“Scott, have I seen you outside of the lab, ever?”

Dr. Sarah Comstock, Assistant Professor of Science, asks Scott DongYoung Kum. Scott is a health science student at Corban, and last spring he spent most of his time in the lab working with visiting professor Dr. Tak Suyama on a natural product synthesis. But the hours of work finally paid off. Scott and Dr. Suyama have successfully found a more expedient way to produce the naturally occurring product pentabromopseudilin (PBP), and they recently had their work published in a peer-reviewed scientific publication.

Scott and Dr. Suyama’s research is significant for a number of reasons. Not only have they succeeded in shortening a chemical process by four steps (which is a lot, in organic chemistry), but even more significant, Scott is only an undergraduate. “A lot of times, undergraduate students get overlooked,” Dr. Comstock explains, “or we get to teach them in a classroom, but they don’t get to participate in the actual projects and real science. So it’s pretty cool that Dr. Suyama would involve students in something that he’s interested in.”

As Scott describes his role in the process, it becomes clear just how labor-intensive research can be. “Most of my responsibility was to set up the reactions: mixing the chemicals together, purifying them, actually seeing how it works.” Depending on which aspect of the synthesis they were working on at the time, Scott would spend up to 20 or 30 hours a week in the lab—all for a single research credit. But the value of the hands-on experience he gained made the hours of work worthwhile.

What, exactly, were Scott and Dr. Suyama working on?

Their research centered around natural product synthesis—or, in the simplest terms, drug development. Dr. Suyama explains that many of the drugs on the market today are actually derived from or inspired by compounds produced in nature. While some drugs are taken directly from nature, others are synthesized, meaning they are created in the lab in a way that mimics biological processes. This is called natural product synthesis.

“The goal of natural product synthesis, as its name suggests, is to prepare or ‘synthesize’ a chemical that is identical to one produced in nature,” Dr. Comstock explains. Natural product synthesis is an essential aspect of drug development, because while many natural products are effective against diseases, they are often too difficult to extract from nature in large enough quantities to be useful. The natural product that Dr. Suyama and Scott succeeded in synthesizing, PBP, occurs in a specific type of marine bacteria and has significant anti-microbial properties—so significant that PBP (or a closely related compound) might be effective against MRSA (Methicillin-resistant Staphylococcus aureus)—which is resistant to many other antibiotics.

Although scientists have known about PBP for several decades, Dr. Suyama observes that “there hasn’t been really active effort to develop PBP into drugs, for a couple of reasons.” First, obtaining the product from the marine organism itself is difficult, and PBP is “hard to isolate in a large enough quantity for clinical studies.” Second, while scientists have discovered how to synthesize PBP in a lab, the shortest synthesis—up until now—required six steps, or six separate chemical reactions. But in the course of their research, Scott and Dr. Suyama have discovered a way to synthesize PBP in a more expedient way than ever before: in only two steps. With the discovery of a shorter synthesis, Scott explains, PBP (and a closely related tricycline compound) could now be produced on a large enough scale to begin testing on mice and eventually humans.

What have been some of the biggest challenges?

Dr. Suyama and Scott’s task was far from easy. Because they were conducting research at a smaller university, their resources on campus were fairly limited. Dr. Suyama and Scott often had to rely on innovative and “scrappy” solutions to problems. For example, Dr. Comstock describes how, to create a low-oxygen environment, they ended up using a yellow balloon hooked up to a syringe and filled with nitrogen. Often, because they lacked some of the tools and equipment found in larger labs, they found themselves using more classic methods of analysis. For example, Dr. Suyama explains that they had to rely heavily on TLC, or thin-layer chromatography, a method that dates back to the 1930s and 40s. But using more classic methods turned out to be exciting more than frustrating. “Some of those really classical analyses, I thought that those were only for the people in textbooks,” Dr. Suyama laughs. “I never thought I’d have to do that myself.” He speaks with awe and enthusiasm. Rather than frustration at the lack of resources, he exhibits a love of problem-solving and a deep respect for the scientists who came before him.

While working in the lab of a smaller institution requires an extra level of creativity and resourcefulness, it comes with unique advantages as well. Dr. Suyama explains that a small academic institution like Corban often has more freedom than bigger institutions to pursue research interests beyond what is easily fundable. “There tends to be a lot of money in diabetic stuff,” Dr. Suyama explains, “a lot of money in anti-cancer drug research, because patients usually have to take those drugs for so long that there’s a lot of money to be made,” and thus more money available for research grants. He explains that funding for antibacterial drug development is harder to come by, so many bigger institutions avoid it. “I think what’s nice about this kind of small-scale academia research is that we’re not bound by what is very fundable and what actually makes money for pharmaceutical companies.”

What was involved in the publication process?

After succeeding in reducing a six-step process to two, Scott and Dr. Suyama’s next step was to get their work published. Dr. Suyama explains that, in order to have your work accepted by a peer-reviewed journal, “there has to be significant original research.” In other words, you have to be able to articulate that you have accomplished something new and show that it will provide significant benefit to society or lay important groundwork for other chemists. In addition to establishing that a discovery is novel and significant, “you have to meticulously analyze and prove the structure of chemicals you’ve made.” Dr. Suyama and Scott, along with a few other researchers whose help had been instrumental in their work, submitted their manuscript to the peer-reviewed journal Tetrahedron Letters, which accepted their research for publication in the August issue.

In addition to the opportunity to have his name in Tetrahedron Letters, Scott has gained invaluable experience that will translate directly to his future career. “It has really been a great experience for me to actually go hands-on,” he reflects, “because this is also the career I’m pursuing. I’ve always wanted to do pharmacology, or something related to drug-making.” He adds, “It’s been really eye-opening for me to see how this process actually works.”

Dr. Comstock expresses how much she’s seen Scott mature as a scientist over the past semester. He’s “applying what he’s learning in his classes and actually understanding it at a higher level, rather than memorizing a series of chemical reactions.” It’s one thing to learn how to be a student, to do simulated or pre-packaged labs; it’s another thing entirely to learn how to be a scientist, to work on something that has real-world significance, but also requires hours of hard work and repetition. Scott has learned what being a scientist actually looks like, which means contributing something novel and significant to society—but which also means spending hours and hours in a lab.

 

View Dr. Suyama and Scott Kum’s full manuscript in Tetrahedron Letters.