From 1850 to 1853 he engaged with his brother in operating a steamboat line upon the Chagres River, Isthmus of Panama.
In 1863, he left the Cariboo and transported the coffin back by ship, crossing overland at the Isthmus of Panama, and eventually returned home where he had the coffin reburied.
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Sailing up the Mandingua River, the expedition crossed the Isthmus of Panama into the Pacific where they raided shipping for several months as well as looting and then burning the town of Chepo, Panama.
In July 1698 it launched its first expedition, led by William Paterson, who hoped to establish a colony in Darien (on the Isthmus of Panama), which could then be used as a trading point between Europe and the Far East.
He was detained after the wreck at St. Thomas, where he conceived the idea of a steamship line from New York to San Francisco via the isthmus of Panama, and wrote about his idea to the Philadelphia United States Gazette and the New York Courier and Enquirer.
In 1851, with Wells and others, he organized the firm of Wells Fargo & Company to conduct an express business between New York and San Francisco by way of the Isthmus of Panama and on the Pacific coast, where it long had a virtual monopoly.
He was consumptive and went to California by way of the isthmus of Panama, and died on his way from San Francisco to Honolulu, and was buried in the Pacific.