A tiny experiment using Artemis II astronaut cells could reshape medicine

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As the four Artemis II astronauts looped around the moon this week before their return trip to Earth, so did four transparent chips, each about the size of a USB thumb drive and seeded with their bone marrow cells.

Each chip is an “avatar” - an attempt to model key aspects of the biology of Victor Glover, Jeremy Hansen, Christina Koch and Reid Wiseman, the four humans whose courage and wonder have captivated the world.

The historic test flight that blasted off from Earth last week lays the groundwork for NASA’s goal of establishing an “enduring human presence” on the moon as a stepping stone to explore the rest of the solar system. But the Avatar program - which stands for A Virtual Astronaut Tissue Analog Response - could also become a key part of that story by helping NASA understand the effects of deep-space flight on human biology, particularly the risks of radiation exposure

For now, the biology experiment aboard the Orion spacecraft is a first step. Will the chips survive the journey? How closely will changes to the cells in the chips mirror what happens in the astronaut’s bodies? Scientists won’t know until after splashdown, when the chips are recovered from the Orion spacecraft.

“This is really a proof-of-concept, because to get space on a mission like this is precious,” said Donald Ingber, founding director of the Wyss Institute for Biologically Inspired Engineering at Harvard University, whose laboratory and start-up company, Emulate, are working with NASA on the project.

The long-term hope is that the chips, which can be used to model different organs, including lungs, livers and hearts, could be sent up in advance of a real human crew. If they reflect what happens to the body, NASA could use them to anticipate health effects and even preselect personalized medical regimens for protecting and treating astronauts based on their own biology.

“I think this is going to pave the way for us in so many ways, in understanding the radiation and microgravity, partial gravity effects on the humans before we send them out,” said Lisa Carnell, director of NASA’s Biological and Physical Sciences Division. “Our phrase is, ‘Know before we go.’ If we want humans to live on the lunar surface in that partial gravity … the goal would be to send[the chips] ahead of time and get an idea of what happen to different organ systems.”

Health in deep space

On Earth, scientists have for years been working to build human organs on a chip. The technology could offer a better way to test whether a drug is toxic or whether it works on human cells. The hope is that the models could improve the efficiency of drug development and help shift away from reliance on animal models that often fail to predict what happens in human biology.

In space, the chips present a new opportunity in a place where there are many unknowns. Deep space presents particular health risks that are difficult to model on Earth. Outside of the protection of Earth’s magnetic field, astronauts will be exposed to galactic cosmic rays, along with hazardous radiation released from solar flares. At the lunar surface, there’s albedo radiation - radiation that penetrates a few meters into the surface and reflects back - a “double whammy that we don’t have any data on,” Carnell said.

Ingber imagines sending up large numbers of chips one day, to observe the variation in how the deep-space environment affects human biology - to discern whether there are differences in people of different ages, sex or other characteristics. Nicola Fox, associate administrator for NASA’s Science Mission Directorate, said bone marrow was chosen as a first test case because it is sensitive to radiation exposure, but she sketched out an even grander vision for future missions.

“This is a pretty sophisticated way to look at the effect on tissue - it’s a safe way of looking at it. You’re not doing experiments on a human subject,” Fox said. “You could do multiple different organs and chain them together to look at the impact.”

To make the chips, astronauts donated platelets several months before the flight through a blood draw. From the leftover blood cells after the platelets were removed, the immature bone marrow cells the scientists needed were purified by using magnetic beads that bind to the surface of the cells. They were then frozen in batches.

Each chip has a network of tiny channels carved into it. Three days before launch, the team from Emulate thawed the astronaut’s cells, mixed them with a gel and seeded the mixture into one of the channels. A parallel channel lined with blood vessel cells feeds the supply of nutrients and oxygen to keep the bone marrow cells alive and growing.

Then, the scientists handed the chips over to Space Tango, the hardware developer that made the unit that keeps the astronaut tissue in the chips alive during their journey through space. There are two sets of four chips each, one to stay on Earth and the other to journey around the moon.

Avatar splashdown

In a laboratory at Kennedy Space Center in Florida, one set of chips has spent the past week sitting in a lab. On board the Orion spacecraft, sometimes visible in the background from videos and photos beamed back to Earth, is a matching set.

Once the astronauts splash down Friday evening in the Pacific Ocean, two scientific teams working in parallel - one in San Diego and the other in Florida - will “fix” the chips to lock in any changes and prepare them for detailed scientific analysis in Boston.

While months of study will be needed to understand what the chips can and can’t reveal about human biology, there will be an early warning signal of success or failure: the presence of air bubbles. It’s always a risk with such experiments, and if air got into the system, the cells won’t grow.

David Chou, the principal investigator of the Avatar project at Emulate and a principal scientist at Harvard University’s Wyss Institute, said that he flew to Houston for the first platelet donation and to thank the astronauts personally for their participation.

The true test of the chips will be in the coming months. Those that went to space will be compared with the matching set that stayed on Earth and to health measurements from the astronauts themselves. Scientists will be looking at the genes that are active in individual cells. They will also be looking for changes in telomeres that are the endcaps of chromosomes, DNA damage and markers of inflammation. If they can begin to show that these astronauts-on-a-chip are reliable markers of what happened in space, it could provide a powerful way to prepare to send humans to live in deep space.

“There is a nonzero probability that some chips will fail - they’re being sent on a rocket around the moon, so who knows,” Chou said. “It’s rare that we get to track a live person and their organ chip through the same process, so that’s definitely one of the things I’m most excited about for this project.”

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