Outer space: The final frontier of biopharma R&D
Merck, Eli Lilly, Novartis, and others have already taken drug discovery to the cosmos. Here's why the ISS U.S. National Lab thinks other life sci firms should follow suit.
To hear drug makers speak of the innovation and scientific potential that drives their projects, you might get the impression that the sky's the limit in the contemporary life sciences industry. But the Center for the Advancement of Science in Space (CASIS) wants to take biopharma to even greater heights—all the way to the U.S. National Laboratory in the International Space Station (ISS).
CASIS has the lofty—and, let's just admit it, downright cool—goal of encouraging companies and innovators down here on Earth to take their research to the cosmos. The organization was tasked with overseeing the ISS U.S. National Lab by NASA in 2011, and describes its mission as maximizing "use of this unparalleled platform for innovation, which can benefit all humankind and inspire a new generation to look to the stars."
That means an intimate involvement with the life sciences industry, from which several major players have already begun to take advantage of the National Lab's unique offerings. During the Biotechnology Innovation Organization (BIO) annual conference in Philadelphia in June, CASIS made a splash by broadcasting a live interview between its president, Greg Johnson, and renowned astronaut Commander Scott Kelly—who just happened to be in outer space orbiting somewhere over Australia at the time.
The broadcast's purpose (other than wowing the crowd) was to explain the type of experiments and research involving the human body that could only be done on an accelerated level in space, such as measuring bone loss and muscle atrophy.
Now, CASIS has a message for the industry at large: If you're interested in the possibility of taking your R&D efforts beyond the bounds of Earth, the National Lab is open for business.
Meet the man who helps take the life sciences to outer space
As a senior research scientist at CASIS, Dr. Mike Roberts has the task of helping entrepreneurs and researchers beam their ideas into outer space.
"My job is helping principal investigators who are interested in doing science on board the National Lab develop their projects," he said in an interview with BioPharma Dive. "Primarily, I would describe it as putting things into a box that can fly.
"All the projects that come to us, whether they're from other government agencies, academic institutions, or industry... have to go through a review process to make sure they're operationally feasible, that it fits within the goals of the ISS National Lab." For instance, the R&D being proposed needs to have a specific Earth benefit that separates it from the more exploration-related themes tackled by NASA.
The promise of microgravity for biopharma R&D
So why would a biopharma company take the effort of sending its research all the way to the ISS? "One of the key factors that makes that investment most valuable for pharma and the life sciences is the ability to experience the microgravity environment, the freefall environment," explained Roberts. "That's one of the foremost unique features of the National Lab."
There are several advantages to this type of environment that have significant implications for drug discovery, drug design, and even drug delivery. And keeping with one of the industry's favorite buzzwords, the initial advantage is disruption.
"From a biological perspective, all life evolved in a 1G environment," said Roberts. "So by removal of that gravity vector, it enables you to explore responses in the biology, physiology, and molecular control of those organisms in an environment that's completely foreign to them. In some cases, that creates a stress on a cell or organism.
"That's typically how we do science, anyway—perturb the system, then see how it responds."
An accelerated model for osteoporosis and muscle atrophy
More specifically, microgravity has an obvious effect on human physiology. Astronauts in space have always had to grapple with the issue of waning bone density and muscle atrophy in a weightless environment. Typically, these problems have been counteracted through regular exercise or specific diets designed to keep astronauts healthy enough to handle the physical requirements of the work they must complete in space.
But for the life sciences, weightlessness also provides for an accelerated basis to observe changes to muscle mass and bone density, as well as the effect of drug candidates on their targets.
"We've learned that some of those effects of that microgravity environment mimic diseases that affect us here on Earth," said Roberts. "That loss of bone mineral density is similar to what we see as we age on Earth, the outcome of osteoporosis, our bones becoming more brittle... It's an actual opportunity to use that environment as an accelerated model of osteoporosis." The same is true for muscular atrophy.
When it comes to actual drug discovery in space, biopharma companies have a clear incentive to use the freefall environment as a catalyst for an accelerated model of disease onset and progression.
"So when [companies] have an interest in particular pathways, where they think they have the ability to affect the outcome, either to prevent the onset of disease or slow its progression, they can look at that particular drug in an animal model [in space]," said Roberts.
CASIS has the capacity to fly the rodent (rats and mice) models used by the industry to the ISS, so biopharma firms can use their placement in microgravity "to study the effectiveness of a particular therapy in an accelerated environment so they get a quick model to understand if they've targeted the right pathway and if they have the right drug to affect an outcome."
A clearer picture of drug targets and an opportunity to improve structure, delivery, & storage
Microgravity also has an effect on gas-liquid separation and microfluidics. And that means that there are even greater advantages to space-based biopharma research than simply speeding up observational outcomes trials.
For instance, the changes in gas-liquid separation may benefit researchers attempting to better understand the physical structures of their drugs and drug targets. One practical application of this is in the development of protein crystal growth, Roberts explained.
"The absence of buoyancy-driven convection and sedimentation, the inability of things to settle out or separate based on density differences [in microgravity], slows the process of protein crystal growth," he said. "That can result in crystals which have a higher-order structure, are more organized, and larger in physical size, which then translates to better structures that can be resolved here on Earth.
"So for folks who are interested in the physical chemistry and understanding the structural biology of drugs and drug targets, they can get much higher-resolution maps of the structure of active sites for drugs and drug targets. That in turn helps them design better drugs with better therapeutic outcomes and less potential toxicity."
For Roberts, one of the most surprising and innovative uses of the ISS National Lab has been for researching new mechanisms of drug delivery and structuring that can have major implications for how a therapeutic is manufactured and stored.
"We have a payload that's sponsored for a large pharma company who has a pretty good idea of what the structure of the [drug] compound is, but interested in ways of trying to repackage it to make it have a longer shelf life without the need for thermal control, without the need for refrigeration and stuff like that," said Roberts.
"One of the things they wanted to understand was how to use the physical structure as a basis for designing a better drug that could last longer. And that was kind of a novel aspect of utilization of that microgravity environment. Before I started with CASIS.... I wasn't aware of the possibility of using that environment for better drug delivery, drug stability, drug formulation type questions."
Big pharma and small biotech—in space
None of this is purely theoretical. At the moment, at least three pharmaceutical giants are conducting research projects aboard the ISS National Lab: Merck, Eli Lilly, and Novartis.
"We've had a long standing relationship with Merck," said Roberts. "They've had an interest since the shuttle flew... in utilizing that environment for protein crystal growth experiments. They've also engaged with CASIS more recently on expanding their research portfolio in microgravity... So in addition to their portfolio in drug discovery, they're actually interested in looking at drug efficacy in animal models."
Eli Lilly also has multiple ongoing collaborations with CASIS, seeking to use the National Lab as hub for understanding drug stability and creating more stable compounds effectively. Lilly is also actively trying to design a drug to combat the loss of bone mineral density by levying research projects on the ISS.
And then there's Novartis, which is using microgravity with the purpose of creating drugs for muscular atrophy—a condition that is significantly more accelerated in space. "We've flown two rodent research experiments from them," said Roberts. "They have several drugs in development that could benefit from a more fundamental understanding of the holistic effects of muscle atrophy in that environment."
The Swiss pharma giant has already completed two flight experiments using mice in an attempt to glean new pathways that may not have been previously explored.
But it's not just the pharmaceutical titans shuttling their research projects to the National Lab. The Boston-based startup Nanobiosym, a biotech focusing on nanotechnologies and genetic outcomes research (the company is also working on a finger-prick test for Ebola, among other things) was one of the winners of a "Galactic Grant" challenge to launch a project on the ISS. The company's goal is to use the setting to see whether or not its technology platform can predict the space into which microorganisms may evolve, including forming antibiotic resistance.
Other smaller biotechs are also conducting ISS-based research in order to take advantage of the absence of buoyancy-driven convection to better understand the physics of drug delivery with the goal of creating better and more precise methods of therapy administration.
The cost of going to the cosmos
If you're a life sciences enthusiast, chances are that all of this sounds irresistibly exciting. But you're probably also wondering: How do these companies, other than the largest biopharma firms, afford these projects?
"On the expense side, yes, it is an expensive and difficult proposition to do R&D in a space environment," admitted Roberts. "Even in low-Earth orbit, like in case of ISS, just a couple 100 miles above the Earth, it's extremely costly... Getting the science up and down is an expensive proposition. Logisitical support isn't cheap either."
Luckily for companies that are interested in microgravity research, CASIS is determined to help get deserving projects to the National Lab alongside other materials that must be shuttled back and forth between Earth and space. "What CASIS was created to do and what we actively do through our co-op agreement with NASA is provide access to that environment through subsidy," said Roberts.
"So, all the cost of the launch infrastructure, the ride up on the rocket, the return of samples or data, the cost of crew operations while on orbit—those are all sunk costs that come with the ISS, and they're not passed on to the investigator who designed a flight experiment. So even though it's prohibitively expensive currently to do that kind of R&D, costs aren't passed on to investigator or consumer."
For large companies, there is an upfront cost of R&D that must be provided, just as with research conducted on Earth. But CASIS doesn't limit itself to dealing with the wealthiest entities in the life sciences who can afford a trip to space.
"For the smaller companies, the more entrepreneurial outfits, we've been able to provide funding internally from CASIS and we've also partnered with large companies such as Boeing, and we have access to funding from some incubator programs that can provide matching funds for companies to have access to the ISS National Lab as a test environment.
"It's all driven by their R&D—if they see a benefit from use of that environment, it's our job to help provide them access to it and get up there."
An invitation from CASIS to the biopharma industry
Ultimately, Roberts has a simple message for biopharma and the life sciences: Come aboard.
"Although there are hurdles to doing research in space—it can be complicated, it can be expensive—none of that should preclude anyone from proposing their idea to go up to the station.
"I would simply emphasize: The ISS National Lab is open for everyone."