As humans venture into deep space travel, plants might become essential to keep astronauts healthy on years-long trips to Mars.
Astronauts have been taking medicines with them on space missions since the beginning of space travel. The crew on the Apollo 11 mission that landed on the Moon carried antibiotics, painkillers, nasal sprays and sleeping pills among other medications. The International Space Station keeps a stock of drugs and equipment ready to deal with a dental emergency or an appendectomy.
But with a trip to Mars on the horizon, it is starting to become evident that the way we produce drugs will not be suited for long-distance space missions.
“The International Space Station is close enough that you can send things up as needed and you can evacuate somebody for medical emergencies,” said Karen McDonald, professor at the University of California, Davis, who studies alternative ways of producing medication that can supply the needs of a prospective mission to Mars.
“The distance is the main problem and challenge with Mars. Drugs will expire for a typical mission to Mars. There may be some unknown situations that arise that you need to create a countermeasure quickly because you can’t rely on supplies from Earth. It will just take too long before it gets there.”
Plants as drug factories
While many drugs, such as aspirin, are produced chemically, in recent years a new generation of biological drugs has started to dominate the market. Most of these drugs are produced in bioreactors by Chinese hamster ovary cells, or CHO cells.
“The type of equipment that you need to grow these cells is extremely complex, because they are fragile,” said Sancha Salgueiro, CEO of the consultancy firm Chart Biotechnology. Plants, on the contrary, do not need such complex equipment. “You just need to be able to grow the plant.”
Using plants to make drugs would mean sending astronauts on a long-distance mission with the means to make the drugs instead of the drugs themselves. “If we’re worried about cancer, for example, there may be five or six different antibody drugs for different cancers that we would want to have up there, but those antibodies may only have a two-year shelf life,” said Julian Ma, a professor at St. George’s University of London who has been studying how to produce drugs in plants for decades.
“The wonderful thing about plant seeds is they last forever with very little degradation. In space, you can crack open the seed tube, grow the plants, and harvest the antibodies that you need.”
In addition, plants are already an essential cargo in space missions. “Plants are going to be used for food. Plants consume carbon dioxide, which there’s a lot of on Mars, and they produce oxygen, which we need, and water,” said McDonald. “Plus, from experiences in the International Space Station, having plants has a psychological benefit for crew members.”
McDonald is working on a NASA-funded project to study whether plants would be a feasible solution to produce medicines in space. Her group has created a transgenic strain of lettuce that produces a protein drug called parathyroid hormone that is used to treat bone loss, a common affliction among astronauts. The plant was created by introducing the gene that contains the instructions to produce human parathyroid hormone into the plant’s DNA. A similar process is used to produce drugs in mammalian cells, with the key difference being that human viruses cannot infect plants.
“Plant viruses have the ability to replicate at very high numbers, but they’re not infectious to people,” explained McDonald. “We can use that to our advantage to make our target protein quickly.”
Another method to produce medicines in plants is the ‘transient expression’ of the desired drug. Instead of permanently modifying its DNA, the plant is temporarily given the genetic instructions needed to produce the desired molecule.
“The key advantage of transient expression is that it is incredibly rapid. You can produce antibodies within four weeks,” said Ma. Transient expression in plants was notably used during the Ebola outbreaks of 2014 to rapidly generate a treatment against the virus. This technology has also been used to produce seasonal flu vaccines soon after the predictions of what the most common flu strains for the year ahead are available.
In space, the technology could theoretically enable astronauts to react quickly to unknown situations where their health is threatened. However, this technology is less advanced and might take longer to develop. “This is an area where we’re just getting started,” said McDonald. “If our goal is to, within a day or two, be able to make and purify a drug in a plant, that’s a pretty challenging thing.”
Getting ready for space
Before plants can become the go-to solution to produce medicines in space missions, there are a few things that need to be solved. “It’s still a relatively immature technology,” said Ma. “All pharmaceuticals are produced by large companies. Since the 70s and 80s, those companies have invested heavily into fermentation systems for producing drugs in bacteria or mammalian cells.”
“The whole regulatory oversight on recombinant pharmaceuticals has been based around these techniques. To replace those technologies with something radically different is difficult.”
Ma has been working to change this situation. In 2015, as part of an EU-funded project, his team showed that an antibody could be made in plants with the same quality as one produced in mammalian cells. Since then, he’s seen regulatory authorities in Europe and the US giving approval to clinical trials testing drugs produced by plants.
Another challenge to producing drugs in space, independently of the method, is the purification process. “If it’s an oral delivery, there’s less stringency regarding the purification techniques that you might use, but if you are injecting something, it has to be very pure,” explained McDonald. “The way we do it here on Earth is very complicated. We’re trying to develop simplified processes that actually use plants to make the reagents needed for the purification process.”
As these technologies keep advancing, they will not only have big implications for space travel. On Earth, producing biological medicines in plants could significantly reduce the costs of producing drugs, especially concerning the expenses of setting up and running manufacturing facilities. This could help combat infections such as HIV, Ebola, dengue, or chikungunya in poor and developing countries.
“The whole area of infectious diseases is pretty well controlled in the West, but most of the interventions that we have are too expensive to have any penetration in developing countries,” said Ma. While there has not been much of a financial incentive for pharma to develop drug manufacturing methods in plants, applications like space travel might help push the field further in this direction.
While it is still early days for the field, the technology to make drugs in transgenic plants has been on development for years. “I think once you’ve got the technology working down on Earth – and we’re pretty close – the main issue will be finding what drugs you want to take with you and making sure you can produce all those drugs in plants,” concluded Ma.
Researchers still have to refine the whole manufacturing process. And, after proving the method works, they will have to test and apply it to the production of multiple different drugs. According to McDonald, with the help of new gene editing technologies such as CRISPR/Cas9, these tasks can be done faster than ever and we could be making drugs in space in just a few years.
Cover illustration by Elena Resko, picture provided by NASA