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UNC MEDICAL BULLETIN
“When Bret joined the lab, I didn’t tell him right away why I was so interested in this project,” Redinbo explains. “Students work very hard, and I don’t want to make them anxious about whether or not an experiment would work.” When the research results showed promise, Redinbo sat down with Wallace and shared his story. “I listened to Matt’s story and then told him I had a personal story to tell him about why I wanted to work on this project. I hadn’t said anything earlier because I didn’t want him to think I was interested only because of my personal connection,” says Wallace. Redinbo says he was stunned when he heard Bret’s story. “The odds are incredibly small, of two people coming together from different backgrounds, with the same personal experience with someone they knew, and then having the opportunity to address scientifically that side effect,“ says Redinbo. Redinbo’s interest in science came early. He remembers hiding in the cloakroom in second grade, reading the eighth grade science textbook and being fascinated. “I wanted to know how do bacteria behave? How do human cells behave?” He also cites the influence of a song by Lou Reed titled “Sword of Damocles,” that Reed wrote after losing a friend to cancer. The lyrics say, “The Sword of Damocles is right above your head/they’re trying a new treatment to get you out of bed/but radiation kills both bad and good/it cannot differentiate/so to cure you they must kill you.” Redinbo, then at UCLA, remembers, “As a graduate student, I was thinking about focusing on cancer, and this song really addresses a key question in cancer research: how do you just kill the cells that you want to kill but not the others?” In fact, as a postdoctoral fellow he began work on the class of drugs that includes CPT-11, studying the drug’s mechanism and effect on intestinal bacteria. Wallace’s path to science was a childhood preference. “I can’t really say there was one defining moment that led me down the path to science, but probably a number of things that simply further piqued my interest. There were two excellent high school science teachers who really got me into chemistry. In college, I had great professors, one with whom I completed my undergraduate research in biophysical chemistry and properties of DNA. Whenever any of these teachers talked about science, they sounded excited and genuinely interested in whatever they were discussing; their enthusiasm was contagious, and I always feel the same way whenever I discuss science. My experience with Stacey helped direct my interests into the biological sciences and cancer research.” Wallace says, “Most people don’t associate scientists
Toxicity of the anticancer drug CPT-11 is alleviated by inhibiting a specific enzyme (pictured here in purple and blue) in human symbiotic gastrointestinal bacteria. Redinbo and Wallace identified compounds (yellow) that target and bind to the enzyme, blocking the reaction that leads to the drug’s debilitating side effects. (Credit: Bret D. Wallace and Matthew R. Redinbo, UNC-Chapel Hill.)
with personal or emotional stories. They think we’re doing the science, but that we don’t connect with the personal stories that go with it.” Redinbo explains, “Emotion is one of your best friends as a scientist, but it can be a big impediment as well. As a scientist you have to be highly rational and highly critical.” They engaged in more than the usual scientific rigor with the CPT-11 research. It charged their science and motivated their careful review of data and results. Redinbo concludes, “The personal interest did have an impact on the research. It caused us to really focus because in talking with Lisa Benkowski, I knew just how acute this side effect was, and Bret knew from talking with Stacey Micoli.” Their personal commitment led to peer-reviewed, published results that point in a promising direction. Dr. Richard Goldberg, UNC Lineberger associate director and physician in chief of the NC Cancer Hospital and an international expert in colon cancer, said, “The research that Dr Redinbo and his colleagues conducted to identify this compound and test it in a pre-clinical model is very promising, and this agent should be considered for human testing. The clinical problem is common enough that this could make a real difference to the care of many patients.”