Dr. Larry DeLucas leads with what he’s most excited about — protein crystallography — casually neglecting to mention the fact that he’s been to outer space.
“My expertise is protein crystallography; I determine the structure of proteins,” DeLucas said. “From that, you can design small molecule drugs to interact with proteins and fight diseases.”
Of course, it was his work in protein crystallography that led him to become an astronaut in the first place. And, perhaps unsurprisingly, it is also protein crystallography that led DeLucas to Predictive Oncology, where he has become an integral part of the team’s mission to eliminate cancer as VP of Operations and President of the Predictive Oncology subsidiary Soluble Biotech.
Blasting off from the laboratory into outer space
DeLucas’s professional career has long focused on studying protein crystals, and he would go to any lengths to get the answers his work demands. That includes blasting off into space aboard the Columbia Space Shuttle in 1992.
“My career as an astronaut began because of a scientist that kind of showed me with a salt crystal they could grow a more perfectly formed one without gravity, DeLucas said. “Protein crystals also grow like small molecules, so we wanted to try and do this with protein crystals.
“Without gravity you can grow a more perfect crystal and after exposing the crystal to an X-ray beam, you are often able to see more detail in the structure, like small hydrogen atoms,” he explained. He immediately resolved to try and go to space to examine how protein crystals form in zero gravity.
After several failed application attempts, DeLucas was finally accepted by NASA to travel into space to conduct his experiment. He spent the next two years preparing for a scientific exploration journey. The trip included not only his experiment on protein crystallization, but more than 30 other research experiments that other astronauts would be performing.
For his experiment, DeLucas brought along 30 proteins. Based on experiments on Earth, he expected them to begin growing in 12 hours or less, but after a full 24 hours in space, there was nothing. Two days passed, then three, and DeLucas began to get worried.
“I thought it was going to be embarrassing!” he said. “But on the fourth day I could see little tiny sparkles and I knew they were growing.”
Through his research, DeLucas concluded that proteins grow more slowly in space. Those that would need only a few days to grow fully would require five to six weeks in space, he said. The result was unexpected, and a bit nerve-wracking, but well worth it. Although they took longer to grow, the crystals were indeed optimal for advancing his research — the same research that would lead him to work with Predictive Oncology to eliminate cancer.
“When you perform an experiment in space, it makes you think differently. As scientists always want a creative part of mindset,” DeLucas said. “Space really pushed me to do that and think about how to cope with a unique environment. That experience helped my career and helped me today to accomplish novel goals here with Predictive Oncology.”
A simple question leads to big answers
Despite his out of this world experience, DeLucas still describes his work in protein crystallography in simple terms, eschewing glamour for practicality. Although he has five degrees, including a Ph.D in biochemistry, and has published 164 peer-reviewed articles in his career, DeLucas boils it down to plain language.
“To determine the structure of a protein, you need it in high concentrations to crystallize,” he said. But, he explained, there’s just one problem with that: “If it’s not soluble or tends to aggregate at higher concentrations, it won’t produce a well-formed crystal thereby preventing you from determining the structure.”
Since outer space isn’t always a feasible option, growing optimal crystals on Earth remained a high priority; it was this simple issue that DeLucas set out to solve next. He figured that by improving the solubility and stability of the proteins he was working with, he’d be able to better study them. In his research, he came across substances known as “excipients.” These inactive substances effectively act as a medium or carrier for proteins, improving their solubility.
“We found these additives to stabilize proteins and solubilize them,” DeLucas said. “Most crystallographers today don’t know what excipients are, but we used them to improve the solubility of the proteins, which we were later able to crystallize.”
Of course, with every solution there comes a new problem. DeLucas noted that the process was labor intensive and required a trial and error approach to determine the right combination of proteins and excipients. That’s when a colleague introduced him to an automated process.
“A colleague of mine, Bill Wilson, who was chair of the Chemistry Department at Mississippi State University, developed a concept that would allow us to quickly analyze protein solubility in different solution conditions and formulations.”
Together, DeLucas, Wilson and DeLucas’ graduate student David Johnson, then developed a machine that would rapidly measure protein solubility. It was the tool DeLucas needed to streamline his work with the excipients. He was on track to create a pure crystal, he thought, and find a way to get a better-than-ever look at the structure of any given protein.
Tapping into the market opportunity of soluble proteins
What had started as a bid to better elucidate the structure of proteins had developed into a wholesale effort to improve drug discovery processes across the board. Solubility is not only important for the crystallization of proteins, but it is also critical for bioavailability of medications like vaccines and antibiotics.
“This technology was very useful for improving the crystals, but I also realized there was a commercial market in terms of protein therapeutics, doing things like solubilizing and stabilizing proteins like vaccines and antibodies,” DeLucas said.
The global protein therapeutics market is worth an estimated $290 billion dollars and DeLucas and team had discovered a way to anticipate the optimal combinations of proteins and excipients to create more soluble, stable and therefore, more effective drugs and vaccines. With this process, he said, they could expedite drug discovery and keep costs down, getting medications to clinical trials more quickly and helping the effective, safe ones reach patients sooner. It also enabled them to more efficiently study proteins that, while highly important, proved challenging and costly to research previously.
“The nice thing about this tech is that unlike what other companies use to determine protein interaction we can also use it for membrane proteins,” DeLucas said. “Membrane proteins represent about 60% to 70% of past drug targets, and 60% to 70% of future drug targets too.
“They’re important, but the difficulty is in getting them soluble,” he added. “The problem is you have to make up multiple solutions, make up a formulation with different concentrations of proteins, measure each one … it can take up to a half a day to determine for one condition.”
Soluble Biotech’s unique approach, which relies on a specialized chromatography column, enables analysts to determine the same information in just 30 minutes. This is made possible by an artificial intelligence (AI) neural network that is able to predict the optimal formulations for medications and vaccines. Human analysts can then validate the neural networks predictions, immediately narrowing down the potential combinations for optimally effective drug formulations.
“So we can provide our customers with the top five formulations for a given condition,” DeLucas said. “Through this process, any formulation that’s predicted will give good solubility, we evaluate it for stability. We give customers a stable formulation that provides maximum solubility.”
Leading Soluble Biotech into a cancer-free future
Under DeLucas’s leadership, Soluble Biotech has moved into a research park in Birmingham, Alabama and is constructing a Good Manufacturing Practices (GMP) facility to help support clients immediately enter their protein therapeutic into clinical trials, expediting the time it takes them to reach U.S. Food and Drug Administration (FDA) approval.
But Soluble Biotech is only one piece of the Predictive Oncology puzzle when it comes to eliminating cancer. Along with the teams at TumorGenesis and Helomics, the work at Soluble Biotech will be used to improve cancer drug discovery and optimize healthcare plans to improve treatment outcomes. Protein crystallography has already brought Larry DeLucas to space; next, it could help bring him and the team at Predictive Oncology to the cusp of eliminating cancer.
