It took more than a year for Deok-Ho Kim, a biomedical engineer at Johns Hopkins University, to prepare for one monthlong experiment. Kim studies cardiac health, working toward developing therapeutics to counter heart diseases. For his experiment, his team developed a leakproof tissue chamber the size of a smartphone and a remote magnet monitor to measure the beating of their experiment’s heart tissues. And then right before the start of his experiment, Kim sent his experiment away to be conducted by strangers he had never met, in a place he had never set foot.
It would take a rocket ride to get there. Kim and his colleagues were to entrust their experiment to the astronauts on the International Space Station, whether or not these astronauts were scientists.
The ISS is a unique environment for research, as its microgravity and the barrage of cosmic radiation it receives are challenging, to put it mildly, to replicate on Earth. More than 3,000 science experiments have been conducted in the more than two decades since the ISS opened its doors for research, and all of them have been conducted by astronauts. Before their missions, astronauts receive crash courses on the requisite experimental techniques, taught by space agency intermediaries who are first trained by the original scientists themselves. During spaceflight, astronauts are guided by mission control’s science experts for the duration of the experiment.
To run an experiment on the ISS, researchers like Kim apply through the proposal calls by space agencies around the world, such as NASA or the European Space Agency. These organizations also cover the costs of the space portion of the experiments of successful applicants, from liftoff to sample return. Kim’s project was facilitated through the Tissue Chips in Space program, a relatively new initiative run by the National Center for Advancing Translational Sciences to accelerate biomedical research and drug development in space. (Tissue chips are cell culture–containing devices, usually the size of a USB stick, that mimic the internal conditions of the human body.) Kim was chosen for the second cohort of the program. He knew before his experiment’s launch that only half of the first cohort’s five experiments had run successfully—some teams’ containers leaked fluid or living samples died out too soon. Kim had anticipated that his own experiment would hit several snags, but it ran without a hitch. “I think we were lucky,” he says.
What may feel like luck belies months of preparation—years in some cases—before an experiment ever leaves Earth. A diverse team of engineers works with the experiment’s creators behind the scenes to adapt a laboratory experiment for space. Several groups contributed to the success of Kim’s experiment: NASA’s knowledgeable consultants, the experienced space hardware developer companies his research team partnered with, and the competent astronauts on the ISS.
Conducting an experiment on the ISS presents unique challenges. Space and astronaut time are limited—about 600 experiments are conducted on the ISS each year, run by only a crew of six or so onboard at a time. Astronauts have highly regulated schedules that are packed with housekeeping (someone has to clean, change out the filters, check on the equipment, and perform fixes, after all) and even exercise, on top of research. Moreover, astronauts may not have the same scientific background as the researchers who proposed the experiments—about half of astronauts have a military background, and the only scientific requirement to qualify for the astronaut program is a master’s degree (or equivalent) in a STEM field. Earthbound scientists launching space-bound experiments must work out all the logistics and provide detailed instructions for the astronauts to perform by proxy. And the scientists usually only have one shot to execute their experiment.
These constraints translate into a golden rule for modifying an experiment for space: simplification. Long before launch, researchers rehearse their experiments in the lab to weed out any superfluous details and flaws. It took more than a year for Sonja Schrepfer, an immunologist at the University of California, San Francisco, and her team to redesign their experiment for space. Her research examines the genetic and molecular markers of aging in the immune system, leveraging space to artificially age biological tissues. Schrepfer’s was one of the successful teams in the first cohort of the Tissue Chips in Space program in 2018, an experience she describes as both exhilarating and nerve-wracking.
The experiment sounds simple enough, at first—let the tissue chips sit quietly in space for three weeks, then freeze the cells right before the return trip—but even that demanded significant remodeling and reorganization. Planning requires a lot of visualizing, she says, as her team had to imagine the day in the life of the astronaut carrying out their experiment, from how fast he could move the tissue chips from the rocket to the incubator to which arrangement of chips and accessories would provide the astronaut the most convenient access to the contents.
Kim says the astronauts “are very disciplined, so they follow instructions very well.” Nonetheless, he says, “we try to minimize the astronaut’s tasks.” His team also reduced the need for astronaut intervention in their experiments. His experimental setup is similar to Schrepfer’s, with additional in situ measurements of his heart tissues and a routine feeding step. On Earth, their heart tissues would be bathed in a nourishing liquid medium that would be replenished every day. For space, Kim’s team upsized their chamber volumes housing the tissues so that an astronaut would only need to switch out the bathwater once a week. “Someday,” he adds, “we can also automate the medium-change process with a robot” to make the process even easier for the astronauts.
Danilo Tagle, the National Center for Advancing Translational Sciences special initiatives director, advises making experiments “astronaut-proof.” That includes “making everything automated as much as possible … so that experiments would run at the push of a button,” he says, “which is very different from how we do experiments here on Earth.”
Where automation isn’t possible, researchers have to rely on astronauts to carry out even the most delicate procedures. But slight differences in how astronauts perform the experiment may introduce variability in the results—a major concern for scientists if they have to reduce their sample size to begin with.
In 2016, Rosamund Smith, a now-retired Eli Lilly cellular biologist, and her team sent only 20 mice to the ISS for a drug experiment—a number Smith normally wouldn’t be comfortable with. Half of the mice were injected with an antibody drug to test whether it could reduce muscular atrophy, a concern for astronauts on long-term missions and people with some conditions back on Earth. With such a small sample size, any changes in the mice’s physiology would need to be drastic to convincingly demonstrate the drug’s efficacy. The different human handlers—the astronauts and the ground scientists (who would take measurements on a set of control mice for comparison)—was a concerning source of potential variability.
Sometimes, researchers can’t even identify the source of the variability. “You may handle the mice much more roughly … if you’re not used to dealing with mice,” says Smith. Ideally, the same person runs the entire experiment to minimize the inconsistencies. “Because, if there was a difference between [the astronaut’s] set of mice and mine, is it because [the astronaut’s] is under microgravity and mine wasn’t? Or was it because the astronaut did it and I did it?” Back on Earth, experiments can be repeated to overcome the impact of minor variations or to confirm a result. Not so in space.
Smith admits that she was nervous at first. In the end, she was amazed to see statistically significant differences among her small group of mice subjects. It was in no small part thanks to the professionalism of the astronauts. Smith remembers observing the astronauts in action through a video livestream, and that she was impressed by their sense of responsibility. Astronaut Tim Peake even worked through lunch break on her experiment, she recalls.
“We’re asking the astronauts to do complex things … that’s not their general training,” says Smith. She attributes her triumphant experiment to “the wonderful efforts of the astronauts and all the experience of the people at NASA … and whomever else we worked with.” Smith adds, “They knew to plan it down to the finest, finest detail.”
But there’s only so much that ground scientists can prepare for. Many factors are beyond the scientists’ control, and each step on the journey to space carries risk. In 2015, Smith’s experiment came close to the ultimate nightmare: a rocket explosion right before her experiment’s own launch. Her eventual launch date was postponed by a year while SpaceX fixed the rocket’s design.
Research bound for the ISS has also been disrupted by the pandemic. Space agencies worldwide had to reduce their in-person staffing and postpone long-awaited missions. And it was not just the launch centers that were affected—any disruption and delay in an early preparatory step, such as the assembly of the necessary equipment, could throw off a project’s timeline and cause researchers to miss their launch windows. Kim was fortunate that his experiment was delivered to the ISS right before the first wave of COVID-19 cases in March. When labs nationwide began shutting their doors and halting nonessential research, Kim’s experiment ran unaffected on the ISS, protected by the cordon sanitaire of space. Kim’s team found it harder to carry out the follow-up experiments on the samples that returned from space six weeks later, due to the lab’s COVID restrictions. Had his launch been delayed, Kim suspects his experiments might not have made it to the ISS at all.
Researchers need to be logistically and psychologically prepared for any surprises that may turn the experiment into a no-go. This one-step-at-a-time, come-what-may mentality is perhaps best exemplified by the astronauts themselves.
“[We] understand that there are many years of Ph.D. level–theses type of work that have gone into each one of these experiments,” says NASA astronaut Chris Cassidy, who returned from the ISS in October. He estimates he spent 60 percent of his day on scientific experiments; the rest of his time was spent on general ISS upkeep. But the gravity of each experiment is not lost on him. On behalf of the astronauts, he says he feels responsible that “we can make a small error and screw up the entire science experiment.” He adds, “Sometimes you get a little nervous when you think about [it] this way. But in reality, every single thing we do up there is like that.”
What does an astronaut have to say on making an experiment astronaut-proof? Clear instruction manuals, Cassidy advises. Annotated diagrams and photos are welcome.
“Where the confusion happens is when the scientists write the experiment thinking that they’re talking to people that speak that same language of research,” says Cassidy, who comes from a military background. “We don’t necessarily.”