SimGerm 1.0 is a simulation strategy game for high school students based on the human immune system. Although the simulation uses multiple learning strategies, the primary strategy is “learning by doing.” A player will be asked to make choices dependent upon the situation. Correctly identifying the problem and choosing the correct immune system cells at the appropriate time will lead to successful completion of the game. Otherwise, scaffolding mechanisms such as hints in the form of an agent provide the player opportunities to learn the material. The primary learning goals are to teach students the sequence of the immune system, to help students think about how the body defends itself from pathogens, and to teach them the different strategies that both the immune system and pathogens use against one another. The design process included interviewing game designers, consulting content experts in biology to ensure content validity, and user testing high school students to measure successful learning outcomes.