Loss of bone mass to be avoided with space grown lettuce

A research team from the American Chemical Society (ACS) has developed a transgenic lettuce to mitigate the loss of bone mass, that can be grown in space.

NASA is currently preparing to send humans to Mars in the 2030s. The 3-year mission will expose astronauts to a long period of microgravity, which will result in them losing bone mass. But now, scientists report a space grown transgenic lettuce that produces a bone-stimulating hormone.

Astronauts could grow this space grown lettuce on the International Space Station (ISS), and this could help guard against bone loss. Additionally, researchers have also noted that the lettuce may also aid in staving off osteoporosis in resource-limited areas here on Earth.

The researchers will present their results today (22 March 2022) at ACS’s spring meeting. This is a hybrid meeting being held both virtually and in person from March 20-24, with on-demand access available March 21-April 8, and will feature more than 12,000 presentations on a wide range of science topics. 

What challenges do astronauts typically face when embarking on a space mission?

Previous studies of astronauts on extended space missions have shown that they lose, on average, more than 1% of bone mass per month spent in space, a condition known as osteopenia.

“Right now, astronauts on the International Space Station have certain exercise regimens to try to maintain bone mass,” explained Kevin Yates, a graduate student who is presenting the work at the meeting. “But they are not typically on the International Space Station for more than 6 months.”

In contrast, it takes about 10 months to get to Mars, and the astronauts would remain for about a year to study the planet before making the trip back to Earth. This means that the astronauts would need access to enough space grown lettuce to confidently last the entire mission.

The 3-year mission could leave astronauts vulnerable to osteopenia, and later, osteoporosis. A medication containing a peptide fragment of human parathyroid hormone (PTH) stimulates bone formation and could possess the ability to help restore bone mass in microgravity. However, it requires daily injections.  

Additionally, transporting large quantities of the medication and syringes and administering it during space missions is impractical. As a result, Yates; Somen Nandi, PhD, Karen McDonald, PhD, and their colleagues wanted to create a method that would result in astronauts being able to produce it themselves.  

How does the space grown lettuce resolve these issues?

This is made possible from the development of space grown lettuce: “Astronauts can carry transgenic seeds, which are very tiny — you can have a few thousand seeds in a vial about the size of your thumb — and grow them just like regular lettuce,” Nandi observed. “They could use the plants to synthesise pharmaceuticals, such as PTH, on an as-required basis and then eat the plants.”

On the ISS, astronauts have already revealed that they can grow regular lettuce in this resource-limited environment. Yates, Nandi, and McDonald, who are at the University of California, wanted to develop a transgenic lettuce that expresses the PTH peptide in a form that could be taken orally, instead of via an injection.

How was this lettuce created?

In order to increase PTH’s stability and bioavailability in the body, during the development of the space grown lettuce, another proteinthe fragment crystallisable (Fc) domain of a human antibody must be added to PTH’s sequence. Previous studies have shown that the Fc fragment increases the time that the attached peptide circulates in the blood, meaning it is more impactful. 

Researchers introduced a gene encoding PTH-Fc to lettuce by infecting plant cells with Agrobacterium tumefaciens — a species of bacteria used in the lab to transfer genes to plants.

The transgenic lettuce plants were screened, as well as their progeny for PTH-Fc production. Preliminary results indicate that, on average, the plants express about 10-12 milligrams of the modified peptide hormone per kilogram of fresh lettuce.

Yates explained that this means that astronauts would need to eat about 380 grams (approximately eight cups) of lettuce daily to get a sufficient dose of the hormone, assuming about 10% bioavailability, which he acknowledges is a considerably large amount to consume.

Transgenic Lettuce
This lettuce produces a bone-stimulating hormone that could help stave off bone loss in space and on Earth.
Credit: Kevin Yates

When will this be offered to astronauts?

“One thing we are doing now is screening all of these transgenic lettuce lines to find the one with the highest PTH-Fc expression,” McDonald added. “We have just looked at a few of them so far, and we observed that the average was 10-12 mg/kg, but we think we might be able to increase that further.

“The higher we can boost the expression, the smaller the amount of lettuce that needs to be consumed.” The team also wants to test how well the transgenic lettuce would grow on the ISS, and whether it produces the same amount of PTH-Fc as it does on Earth.

Although the researchers have not yet tasted the lettuce, because its safety has not been established, they anticipate that it will taste very similar to its regular counterpart, like most other transgenic plants.  

Before the transgenic lettuce can grace astronauts’ plates, the researchers must optimise the PTH-Fc expression levels. Then they will test the lettuce for its ability to safely prevent bone loss in animal models and human clinical trials.  

Yates concluded: “I would be very surprised that if, by the time we send astronauts to Mars, plants are not being used to produce pharmaceuticals and other beneficial compounds.”

The researchers acknowledge support and funding from NASA through the Center for the Utilisation of Biological Engineering in Space (CUBES).

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