He was the son of missionary William Milne, was one of the twins born on a ship on voyage from Canton to Malacca.
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On July 29, 1839, he left for China, accompanied by James Legge and Dr. Benjamin Hobson;they landed in Macao on December 18.
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Medhurst was ordained at Malacca in 1819, and engaged in missionary labours, first at Penang, then at Batavia - and finally, when peace was concluded with China in 1842, at Shanghai where he founded the London Missionary Society Press (墨海書館) together with William Muirhead, Joseph Edkins, and William Charles Milne.