In the mid-seventeenth century theories of matter rested on one of two old schemes: Aristotle's four elements (earth, water, air, fire) or the Paracelsian three principles (sulphur, mercury, salt). Both were defended by interpretation rather than tested by experiment; the products a substance gave on burning were read as proof that it 'consisted of' those principles.

The Sceptical Chymist, published by Robert Boyle in 1661, is a critique cast as a dialogue. Its main argument is simple: the number of products separated from the same substance varies with the method used, so the fragments fire yields cannot be taken for a substance's true constituents. Boyle proposes instead an operational definition: an element is what cannot be broken into simpler substances by available methods. The definition is provisional — improve the methods and the list changes; Lavoisier's list in the eighteenth century was built on exactly this logic.

Boyle's second contribution is methodological. His experiments with the air pump developed with Hooke established the inverse relation between a gas's volume and its pressure (Boyle's law); more important still was that he wrote his reports in enough detail for others to repeat them and reported failed attempts too. As a founding fellow of the Royal Society he helped institutionalise the idea that knowledge is produced by witnessed, repeatable experiment. What is striking is that Boyle never abandoned alchemy: he believed in the transmutation of metals and worked on it all his life. Chemistry's separation from alchemy was not a moment of rupture but a slow change of criteria.