Catholic theologians found René Descartes’ doubt in the existence of God too convincing to be resolved by his ontological argument. Others were left with a division of the world into two radically different substances of mind and matter, a dualism very difficult to resolve. Mind could be directly introspected, but it eluded science. Matter—by which Descartes meant insensible particles that had only size, shape, quantity, and mass (primary qualities)—was the ultimate subject of science.

Descartes believed that we know less about matter than mind. The question was, “How are mind and matter connected?” Descartes’ ideas of substance, his dualism, and the mind-body problem preoccupied his contemporaries and successors. Benedict de Spinoza (1632–1677) reacted with a dual-aspect theory of God and nature. Nicolas Malebranche (1638–1715) tried to answer the question of how mind and matter were connected, with his theory of occasionalism. Gottfried Leibniz (1646–1716) also had a version of occasionalism in his theory of pre-established harmony. On the empiricist side, Thomas Hobbes (1588–1679) insisted on the nonexistence of anything nonmaterial and John Locke (1632–1704) directly attacked Descartes’ idea of substance.

Descartes thought that substance was what held matter together and what held mind together, even though substance could not be experienced directly. According to Descartes all physical things were material substance and all mental things immaterial substance.