Splice, from director Vincenzo Natali, is in the best tradition of sci-fi and horror B-movies that operate on a number of levels. A visceral and unsettling tale of a biotech experiment gone awry - genetic engineers mix human and animal DNA to create a hybrid that looks like a supermodel with chicken legs and a tail - the film is:

1. A dark, scary, icky thriller.

2. A cautionary tale about messing with genomes ("If God didn't want us to explore His domain, why did he give us a map?" grumbles Adrien Brody, who plays the male half of the film's brainiac-hipster-scientist couple.)

3. A really disturbing allegory about parenting and procreation.

"I think that all young parents should watch this movie," says Natali, with a merrily demented chuckle.

Natali, 41, stopped in town recently to talk up his movie - a movie he spent almost a decade struggling to get made. A modest ($26 million) Canadian-French coproduction starring Brody and Sarah Polley as partners in science, and in bed, Splice was off the radar until it screened in January at the Sundance Film Festival. Sure, it had fantasy king Guillermo Del Toro's name attached as an executive producer, but still, Natali didn't have high hopes.

"At that stage, it looked pretty much like Splice was going to get a very small release, or possibly go straight to DVD," he says, "for the simple reason that the economic climate in the independent film world is just so bad. It's almost impossible to sell a movie to a major theatrical distributor."

But then Joel Silver - producer of the Matrix, Die Hard, and Lethal Weapon franchises, and this winter's blockbuster Sherlock Holmes - heard about Splice. And saw it at its Sundance premiere.

And then he bought it, and put his Dark Castle Entertainment imprimatur on it, and because Dark Castle has a distribution deal with Warner Bros., Splice got on the studio's release slate. The film opened Friday.

"Never in my wildest dreams did I expect this movie to be released by a major studio at the height of summer," Natali says. "It would have seemed ridiculous to me if you had mentioned it three months ago."

Natali - whose previous films include the well-regarded though little-seen Cube and Cypher - made Splice in Toronto, his home until he relocated to Los Angeles a few years back. But the Ontario locales and crew are only one reason Splice is remindful of the early works of Canadian creepmeister David Cronenberg, the man behind Rabid (zombies!), The Brood (mutant kids!), and Scanners (psychic psychos!).

Splice has the dark, indrawn look and feel of those vintage Cronenberg titles, and Natali acknowledges the influence.

"Absolutely," he says. "Listen, I think once you step into the realm of bio-horror, David Cronenberg has a trademark, so there's some Cronenberg DNA in there, for sure."

There's also a distinctly claustrophobic, cloistered vibe, as if the world at large doesn't really matter, and it's all about Brody and Polley's characters and their struggle to raise their spawn.

"Of course, Canadians spend all of their time thinking about Americans, and Americans don't even think about Canada," Natali says. "But I often think that part of the difference between America and Canada is that Americans look outward, and Canadians tend to look inward. I don't know if it's to do with climate, or that we're some mix of American and European cultures, I don't know what it is. But it definitely is a more hermetic kind of society, and a more introspective one."

Another influence that Natali cops to is the Philadelphia comic artist Charles Burns. In fact, at certain angles, when the hybrid creature Dren (portrayed in her accelerated adult form by the French actress Delphine Chanéac) turns seductive, and clothesless, and flicks her long reptilian tail, she resembles the teenage mutant muse from Burns' Black Hole.

"Oh yeah, I love Charles Burns," the filmmaker says. "I'm very familiar with Black Hole. Listen, Cronenberg is clearly the father of this, but I think Cronenberg has many children - his brood, as it were - and definitely Charles Burns is one of them. And I can think of a few others.

"This is an expanding field. I think that bio-horror is on an upswing, because it's just where we're headed. It's an interesting time. With the research that I did for the film, I was just astounded at how multifaceted the genetic research is, and all the potential places it could be leading us. . . . We're headed towards the post-human era. It's going to get interesting.

"It's going to get weird."

Short subjects. Variety reports that Madonna, the pop diva who adopted Britain as her home - and a British accent of sorts to go with it - is planning her second film behind the camera. Her directorial debut was Filth and Wisdom, the 2008 art-house entry about three artsy London flatmates. This one is a little higher-brow: W.E. examines the affair between King Edward VIII and American divorcee Wallis Simpson, a relationship that led to Edward's abdicating the throne. James D'Arcy (Master and Commander, Mansfield Park) will play the lovestruck royal; Andrea Riseborough, who portrayed Margaret Thatcher in a 2008 British TV biopic, is Simpson; and Abbie Cornish and Oscar Isaac are a contemporary couple whose relationship parallels the historic one. Madonna will yell "Action!" at the beginning of July. . . . New York magazine's "Vulture" blog reports that Sam Mendes, off the hook on directing the 23d James Bond (the 007 project is a victim of the MGM meltdown), has latched onto Ian McEwan's slim novel On Chesil Beach as his next feature, possibly with An Education's Carey Mulligan as the young bride fumbling with her young groom in a painfully awkward and unsuccessful honeymoon. Mendes can use Madonna's "Like a Virgin" for the closing credits.

Contact movie critic Steven Rea at 215-854-5629 or srea@phillynews.com. Read his blog, "On Movies Online," at http://www.philly.com/philly/blogs/onmovies/