Beginning with leprosy, Foucault analyzes a complex series of themes. He attempts to show the position of madness before the classical period. He charts a series of intellectual changes and a reorganization of knowledge about madness. The Narrenschiff, or ship of fools, is a symbol of the changing status of madness, which is linked to a wider network of symbols. The fifteenth century book from which the Narrenschiff is drawn, written by Sebastian Brandt, mixes woodcut images of madness with text. Many readers have pointed out that this is Foucault's only source for the ship of fools; there is little evidence that the ship actually existed.

Writers before Foucault have discussed the great significance of death in European culture in the late middle ages. Churches and tombs had images of skeletons and of Death itself. Death was not marginalized, but existed at the heart of people's life. However, it was also something that was opposed to life. This is how Foucault can see madness as both replacing and resembling death. Madness resembled death because it was a frightening phenomenon that threatened life and reason. But it also replaced death as a concern because people's concerns changed.

Madness took up the role of death, but also became linked to the theme of apocalypse. The apocalypse was a Christian explanation of the end of the world and the second coming of Christ; it was an absolutely central idea in the Middle Ages and Renaissance. Foucault feels that madness was a way of expressing and locating concerns about the darker side of life and fear about the end of the world. These shifts in the cultural meaning of madness had an underlying structure. For Foucault, the relationship between language and madness is an important one. This period is one in which language and imagery changed. In Brandt's book, text and pictures were closely related. Writing about madness and seeing it were almost the same thing. Brandt's images cannot express or explain madness on their own, but in the Renaissance they slowly create their own freestanding representation of madness.

Foucault considers the development of the literary representation of madness by Shakespeare and Cervantes. Madness in King Lear and Don Quixote becomes a kind of ultimate limit. Being mad is the worst thing that can happen to anyone, partly because it destroys humanity. But Foucault recognizes that this is an image of madness that reverses and alters reality. It is a "trompe d'oeil" (French for an image that deceives the eye) because it misleads the audience about its essential truth.

All these themes and images slowly alter in the classical period. Madness no longer relates to the apocalypse or the limit of human experience; it also moves to the forefront of human consciousness. As it becomes the most important sin, it has a greater cultural role. A situation arises that gives the mad a kind of temporary respite. While madness is not the source of fear, it is located in the world and accepted by the majority of people. It can do this because its intellectual context had changed; certain cultural themes change, and madness changes with them. Perhaps the ultimate contrast in this book is between madness in the Renaissance and in the present day, where it is located and isolated within certain medical and psychiatric disciplines, and marginalized within the world. By drawing this contrast, Foucault is not claiming that the Renaissance had a "better" idea of madness, or that we should return to such a relatively tolerant attitude. Indeed, he would argue that such a return is absolutely impossible. What he wants to do is to make us consider the role of madness in the modern world, and stop believing that "modern" madness is the only form that insanity can take.

Foucault sees the physical disappearance of leprosy, and of leper houses, as just as important as the cultural changes he charts. A space opens up as leprosy vanishes. It is almost as if a permanent space exists in which certain people can be defined and excluded; when leprosy no longer fills this space, madness appears to occupy it. Madness did not exactly replace leprosy, but the shift between the two conditions represented a move from a concern with diseased bodies to a concern with abnormal behavior, and diseased minds. Foucault can be criticized for his analysis of leprosy, which did not vanish entirely. He frequently uses such flamboyant contrasts to point out the contrast between classical madness and its predecessors.

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