Problem-based learning (PBL) fosters both content knowledge and content understanding, improves critical and process thinking skills, and promotes peer-to-peer learning, leadership, and teamwork (Hmelo-Silver 2004). Instructors support the PBL process by guiding students through activities that challenge their current knowledge and understanding of a topic (Hung 2011). In the activity presented in this article, the authors pair the PBL approach with an emphasis on argumentation to investigate transcription, translation, and protein folding by comparing normal hemoglobin with sickle-cell hemoglobin.