Seward was born in on May 16, 1801, in the small community of Florida, New York, in Orange County. He was the fourth son of Samuel Sweezy Seward and his wife Mary (Jennings) Seward. Samuel Seward was a wealthy landowner and slaveholder in New York State; slavery was not fully abolished in the state until 1827. Florida was located some 60 miles (97 km) north of New York City, west of the Hudson River, and was a small rural village of perhaps a dozen homes.

Despite his public nonchalance, Seward was devastated by his convention loss, as were many of his supporters. The New Yorker was the best-known and most popular Republican, and his defeat shocked many in the North, who felt that Lincoln had been nominated through chicanery. Although Seward sent a letter stating Weed was not to blame, Seward's political manager took the defeat hard. Seward was initially inclined to retire from public life, but received many letters from supporters: distrustful of Lincoln, they urged Seward to remain involved in politics. On his way to Washington to return to Senate duties, he stopped in Albany to confer with Weed, who had gone to Lincoln's home in Springfield, Illinois to meet with the candidate, and had been very impressed at Lincoln's political understanding. At the Capitol, Seward received sympathy even from sectional foes such as Jefferson Davis.  Lincoln faced three major opponents. A split in the Democratic Party had led northerners to nominate Senator Douglas, while southerners chose Vice President John C. Breckinridge. The Constitutional Union Party, a new party consisting mostly of former Southern Whigs, selected former Tennessee senator John Bell. As Lincoln would not even be on the ballot in ten southern states, he needed to win almost every northern state to take the presidency. Douglas was said to be strong in Illinois and Indiana, and if he took those, the election might be thrown into the House of Representatives. Seward was urged to undertake a campaign tour of the Midwest in support of Lincoln and did so for five weeks in September and October, attracting huge crowds. He journeyed by rail and boat as far north as Saint Paul, Minnesota, into the border state of Missouri at St. Louis, and even to Kansas Territory, though it had no electoral votes to cast in the election. When the train passed through Springfield, Seward and Lincoln were introduced, with Lincoln appearing "embarrassed" and Seward "constrained". In his oratory, Seward spoke of the U.S. as a "tower of freedom", a Union that might even include Canada, Latin America, and Russian America.  New York was key to the election; a Lincoln loss there would deadlock the Electoral College. Soon after his return from his Midwest tour, Seward embarked on another, speaking to large crowds across the state of New York. At Weed's urging he went to New York City and gave a patriotic speech before a large crowd on November 3, only three days before the election. On Election Day, Lincoln carried most Northern states, while Breckinridge took the Deep South, Bell three border states, and Douglas won Missouri--the only state Seward campaigned in that Lincoln did not win. Lincoln was elected.

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Despite his public nonchalance, Seward was devastated by his convention loss, as were many of his supporters.