Previous discussions of the origins of writing in the Ancient Near East have not incorporated the neuroscience of literacy, which suggests that when southern Mesopotamians wrote marks on clay in the late fourth millennium, they inadvertently reorganized their neural activity, a factor in manipulating the writing system to reflect language, yielding literacy through a combination of neurofunctional change and increased script fidelity to language. Such a development appears to take place only with a sufficient demand for writing and reading, such as that posed by a state-level bureaucracy; the use of a material with suitable characteristics; and the production of marks that are conventionalized, handwritten, simple and non-numerical. From the perspective of Material Engagement Theory (MET), writing and reading represent the interactivity of bodies, materiality and brains: movements of hands, arms and eyes; clay and the implements used to mark it and form characters; and vision, motor planning, object recognition and language. Literacy is a cognitive change that emerges from and depends upon the nexus of interactivity of the components.