Systems and methods for use in playing biotic games having a biologically active material as a component. Various games that provide for one or more human players to interact with biologically active materials are disclosed. The game apparatus includes a replaceable cartridge having a chamber in which a biologically active component such as a single-celled organism or a biologically active compound is contained. A stimulus controller accepts instructions from a human user and provides a stimulus to the biologically active component. A response receiver accepts a signal indicative of a response of the biologically active component. A display is provided to display to the user information indicative of the response of the biologically active component, and a game score. A computer-based game controller includes a set of pre-defined rules of play that define a game and that comprise pre-defined rules of scoring for the game.