On a long-duration space flight, such as those planned for missions to Mars and beyond, bone loss can be a severe impediment. But now, scientists found a solution that could solve this problem.
In a new study, scientists reported transgenic lettuce that produces a bone-stimulating hormone. Someday, astronauts could grow the lettuce in space and help guard against bone loss. It can also prevent osteoporosis in resource-limited areas here on Earth.
The proximal femoral bone loses 1.5 percent of its mass per month or roughly 10 percent over a six-month stay in space. This condition is known as osteopenia.
Kevin Yates, a graduate student presenting the work at the meeting, said, “Right now, astronauts on the International Space Station have certain exercise regimens to maintain bone mass. But they’re not typically on the International Space Station for more than six months.”
“In contrast, it takes about ten months to get to Mars, and the astronauts would remain for about a year to study the planet before making the trip home to Earth.”
NASA is planning to send humans on Mars sometime in the 2030s. This 3-year mission will expose astronauts to microgravity for a long duration. It could leave them vulnerable to osteopenia and, later, osteoporosis.
A medication containing peptide fragments of human parathyroid hormone (PTH) stimulates bone formation. It also helps restore bone mass in microgravity, requiring daily injections. However, transporting large quantities of the medication and syringes and administering them during space missions is impractical.
So Yates; Somen Nandi, Ph.D.; Karen McDonald, Ph.D.; and their colleagues wanted to find a way for astronauts to produce it themselves — while also enjoying some tasty greens, which are severely lacking in astronauts’ mostly canned and freeze-dried diets.
Nandi said, “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. They could use the plants to synthesize pharmaceuticals, such as PTH, on an as-required basis and then eat the plants.”
It is possible to grow regular lettuce in International Space Station. Yates, Nandi, and McDonald, who is at the University of California, Davis, wanted to develop transgenic lettuce that expresses the PTH peptide in a form that could be taken orally instead of by injection. The special lettuce might also help treat osteopenia in regions of Earth that lack access to traditional medications.
To increase PTH’s stability and bioavailability in the body, they attached a piece of another protein, the fragment crystallizable (Fc) domain of a human antibody, to PTH’s sequence. The Fc fragment increases the time the attached peptide circulates in the blood, making it more effective.
Scientists attached a gene encoding PTH-Fc to lettuce. They did this by infecting plant cells with Agrobacterium tumefaciens — a species of bacteria used in the lab to transfer genes to plants.
Screening the transgenic lettuce plants to determine their progeny for PTH-Fc production reveals that they express about 10-12 milligrams of the modified peptide hormone per kilogram of fresh lettuce.
According to Yates, astronauts would need to eat about 380 grams, or about 8 cups, of lettuce daily to get a sufficient dose of the hormone, assuming about 10% bioavailability, which he acknowledges is a “pretty big salad.”
McDonald said, “One thing we’re doing now is screening all of these transgenic lettuce lines to find the one with the highest PTH-Fc expression. We’ve 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.”
Scientists are yet to establish the safety of this lettuce. Hence they haven’t tasted it. They predict that it will taste very similar to regular lettuce. Before serving it in astronauts’ plates, scientists need to optimize the PTH-Fc expression levels. Later, they will test the lettuce for its ability to safely prevent bone loss in animal models and human clinical trials.
Scientists presented their results at the spring meeting of the American Chemical Society (ACS). ACS Spring 2022 is a hybrid meeting held virtually and in-person March 20-24, with on-demand access available March 21-April 8. The meeting features more than 12,000 presentations on a wide range of science topics.