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Billy Hartnell
Hartnell's performance in This Sporting Life was noted by Verity Lambert, the producer who was setting up a new science-fiction television series for the BBC entitled Doctor Who; and, mainly on the strength of that performance, Lambert offered him the title role. Although Hartnell was initially uncertain about accepting a part in what was pitched to him as a children's series, in part due to his success in films, Lambert and director Waris Hussein convinced him to take the part, and it became the character for which he gained the highest profile and is now most remembered. Hartnell later revealed that he took the role because it led him away from the gruff, military parts in which he had become typecast, and, having two grandchildren of his own, he came to relish particularly the attention and affection that playing the character brought him from children. His first episode of Doctor Who aired on 23 November 1963.

Doctor Who earned Hartnell a regular salary of £315 per episode by 1966 (in the era of 48 weeks per year production on the series), equivalent to £4,050 a week in modern terms. By comparison, in 1966 his co-stars Anneke Wills and Michael Craze were earning £68 and £52 per episode at the same time, respectively. Throughout his tenure as the Doctor, William Hartnell wore a wig when playing the part, as the character had long hair.

According to some of his colleagues on Doctor Who, he could be a difficult person to work with. Others, though, such as actors Peter Purves and William Russell, and producer Verity Lambert, spoke glowingly of him after more than forty years. Among the more caustic accounts, Nicholas Courtney, in his audio memoirs, recalled that during the recording of The Daleks' Master Plan, Hartnell mentioned that an extra on the set was Jewish, Courtney's inference being that Hartnell was prejudiced. In an interview in 2008, Courtney claimed that Hartnell "was quite nationalist-minded, a bit intolerant of other races, I think."

Hartnell's deteriorating health (he suffered from arteriosclerosis, which began to affect his ability to learn his lines), as well as poor relations with a new production team on the series following the departure of Verity Lambert, ultimately led to his leaving Doctor Who in 1966.

When he departed, the producer of the show came up with a unique idea: that since the Doctor is an alien, he can transform himself physically, thereby renewing himself. William Hartnell himself suggested the new Doctor, stating that "There's only one man in England who can take over, and that's Patrick Troughton". In the fourth episode of the serial The Tenth Planet, the First Doctor regenerated into Troughton's Second Doctor.