The handwritten manuscript for one of Sir Arthur Conan Doyle's first Sherlock Holmes mysteries, could fetch a record £1 million at auction next month. The Edinburgh-born author wrote The Sign of Four in 1889 as the second novel featuring the famous detective and his assistant Dr Watson. Published the following year, the murder mystery has since been adapted for the screen numerous times with Peter Cushing, Peter O'Toole and Benedict Cumberbatch among the stars portraying Holmes.The 160 page bound manuscript, signed twice by the author, will go under the hammer at Sotheby's in New York on June 26. Considered "the most significant Conan Doyle manuscript ever to be auctioned", it is estimated at £650,000-1,000,000.Originally titled "The Sign of The Four", the novel saw the return of Holmes two years after the first novel, A Study in Scarlet. Conan Doyle was commissioned to write the story by Joseph Marshall Stoddart, managing editor of the American publication Lippincott's Monthly Magazine, over a dinner at the Langham Hotel in London, also attended by Oscar Wilde.By the end of the evening, Conan Doyle had agreed to write The Sign of Four for the magazine, while Wilde committed to producing "The Picture of Dorian Gray." The novel appeared in Lippincott's Magazine in February 1890 and was then published in book form by Spencer Blackett in October the same year. Conan Doyle's manuscript contains edits to "Americanise" the text for publication in the US. Richard Austin, Sotheby’s Global Head of Books & Manuscripts, said: "Sir Arthur Conan Doyle is one of the most universally beloved writers, whose classic tales of Sherlock Holmes have delighted readers for more than a century. "The autograph manuscript of Conan Doyle’s iconic work, 'The Sign of Four,' is an exceptionally rare piece of literary history, offering a unique glimpse into Doyle's writing process. "Complemented by a collection of intimate letters exchanged between Doyle and his publisher, J. M. Stoddart, the ensemble provides a rich tapestry of insight into the preparation of Holmes for an American audience, cementing his legacy in the pantheon of literature's great characters." Conan Doyle was born in Edinburgh on 22 May 1859. He studied at the University of Edinburgh Medical School from 1876 to 1881, and modelled Sherlock Holmes in part on his former university teacher Joseph Bell. Like Holmes, Bell was noted for drawing broad conclusions from minute observations. The manuscript for The Sign of Four is offered as part of "The Library of Dr Rodney P Swantko", the late American surgeon and "meticulous collector" of 19th and 20th century literature. Also in the sale is Victorian illustrator Sidney Paget's original drawing for the illustration "The Death of Sherlock Holmes" for the Conan Doyle short story "The Final Problem". It was Paget's image of Sherlock Holmes from the original publication of Doyle's stories in The Strand Magazine that formed the popular view of the character recognised to this day.