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James Duff Duff was born on 20 November 1860 in Alvah, Banff, Scotland, son of James Duff (1828-1898), a retired colonel of the 74th Highlanders, and Jane Bracken Dunlop (1829-1919). He and his twin brother Alan Colquhoun Duff (1860-1897, of the Indian Civil Service) were among the first pupils at Fettes College, Edinburgh. J. D. Duff came as a scholar to Trinity in Michaelmas 1878, was awarded the Porson Prize in 1881 and took a first in the Classical Tripos in 1882. Elected a Fellow in 1883, and later a College Lecturer, he remained in Cambridge for the rest of his life, also teaching at Girton College. He edited Lucretius, but is perhaps best known for his work on 'Silver Latin' writers such as Juvenal, Pliny and Seneca. Having taught himself Russian in order to read the novels of Tolstoy and especially Turgenev, which he had much admired in French translation, in their original language, from 1917 on he published several translations from Russian. These included works by Lermontov, Aksakov and Tolstoy. He never visited Russia, but corresponded in Russian with friends such as Alexandra Grigorievna Pashkova, the wife of a Russian landowner, whose two sons were Trinity undergraduates.

In 1890 Duff proposed marriage to Laura Eleanor Lenox-Conyngham (1871-1956), daughter of Sir William Lenox-Conyngham of Springhill, co. Londonderry, but then suffered a nervous collapse and put himself under the care of the eminent psychiatrist George Henry Savage (1842-1921) . His friends and fellow members of the Apostles Society, Henry Babington Smith and Arthur Clough, took him to Italy and Switzerland to nurse him back to health. On his return to England, Duff broke off the engagement and returned to his duties at Trinity, but they eventually married in December 1895 and had five children: Lieutenant-General Alan Colquhoun Duff (1896-1973) who published novels under the pseudonym Hugh Imber; Sir James Fitzjames Duff (1898-1970), educationist and academic administrator; Patrick William Duff (1901-1991), Regius Professor of Civil Law at Trinity College, Cambridge; Mary Geraldine Duff (1904-1995), principal at Norwich Training College, Norwich; and Hester Laura Elisabeth Duff (1912-2001). He died at his home in Cambridge on 25 April 1940, aged seventy-nine.