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It is strange but true that one of the most human, emotionally complex movies at the Venice Film Festival features a cast of puppets.

Critics are singing the praises of Anomalisa, which was written by Charlie Kaufman — the imaginative wordsmith who scripted Being John Malkovich and Eternal Sunshine of the Spotless Mind — and co-directed by Kaufman and stop-motion animator Duke Johnson.

Tender, funny and unsettling, it follows motivational speaker Michael Stone on a soul-sapping business trip to Cincinnati as he struggles to understand why he feels disconnected from the world and almost everyone in it.

The film was adapted from a play written by Kaufman as Francis Fregoli — a name taken from Fregoli Syndrome, a rare disorder that makes people think everyone else in the world is one person.

Kaufman said the syndrome struck him as “a metaphor for some sort of alienation or dissociation.”

He realized that he could replicate the feeling “with three actors, and one of them plays 50 characters”.

In Anomalisa, David Thewlis voices Stone, Jennifer Jason Leigh plays call-centre employee Lisa, the one person with whom he feels a connection, and Tom Noonan portrays everyone else, from Stone’s wife and son to a cab driver and hotel staff.

The eerie vocal similarity is one of many unnerving aspects of the film that melds emotional authenticity with stop-motion animation. The characters are visibly puppets — you can see the seams joining the segments of their heads — but also incredibly detailed and intensely life-like.

The most remarkable sequence is an explicit, highly believable sex scene that’s a long way from the comic puppet-sex of Trey Parker and Matt Stone’s Team America: World Police.

“We didn’t want it to be played for laughs,” Kaufman said during an interview in Venice on Wednesday. “We wanted it to be real. Not, ‘Oh, look — it’s puppets having sex.’

“People have said that it’s really uncomfortable,” he added approvingly. “They feel like they’re eavesdropping on something they shouldn’t be.”

Johnson says the hand-crafted nature of stop-motion animation gives it a quality computer animation lacks.

“Your brain can perceive when something is real, when it exists in real space and time,” he said. “When you’re looking at stop-motion, on some level you’re aware that things really exist, and that somebody was manipulating them and interacting with them.

“You can kind of see the brush strokes in the process, and it adds a level of soulfulness and life to it.”

Stop-motion is also labour intensive. Anomalisa took two years to shoot, at the rate of about two seconds of screen time a day.

Kaufman’s fans have had to learn to be patient. It has been seven years since his last film, Synecdoche, New York — a critical hit but a box-office flop.

“Seven years, 35 days and six hours,” deadpanned Kaufman. “It wasn’t my choice. I’ve been working. I’ve been trying to get things made. I’ve written three scripts and three pilots, one of which I shot but didn’t get picked up. I’m writing a novel.

“I’m trying. The business got harder in 2008. I think people are taking less chances because of the economy.”

Anomalisa was funded independently, with the first $400,000 (Dh1.46 million) raised through crowd-funding platform Kickstarter.

In Venice, the film is a strong contender for the Golden Lion top prize, which will be awarded on Saturday. Critical kudos don’t ensure commercial success — but at least Kaufman sounds creatively energised by his stop-motion adventure.

“I had this idea of trying to do a stop-action movie with real people, posing them and stuff,” he said. “I don’t think it’s possible, but I thought it would be really interesting if we could get the level of detail that you get with these puppets.”

He mulled over the logistical difficulties while looking out over the Venice lagoon.

“I don’t think people can hold their poses that well. It would be too shaky. How do you keep them from blinking or moving their eyes?

“You could have fake eyes — that would be the solution.”