“The more comfortable we become with being stupid, the deeper we will wade into the unknown and the more likely we are to make big discoveries,” wrote Martin A. Schwartz, Ph.D., in his popular essay The Importance of Stupidity in Scientific Research. Cancer researcher Ross B. Mikkelsen, Ph.D., member of the Radiation Biology and Oncology research program at VCU Massey Cancer Center, shares this sentiment with his students. He says, “researchers aren’t stupid because we make stupid mistakes, but because we don’t know what’s on the other side of an experiment. On the other hand, when you do find out what’s on the other side, you get a high that you can’t beat.”
Mikkelsen, professor and division chair of Molecular Radiobiology and Targeted Imaging in the Department of Radiation Oncology and associate director for the M.D./Ph.D. program at VCU School of Medicine, joined VCU over 25 years ago, only a year after the Department of Radiation Oncology was established. “I’m the oldest man in the department,” he says with a laugh. Before coming to VCU to conduct cancer research at Massey, Mikkelsen was studying another well-known illness, malaria, at Tufts University School of Medicine.
Mikkelsen’s lab currently conducts experiments aimed at gaining a better understanding of the underlying mechanisms of how tumor cells and normal cells respond to radiation. “The idea of my research is to increase the so-called ‘therapeutic ratio,’ or the act of increasing the number of tumor cells killed while decreasing the amount of toxicity to normal, healthy cells,” he says.
His research focuses on nitric oxide synthases (NOSs). Nitric oxide (NO) is a molecule that our body produces to help cells communicate with each other by transmitting signals throughout the body. Normal cells create NO, but it is potentially lethal to cancer cells. NOSs are a family of enzymes that foster the production of NO. So, Mikkelsen modifies NOS activities to kill cancer cells without harming the normal cells. “We are combining this research with radiation therapy in an effort to make the treatment more effective and safe,” he explains.
Mikkelsen has a 25-year record of funding from the National Institutes of Health to support his research, and his studies have been published in more than 30 academic journals. He has served as co-chairman for the Physical Imaging Review Panel for the Department of Defense Prostate Cancer Program and as member of many initiatives led by the National Cancer Institute and National Institute of Allergy and Infectious Diseases.
Moving forward, Mikkelsen predicts that the future of radiation therapy is in imaging and focused treatment. “Imaging is becoming so advanced, and in radiotherapy, we are getting really good at being able to focus the doses of radiation into the tumor site while minimizing the amount of normal tissue toxicity. We are very fortunate to have excellent small animal imaging facilities here at Massey for our research,” he says.
When Mikkelsen is not working away in the lab, he is shaping the minds of future cancer researchers. “I’ve worked with middle-schoolers—all the way up to my M.D./Ph.D. students,” he says. “Their excitement is infectious.” He recently worked with a 14-year-old, who, despite never having taken a high school chemistry class, was able to learn from Mikkelsen’s team and go on to win awards for his research. But, Mikkelsen says that his work is not all fun and awards. “I think a lot of students get discouraged because our work is so difficult. Unlike some other research where you know what the answer is and you’re working towards it; in basic science, you truly don’t know the answer. You have to keep your excitement going; otherwise, you won’t succeed.”
That enthusiasm has helped keep Mikkelsen succeeding for over 35 years. “Even after all this time, I still get excited about a new finding—just as my students do,” he says.