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Annie Glenn (class of 1941), civic leader; wife of John Glenn (Government and politics)
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John Glenn (class of 1942), former astronaut, Democratic U.S. Senator from Ohio (1975-1999), candidate for 1984 Democratic presidential nomination (Government and politics)
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President Warren G. Harding (via Muskingum's assumption of Ohio Central College) (Government and politics)
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Earl R. Lewis (class of 1911), former Republican U.S. Representative from Ohio, 1939–40 and 1943–48 (Government and politics)
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Sean Logan (class of 1988), current Director of the Ohio Department of Natural Resources; former Columbiana County, Ohio Commissioner (Government and politics)
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Francis Scott McBride (class of 1895), leader of prohibition; longtime National Superintendent of the U.S. Anti-Saloon League (Government and politics)
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John Willis Menard (via Iberia College and Ohio Central College), first African-American to address the U.S. House of Representatives, in 1869 (Government and politics)
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C. Ellis Moore (class of 1907), Republican U.S. Representative from Ohio, 1919-1933 (Government and politics)
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Charles J. Pilliod, Jr. (class of 1941), United States Ambassador to Mexico, 1986-1989 (Government and politics)
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Robert T. Secrest (class of 1926), Democratic U.S. Representative from Ohio, 1933-1967 (Government and politics)
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Wilbur F. Simlik (class of 1943), Major general in the Marine Corps (Government and politics)
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Robert M. Warner (class of 1949), sixth Archivist of the United States (Government and politics)
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Jack Hanna (class of 1969), former Columbus Zoo and Aquarium director; television personality (Entertainment)
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Agnes Moorehead (class of 1923), Emmy Award-winning actress (Bewitched); member of the Delta Gamma Theta Sorority (Entertainment)
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David Budbill (class of 1962), poet, author and playwright (Arts)
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Laurence Overmire (valedictorian, class of 1979), poet, author, actor, playwright (Arts)
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Dennis Berkey (class of 1969), President, Worcester Polytechnic Institute (Education)
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William Rainey Harper (class of 1870), first President, University of Chicago (Education)
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Richard Pipes (class of 1944), Professor of History Emeritus, Harvard University (Education)
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William Oxley Thompson (class of 1870), President of The Ohio State University and Miami University (Education)
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Philip Caldwell (class of 1940), retired CEO of Ford Motor Company (Business)
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Darrell Hazell (class of 1986), wide receivers coach for the Minnesota Vikings of the NFL (Sports)
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Jim Heacock (class of 1970), defensive coordinator and defensive line coach at Ohio State University (Sports)
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Edgar "Ed" Sherman (class of 1936), legendary Muskingum head football coach for 22 years; College Football Hall of Fame inductee (Sports)
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Tim Timmons, Major League Baseball umpire (Sports)
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Brandon Todd, known as the 5'5 dunker, played for the 2001, 2002, and 2003 All-Ohio team with LeBron James; developed an athletic training program called "FlytRight" (Sports)
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John Glenn (class of 1942), first American to orbit the earth, oldest man ever in space (Science)
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