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The versatile Williamson was born of Scotch-Irish descent at West Nottingham, PA., in 1735. He was the eldest son in a large family, whose head was a clothier. Hoping he would become a Presbyterian minister, his parents oriented his education toward that calling. After attending preparatory schools at New London Cross Roads, DE, and Newark, DE, he entered the first class of the College of Philadelphia (later part of the University of Pennsylvania) and took his degree in 1757.

The next 2 years, at Shippensburg, PA, Williamson spent settling his father's estate. Then training in Connecticut for the ministry, he soon became a licensed Presbyterian preacher but was never ordained. Around this time, he also took a position as professor of mathematics at his alma mater.

In 1764 Williamson abandoned these pursuits and studied medicine at Edinburgh, London, and Utrecht, eventually obtaining a degree from the University of Utrecht. Returning to Philadelphia, he began to practice but found it to be emotionally exhausting. His pursuit of scientific interests continued, and in 1768 he became a member of the American Philosophical Society. The next year, he served on a commission that observed the transits of Venus and Mercury. In 1771 he wrote An Essay on Comets, in which he advanced several original ideas. As a result, the University of Leyden awarded him an LL.D. degree.

In 1773, to raise money for an academy in Newark, DE., Williamson made a trip to the West Indies and then to Europe. Sailing from Boston, he saw the Tea Party and carried news of it to London. When the British Privy Council called on him to testify as to what he had seen, he warned the councilors that the colonies would rebel if the British did not change their policies. While in England, he struck up a close friendship with fellow-scientist Benjamin Franklin, and they cooperated in electrical experiments. Moreover, Williamson furnished to Franklin the letters of Massachusetts Royal Governor Thomas Hutchinson to his lieutenant governor that created a sensation and tended to further alienate the mother country and colonies.

In 1775 a pamphlet Williamson had written while in England, called The Plea of the Colonies, was published. It solicited the support of the English Whigs for the American cause. When the United States proclaimed their independence the next year, Williamson was in the Netherlands. He soon sailed back to the United States, settling first in Charleston, SC, and then in Edenton, NC. There, he prospered in a mercantile business that traded with the French West Indies and once again took up the practice of medicine.

Williamson applied for a medical post with the patriot forces, but found all such positions filled. The governor of North Carolina, however, soon called on his specialized skills, and he became surgeon-general of state troops. After the Battle of Camden, SC, he frequently crossed British lines to tend to the wounded. He also prevented sickness among the troops by paying close attention to food, clothing, shelter, and hygiene.

After the war, Williamson began his political career. In 1782 he was elected to the lower house of the state legislature and to the Continental Congress. Three years later, he left Congress and returned to his legislative seat. In 1786 he was chosen to represent his state at the Annapolis Convention but arrived too late to take part. The next year, he again served in Congress (1787-89) and was chosen as a delegate to the Constitutional Convention. Attending faithfully and demonstrating keen debating skill, he served on five committees, notably on the Committee on Postponed Matters, and played a significant part in the proceedings, particularly the major compromise on representation.

After the convention, Williamson worked for ratification of the Constitution in North Carolina. In 1788 he was chosen to settle outstanding accounts between the state and the federal government. The next year, he was elected to the first U.S. House of Representatives, where he served two terms. In 1789 he married Maria Apthorpe, who bore at least two sons.

In 1793 Williamson moved to New York City to facilitate his literary and philanthropic pursuits. Over the years, he published many political, educational, economic, historical, and scientific works, but the last earned him the most praise. The University of Leyden awarded him an honorary degree. In addition, he was an original trustee of the University of North Carolina and later held trusteeships at the College of Physicians and Surgeons and the University of the State of New York. He was also a founder of the Literary and Philosophical Society of New York and a prominent member of the New-York Historical Society.

In 1819, at the age of 83, Williamson died in New York City and was buried at Trinity Church.

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