Eli Lilly & Company is willing to go the extra mile for research and development—230 miles straight up, in fact—to the International Space Station (ISS). Eli Lilly scientists were among the first to mass-produce penicillin, the polio vaccine, and insulin, with the aim to save lives through research and quality control. Now, 140 years since its founding, this major pharmaceutical company is again breaking new ground with the launch of multiple experiments to the ISS. Why are they going so far? The stable, persistent microgravity environment on the ISS cannot be found on Earth. Eli Lilly is planning to conduct five experiments on the ISS U.S. National Laboratory over the next year; science conducted in space to make discoveries that will improve life on Earth. Three of the five experiments are launching on the SpaceX-8 mission: two performing the delicate process of protein crystal growth and one testing a new treatment for muscle wasting.
Protein Crystallography to Enable Structure-Based Drug Design, from Kristofer R. Gonzalez-DeWitt; and
The Effect of Microgravity on the Co-crystallization of a Membrane Protein with a Medically Relevant Compound, from Michael J. Hickey
The process of growing protein crystals is very specialized. Individual protein molecules must be coaxed to align uniformly into repeating patterns to form a 3-D crystallized structure. High-quality crystals are thus difficult to grow and can be extremely fragile. This is where space can provide an advantage. In a gravity environment, proteins often sediment out of a solution before they can properly align. Gravity is also responsible for convective forces, a type of fluid movement that further disrupts the crystallization process. By performing protein crystallization experiments in the functional absence of gravity on the ISS, Eli Lilly researchers are, in a way, hanging a “Do Not Disturb” sign—seeking to maximize the potential for high-quality crystal growth.
The usefulness of protein crystals to a pharmaceutical company such as Eli Lilly is in analyzing crystal structure—to gather clues about the unique features of the individual proteins. Scientists do this using “X-ray diffraction,” the same technique that famously revealed the structure of DNA. By determining the structure of a protein involved in disease, for example, one can see features that would be good target areas where new drugs might bind. Toward this end, Eli Lilly is specifically growing crystals of not only individual proteins, but also proteins bound together with potential drugs (a technique called “co-crystallization”). Results from the SpaceX-8 experiments could give the researchers a better understanding of the drug-protein interaction, allowing them to improve structure-based drug design efforts.
Assessment of Myostatin Inhibition to Prevent Skeletal Muscle Atrophy and Weakness in Mice Exposed to Long-Duration Spaceflight, from Dr. Rosamund Smith
In addition to exploring crystal growth in space for drug discovery, Eli Lilly is also tackling drug development from a different angle—seeking to improve treatments for muscle loss through spaceflight drug testing. Muscle “wasting” is a common disease of bed-ridden patients, such as those recovering from surgery, those with paralysis, the chronically ill, and the elderly. In many ways, microgravity mimics the effects of the immobility experienced by these patients. Moreover, muscle wasting on Earth is a slow process, but it occurs quickly in space because muscles are “unloaded” in microgravity and researchers can see effects much faster. This is true whether evaluating humans (to improve astronaut health for long-duration spaceflight) or animal models, such as rodents, worms, or flies. Animal models have been studied on Earth and in space for decades, but the ISS National Lab provides an opportunity for longer-term studies that have the potential to translate more quickly into applications to improve human health on Earth.
Humans have a naturally occurring regulator of muscle growth in our DNA: a gene called myostatin. From this gene, a protein is produced that binds to cells and signals muscle growth to stop. It may seem counterintuitive that our bodies would negatively regulate muscle growth, but muscle overgrowth can be unhealthy and a burden on the body’s systems. Interestingly, however, stopping this regulation by myostatin might represent an effective way to treat muscle wasting. The third Eli Lilly experiment on SpaceX-8 is assessing just that, by testing a drug that blocks the myostatin protein. By using this drug on rodents in space, researchers may be able to observe a fast-tracked model of whether this drug is protecting the animals from spaceflight-induced muscle loss. Back on Earth, Eli Lilly can use these observations to better understand the role of myostatin in muscle loss, the effectiveness of the drug, and the mechanisms of changing muscle mass and function in space—all to improve the quality of life on Earth.