John Wyeth was born in Massachusetts in 1770. After apprenticing with a printer, he became manager of a printing company in Santo Domingo at the age of 21. He barely escaped the insurrection there with his life. In 1792, he returned to America, where he again became involved in publishing. He co-owned a newspaper in Harrisburg, Pennsylvania. In 1793, President George Washington appointed him postmaster, but five years later President John Adams declared the position to be incompatible with his involvement in newspapers.

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