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 Avignon, as private physician to three Popes in succession, and the numerous calls made upon him for professional advice and especially for surgical assistance by people living at a long distance from Lyons—compelled him repeatedly to absent himself from his home, sometimes for several days at a time. In 1348 the plague visited Avignon and carried off large numbers of people, the poet Petrarch's Laura being one of the victims. During that terrible epidemic Guy was most faithful in his devotion to Clement VI. and to many others who needed his professional services. In 1357 he was promoted by Innocent VI. to the office of Provost of Saint-Just. In 1363 when—according to, his own declaration—he was an old man, he wrote the treatise on surgery which has rendered his name famous in the history of medicine. His death occurred about July 23, 1368.

Guy was not, as some writers have asserted, a professor of surgery in the University of Montpellier; he was simply a physician who had won at that institution the title of "Master in Medicine"—the highest grade conferred by the university authorities, and one which necessarily implied that the recipient had given a certain number of public readings on medical topics. And yet in actual practice Guy manifested a strong preference for the management of diseases which demanded surgical treatment. His writings, furthermore, make it clear that he had a strong affection for the institution in which he had been both a student and in some measure an instructor.

The book which Guy de Chauliac wrote, and which bears the title "La Grande Chirurgie," is described by Malgaigne, one of the most distinguished French surgeons of the nineteenth century, in the following terms: "I do not hesitate to say that, with the single exception of the book written by Hippocrates, there is not a work on surgery, no matter in what language written, which ranks higher than, or is even equal to, the magnificent treatise of Guy de Chauliac." Although most surgeons of the present day will scarcely assent to praise of such an extravagant