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Born at Fawsley in Northamptonshire, Wilkins was educated at Oxford University, graduating in 1631. He was a parliamentarian during the English Civil War and became warden of Wadham College, Oxford University. In 1659 he was appointed master of Trinity College, Cambridge University. After the Restoration he lost his post but regained favor to become bishop of Chester.

Wilkins's chief contribution to the development of science was his part in founding the Royal Society. His influence can be traced back to his student days at Oxford when he collected around him a lively group of philosophers and scientists who later became founder members of the society in 1662. His own writings covered a wide range of fields and although he had a certain amount of mathematical knowledge he was more a practical scientist. His Discovery of a World in the Moon (1638) is a fantasy in which he speculated about the structure of the Moon. A later semimathematical work, Mathematical Magick, deals with the principles of machine design and in it Wilkins argued that perpetual motion is a theoretical possibility. One nonscientific interest to which Wilkins devoted much time was his project of devising a universal language.