Mars is a long way off. Other planets in the solar system are even more so, as for other solar systems, we can’t even fathom visiting them yet. In a journey pitted with unknown dangers and disease, even weightlessness can cause severe damage to the human body. Without the possibility of restocking supply, how can space agencies ensure that galactic explorers are equipped with life-saving drugs?
While the ISS space station silently orbits above the Earth, the astronauts aboard it float inside, almost weightless as they go about their daily work. This weightlessness triggers a lot of health problems, including chronic medical conditions. The long list of illnesses these professionals can suffer includes a loss of muscle mass and bone density, impaired vision, decreased kidney function, diminished neurological responses, and a compromised immune system.
If we were to carry out even longer missions in space, the effects would be even more severe — and it goes without saying that any such mission must ensure the health and wellbeing of astronauts.
But the average commercial drug comes to the end of its shelf-life after only two years (biologics will only last six months even with refrigeration). Upcoming missions to Mars will not be possible without developing and producing pharmaceuticals within the cramped quarters of a spacecraft. And this is where NASA’s space medicine program, the Translational Research Institute for Space Health (TRISH), comes in.
The project is run by the Baylor College of Medicine (BCM), the Massachusetts Institute of Technology (MIT), and the University of California, Davis (UC Davis), and focuses on “just-in-time or on-demand drugs.” These medicines, encompassing drug-producing plants and personalized microbial therapies, can be produced by astronauts on board a vessel or on the surface of the red planet as and when they’re needed.
“The space environment causes rapid body changes. This can help us understand how we humans react to and overcome stress. Ensuring that space explorers remain healthy pushes us to invent new approaches for early detection and prevention of medical conditions,” says Dr. Dorit Donoviel, executive director of TRISH at BCM.
“Studying a broad range of people in space increases our knowledge of human biology. TRISH’s EXPAND program will leverage opportunities with commercial spaceflight providers and their willing crew to open up new research horizons,” he adds.
How will astronauts produce interstellar drugs?
Right now, astronauts on the International Space Station have certain exercise regimens to try to maintain bone mass, says Kevin Yates, a TRISH scientist at UC Davis — even as they’re only on the ISS for a few months. Developing medicine and programs for deep space missions would have to be on the timeline of years, not months.
Excitingly, this is precisely what Kevin Yates and his colleagues have achieved with a new biological drug factory that saw them bioengineer lettuce containing a human version of parathyroid hormone (PTH).
The hormone, which helps to stimulate bone growth in the body, is naturally produced by the parathyroid gland and is commonly synthesized to counteract bone loss caused by arthritis. This proprietary technology could prove to be a lifesaver on the icy surface of the red planet.
In their presentation at the spring meeting of the American Chemical Society in San Diego, the team described how they were able to transfer the human hormone into the lettuce plants by attaching a synthetic version of the DNA encoding the hormone into the genome of a soil bacterium called Agrobacterium tumefaciens. The young lettuce plants were then ‘infected’ with this synthetic bacteria, integrating their drug-producing genome into its own – after which the lettuce began producing PTH.
TRISH has also screened a number of the plants observing that the most fruitful specimens produced roughly 12 milligrams of PTH per kilogram of lettuce leaves – Meaning a person would need approximately eight cups (380 grams) of lettuce a day to get enough of the hormone. For context, a standard head of lettuce weighs around 300 grams: that’s a lot of lettuce!
“One thing we’re doing now is screening all of these transgenic lettuce lines to find the one with the highest PTH-Fc expression,” explained Dr. Karen McDonald, another TRISH researcher.
‘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.” So “the higher we can boost the expression, the smaller the amount of lettuce that needs to be consumed,” she goes on.
What other drugs will transgenic lettuce spawn?
Unfortunately, the researchers have been unable to taste the lettuce with toxicology studies needed before human consumption due to safety constraints.
Speaking from UC Davis, the team says they now plan to send their transgenic lettuce seeds to the ISS to evaluate how microgravity and space radiation affects them. And intend to cultivate lettuce seeds containing granulocyte-colony stimulating factor (GCSF) or granulocyte-macrophage colony-stimulating factor (GMCSF) – used to increase the number of blood cells in the patients here on earth.
Yates surmises: “I would be very surprised that if, by the time we send astronauts to Mars, plants aren’t being used to produce pharmaceuticals and other beneficial compounds.”
A drug factory in astronaut’s stomachs
Another of TRISH’s projects, based at MIT, involves an ingested device that converts certain bacteria into a specific drug. This non-bulky drug delivery device is swallowed by the astronauts, residing in their stomach for a specific period, gradually releasing the drug it manufactures into their body whereupon it’s expelled safely.
MIT’s proof of concept uses the bacterial species E. coli to produce caffeine (a stimulant), melatonin (to counteract sleep problems), and paracetamol (a well-known pain killer) within the device. And once the production of these over-the-counter medications is validated, it is hoped that the team can expand this device’s capacity to more drugs.
However, unlike TRISH’s transgenic lettuce, this device is still in the early stages. But there are other non-TRISH-funded projects currently being worked on with a sturdy pile of whitepapers to their name. One of the most promising, from Eindhoven University, uses sunlight to power artificial leaves, which in turn act as reactors to produce a cornucopia of different pharmaceuticals.
The device, made from silicone rubber, can even work under cloudy skies where its micro-channels bring chemicals into direct contact with sunlight. Like a natural plant using photosynthesis, the artificial leaves act as a ‘mini-reactor’ to generate enough energy from the sun to perform complex chemical reactions.
They do this using in-built luminescent solar concentrators to harvest radiation, causing the molecules being pumped through their narrow channels to react and form the end product, which then flows to the edge of the ‘leaves.’ The researchers have also trialed their technology in natural sunlight with promising results.
And regarding the encouraging data from TRISH, Dr. Dorit Donoviel concludes:
“The Institute is proud to fund this group of innovators working to support human health for deep space exploration. This work moves us all closer to the day we will send humans to Mars.”