It sounds like the premise of a thousand monster movies: Brilliant but reckless scientists perform an ill-advised experiment, unleashing into the world a deadly beast. Havoc reigns. People die. Mankind once again pays the ultimate price for trying to play God.

The difference, in Vincenzo Natali’s chilling, cerebral Splice, is that the premise is handled with unusual restraint. Rather than embracing the sensational, Natali, who co-wrote the original story, seems more interested in the human drama that unfolds as two genetic engineers, played by Adrien Brody and Sarah Polley, form a precarious bond with the creature their human-DNA experiment has produced.

And that is precisely the point. Natali, 41, who spent 12 years trying to get the movie made – he calls it a personal story that kept calling him back – believes Splice is as much a meditation on modern science and dysfunctional relationships as it is a creature feature.

“There’s a hunger out there for this,” he says. “The real genetic-engineering technology that exists and the issues it raises are very much in the public consciousness. And the sexual component of the film is something we’ve seen in science-fiction literature but not in movies – at least not treated in a mature way.”

The sexual component he’s referring to – without spoiling the movie’s secrets, it’s creepier than it is erotic – is edgy enough that Natali never thought to screen Splice for mega-producer Joel Silver, who became the project’s unlikely guardian angel after this year’s Sundance Film Festival. Was the Canadian director worried that Silver would caution him to lighten up the movie’s darkest moments?

“I didn’t know what was going to happen after Warner Bros. picked up the film,” he admits. “They have completely embraced everything that is disturbing and weird about it, and I attribute that to Joel. He’s one of the only producers who knows what he likes and has the power to make it happen. It’s nothing less than a miracle.”

Natali doesn’t want to talk about the ending of Splice – at least not in print – but he acknowledges that it leaves the door open for a sequel. That wasn’t intentional. But having toiled for years as an independent filmmaker before enjoying what he calls a “fantastic marriage” with a major studio, he says he’ll be back, in some capacity, if the story continues.

“My first film, Cube [1997], has two sequels that I had nothing to do with,” he says. “I don’t want to say anything disparaging about those movies, but it’s not what I would have done. People assume I was responsible for them, and I wasn’t.

“If Warner Bros. wants a Splice sequel, I’d want to be involved in shepherding the story along in the direction I would have taken it. And after working with them, I wondered why I was ever an independent. It was an incredible experience. I would definitely do it again.”

You can’t blame Natali if he seems delighted by even the possibility of a second act. Six months ago, he didn’t think Splice was going to get made at all. Since then, with Silver and co-producer Guillermo del Toro’s backing, he has brought the movie to festivals in Glasgow, London and Gérardmer, France, before returning to America for the first time since Sundance to screen it at the San Francisco Film Festival. The verdict?

“The people who like the movie,” he says, “are responding to the fact that there’s an emotional component to it. It’s about the relationship between the creator and the creation. It’s about what is acceptable and what isn’t. And the people who don’t like it are probably responding to the same things.

“Look, if I’d had to take the sex out of this movie, I wouldn’t have made it. There have been other monster movies that had sex, but they don’t treat it seriously. This is a movie that looks at things in great detail, that examines the nuances in the interactions between its characters. We watch the humans turn into monsters as the monster reveals its humanity. That was the whole point.”