In this article, the authors offer a new perspective on how the administration of Compound E (ie, cortisone) to a volunteer Mayo Clinic patient with rheumatoid arthritis and the patient's subsequent miraculous improvement led not only to a major, successful clinical trial but also a Nobel Prize. The early and late side effects as an undesirable outcome of treatment of corticosteroids would soon follow. Corticosteroid side effects became known in popular culture, first through an indepth article in The New Yorker by medical journalist Berton Roueché, and later through a major fiction film, Bigger than Life, directed by Nicholas Ray. The film used cortisone as a plot device to "unmask" what the filmmaker perceived to be the lie of middle class prosperity in America of the 1950s. Bigger than Life is also a cinematic argument against the use of cortisone. Dr. Philip Hench was also connected to Bigger than Life, and the Ray-Hench connection is further explored based on newly found material. The discovery of "wonder drug" cortisone and its potential side effects-all carefully described in the Roueché article but exaggerated in Nicholas Ray's film in the 1950s-show how medicine can be portrayed in popular culture.