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The story begins before World War I, when young Lou Gehrig begins dreaming of becoming a professional ballplayer. Lou's immigrant parents (Elsa Jansen and Ludwig Stossel) insist that the boy attend Columbia University to become an engineer. While in college, Lou becomes a star athlete, and, with the help of sports journalist Sam Blake (Walter Brennan), he is signed by the New York Yankees and joins their big-league lineup in 1925; real-life Yanks Babe Ruth, Bill Dickey, Bob Meusel and Mark Koenig play themselves. He earns the nickname "The Iron Man of Baseball" because he never misses a game but In 1939, Lou discovers that he has a fatal neurological disease called amyotrophic lateral sclerosis (now known, of course, as "Lou Gehrig's Disease").