It is impossible to believe that Cantacuzenos from this time onwards did not realize the danger to which he had exposed the state and the noose into which he had put his neck. The papal archives and the writings of Cantacuzenos himself reveal the fact that as early as 1347 Cantacuzenos had appealed to the Pope to unite the western princes in a crusade against the Osmanlis,[201] that these negotiations were renewed in 1349[202] and 1350,[203] and that in 1353 a last definite appeal was made to Clement by Cantacuzenos for relief against those whom he had invited into Europe to fight his battles.[204] The five years between 1348 and 1353 gave rise to three events which were fatal to the Byzantine Empire. They made possible the permanent foothold of the Osmanlis in Europe. A man’s own efforts and a man’s ability are not the sole factors in his success. Work and genius avail nothing where opportunity is lacking. Circumstances over which he has no control contribute largely to the making of a man. Orkhan, at this culminating stage of his career, when he was ready to lead his people into the promised land, was aided by the ‘black death’, the war between Venice and Genoa, and the conflict between John Cantacuzenos and John Palaeologos. The ‘black death’ was first heard of in the Euxine ports. It reached Constantinople in 1347, and spread to Europe the following year. In Italy it was universal, and lasted three years. From 15 to 20 per cent. of the total population died.[205] In the maritime cities that had been in close contact with the East, the duration of the epidemic was longer and the mortality higher. The moral and economic effect was great throughout Europe. Men looked with horror upon this inexplicable malady, which struck down every fifth person. It gave no warning. There were few recoveries. For years after the last case was recorded there was nervous fear of its return. Communications with the Levant had been partially cut off.[206] Full intercourse was not resumed until after Orkhan and the Osmanlis were rooted in Macedonia and Thrace. Orkhan had no crusade to fear as long as there lingered in the minds of the European peoples the memory of this scourge. The bravest and most adventurous were unwilling to fight the angel of death. Plagues continued to visit the coast cities of the Balkan peninsula and Asia Minor from time to time during the rest of the fourteenth and the first thirty years of the fifteenth century. Between 1348 and 1431, nine great plagues are recorded.[207] These dates coincide with the most aggressive period of Ottoman conquest. As the city population was very largely Greek and Christian, we cannot over-estimate the importance of these epidemics. They were a valuable auxiliary in enabling the Osmanlis to advance and assimilate without formidable opposition.