In 1933, Anna Olson is terrified by the unknown. At age 16 she is committed to a large state institution, and labeled as epileptic and "feebleminded," both which she knows are wrong. Anna discovers a group of girls her age with epilepsy who help ease her fears.

Together they adapt, learning that life is hard with physical and mental dangers at every turn. But they are not alone; the young women join over a thousand other patients working long hours at menial jobs. As she struggles to find her way out, to be free, she sinks deeper into the chaos, noise, and heartache that comes with living in a large institution.

A mysterious man preys on Anna and her friends, eventually raping two of them. Administrators lie to them, promising them discharges if they agree to become sterilized. As the years pass, the accumulated pressure of confinement in close quarters with thousands of people takes a toll on Anna's mind and body. Still, she never loses hope that someday her nightmare will end.

In American Isolation by Kirby Nielsen, the reader lives with Anna Olson in Helmhurst, one of the large, horrible institutions from America's recent history.