Space Is The New Frontier For Life Sciences Research
By Deborah Borfitz
September 16, 2019 | Advances in microfluidics, the shift from animal-based to cell-based models of drug research, and the ability to grow larger and more perfect protein crystals in microgravity have all helped propel space-based research into a thriving commercial enterprise. Numerous pharmaceutical companies—including Novartis, Merck and Eli Lily—have flown their research experiments to the International Space Station (ISS) National Laboratory, as have companies large and small with technologies for drug delivery and discovery.
So says Mike Roberts, Ph.D., deputy chief scientist for the nonprofit Center for the Advancement of Science in Space (CASIS), which has managed the ISS National Laboratory for the past eight years. The national laboratory, established by the 2005 NASA Authorization Act, has hosted well over 300 sponsored projects. In addition to ISS National Lab-sponsored research, the National Aeronautics and Space Administration (NASA) and international partner agencies sponsor research that focuses on the life sciences addressing crew performance and "making sure we as humans can live and work in space."
It has been known for some time that exposure to that environment has profound effects on physiology, Roberts says, only some of which resolve quickly when people return to earth. The musculoskeletal impacts are of concern to NASA and the National Institutes of Health (NIH) as well as pharmaceutical companies interested in testing therapeutics designed to treat musculoskeletal diseases such as osteoporosis.
Being in space "may change the balance of bone rebuilding and bone regeneration," Roberts explains. During long space missions, astronauts will typically lose 1%-2% of their bone mass per month if they don’t exercise and take medications to maintain bone density.
The same types of effects happen with muscle, he adds. "Crew members tend to use their legs less in microgravity and if they don't do resistive and aerobic exercise every day they would lose a significant amount of their muscle." The muscle loss can in some cases mimic conditions ranging from the normal aging process to muscle atrophy (cachexia) associated with cancer.
Several biomedical experiments are currently underway in space, Roberts says, including one sponsored by the ISS National Lab looking at the effects of microgravity on mice of different ages that neither have access to exercise equipment nor receive drugs to combat bone loss. Biospecimens from those animals will be made available to the research community in support of research and technology development.
To maximize the science impact, biospecimens from rodent reference missions typically go to research teams for sharing rather than a single investigator testing one hypothesis, says Roberts. Investigator proposals are reviewed not only for their scientific merit but also from the perspective of earthly benefit, meaning experiments related to one muscle group or a disease affecting a smaller segment of the population may not be as valuable as those focused on osteoporosis or cancer. Of the 30 or so requests that might come in for biospecimen sharing, about one-third are selected.
In addition to responding to research solicitations from CASIS (using the ISS National Laboratory name brand) and their partners at the NIH and the National Science Foundation (NSF), investigators can also submit a concept at any time on any topic, says Roberts. Provided it has a clearly defined scientific goal that can only be addressed in space, and benefits humanity, the ISS National Laboratory will partner with them to develop a proposal. Over 100 such proposals come in every year.
As with all missions to the orbiting laboratory, NASA covers the cost of getting experiments and cargo up to the space station and returning samples back, and the ISS National Laboratory has access to one-half of the up-mass, down-mass and crew's time, says Roberts.
Individual companies are typically responsible for all supplies and the cost of conducting the experiment at the space station, including the box in which the science makes the journey, Roberts says. Commercial implementation partner services may charge anywhere from $50,000 to $100,000 for a box housing protein crystal. A project requiring human cells that must be fed, kept warm and moved around could run half a million dollars.
Among the iconic Fortune 500 companies that have used the ISS National Laboratory, Novartis was the first on board with two different research missions, Roberts says. Eli Lilly has flown even more experiments to date, as has Merck—in addition to about a half dozen others with NASA’s space shuttle program before its 2011 conclusion. Amgen also flew a series of experiments on the space shuttle fleet and used the data to accelerate market approval of its osteoporosis drug Prolia.
Small startups have likewise been testing technologies at the ISS National Laboratory, says Roberts. For example, a principal investigator at Houston Methodist Hospital is conducting a series of experiments testing components of a nanochannel drug delivery device that can be implanted or placed on the skin for more reliable and consistent drug delivery. The investigator recently partnered with Novartis to test the drug delivery device in a rodent model of human disease. Another startup is interested in testing the capability of the device to deliver a therapeutic under development.
Merck has been focused primarily on protein crystal growth in microgravity to get better structural information both about therapeutic agents and targets, he says. In microgravity, molecules come together more slowly than on earth, resulting in higher quality crystals that can be brought back to earth. The technology has been used to study drugs for HIV, hepatitis C and cholesterol lowering.
A significant amount of work is happening at the ISS National Lab around tissue chip technologies facilitating high-throughput drug screening, via an ongoing partnership with the National Center for Advancing Translational Sciences (NCATS) at the NIH, says Roberts. The Defense Advanced Research Projects Agency (DARPA) is also investing significant sums on the technology, which will allow researchers to put human cells inside of a tiny device engineered to promote their growth in an environment replicating some aspects of the human body. In some instances, the microgravity environment induces the cells to behave much like tissues or entire organs on earth, he adds.
"It's not mature technology yet," Roberts says, "but if it pans out, that removes the need for animal-based models to test drugs and provides a far more reliable indicator of the safety, efficacy and side effects associated with drugs in human cells." Another advantage is that the tissue chips can be populated with an individual's own cells, making personalized responses to a drug or class of drugs possible.
The Massachusetts Institute of Technology (MIT) and Boston-based Emulate both recently sent up payloads to the space station as part of the NCATS tissue chips program, Roberts notes. MIT is developing an organ-on-a-chip system using human tissues to test the potential of osteoarthritis drugs to block the degradation of cartilage and bone, which accelerates in space.
Emulate has organ-on-chips technology to emulate human biology and response to chemicals and drugs, to help identify biology-driving mechanisms of diseases such as Alzheimer's, says Roberts. Its latest project at the ISS National Lab is a blood-brain barrier chip to better understand how the filtering mechanism functions in the human body. Removing the force of gravity makes it easier to pinpoint certain targets for opening the blood-brain barrier to get drugs through.
Since 2013, the ISS National Lab has partnered with Boeing to grant up to $500,000 each year toward innovative research through Boston's MassChallenge startup accelerator, Roberts says. Young companies around the country are thereby equipped with the tools and resources to foster their success. It's likely many of them never considered space a venue for product development, he adds.
LambdaVision, a small business startup based in Connecticut, was one Technology in Space award recipient, Roberts notes. The company is working on a thin, protein-based membrane that gets implanted behind the retina to replace the function of damaged cells.
The retinal implant is designed to help recover vision for patients who have lost their sight due to macular degeneration or retinitis pigmentosa, he says. Manufacturing it in space is expected to produce a more stable and homogenous product than is possible on earth.
Other MassChallenge awardees include companies looking at therapeutic agents for combatting cancer, those combining cancer-fighting drugs with molecules that increase their targeting efficiency, and others exploring innovative ways to prevent tumor growth. Many past awardees have conducted experiments at the ISS National Lab. These include LambdaVision as well as Angiex, based in Cambridge, Massachusetts, which is developing a cancer therapy.
Angiex has been looking at endothelial cells, which survive far longer in space than on the ground and inhabit every blood vessel in the body, Roberts says. They're being nurtured like miniature crew members in a biocell habitat at the ISS National Lab and treated with varying levels of a chemotherapy drug designed to stop tumor blood supply from growing.
"To me, those types of experiments demonstrate the value of a laboratory in space," says Roberts. "They show that [the ISS National Lab] is… not just about learning what we can in space because it's there but using it as a unique environment to challenge the approaches we've used for solving problems here on earth."
Cost is one of the major hurdles to conducting experiments in space. "It will always be more expensive to do research in a remote environment, especially a harsh environment like space where you're traveling around the earth at 17,500 miles an hour," Roberts says. The cost of getting the science to the space station and data and samples back is another barrier that has been addressed by subsidies and NASA's taxpayer-supported commercial cargo program. Research in space would otherwise be prohibitively expensive.
Roberts offered a ballpark estimate of the cost of a space experiment at a little over seven million dollars—considering the up-mass, down-mass, crew time and needed resupply services—although the actual cost can vary widely depending on the complexity of the experiment.
SpaceX and Northrup Grumman have also been reducing the cost of getting things into space and getting stuff back home, he adds. And late next year, the Sierra Nevada Corporation's new cargo spacecraft will make its first flight. Dream Chaser will have foldable wings, opening new possibilities for getting samples up to the ISS and returning them gently back to earth, Roberts says.
Another limitation, related to throughput, may not be addressable until animals are more the exception than the rule in preclinical studies, says Roberts. A pair of crew members are available for up to 100 hours of experiment time over six months—approximating what a dedicated graduate student might devote to a study over the course of one week.
Then there are the logistical constraints. Rockets are now heading to the ISS National Lab every three or four months, says Roberts, "but that still pales in comparison to what we can put on a cart and wheel to a laboratory down the hall from you."
Planning and Support
Between the ISS National Laboratory and NASA, plenty of resources are available to answer questions, guide study design and, in some cases, put co-investigators on experiments, says Roberts. Companies also have access to all the services and hardware they'd need to successfully conduct studies in a microgravity environment.
Protocols are necessarily different for research in space, says Roberts, where "fluids and gases don't go where you think they're going to go; heavy stuff doesn't settle down to the bottom and lighter stuff doesn't float up to the top." An animal model would require having hardware designed to provide food, water and otherwise meet the survival requirements of that organism, he adds. Cells, as well as animals, would need a properly maintained CO2 and pH environment.
Researchers can't control the g-force of a rocket launch, but they can get around the issue by keeping cells in a quiescent state (e.g., freeze them) for the ride up and perhaps sending only the data back home. Extra planning is also required to allow for replication of the experiment while in orbit, since human errors in implementing the protocol aren't always as easily correctable in space as in an earth-based laboratory.
Interest in sponsoring research in space is coming not just from life science companies but also the federal government via grants being awarded by the NIH and the NSF for projects addressing health issues of everyday Americans, says Roberts. In another five years, he predicts, more commercial providers will be joining NASA as drivers of exploration—building new platforms that may attach to the ISS or be separate "free flyers."