual limit for workers in nuclear power plants. A landing mission lasting 860 days would subject astronauts to radiation of 1.01 sieverts, increasing their lifelong excess cancer risk by about 5% and raising the specter of other health problems. Acute radiation sickness can result in vomiting and fatigue, and long-term radiation exposure can mean a greater likelihood of heart disease and may damage the central nervous system.

Reducing these risks will require better shielding methods for spacecraft, and new ways to prepare, protect and repair the human body. Various types of radiation are known to damage DNA, causing cells to mutate in ways that can lead to cancer and other problems. Fogarty notes that understanding genetic vulnerabilities could eventually help identify those most at risk of harm from radiation—revealing a heightened likelihood of developing particular kinds of cancer, for example—and prompt closer monitoring or additional countermeasures for those astronauts. Scientists in the Harvard Consortium for Space Genetics, in the department of genetics at Harvard Medical School, are developing ways to assess and combat genome damage from radiation.

New drugs may also become available. Cellular damage from radiation stems from the formation of reactive oxygen species, also known as free radicals. Molecules that remove free radicals—antioxidants—are a first line of defense. WR-2721, an antioxidant drug used to treat acute radiation exposure, can be toxic and has other undesirable side effects, but another drug, PrC-210 (aminothiol), still being tested, appears to offer the same benefits with fewer adverse effects.

Much of the space radiation research is conducted at the NASA Space Radiation Laboratory, part of the Brookhaven National Laboratory on Long Island, N.Y., where scientists can simulate what an astronaut would experience during a two-year mission to Mars and test the effects of radiation on cells, tissue and DNA. But the future may hold a laboratory farther afield. NASA Gateway, a space transit hub and research station planned for Moon orbit, where space radiation is in full effect, could be ready as early as the 2020s.

WHEREAS MICROGRAVITY AND RADIATION will be givens for any Mars voyage, preparing for other medical problems calls for more speculation—and a tough calculation of which supplies to pack and protocols to prepare. A catastrophic accident or an acute medical condition requiring emergency care could severely hamper a Mars mission, says Kris Lehnhardt, an emergency room physician and deputy element scientist in the Exploration Medical Capability group of NASA’s HRP. Lehnhardt’s group examines how often particular medical conditions have happened on previous space flights, compares them with their frequency on the ground and runs many thousands of computer simulations to find the top 100 things most likely to go wrong. “Then we look at what it would take to treat each condition,” he says. “From there we develop a resource list.”

Once astronauts land on Mars, where gravity is roughly a third of what it is on Earth, and start exploring, “people are going to be falling a lot,” Lehnhardt says. “You can try to protect the most fragile spots, like the wrist.” Fractures may happen anyway, so his team plans to include pain medication or sedation and splinting materials, and for more complex fractures, it will map out the best ways to address the injury.

For an emergency that calls for something major—open abdominal surgery, say—the options will necessarily be limited. Such an operation would require a prohibitive amount of equipment and would be complicated by microgravity, which makes it difficult to create a sterile operating enclosure and, with other objects possibly floating into view, to maintain a clear field of vision for surgery. Lehnhardt imagines surgery would be attempted only as a last resort, factoring in the unique considerations of every risky action in space. “You have to ask which things you can do without and what conditions you may treat partially or not at all, either because it’s not serious or because it’s futile,” he says.

A mission to Mars would need a physician on board, Fogarty says, and that doctor would complete training modules in several specialties—even learning to do things such as dental extractions. Other crew members would be trained in first aid and basic life support and would most likely do in-flight computer-based simulations to maintain proficiency.

For less urgent problems, crews could consult with the ground, though it could take up to 42 minutes to transmit an image or question to Earth from near Mars and receive an answer. As an alternative, astronauts probably will have access to an artificial intelligence decision-support system that will consider crew members’ electronic medical records—constantly updated with vital signs—including blood pressure readings, exercise routines, carbon dioxide levels and their most recent medical conversations with the ground. Automating medical systems will be important, whether it’s the crew doctor or another team member performing a procedure. “We know that the more a person needs to think about, the easier it is to miss a step,” Lehnhardt says.

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BEHAVIORAL HEALTH ISSUES COULD be among the most perplexing on a Mars journey. It’s very difficult to know what will happen to a group of people confined indefinitely to a small space, isolated from normal social interactions and extraordinarily far from home. Neuropsychological challenges could include anxiety and depression or more serious complications, such as hallucinations and psychosis.

Cosmonauts on Soviet space stations in the 1970s were the first humans to be away from Earth for six months or more, and some of them showed significant signs of psychic distress, leading to the termination of several missions. And whereas crews on the ISS, during stays lasting around six months, have managed to avoid major mental issues, they have been helped by close proximity to Earth.

“They have lots of interaction with the ground and plenty of work and experiments to do,” says Gary Strangman, director of the Neural Systems Group at Massachusetts General Hospital and an innovation specialist with the Translational Research Institute for Space Health at Baylor College of Medicine in Houston. On a round-trip in which each leg will take several months to a year, however, with the signal from home becoming ever more distant, a Mars crew will be much more isolated.

ASTRONAUTS WILL BE SCREENED carefully for major mental disorders and antisocial tendencies, and planners will try to assemble a crew with compatible personalities to work together through months of boredom and whatever emergencies occur. Even then, however, individual sensitivity to the stresses of spaceflight will vary, particularly on such an extended voyage, says David Dinges, professor of psychiatry at the University of Pennsylvania, who led a scientific team at the National Space Biomedical Research Institute.

To get an idea of what problems might arise, researchers study the behavior and performance of people who work in very isolated conditions on Earth—submarine crews and Antarctic researchers, for example. NASA also operates space-analog research stations in remote locations on land and under water. At the Johnson Space Center’s Human Exploration Research Analog facility, volunteer crews are sealed inside a three-story mock spaceship for trip simulations of six weeks or more.

During the longest of the three Mars 500 simulations, which were conducted between 2007 and 2011, a six-person international crew lived and worked in a 550-cubic-meter “spaceship” in Moscow for 520 days. The men in this experiment, who performed daily maintenance work, scientific experiments and exercise, were isolated from Earth’s light-dark cycles, temperatures and seasonal conditions. They received limited food and water, had to deal with simulated emergencies and experienced communication delays similar to those of a Mars mission. “In that crew of six, two coped really effectively, and the other four experienced a variety of behavioral health problems,” says Dinges, who has published two papers analyzing the crew members’ behavioral changes. Those included mild to moderate depression, stress and physical exhaustion, conflicts with other crew members and with ground control, and altered sleep patterns. Two of the men accounted for 85% of the behavioral health issues.

Sleep problems can be particularly debilitating. Recent astronauts have averaged only about six hours of sleep a day—a level that can lead to cognitive and neurobehavioral deficits—and the lack of a daily cycle of light and dark can add to the toll. On a trip to Mars, blue-enriched LED lights like those recently installed on the ISS can be adjusted to enhance alertness or promote sleep, and sleep aids may help maintain a circadian rhythm of sleep and wakefulness. It will also be important for astronauts to get regular downtime to bolster mood and performance.

Because time delays won’t permit real-time conversations with a psychologist on Earth, Dinges and others are working on technology to perform behavioral and performance assessments. Having astronauts write in a digital diary, for example, could create a record of their thoughts and mental states while also serving as self-therapy. Dinges and his colleagues are also developing computerized tests to help the astronauts size up their own emotional processing, spatial orientation and risk decision-making, among other cognitive factors. “We’ll have algorithms to give crew members a sense of their own profile, along with countermeasures for any deficits they discover,” Dinges says. Those could include antidepressant medications, behavior modification exercises or even a chat with an artificial intelligence “therapist.”

A voyage through space, like any venture of exploration, comes with a measure of risk that no amount of planning can eliminate entirely. Those preparing the Mars mission are doing their best to mitigate psychological and physiological harm, but they also recognize that on launch day, much will be out of their hands, Fogarty says. “We look at the Human Research Program as an occupational health program,” she says, one in which thousands will have lent their expertise to minimize threats, provide protection and outline responses to any possible emergency. Together, they hope to have everything in place for those whose occupation takes them 140 million miles from home.