A trip to Mars could come at a heartbreaking cost

When astronauts first travel to Mars or anywhere else in deep space, they will have to contend with two problems that our planet protects us from on its surface—radiation and weightlessness. Scientists already know both can have a profound impact on the human body, but the extent of that impact and how long it can last remain a mystery.

A new paper by researchers at the Medical College of Wisconsin, published in PLOS ONE, tackles those questions and unfortunately comes up with some less-than-ideal answers about the long-term implications of deep-space exposure.

Simulating deep space on Earth

Humanity hasn't yet built a deep-space research lab where researchers can run experiments in the actual environment of deep space. So researchers generally have to make do with what they have on the ground. And since running these types of long-term exposure experiments on humans is both impractical and unethical, the researchers turned to a cornerstone of biological testing—rats.

To simulate weightlessness in earthbound rats, NASA developed a protocol called hindlimb unloading (HLU). In this experiment, middle-aged rats, chosen to mimic the typical age of career astronauts, had their back legs lifted off the ground at a 30-degree angle by specialized harnesses connected to their tails for 30 days.

This tilt shifts much of the body's fluids to the head and takes the weight off their lower bodies at least, which is about as close as the researchers can get to mimicking what happens to astronauts when they are floating in microgravity.

Recreating radiation is harder and requires specialized equipment. Luckily, NASA has developed just such equipment. At Brookhaven National Laboratory, the NASA Space Radiation Laboratory is capable of simulating the radiation environment that constantly bombards the solar system outside the protective shell of Earth's atmosphere.

For this experiment, scientists used a five-ion, six-beam cosmic ray simulator dubbed "simGCRsim." It blasts a target with high-speed protons and heavy ions like silicon and iron that could potentially make their way through the hull shielding of a ship going to Mars.

Under the experimental protocol described in the paper, the rats were "unloaded" for five days, bombarded for a few minutes at extremely high radiation levels meant to mimic months of exposure, and then kept with their hind legs suspended for another 25 days. After that, they were allowed to live out the rest of their lives, with the monitoring period of about a year equivalent to around 25 years of human life.

Heart scarring emerged long after exposure

There were three primary findings described in the paper, but the one that was originally the researchers' focal point concerned the heart. With a dose of 1.5 gray (a measure of absorbed radiation dose), the rats began to develop perivascular fibrosis—a type of scar tissue that wrapped around the coronary vessels that feed blood to the heart.

By 270 days after the radiation exposure, the scar tissue had doubled in size, squeezing the blood vessels to a point where a heart attack became much more likely. Interestingly, the weightlessness simulation had essentially no effect on this outcome—it appeared to be entirely caused by the radiation.

When the researchers exposed the rats to a lower dose that was more akin to the total radiation exposure astronauts would receive over a three-year mission to Mars, they noted that the heart scarring wasn't visible right away. But a year after the exposure, 83% of rats had developed it. That means the effects of radiation might take decades of a human lifespan to present themselves.

Radiation hindered immune recovery

Another concerning finding was the protocol's impact on the rats' immune systems. Months after their exposure, the rats' spleens were still missing two-thirds of their natural killer (NK) cells. These cells wipe out virus-infected cells and, critically, cancerous ones, so a lasting dip in their population leaves the entire immune system compromised.

Microgravity and radiation worked in tandem here to create these effects—rats that were exposed only to microgravity eventually recovered to normal cellular levels. But if they were also hit with radiation, the recovery was muted—it appeared that the cosmic rays stunted the bone marrow's ability to respond to physiological stress.

Mutations linked to cancer and cardiovascular risk

Still more bad news came when the researchers sequenced the genomes of the rats' white blood cells. At 235 days after exposure to the radiation, the researchers noted a series of permanent mutations in a number of genes, some of which are directly tied to clonal hematopoiesis of indeterminate potential (CHIP). On Earth, CHIP starts to appear as we age, when a single mutated blood cell starts outcompeting its neighbors.

That might not sound too bad, but this particular mutated blood cell carries an increased risk of leukemia as well as quadrupling the risk of heart attacks and strokes, since these cells cause extra inflammation in arterial walls. Exposure to radiation seemingly fast-forwarded the clock on those changes, severely compromising the cardiovascular system much more quickly than is typical for a rodent lifespan.

Uncertainties remain about prolonged exposure

As the researchers themselves note, there are some limitations to this experiment. Crucially, the dose of radiation was delivered all at once rather than through continual exposure over months or years. It's unclear whether cellular repair mechanisms would be able to keep up in combating the effects observed in the rats, or whether the long-term effects would accrue regardless of those repair efforts. Also, the fact that the experiment was run only on male rats means a large proportion of the potential astronaut population might respond differently.

For now, none of this is particularly good news for the future of long-term spaceflight. But it's also likely not very surprising to the biologists who study these effects. We knew making our way outside Earth's protective shell was going to be hard. This study just helps quantify the types of problems that we will eventually have to deal with.