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During the early nineteenth century, men of science in the United States investigated the sexual fecundity of mixed-race women in their attempts to establish an empirically based theory of race. Although much has been written about this theory, known as polygenism, as the first "scientific" approach to race, less focus has been given to the role that the bodies and behaviors of mixed-race women played in this new science. Uncovering details of this nineteenth-century science of hybridity will allow scholars in American studies to locate the formation of the American secular biopolitical state within the economic and social institutions of chattel slavery. Specifically, when we recognize that polygenists set aside the authority of Scripture in their desire for an empirical approach to race, we see the beginnings of the biopolitical confidence that human sexual choices are the engineering mechanism of the racial composition of modern nation-states. By the early twentieth century this confidence prompted American elites to argue that nation-states have a duty to utilize scientific knowledge about human sexuality to control, manage, and define their racial outcomes. By centering the lives and experiences of mixed-race women, this essay goes beyond intellectual history in its analysis of the emergence of the biopolitical state in early American history.