Lasso

Mouse poop might get humans to Mars

Researchers are testing how life on the International Space Station affects the microbiome.

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hen astronauts on the International Space Station need to go number two, they direct their poo through a narrow hole into a carefully sealed toilet. Eventually, their waste bursts into flames when jettisoned into Earth’s atmosphere. The fate of the feces of 20 mice tagging along on the ISS this year won’t be quite as flashy, but it’s just as dramatic. The rodents, who shot into space on June 29, made a voyage to the station to provide scientists data on the effects of microgravity on their bodies and internal rhythms—part of which will be captured in their poop. Sound familiar? It should. In 2015, NASA did the same thing, but with people. The Rodent Research-7 study is a sibling of the Twins Study, during which astronaut Scott Kelly spent a year on the station while his brother, Mark Kelly, acted as a control back on Earth. Scientists have spent years poring over the data generated by the experiment—among them, the researchers who designed the mouse mission.

This mouse madness has a laundry list of questions to answer. Led by principal investigators Fred Turek and Martha Vitaterna of Northwestern University at Evanston, Illinois, researchers at multiple institutions will examine how microgravity affects (or disrupts) the animals' gut microbiome, gastrointestinal function, immune function, metabolism, and sleep and circadian rhythms.

"We're bringing biology to the space program," says Turek, who has a long history helping NASA confront the physical challenges of spaceflight. Whether seated at his messy desk or wandering the halls of his lab, which is devoted to circadian-rhythm research, Turek almost vibrates with enthusiasm for all things extraterrestrial. He wears a thick denim shirt emblazoned with the NASA logo and waxes poetic about how, once upon a time, he took hamsters up on the "vomit comet"—a colloquial name for the reduced-gravity aircraft used by NASA to test microgravity conditions without leaving Earth's atmosphere—and advised the agency on whether to send John Glenn back to space at the age of 77 (the spaceman did indeed take one more trip).

But Turek's daily life is devoted to something pretty down-to-earth: shut-eye. He's responsible for much of what we know about the body's biological rhythms, including the discovery of the gene that appears to run mammals' 24-hour circadian clock. This internal clock keeps mammals synced to the rising and setting of the sun, running systems such as sleep and body temperature, and affecting things like body weight, disease susceptibility, and more.

That led Turek down an unexpected path to poop. It turns out that when a person alters their normal sleep-wake cycle, the community of microorganisms in their gut—their microbiome—changes too. And the more scientists learn about the gut microbiome, the more aspects of human health they believe it affects. Now Turek and Vitaterna devote much of their time to looking at how the microbiome affects the rhythms that run the human body.

“Mice aren’t furry little humans,” Vitaterna says, swatting at a fruit fly—an escapee from a nearby lab’s experiments on the tiny insects’ biological clocks. But since rodents share so many genetic and behavioral characteristics with us, she explains, they’re as close as it comes to an experimental analog.

Nor is the experiment identical to the Twins Study. You could call it fraternal.

space mouse
One subject made a daring escape.Lasso

For all their similarities, the Kelly twins led very different lives on Earth and in space. In contrast, RR-7's rodents will have much more restricted (and predictable) existences. Here and there, they'll occupy identical habitats, eat the same delicious mouse chow, and do everything in synchronized environmental conditions. Up in space, the mice live in an enclosed habitat complete with a metal grid that floating rodents can grab onto, and features that make sure mice live separately from their own waste—and that turds don't make their way into the rest of the station. Back down on Earth, the control rodents live in the exact same enclosure and conditions (except for that whole gravity thing).

Data from the space station is beamed to the George C. Marshall Space Flight Center in Alabama, where it’s stored and archived. Relevant data is also relayed to the Kennedy Space Center in Florida, where technicians program the mouse habitat to match the environmental conditions of the ISS. The Earth mice are on a three-day delay from their space brethren so the team can base their control conditions on exact measurements from the space station. Everything from temperature to humidity to CO2 levels matches the ISS exactly, as do all procedures, from animal handling to feeding to cage changing.

Though all the mice will be subjected to a barrage of tests, the ones conducted in space will require a bit more finesse than earthly experiments. While it’s easy to, say, snag a piece of mouse feces or perform a quick experiment on Earth, it’s not quite as simple to handle a wriggling mouse without gravity’s assistance. Despite the trickier conditions, astronauts will acquire a precious poo pellet from each mouse every two weeks. They’ll measure each creature’s mass and bone density at least twice over the course of the experiment, draw blood, and film their habitat for three 48-hour periods too. Then, at the end of 30 days, they’ll “process” 10 of the mice (a polite euphemism for euthanasia and dissection). The surviving 10 will live on for another two months before making the same sacrifice.

Three months is a long time in mouse years—about 5 percent of an average mouse’s entire life—and the wait will seem nearly endless to the team at Northwestern. Their real work begins once the mice make it back to Earth. Inside their cluttered research lab, technicians will assess the protein levels and hormonal profiles of the deceased mice, and assess the behavior captured on the video recordings. Technicians will also dissolve the feces in saline, extract each pellet’s DNA, and sequence it.

“They’re precious samples,” Chris Olker, a research technologist who will run some of the tests, says of the poo. Olker, quietly cynical in his band T-shirt as he walks through a maze of identical hallways on the way to the lab, snaps into earnestness when he talks about the mice he breeds, dissects, and studies.

There are a million ways to fail, the tech team explains. Every spilled vial or mismeasured chemical could trash years of preparation and negate the careful dance taking place in space as we speak.

There’s already been a challenge to the carefully planned mission. Before liftoff, the team ran into a snafu thanks to a particularly playful mouse. “We did change our minds which cage of 10 to send,” Vitaterna says. She had become “kind of obsessive” about observing every aspect of the mice, from body weight to appearance, and when she noticed that one of the mice jumped out of its cage, she worried that it would cause problems in space. Instead, the team dipped into one of their seemingly endless contingency plans—a side effect of intense planning and coordination with NASA—and decided to send an entirely different cage of 10 mice during the last week before launch. Now, the mice that almost didn’t make the cut are up in space, sleeping and pooping weightlessly, while their more-active siblings act as controls on Earth.

Locked in their droppings is data that will show whether and how the lack of gravity affected the gut microbiome—a carefully balanced group of microbes that, in turn, can affect everything from immunity to body weight to the risk of cancer, mental health issues, and diabetes.

Researchers hope to use that information to probe the links between circadian-rhythm disruption and other bodily systems in mice—and humans. NASA intends to incorporate what it learns into plans to send humans safely to Mars, a journey that will require nine months in transit and an unknown amount of time on a planet with less than half of Earth’s gravity.

It could take years or even decades for the bodies of astronauts like Kelly to reveal the effects of their time in space, so NASA is placing plenty of hope—and trust—in accelerated rodent experiments. RR-7 is just one facet of a bigger program aimed at understanding what microgravity might do to astronauts who spend lots of time aloft.

The program, which made its maiden flight in 2014, is seen as a quicker and more-cost-effective way to profile the risks of extended space travel. So far, mice have yielded data on muscle-tissue loss, neurological changes in space, how bones grow and heal, and blood vessels in the brain and eye.

The sooner NASA knows about the possible pitfalls of months in space, the sooner it can develop ways to offset them—and avoid potentially fatal surprises when astronauts come home from Mars and other far-flung missions in microgravity.

That was the point of the Twins Test too. The public won’t know specifics about the results until later this year, and Vitaterna is coy about those experiments. But ask her about the mouse pellets that could one day help humans get to Mars, and she drops her reserve. “I love that we can get so much from waste material,” she says, grinning. “It’s like getting something for nothing.”