September 1888. A 29-year-old Arthur Conan Doyle practices medicine by day and writes at night. His first Sherlock Holmes story, A Study in Scarlet, although gaining critical and popular success, has only netted him 25 pounds. Embittered by the experience, he vows never to write another "crime story". Then a messenger arrives with a mysterious summons from former Prime Minister William Gladstone, asking him to come to London immediately.
Once there, he is offered one month's employment to assist the Metropolitan Police as a "consultant" in their hunt for the serial killer soon to be known as Jack the Ripper. Doyle agrees on the stipulation his old professor of surgery, Professor Joseph Bell — Doyle's inspiration for Sherlock Holmes — agrees to work with him. Bell agrees, and soon the two are joined by Miss Margaret Harkness, an author residing in the East End who knows how to use a Derringer and serves as their guide and companion.
Pursuing leads through the dank alleys and courtyards of Whitechapel, they come upon the body of a savagely murdered fifth victim. Soon it becomes clear that the hunters have become the hunted when a knife-wielding figure approaches.