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St. Louis is the second-largest city in Missouri. It sits near the confluence of the Mississippi River, which forms the state border with Illinois, and the Missouri River. As of 2019, the city proper had an estimated population of around 300,000, while the bi-state metropolitan area had an estimated population of over 2.8 million, making it the largest metropolitan area in Missouri, the second-largest in Illinois, the seventh-largest in the Great Lakes Megalopolis, and the 22nd-largest in the United States.
Before European settlement, the area was a regional center of Native American Mississippian culture. St. Louis was founded on February 14, 1764 by French fur traders Gilbert Antoine de St. Maxent, Pierre Laclède and Auguste Chouteau, who named it for Louis IX of France. In 1764, following France's defeat in the Seven Years' War, the area was ceded to Spain. In 1800, it was retroceded to France, which sold it three years later to the United States as part of the Louisiana Purchase; the city was then the point of embarkation for the Corps of Discovery on the Lewis and Clark Expedition. In the 19th century, St. Louis became a major port on the Mississippi River; from 1870 until the 1920 census, it was the fourth-largest city in the country. It separated from St. Louis County in 1877, becoming an independent city and limiting its own political boundaries. St. Louis had a brief run as a world-class city in the early 20th century. In 1904, it hosted the Louisiana Purchase Exposition and the Summer Olympics.
A "Gamma" global city with a metropolitan GDP of more than $160 billion in 2017 metropolitan St. Louis has a diverse economy with strengths in the service, manufacturing, trade, transportation, and tourism industries. It is home to nine of the ten Fortune 500 companies based in Missouri. Major companies headquartered or with significant operations in the city include Ameren Corporation, Peabody Energy, Nestlé Purina PetCare, Anheuser-Busch, Wells Fargo Advisors, Stifel Financial, Spire, Inc., MilliporeSigma, FleishmanHillard, Square, Inc., U.S. Bank, Anthem BlueCross and Blue Shield, Federal Reserve Bank of St. Louis, U.S. Department of Agriculture, National Geospatial-Intelligence Agency, Centene Corporation, and Express Scripts.
Major research universities include Saint Louis University and Washington University in St. Louis. The Washington University Medical Center in the Central West End neighborhood hosts an agglomeration of medical and pharmaceutical institutions, including Barnes-Jewish Hospital.