The GREAT LAKES SCIENCE CENTER, located at 601 Erieside Avenue, opened in July of 1996 in the North Coast Harbor district of Cleveland's lakefront. (See also: ROCK AND ROLL HALL OF FAME AND MUSEUM and CLEVELAND BROWNS STADIUM.) The center grew out of a mid-1980s proposal to establish a Great Lakes maritime museum on the lakefront, a plan spearheaded initially by the GREAT LAKES HISTORICAL SOCIETY and several faculty members of CLEVELAND STATE UNIVERSITY. By 1990, when a planning board was organized, the project had taken on the more ambitious form of a $55 million interactive education center dedicated to "the environment, science, and technology of the Great Lakes Region." Major donors over the following six years of planning and construction included the GEORGE GUND FOUNDATION, CLEVELAND CLINIC FOUNDATION, Ford Motor Company, BP Amoco, Society Bank, Ameritech, and TRW. The building itself was designed by Boston museum architect E. Verner Johnson. Upon opening, the center featured roughly 350 science exhibits and activities organized into three floors, each dedicated to one of its educational themes (environment, science and technology), as well as an Omnimax wide-screen movie theatre.

In its first two years of operation the center drew over one million visitors, including many Cleveland area school groups. In 1998, the Board initiated a $12.5 million endowment, receiving its principal funding from the George Gund Foundation. Touring exhibitions such as Robot Zoo (2001) and Titanic (2002), in combination with Omnimax theatre attendance, sustained the center's relatively profitable operations into the mid-2000s. In 2004, founding President and Executive Director Richard Coyne retired and was succeeded by Linda Abraham-Silver. Under Abraham-Silver, the Board announced plans to increase the center's educational programming and develop stronger ties with local schools.

In 2005, as part of Cleveland's lakefront development plan, the STEAMSHIP WILLIAM G. MATHER MUSEUM was relocated to a neighboring spot at Dock 32 from its former docking place at the East 9th Street Pier. The move allowed the center to share ticketing, educational programs, and parking with the Mather. The following year, the Harbor Heritage Society, which owned and operated the Mather, donated the museum to the center, and plans were made for an all-weather connector to be built between the two facilities. That same year, a 150-foot-tall wind turbine was erected on the center's front lawn to demonstrate renewable energy.

In 2007, Abraham-Silver continued in her position as President and Executive Director.

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