Researchers are studying compounds that can fend off the hazards of interplanetary travel. Illustration by Andy Busc

Take These Drugs to Get to Mars

Space brain and other cosmic problems demand new kinds of pharmaceutical protection.

I f humans are going to travel to Mars in the next decade or so, as NASA officially intends, it may take a medical breakthrough.

One of the biggest unsolved problems of space flight comes from very tiny stuff: high-speed, electrically charged particles of space radiation. Some of it flares off our own sun from time to time, and even in between those moments, space is filled with another kind, known as galactic cosmic rays: a low hum of heavy ions from beyond the solar system. Unlike electromagnetic radiation from X-ray machines, some of the most hazardous space radiation consists of protons and heavier — and thus more damaging — particles. It can wreak havoc on DNA, proteins, and other important molecules.

Astronauts probably can’t avoid it once they leave the protection of Earth’s magnetic field, which deflects most of space’s harmful particles. A metal shield strong enough to offer protection would probably make a spacecraft too heavy to fly.

And while it might be possible to use gene therapy to make astronauts more radiation-resistant, there’s little chance of that happening in time for NASA to meet its stated goal of sending humans to Mars by the 2030s.

In the meantime, our best answer may be drugs.

For example, experiments with mice suggest that a drug called CDDO, which enhances the body’s ability to repair DNA and respond to inflammation, can reduce the risk of radiation-induced cancer, says Jerry Shay, a molecular biologist at the University of Texas, Southwestern. The drug is already undergoing clinical trials as a cancer therapy.

“Once it’s approved for these human disorders, it will be very simple based on our published data and that of others to convince NASA that maybe this is something they should take on a long-term space mission,” says Shay, who is also a paid member of the scientific advisory board at Reata, the company that makes CDDO.

The most immediate threat to a Mars mission might be “space brain.” A mind that’s less than sharp can jeopardize the whole mission.

While cancer takes years to develop, the most immediate threat to a Mars mission might be so-called space brain. “The only functional outcome that NASA cares about is cognition,” says Charles Limoli, a biologist at the University of California, Irvine. He’s found that after mice are exposed to radiation, the fingerlike extensions that branch off their neurons, called dendrites, are shorter and less extensive. Studies also show radiation makes mice forgetful, more anxious, and less social. A mind that’s anything less than sharp can jeopardize the whole mission.

But solutions are in the works. In May, researchers led by Susanna Rosi at the University of California, San Francisco, found that an anti-inflammatory drug called PLX5622, which has undergone clinical trials to treat rheumatoid arthritis, seemed to prevent long-term memory loss in mice exposed to radiation. Previous research suggested that radiation affects the brain’s immune cells, called microglia, which are killed by PLX5622. Rosi’s team found that killing the microglia in irradiated mice, and then allowing the brain to regrow the cells anew, prevented those animals from losing memory.

That research is promising, Limoli says, but because the drug has such a wide target — it wipes out almost an entire class of cells — it probably won’t be what NASA ultimately uses. His group also has found positive results with PLX5622 but has been researching several other options to alleviate space brain. Those drugs increase antioxidants, reduce inflammation, or affect how certain genes in the brain are activated, or expressed.

Because clinical trials require so much time and so many resources, NASA will ideally repurpose drugs that are already FDA-approved for cancer or other conditions. But how effective they’ll be in space isn’t clear—there are limitations to Earth-based studies. Even the best experiments down here, such as those at NASA’s Space Radiation Laboratory at Brookhaven National Laboratory, can’t fully recreate the experience of being pelted with galactic cosmic rays.

Without knowing specifically how space radiation harms humans, it’s hard to identify precise pharmaceutical remedies, says Jeff Chancellor, a physicist at Texas A&M University. He adds that there’s not yet enough evidence to know for sure whether space radiation poses a prohibitive risk. “My gut is telling me we’re overestimating it,” says Chancellor, whose wife is an astronaut scheduled to return from the International Space Station in December.

“Maybe we’ll find out the human body adapts,” he says. “It’s a pretty amazing machine.”