In 1664 Doctor Olaf Van Schuler fled the Old World and arrived in New Amsterdam with his lunatic mother, two bags of medical implements, and a carefully guarded book of his own medicines. He was the first of what would become a long line of peculiar physicians. Among them, a physician who believes in spontaneous combustion; a mysterious doctor who seeks to heal people by using animal magnetism; a female phrenologist with a flair for analyzing character; and a surgeon who, as a last resort, performs a lobotomy on his own sister. Plagued by madness and guided by an intense desire to cure human affliction, each generation of this unusual family is caught up in the science of its day. As the make their way in the world, New York City, too, evolves - from the dark and gritty town of the 17th century to the towering, frenetic metropolis of today.