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Lord Jeffrey Amherst ordered blankets contaminated from smallpox victims to be distributed in 1763 to the tribes surrounding the fort.

The disease spread into other areas, infected other tribes, and killed hundreds of thousands.

The French built Fort Duquesne based on La Salle's 1669 claims.

The French and Indian War, the North American front of the Seven Years' War, began with the future Pittsburgh as its center.

The city features 30 skyscrapers, two inclined railways, a pre-revolutionary fortification and the Point State Park at the confluence of the rivers.

The city developed as a vital link of the Atlantic coast and Midwest, as the mineral-rich Allegheny Mountains made the area coveted by the French and British empires, Virginians, Whiskey Rebels, and Civil War raiders.

On April 16, 1771, the city's first civilian local government was created as Pitt Township.

During Pontiac's Rebellion, native tribes conducted a siege of Fort Pitt for two months until Colonel Henry Bouquet relieved it after the Battle of Bushy Run.

Fort Pitt is notable as the site of an early use of smallpox for biological warfare.

During this period, the powerful nations of the Iroquois Confederacy, based in New York, had maintained control of much of the Ohio Valley as hunting grounds by right of conquest after defeating other tribes.

By the terms of the 1768 Treaty of Fort Stanwix, the Penns were allowed to purchase the modern region from the Iroquois.

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By 1815, Pittsburgh was producing significant quantities of iron, brass, tin, and glass.