This pedagogical article discusses sources and methods for teaching the history of imperial science and medicine in the Nahua world from 1400 to 1600, a period that ranges from the spectacular growth of the Aztec Empire through the conquest to the creation of New Spain. By providing students tools to explore non-European ontologies and world-building, this article presents several exercises in which students act as archival researchers and themselves puzzle out the complexities of information transfer in the archive of sixteenth-century Latin America. Combining European paleography workshops, linguistic tools pioneered by the IDIEZ Nahuatl program, the study of Mesoamerican archeological objects, and an engagement with Mexican medicinal plants to recreate early modern remedies, students gain access to a world of New Spanish knowledge-creation.

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