A number of philosophical societies were formed, which were centers of the city's intellectual life: the Philadelphia Society for Promoting Agriculture (1785), the Pennsylvania Society for the Encouragement of Manufactures and the Useful Arts (1787), the Academy of Natural Sciences (1812), and the Franklin Institute (1824).

These societies developed and financed new industries, attracting skilled and knowledgeable immigrants from Europe. The city remained the young nation's largest until the late 18th century, being both a financial and a cultural center for America.

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In 1638, Swedish settlers led by renegade Dutch established the colony of New Sweden at Fort Christina (present-day Wilmington, Delaware) and quickly spread out in the valley.

In 1644, New Sweden supported the Susquehannocks in their military defeat of the English colony of Maryland.

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The English conquered the New Netherland colony in 1664, though the situation did not change substantially until 1682 when the area was included in William Penn's charter for Pennsylvania.

In 1681, in partial repayment of a debt, Charles II of England granted Penn a charter for what would become the Pennsylvania colony.

Lenape communities were weakened by newly introduced diseases, mainly smallpox, and violent conflict with Europeans. Surviving Lenape moved west into the upper Ohio River basin.

The American Revolutionary War and United States' independence pushed them further west.

Despite the royal charter, Penn bought the land from the local Lenape to be on good terms with the Native Americans and ensure peace for his colony.