Luzzatti was born of Jewish parents in Venice on 11 March 1841. After completing his studies in law at the University of Padua, he attracted the attention of the Austrian police by his lectures on political economy, and was obliged to emigrate after starting a mutual aid society among gondoliers. In 1863 he obtained a professorship at the Milan Technical Institute; in 1867 he was appointed professor of constitutional law at Padua, whence he was transferred to the University of Rome. Gifted with eloquence and energy, he popularized the economic ideas of Franz Hermann Schulze-Delitzsch in Italy, worked for the establishment of a commercial college at Venice, and contributed to the spread of people's banks on a basis of limited liability throughout the country.

He was minister of agriculture in the second Sonnino Cabinet (December 2, 1909 - March 21, 1910), and on the resignation of the latter was called upon to form a cabinet himself. His administration, which lasted until March 18, 1911, was not very successful and fell over a proposed electoral reform. Although a man of first-class financial ability, great honesty and wide culture, he had not the strength of character necessary to lead a government: he showed lack of energy in dealing with opposition and tried to avoid all measures likely to make him unpopular. Furthermore, he never realized that with the chamber, as it was then constituted, he only held office at Giolitti's good pleasure.  During the First World War, he was consistently pro-Ally and strongly supported Italian intervention, but his tone was on the whole pessimistic. Although he did not take office while the war lasted, he was always consulted on all financial matters, and his sound advice was generally followed.  He became treasury minister in the second incarnation of the Nitti cabinet (March 12 - May 10, 1920), but did not resume office in the third. At the general elections of May 1921, he decided not to stand for parliament again, and was made a senator. In spite of his advanced age, he continued to write on economic and financial problems with his accustomed lucidity and soundness of judgment, insisting on the necessity for Italy to return to free trade and to reduce government interference in business matters to a minimum.

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