St. Louis developed as a major port on the Mississippi River, and by 1904, it was the fourth-largest city in the country. The city is home to sixteen Fortune 1000 companies, six of which are also Fortune 500 companies, including Centene Corporation, Reinsurance Group of America, Emerson Electric, Edward Jones, Graybar Electric, and Ameren. Major corporations headquartered in the region include Anheuser-Busch, Bunge Global, Wells Fargo Advisors, Enterprise Holdings, and World Wide Technology. The Federal Reserve Bank of St. Louis is one of two federal reserve banks in Missouri. The city is a center of medicine and biotechnology, with the Washington University School of Medicine affiliated with Barnes-Jewish Hospital, the fifth largest hospital in the world. The McDonnell Genome Institute at Washington University played a major role in the Human Genome Project. The Cortex Innovation Community, founded in 2002, has become a multi-billion dollar economic engine for the region, with companies such as Microsoft and Boeing currently leasing office space. The city's economy has strengths in the service, manufacturing, trade, transportation, and aviation industries. The St. Louis Rams of the National Football League controversially returned to Los Angeles in 2016, and the city sued the NFL in 2017, alleging the league breached its own relocation guidelines to profit at the expense of the city. In 2021, the NFL and Rams owner Stan Kroenke agreed to settle out of court with the city for $790 million.