IU Researcher's Drug Quest Endures in War-Torn Kyiv

It was 3 a.m. when William L. Scott was awakened by the blaring air raid alert from his phone. Click. Silenced.

Amid a weeklong stay in Kyiv, Ukraine, Scott had gotten used to these alerts; they were part of daily life. But this one was different. The sounds Scott heard shortly after echoed with a sobering reality.

The idea of traveling into an active war zone would give many pause. The family of Scott, a professor of chemistry at the Indiana University School of Science at IU Indianapolis, had their reservations about him going. But to him, going to Ukraine presented the perfect opportunity to reinforce the idea of his Distributed Drug Discovery program, known as D3, operating without geographical or political constraints.

William L. Scott, left, is a research professor at the IU School of Science in Indianapolis. His focus areas include medicinal and organic chemistry. Photo courtesy of William L. Scott

Building a worldwide community

D3 gained its roots in February 2003 as Scott read the news of the ill-fated Columbia space shuttle disaster. Scott, who had recently transitioned to a faculty position at the School of Science from a pharmaceutical career at Eli Lilly and Company, thought about how the common goal of space exploration had brought together people across multiple specialized disciplines, and thus, D3 was born.

"I thought, why not, in an academic environment, make it one of our challenges?" he said. "Not outer space, but trying to find drugs for developing world diseases, neglected diseases and infectious diseases."

D3's goal is to accelerate drug discovery for developing and neglected diseases such as antibiotic-resistant bacteria or COVID-19, using low-cost equipment, essentially allowing anyone within the world of science and chemistry to perform affordable research. Supporting the equipment is a virtual molecular catalog of more than 70,000 easy-to-synthesize N-acyl unnatural amino acids, their methyl esters and primary amides.

With this effort in mind, Scott has established working relationships with academic institutions across the world, unifying scientists from different countries, cultures and backgrounds, all to speed up the drug discovery process.

Scott's D3 program has also taken him to Cuba, where he led a workshop for students at the University of Havana. Photo courtesy of William L. ScottThe program recently identified unnatural dipeptides with potent antimicrobial activity against Pseudomonas aeruginosa, a dangerous and highly resistant bacteria that exists in water, plants and soil. It also created molecules that inhibit Mpro, the main proteolytic enzyme required for the COVID-19 virus to replicate.

Efforts like these have not only benefited local and global communities, but they give IU students valuable research and development opportunities, opening the door to employment at global pharmaceutical companies.

While D3's mission has led Scott to several places in Europe, Africa and the Caribbean, it had never presented him with a 14-hour train ride, bunked in a sleeper cabin with two others, traveling into a country actively engaged in warfare.

Thriving through uncertainty

Twenty minutes after the air raid alert, Scott heard a sudden buzzing outside his window. This was quickly followed by a rhythmic thumping, a loud explosion and the sounds of metal tinkling onto the street below.

The likely culprit? A drone being struck down. But the fact that it happened right above his host's house served as a harsh reminder. And yet, the next morning, there was little to no evidence. Life moved along as normal.

Taras Shevchenko National University is the third oldest university in Ukraine. Photo courtesy of William L. Scott"In the morning, I didn't see any evidence of damage," Scott said. "Kids were outside with their backpacks, and their parents were with them, walking them to school. And it's like, when you put these two things together, I guess it was just a sign that people have to continue to lead their lives, and they're doing the best they can."

This sentiment - living an everyday life despite being under constant threat - was on full display at Taras Shevchenko National University, where Scott lectured for 10 days in late September.

The graduate and undergraduate students were attentive and actively engaged with Scott's lectures. Many showed him around Kyiv, as did his host, highlighting their favorite spots.

"That the teachers and students could carry on life and have somebody like me come over and help do lectures in a lab under the circumstances was really impressive," he said.

There was a slight language barrier, as expected, but he said it was hardly an issue. Plus, concepts in chemistry are universal, and the students' understanding of them played a crucial role.

"Chemistry is a very visual discipline in terms of how you talk about it," Scott said. "We draw structures, we draw arrows showing mechanisms, we show big collections of molecules. That's the universal language, and one that keeps us all on the same page."

Kyiv experience underscores D3's mission

In an odd, nearly fate-driven circumstance, Scott's tour of Kyiv placed him in the quiet confines of Baikove Cemetery, staring at a monument dedicated to Leonid Kadenyuk, the first astronaut of independent Ukraine to fly into outer space. In 1997, Kadenyuk flew on NASA's Columbia for mission STS-87.

Also listed on the monument was Kalpana Chawla, a fellow member of STS-87 and one of the seven astronauts who lost their lives upon Columbia's re-entry in 2003.

Reading Chawla's name brought Scott back to D3's origins, the places he's been, its purpose in uniting people across the world, and its growth in all the years that've followed.

"There were these things that weaved together and impacted me, and seeing Chawla's name on Kadenyuk's memorial was one of them," Scott said. "It made me reflect on the tension, in terms of bringing people together. But at the same time, there are things that can unite us.

"Hopefully the students - with the main goal of D3 being educating students across the world in drug discovery and chemistry - see that they're part of a bigger cause."