Spiegel grew up in Baltimore, Maryland in a secular Jewish household. Her father was the great-grandson of Joseph Spiegel, the founder of the Spiegel Catalog. Her great-aunt was civil rights activist Polly Spiegel Cowan. She studied the violin seriously from a very young age at the Peabody Preparatory in Baltimore, but quit to go to college.[4] After graduating from Oberlin College, Spiegel moved to Chicago, where she saw an announcement in a newspaper about a fledgling local show for WBEZ called Your American Playhouse: Documentaries About American Life. In 1995 Spiegel began correspondence with the show's producer, Ira Glass, who took her on as an intern.[4] In 1996 the show changed its name to This American Life and was picked up nationally by Public Radio International, by which time Spiegel was producing pieces for the show. That year Spiegel and the show's other producers won the George Foster Peabody Award[5]
During her years on NPR's science desk Spiegel covered psychology and human behavior, with an emphasis on looking at how ideas about emotions come into existence and evolve.[3] In 2008 she won the Robert F. Kennedy Journalism Award for her piece "Stuck and Suicidal in a Post-Katrina Trailer Park". In 2010 she won the Erikson Institute Prize for Excellence in Mental Health Media.[9] In 2021 she won a John B Oakes award from Columbia University for her environmental reporting. In 2022, after returning to This American Life, she was on the team that produced "The Pink House at the Center of the World", an episode about the overturn of Roe v Wade that won a Peabody. Spiegel's science reporting has also been featured in The New York Times and The New Yorker.[3]