Imagine you’re an astronaut, hurtling through space in a shuttle on a manned mission to Mars. You and your crew have spent years preparing for this, and you all started the trip in tip-top shape. But now, a few months into the journey, you’re not feeling so hot. You’ve developed osteoporosis and some muscle loss, and you need medicine.
Luckily, the crew has access to an “astropharmacy”—a set of biological tools and equipment that could be used to manufacture small doses of customized protein and peptide-based drugs on demand, as needed, nimbly and quickly. Within 24 hours, your crewmates can grow your drug in bacteria, separate it out for you to take, help you feel better, and allow you to carry on with the mission.
A project of Lynn Rothschild and her team at NASA Ames Research Center, the astropharmacy would be stocked with hardy, genetically engineered spores of Bacillus subtilis bacteria ahead of launch. Freeze-dried spores, like seeds, can be saved for years without refrigeration.
With a library of thousands of spores, all programmed to produce different drugs we know astronauts are likely to need, long-haul space missions can be fully stocked with medical supplies.
Why bring drugs into space?
We know that the microgravity environment of space can disrupt a number of systems within the human body. For example, bones and muscles deteriorate, leading to osteoporosis and other problems; the filtration rate of kidneys increases, which can create kidney stones; the redistribution of fluid in the body can lead to “chicken legs” and puffy faces, and cardiovascular systems can experience extreme stress.
Standards for astronaut fitness have played a major role in determining who gets to go to space because astronauts with significant existing medical conditions could get sick, threatening the safety of the crew and the success of a mission if they aren’t promptly treated. But for long-haul missions, an astronaut’s research speciality may be more critical than perfect health. And, as space is corporatized and opened for space tourism, health standards will likely be relaxed, necessitating an evolution in space medicine and pharmaceuticals, according to a recent paper by space medicine experts at the United Kingdom’s Royal Air Force Centre of Aviation Medicine.
“You could have a library of thousands and thousands of kinds of drugs engineered into different cells.”
Luckily, protein-based drugs, many of which are approved by regulators for safety and efficacy and are routinely used clinically here on Earth (like insulin, for example), could be the key to treating many of the illnesses that astronauts develop in space. The astropharmacy spores are already proven to be space-hardy, and when they’re needed, all the crew has to do to make instant biopharmaceuticals is add some culture medium. The cells begin to secrete whatever they’ve been programmed to make, such as teriparatide, a hormone to treat osteoporosis, or G-CSF, a bone marrow stimulator that produces white blood cells. Then, after purifying the batch using microfluidics, you’re “good to go,” says Rothschild, senior research scientist at NASA’s Ames Research Center.
“You could have a library of thousands and thousands of kinds of drugs engineered into different cells,” Rothschild says.
Traditional pharmaceuticals, like pills, are not so heavy on their own, but the number of bottles you might ever need on a long-haul space journey would take up a lot of limited storage space that might otherwise be put to better use—like carrying farming equipment or the makings of habitats for people to live in on other rocks.
An astropharmacy would add payload to the mission as well. There would need to be supplies of the media and chemicals required to grow the bacteria and isolate the drugs, Petri dishes and flasks to grow them in, and microfluidic equipment to separate them out. But a single set of tools supplemented by a huge library of featherweight drug-producing spores could be designed to add minimal extra weight. Plus, the lab staples that would be needed for the astropharmacy would likely be standard issue for missions to Mars anyway.
In some ways, this approach would be the only way to bring protein-based biological drugs into space. Biologicals tend to expire more rapidly than other drugs, and their shelf life may be only six months to a year. Many also need to be refrigerated, an issue we’ve seen with COVID vaccines. Shuttles start getting packed months before a mission launches, and packing medicine that could expire before launch just isn’t practical.
Plus, says Kristin Fabre, chief scientist at Baylor College of Medicine’s Translational Research Institute for Space Health Research (TRISH), it’s challenging to know how terrestrial biopharmaceuticals will react in the body in space. And we still don’t entirely understand how the body will handle extreme levels of radiation from galactic cosmic rays.
“If I’m sitting on a spacecraft on my way to Mars, I want to think about what’s going to be important to take with me. But we don’t know what kinds of medical scenarios are going to hit us,” Fabre says. She and her team at TRISH are also building tools to prepare for the unknown medical issues of space travel by finding ways, similar to Rothschild’s astropharmacy, to save time and storage capacity but still be fully stocked for a medical emergency.
“We don’t want to have half our cargo be [drugs],” says Fabre. “We don’t know how stable these drugs will be, we don’t know how well they would survive flight, or exposure to radiation over a period of time, or how safe and effective these drugs are going to stay, particularly if they’re a biologic or a protein.”
While not connected to the astropharmacy project at Ames, Fabre is an expert in tissue-on-a-chip technology, and she leads a team that has also been working on developing on-demand biologicals for space.
There are likely going to be technological hurdles to overcome for an astropharmacy to be realistic. In order for a space crew to use the astropharmacy spores to create a personalized solution on demand, those spores will have to be created in synthetic biology laboratories here on Earth by genetically engineering microbes to contain the necessary enzymes and biochemical pathways needed to produce the drugs. The growth and separation protocols will need to be worked out, and although the Brown-Stanford-Princeton iGem team that Rothschild advises created a prototype of the astropharmacy system, everything will still have to be tested in the microgravity of space.
Of course, any astropharmacy will also need to have all the usual suspects of a well-stocked medicine cabinet and the ability to produce drugs that cannot be grown in bacteria.
Tender greens by prescription
“Sometimes you just need to make some ibuprofen,” Fabre says. And sometimes you may just need to eat healthier. The astropharmacy is but one tool in a “Swiss Army-knife approach” to sustaining health in space, she suggests.
Fabre believes that tissue-on-a-chip technology programmed with the individual stem cells of crew members ahead of launch could be used to develop on-demand stem cell therapies or personalized drugs for individual crew members.
Researchers at TRISH and their partners are also considering the overall connectivity of systems of the human body, such as the interactivity of the brain and the gut microbiome. At MIT, Robert Langer has developed the “mother machine,” an ingestible device that takes up residence in an astronaut’s stomach and delivers drugs like caffeine, melatonin, and acetaminophen to the body, potentially treating the effects of isolation on the body.
“It would be cool if we could get to a point when you could just eat the lettuce in order to get the drug.”
Another promising TRISH-funded project, from Karen McDonald at UC Davis, proposes to use genetically modified lettuce to grow proteins on demand. There is still a lot of work to be done to determine the best ways to isolate and purify proteins from lettuce, but Fabre says she is “trying to push the boundaries.” The next steps will be to figure out the efficacy, bioavailability, pharmacology, and so on, to predict the right dosing.
“It would be cool if we could get to a point when you could just eat the lettuce in order to get the drug,” says Fabre. “You can take your drugs with a nice balsamic vinegar!”
All these ideas also have enormous potential for terrestrial medicine, says Rothschild, something she says she is “bullish” about pointing out.
In the end, even if future astronauts never realize the lofty ambition of an astropharmacy in space, the technology is likely to make a huge down-to-Earth impact by providing kits for making doses of drugs available to people in remote and low-income places, like Antarctica or rural Asia, and, Rothschild hopes, pushing the dream of personalized therapies for people with rare or orphan diseases.
“If we can do this for space, think about how pharma can reach their patients here on Earth with stable, effective, and safe compounds in hard-to-reach patients,” says Fabre.