NASA plans to fly a mission to Mars by 2035. But the space agency is worried about what months of space travel and potentially years on another planet will do to its astronauts.

Humans evolved to live in Earth’s gravity. We are weightless in space, and the surface of Mars has just 38 percent of the gravity we’re used to. Life on the International Space Station (ISS) has proven that long-term existence in low gravity wears on the body: muscles and bones weaken. Vision gets fuzzy. Even genes seem to change, with some turning on or off in unusual patterns. And only some genes return to normal when the astronaut comes home.

In addition, the cosmic radiation that bombards spaceships and the unprotected surfaces of other planets has caused dementia and other issues in mice and rats.

Scientist Ting Wu, who directs Harvard Medical School's Consortium for Space Genetics, sees genetics as a solution to these problems. But first, scientists must learn to manipulate genes to fix themselves.

Unless we resolve the genetic damage caused by space travel, missions will be limited to areas within close proximity of Earth, says Wu, whose own research suggests it may some day be possible to turn on a repair mechanism hidden deep within our genes.

Wu and her colleagues at the Consortium are now considering how to find — or build — an astronaut that's genetically equipped to withstand the damages caused by low gravity and space radiation.

Retired NASA Astronaut Mark Kelly, left, fist pumps his identical twin brother, Scott Kelly, while Scott was in quarantine before his one-year mission to the space station in 2015. To maximize the knowledge gained from Scott's mission, NASA also studied his brother, who remained on Earth. Since they're identical twins, researchers had a first-of-a-kind chance to understand how the human body changes in space. NASA

The Ravages of Space

A mission to Mars is expected to take about three years, with eight months of travel in each direction and 18 months on the red planet. Scientists are still trying to understand the toll that such a journey might take on humans, says Dr. Kris Lehnhardt, an emergency room physician at George Washington University’s School of Medicine and Health Sciences.

The rigorous 2.5-hour workout that astronauts are required to follow each day on the ISS has reduced the consequences of long periods in zero gravity, but it’s unclear whether this routine would be practical for long-duration missions or life on other planets.

At this point, NASA has no way to simulate Mars’ reduced gravity, or determine how best to train astronauts to cope with the change, says Lehnhardt, who is also an expert in aerospace medicine. “It could be that 38 percent on the ground is enough to maintain our bone, muscle, heart, and [balance] system, but we don’t know because we’ve never been able to study it.”

NASA astronaut Sunita Williams cycles on the International Space Station while participating in the first "triathlon in space" in 2012. NASA

Some astronauts lose their ability to see long distances during months spent in space, while the vision of others is narrowed or clouded with black dots. These problems sometimes correct themselves when the astronaut returns home, with men seeming to suffer more than women. But scientists don’t know what causes the changes or the differences, Lehnhardt says.

The vestibular system, which controls balance and coordination, is also thrown out of whack in zero gravity. The heart can change shape and the regulation of blood pressure can be affected, making astronauts susceptible to fainting when they first return home.

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Muscle and bone generally rebuild quickly when back in Earth’s gravity, but bone grows back brittle, Lehnhardt says. And as bones lose their mineral content in low gravity, the minerals can crystallize into painful kidney stones.

Scientists have to better understand these problems before they can be corrected, Lehnhardt says, and if humans are really going to live on other planets, NASA will also have to discover how low gravity and radiation might affect reproduction.

Building a Better Astronaut

Efforts to make astronauts safe and comfortable during extended periods in space are just beginning, and the Space Genetics Consortium seems to be leading the charge. NASA declined to comment on these efforts, saying, “It is not appropriate for NASA to speculate on research we’re not conducting.”

Consortium researchers are now working with cells in culture, but they hope to have something relevant for humans in time for NASA’s voyage to Mars.

It might be simplest to pick astronauts who already have genetic mutations that are ideal for space travel. NASA recently had its pick from among more than 18,000 applicants to fill about a dozen slots in its 2017 astronaut class. In the future, it might be possible to focus these selections on people who carry natural protections against radiation exposure or bone loss once such genes are identified.

Former NASA administrator Charles Bolden is supportive of Harvard’s space genetics project but worries that such a selection process could encourage the quest to create a superior race to live on Mars. But current laws forbid selecting federal employees based on genetic traits, Lehnhardt notes.

Instead, genetic diversity and a clearer understanding of the genetic toll of space travel could help NASA develop protective devices and other solutions, says Bolden, a former astronaut who spent nine days in space without any health issues.

Consortium scientists expect that someday they’ll be able to tinker with genes to better prepare travelers for the rigors of space. They might be able to turn on genes involved in damage repair, for instance, or deactivate genes that lead to muscle loss. Scientists are already using several gene-editing techniques, including CRISPR, to turn off or on targeted genes. But these technologies are not yet safe enough or specific enough to use on humans.

“The technology works today. It’s just a question of optimization,” says Christopher Mason, a consortium member and biophysicist at Weill Cornell Medical Center in New York.

In experiments at Mason’s lab, students are now adding extra copies of a DNA-repair gene to human cells in a dish. He hopes to soon send these modified cells into space to see if they can function in low gravity while being subjected to radiation.

Harvard's Wu has a theory — still not widely accepted — that some genetic material may play a role in repairing genome breaks caused by factors like radiation. She would like to manipulate the 500-million-year-old “ultra-conserved” genetic material to track down and destroy damaged cells that she says are among the most prohibitive problems of working, playing, living in space.

“If we can get a handle on these ultra-conserved elements, we may be able to reduce dangers of ionizing radiation,” she says. Wu is now developing technology to identify the breaks and track genetic repair mechanisms and is studying how the extreme environment of space might affect how genes are packaged inside our cells.

George Church, a geneticist at Harvard Medical School and Wu’s husband, is also investigating natural mutations that help bacteria and human cells resist radiation.

Some strains of E. coli bacteria are 10 to 1,000-times more radiation resistant than others, Church says. He is focusing on a combination of four mutations that seem to be the most protective for the bacteria. If a similar group of mutations prove safe and effective in mice and perhaps primates, they could then be tested — and eventually made — in humans, Church says.

Scott Kelly of NASA is helped out of the Soyuz spacecraft as he returned to Earth in 2016 after 340 days in space. Bill Ingalls / NASA

Looking Further into the Future

Church says he sometimes worries that a giant asteroid might someday hit Earth. Or that climate change will jeopardize our species. Or that he and other researchers will achieve their goal of helping people live longer, healthier lives — creating an urgent need to reduce overpopulation.

Regardless of the reason, people will one day need to a new place to live, Church and Mason each say — so they feel an ethical imperative to make life in space safer.

“I think our species has a duty to keep: which is to preserve life and prevent extinction not only of ourselves, but of other critters as well,” Mason says.

Mason admits to being anxious that scientists will overestimate their abilities to cope with the challenges of space. “I worry the most about hubris,” he says, urging a careful route forward for people like himself.

“We really think we know what we’re doing," he says. "But of course, we can be wrong.”

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