How to Sequence DNA in Space
“I didn’t want to screw it up,” thought Kate Rubins, the first person to carry out this experiment in microgravity.
The International Space Station is one big research laboratory. Its earliest research objectives, back in 2000, were pretty straightforward: keep humans alive. Since then, the number of experiments conducted aboard the station has ballooned, and astronauts and cosmonauts spend their days studying how terrestrial science and technology works in microgravity. Over the years, the station’s residents have grown zucchini, beheaded flatworms, maneuvered humanoid robots, tended to mouse embryos, watched the muscles of zebrafish atrophy, and drawn their own blood, using their own bodies as test subjects. Scrolling through NASA’s full list of experiments, one gets the sense that almost any experiment that can be done in a lab on Earth can be replicated in one floating 200 miles above.
So it shouldn’t be too surprising that humans have successfully sequenced DNA in space.
Last summer, NASA dispatched Kate Rubins, a microbiologist with a doctorate in cancer biology, to try it for the first time. Rubins has spent her career studying infectious diseases and worked with the U.S. Army to develop therapies for the Ebola and Lassa viruses. She has sequenced the DNA of different organisms plenty of times on the ground, but the process was a little bit more nerve-wracking on the space station. “I didn’t want to screw it up,” she says.
I spoke to Rubins during her recent visit to NASA headquarters in Washington, D.C. about the experiments she worked on during her four-month stint on the ISS. Our conversation, edited for length and clarity, is below.
But first, a brief rundown of how DNA sequencing actually works. Rubins used a specially made biomolecule sequencing device, a miniature version of the microwave-sized hardware on Earth. DNA samples are fed into its protein nanopores, tiny structures embedded in a synthetic cell membrane. The device sends an ion current through this membrane. When the bases of DNA—guanine, adenine, thymine, and cytosine—move through nanopores, they each create a change in the current. The device measures these tiny disruptions, and scientists use them to determine the sequence of the bases. For the human carrying this out, it’s actually pretty easy.
OK, let’s go.
Koren: So when you first got to the space station, knowing what you know about how communicable disease works, did you ever have a moment when you realized, I’m in a giant tube of germs?
Rubins: So we’re in a giant tube of germs all the time, right? Not to scare you. Sitting here, this room is filled with germs. Most germs aren’t bad. You’re in a microbial environment all the time. What’s interesting is that we’ve actually had this microbial environment that’s been separate from Earth for 16 years. We haven’t had real problems with disease outbreaks or that kind of thing happening on the space station, but it is interesting to potentially study its microbial environment, what different species of bacteria there are, and how that changes over time. I would actually say it’s a little bit better, from an infectious disease perspective, to be isolated. So you’re with three or six people, but you actually have less chance of being sick because it’s not like you’re going through an airport or a subway ride where you’re in contact with a bunch of people.
Koren: How did you start preparing for the DNA-sequencing experiment?
Rubins: We’d been working on it for a while. One of the questions we had was, how is the equipment going to survive launch? So we did launch vibration tests. We were also unsure about what would happen in microgravity—you get a lot of bubbles forming [in the solution]. Could we prevent bubbles from forming? We ended up deciding to sequence a mix of non-pathogenic viruses, bacteria, and mouse DNA because that gives you the range and complexity all the way from virus to mammalian organism.
Koren: Was there doubt it would work?
Rubins: Yeah, it was really an experiment. We were testing this technology and our question was, is this going be successful? And it was, luckily. But that’s pretty much everything in science. You have a hypothesis, you go in, you test it, analyze the results, and see if you have to change anything about the experiment.
Koren: How did the experience compare to sequencing DNA on Earth?
Rubins: I was surprised at how well it worked. I had tried it out a few times on the ground just to see how the mechanics of loading everything would work, and then it’s pretty different in microgravity, right? You put the pipette on the sequencing flow cell, and you shoot back off in the opposite direction with the same amount of force that you put on the pipette. Anytime you’re handling something, you have to stabilize yourself, so that took a little bit to get used to. I brought some foot restraints over and got myself hooked in. The first time I did it, I had a head lamp on so I could see really well, and some magnifying glasses.
Koren: How many runs did it take before it worked?
Rubins: It was actually successful on the first try, so that was great. We had some extra samples just in case it didn’t work the first time, so we started actually changing the experiment a little bit. We altered a few parameters, like the length of time that the reaction runs. They all worked.
Koren: What was your reaction after that first successful run?
Rubins: I was extremely excited. I was really nervous loading it the first time. I’m usually not nervous when I’m just doing a normal bit of pipetting, but I didn’t want to screw it up. There was a little bit of adrenaline going. It’s within 10 minutes that you start to see the first sequence coming through.
Koren: Did it feel like 10 minutes? Because when you’re anticipating something, time can feel like it’s moving slowly.
Rubins: Oh, no! I was like, I can’t even be here. I’ve got to float away and try to keep myself busy. And then I’d come back and check again, and then I’d float away again. We had a communications loop open with the ground team, so when we did start to see everything come through, they put the speaker on so I could hear them all clapping and cheering.
Koren: You also spent some time culturing human heart cells on the ISS. What was that like?
Rubins: You’re tending to the cells—you have to change the media [in the cell culture], you have to resupply them with nutrients. Instead of having the open cell-culture plate, they’ve got lure locks that are designed for space, and you can change the media with a little syringe. It took quite a long time to do the cell-culture change. I was nervous because I didn’t want to contaminate the cell culture; if you get bacteria in there, it’ll overgrow your culture and kill the cells and ruin the experiment. You have to work on very sterile techniques. It’s like prepping for surgery. You don’t want any microbes getting in the patient.
Koren: You’ve said you watched the heart cells beat in unison. How many cells does it take to see that?
Rubins: You can see 20 to 100 cells. For the most part, they’re in sheets or forming clumps or groups of cells, so you can see them together just synchronize that beating.
Koren: And is that weird to see?
Rubins: It was very cool. When I pulled the microscope out, the cosmonauts would come down from the Russian segment of the space station and everybody would float past because they liked watching it. There’s something fascinating about seeing down to the microscopic level and actually watching these heart cells beat.