Genetically modified space lettuce could help keep astronauts’ bones healthy on long trip to Mars

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Researchers at UC Davis are developing transgenic lettuce that could one day provide medicine as well as morale-boosting food on the International Space Station and beyond

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Astronauts took their first bite of space lettuce in 2015. “Outredgeous” red romaine made history as the inaugural food to be grown, harvested and eaten in orbit — though astronauts still have a way to go until they can make a salad. To grow flowering plants such as tomatoes, cucumbers and bell peppers, they’ll have to fill in for bees as pollinators.

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Even on its own, without other salad components, the space lettuce tasted “awesome,” according to American astronaut Kjell Lindgren. Albeit with a touch more bitterness than Earth-grown lettuce because, just like humans, the plants were stressed by microgravity on the International Space Station (ISS).

Space lettuce doesn’t just taste great. It’s nutritious, too. A 2020 study published in the journal Frontiers in Plant Science found it contained the same vitamins and minerals as lettuce grown on Earth.

Now, in a proof of concept funded by NASA through the Center for Utilization of Biological Engineering in Space (CUBES), researchers at University of California, Davis, College of Engineering are developing transgenic lettuce that could one day provide medicine as well as morale-boosting food on the ISS and beyond.

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NASA anticipates sending humans to Mars in the 2030s and expects a one-way trip to take roughly nine months. To mitigate bone density loss on the 225 million-kilometre deep-space journey, the researchers have developed a genetically modified lettuce that produces a bone-stimulating drug.

“In microgravity there are a number of physiological effects on the human body, one of which is the reduction in bone mineral density,” Kevin Yates, a graduate student working with professor Karen McDonald and adjunct professor Somen Nandi at UC Davis, explained in a presentation at the spring meeting of the American Chemical Society.

“So, normally in the gravity of Earth, the body constantly breaks down bone and rebuilds it to repair microfractures and to regulate the supply of calcium in the blood. But this goes out of balance in microgravity.”

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It would be a good break from powdered and dehydrated food

Studies have shown that exercise alone is not enough to prevent bone density loss in space, said Yates. If their proof of concept is successful, astronauts could grow their own treatment on long spaceflights, such as the roughly 21-month round-trip journey to Mars (nine to get there, three to wait for suitable planetary alignment, and nine to return to Earth).

Deep-space journeys would require astronauts to carry and replenish supplies of perishable medicines, such as parathyroid hormone (PTH), which is the injectable drug used to protect their bones. Transgenic seeds would make for lighter, more robust cargo.

The researchers chose lettuce as their vehicle for PTH because it has been grown successfully on the ISS, says Nandi in an interview with the National Post. It’s also very productive: One plant generates thousands of seeds.

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“You get this biological amplification of the amount of material,” McDonald said in the presentation. “So, it’s a very simple and cost-effective way to make a therapeutic.”

The team landed on two types of lettuce for their proof of concept: romaine and crisphead (a.k.a. iceberg). The former grows well in the conditions they would expect to have in space; they selected the latter because it showed the best performance in their initial selection.

When growing plants in space, it’s important to consider their phenotypes and morphology, Yates says in an interview with the National Post. “You have to consider how much area do you need to grow a plant? How tall does it get? How spread out are the leaves? How susceptible is it to tipburn from getting too much light?

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“So, you want to pick a plant that’s best suited to grow in the type of plant reactor you’re going to grow it in.”

Transgenic lettuce
Astronauts could potentially grow their own treatment for bone density loss on long spaceflights, such as to Mars and back, say UC Davis researchers. Photo by Kevin Yates /UC Davis

Astronauts would need to eat about eight cups of lettuce a day to get the desired dosage. Since that’s a lot of salad, the researchers are trying to increase the amount of the drug so that astronauts don’t have to consume as much.

“We’re optimistic that we can … (improve it),” says Nandi. “So, this is not a final number.”

Yates adds that the behaviour of the molecule — which is composed of two parts — will also affect the dosage. Once they have tested it in animal models, they will be able to determine how the two parts bind. “That also can affect the dose by potentially halving it.”

Further testing is needed to determine the bioavailability of the lettuce’s bone-stimulating medicine, Nandi says. The team is also evaluating other factors, such as how much of the drug the plants can produce, which leaves contain the highest levels and the ideal harvest time.

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The researchers hope to test the lettuce in space conditions and analyze its stability over multiple generations to ensure it maintains its production level.

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While the lettuce grown on the ISS has proven to have a pleasantly bitter, rocket-like taste, the flavour of the team’s transgenic variety remains to be experienced. Before humans can eat it, animal studies and clinical trials need to be done to test its efficacy and safety.

But Yates hopes that it will taste “every bit as delicious as regular lettuce and that it would be a good break from powdered and dehydrated food that long-duration space travellers might otherwise be eating most of the time.”

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Nandi notes that “the opportunity is outstanding” for their transgenic lettuce on Earth as well as in deep space.

At CUBES, they specialize in using biology to solve challenges in low-resource environments. The technologies they design for use on spacecrafts or planetary surfaces can improve life on Earth too.

“There are places where medicine is needed, but it’s not feasible to set up a facility that can manufacture therapeutic proteins. But it would be possible to build a greenhouse, for example, and grow plants to produce medicine,” says Yates.

“So, a lot of things that we develop for spaceflight also definitely have applications on Earth.”



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