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Pandem-Sim is a live, role-playing simulation (LRPS) for high school STEM education. Classrooms of students perform as research teams responding to incoming demographic and medical data from people sickened by an unidentified infectious disease. During the 90-minute simulation, students analyze realistic data to characterize and identify the responsible pathogen, and to recommend containment and treatment strategies. To stop the disease outbreak students must apply critical thinking to prior and newly-learned knowledge about biology and mathematics. Research and evaluation of 46 teachers and nearly 1100 students will determine the impact of this LRPS on content learning, scientific interest, and career motivation using a random block design experiment. As a videoconferenced experience, Pandem-Sim is immediately scalable for use anywhere in the world.