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Milligan started his comic career with short stories for 2000 AD in the early 1980s. By 1986, Milligan had his first ongoing strip in 2000 AD called Bad Company, with artists Brett Ewins and Brendan McCarthy. Bad Company was a science fiction war story in 2000 AD, it was immensely popular and helped Milligan become better known.
Concurrently, Milligan, Ewins and McCarthy had been working on the anthology title, Strange Days for Eclipse Comics. Strange Days featured three strips, Paradax, Freakwave and Johnny Nemo. Milligan, McCarthy and Ewins produced three issues of this psychedelic comic, it was not a great seller but it picked up a small, loyal readership. The most conventional strip, Johnny Nemo, had its own series while the more quirky Paradax had a two issue series published by Vortex Comics in 1987.
By 1989 Milligan was swapping between more conventional strips such as Bad Company, while still writing his more surreal efforts in 2000AD, such as Hewligan's Haircut with artist Jamie Hewlett. Milligan with artist Jim McCarthy created the Steve Ditko-inspired Bix Barton. This was first run as a black and white strip for its first outing ("Barton's Beasts") the second strip was called "Carry On Barton" (originally "Carry On Snuffing"), the strip was very popular and was a precursor of Devlin Waugh and others.
In 1989 he had his first work published by DC Comics. Skreemer was a six issue mini series with art by Brett Ewins that was somewhat lost in the midst of the so-called "British Invasion" of American comics of the time. A dark post-apocalyptic gangster story, it did receive critical acclaim but did not sell well. Milligan however was soon to become a regular writer for DC while still working on his more personal comics in the UK in comics such as 2000AD, and its spin off titles Crisis and Revolver.
Skin (art by Brendan McCarthy) was the story of a young thalidomide skinhead in 1970s London, and his attempts to deal with his disability and the world in general. The strip was due to feature in Crisis in 1990 but the publishers, Fleetway were worried by the controversial subject matter, plus they were concerned with the explicit use of language in the story. The printers refused to print it, blaming the graphic language and controversial subject matter as a reason. The story remained in limbo until eventually being published as a graphic novel by Tundra with little, or no controversy. It remains one of Milligan's most powerful and acclaimed works.
Milligan had started to revamp Steve Ditko's character Shade, the Changing Man for DC Comics in 1990. This proved to be his largest break into American comics and came at the end of the first wave of "The British Invasion" of comics. Milligan updated and adapted many of Ditko's concepts, while adding his own ideas to embark upon one of the most bizarre titles published by DC. In 1993, it was one of the first wave of Vertigo titles with issue 33. It was a steady seller but it was cancelled with issue 70. A one-off story for Vertigo's tenth anniversary was published in 2003.
Milligan also succeeded Grant Morrison on Animal Man for a six issue run in 1991, and became the regular writer of Batman in Detective Comics in the same year. It was during one meeting of Batman writers that Milligan came up with the initial idea which led to the Knightfall storyline which was to cross over all the Batman family of titles. Milligan however had finished writing Detective Comics and was not involved with the crossover.
Milligan also created the highly acclaimed Enigma, with artist Duncan Fegredo for Vertigo in 1993. In this, Milligan introduced a gay superhero and dealt with his subject manner in his usual surreal way. Milligan quickly followed this up with The Extremist with artist Ted McKeever. Both titles dealt with taboo subjects for a mainstream publisher, but were applauded by their handling of these subjects.
Milligan spent the remainder of the decade writing one-off specials such as Face and The Eaters, or mini-series like Egypt and Tank Girl with its creator Jamie Hewlett providing art as well as acting as advisory editor to Paul Honeyford's Fighting Figurines. Milligan and Brendan McCarthy's psychedelic classic Rogan Gosh was reprinted in a collected edition by Vertigo in 1996, after being first serialised six years earlier in Revolver.
Milligan rounded out the decade by writing a four issue mini series featuring The Human Target. Proving to be Milligan's most conventional title for DC so far, it was also very popular and brought him to the attention of many who had been unaware of him and his works.
In 2001 Marvel Comics was undergoing a revamp by its new editor-in-chief Joe Quesada and one of his aims was to revamp the X-Men family of titles. Milligan was given X-Force to write with issue 116, and right away he removed the Rob Liefeld style superheroics and replaced it with a more satirical tone. Milligan and artist Mike Allred also removed the traditional superhero names and replaced them with names which sounded more like product brand names. Characters such as the Orphan, the Anarchist, U-Go Girl, Phat, Vivisector, Venus Dee Milo, Dead Girl and Doop formed this new team. This was not well received by some fans of the title, and many wanted "their" X-Force back, a comment Milligan would later parody in the pages of the title. These criticisms aside, the title sold well and even received mainstream media coverage both in America and Europe.
Milligan's run was acclaimed for its different take on the super hero genre, however X-Force was cancelled with issue 129 so it could become X-Statix, with Allred still as artist. It was on X-Statix that Milligan would once again become controversial when a proposed plotline was to feature a resurrected Princess Diana as a superhero and X-Statix team member. News of this spread to the press, including the British tabloid newspaper The Daily Mail who strongly objected to the idea. Eventually the character of Diana was altered, as were the references to the Royal Family but not before the story had been reported around the world. This aside, X-Statix was cancelled with issue 26, though several trade paperbacks were released.
Milligan's recent film work includes the screenplay for Pilgrim (a 2000 movie sometimes shown as Inferno), which stars Ray Liotta. He also scripted the 2002 adaptation of the Melvin Burgess novel An Angel for May. He was the regular writer on X-Men with artist Salvador Larroca in 2005, writing issues #166-187. Milligan returned to Human Target with a straight to graphic novel story "Final Cut", after which he wrote all of 21 issues of the ongoing series for Vertigo.
In 2006 he wrote a five issue mini series titled X-Statix Presents: Dead Girl with artist Nick Dragotta and co-creator Mike Allred for Marvel Comics.
In 2007, Milligan will write a continuing series featuring Infinity, Inc. Max Fiumara is scheduled to do art chores on the book. In July 2007 a Wildstorm series by Milligan started, called The Programme. It features the revival of a Soviet Cold War superhero. Milligan has also been involved in 2007's Batman crossover, The Resurrection of Ra's al Ghul, by writing the lead-in Batman Annual #26, as well as the parts of the series in the Robin monthly title. Milligan recently penned the script for the BBC interactive animated series "Meta4orce".
It was announced in October 2008 that Milligan would be taking over writing duties on the long-running Vertigo comic series Hellblazer. He also wrote the 2008 seasonal one-shot "Moon Knight: Silent Knight" with artist Laurence Campbell. At Vertigo he is also writing Greek Street, set in the London street of the same name. He also wrote the critically acclaimed miniseries Sub-Mariner: The Depths for Marvel's Marvel Knights imprint which ended in March 2008.