In the fifteenth century, during which it broke out seventeen times in different places in Europe, it was of the more consequence to oppose a barrier to its entrance from Asia, Africa, and Greece (which had become Turkish); for it would have been difficult for it to maintain itself indigenously any longer. Among the southern commercial states, however, which were called on to make the greatest exertions to this end, it was principally Venice, formerly so severely attacked by the Black Plague, that put the necessary restraint upon perilous profits of the merchant. Until towards the end of the fifteenth century, the very considerable intercourse with the East was free and unimpeded. Ships of commercial cities had often brought over the plague: nay, the former irruption of the "Great Mortality" itself had been occasioned by navigators. For, as in the latter end of autumn, 1347, four ships full of plague-patients returned from the Levant to Genoa, the disease spread itself there with astonishing rapidity. On this account, in the following year, the Genoese forbade the entrance of suspected ships into their port. These sailed to Pisa and other cities on the coast, where already nature had made such mighty preparations for the reception of the Black Plague, and what we have already described took place in consequence. In the year 1485, when, among the cities of northern Italy, Milan especially felt the scourge of the plague, a special Council of Health, consisting of three nobles, was established at Venice, who probably tried everything in their power to prevent the entrance of this disease, and gradually called into activity all those regulations which have served in later times as a pattern for the other southern states of Europe. Their endeavours were, however, not crowned with complete success; on which account their powers were increased, in the year 1504, by granting them the right of life and death over those who violated the regulations. Bills of health were probably first introduced in the year 1527, during a fatal plague which visited Italy for five years (1525-30), and called forth redoubled caution.