Annihilation is a story about transformation and obliteration, which is fitting considering that it synthesizes various genre predecessors into something wholly unique while simultaneously laying to waste the stolid conventions that now dominate franchise-blockbuster moviemaking.

An intellectually ambitious, formally striking, and altogether out-there odyssey, Alex Garland’s film begins conventionally before spiraling into ever-more-hallucinatory realms, its every element in perfect harmony with its larger themes—all of which resound not as definitive statements but as haunting questions that linger long after the credits have rolled. In just about every respect, it’s the finest cinematic sci-fi in years—or, at least, since Garland’s prior Ex Machina.

That 2015 gem, in which Domhnall Gleeson’s computer whiz is tasked by Oscar Isaac’s reclusive CEO to administer a Turing test to Alicia Vikander’s robot (in order to deduce whether she has genuine artificial intelligence), was a more realistic sort of future saga. As has so often been the case in the illustrious career of Garland—the scribe of 28 Days Later, Sunshine, Never Let Me Go and the exceptionally awesome Dredd—Annihilation finds the writer/director pendulum-swinging back toward trippier territory, which in this case is a loose adaptation of Jeff VanderMeer’s 2014 novel (the first part of his “Southern Reach” trilogy). Devoid of gadgets and gizmos that might be on our semi-distant horizon, the filmmaker’s latest is a slow, suspenseful slide into the vast unknown—or, to be precise, into the deep, dank origins of creation.

Annihilation begins with Lena (Natalie Portman) seated in a sealed-off chamber, being grilled by a hazmat-suited man (Benedict Wong) about how she survived in an unspecified locale for four months without food—as well as the fates of her (clearly MIA) comrades. Before we can get our bearings, Garland cuts to a meteor hurtling through space, its final destination an Earth lighthouse that, upon being struck, is enveloped in an explosion of churning liquid-y material that resembles the rainbow swirls made by children’s giant bubble wands. Without explanation, Garland then jumps backwards to the past, to witness Lena, a biologist who used to be in the military, lecturing college students about the first ever organic cell division, and the “rhythm of the dividing pair,” which she states is the structure governing all that lives and die—including, as it turns out, Annihilation itself.

At home, Lena pines for Kane (Oliver Isaac), her soldier husband, only to be shocked when—after twelve months away—he suddenly materializes in the house, albeit confused about the secretive mission he was on (“I don’t know where it was, or what it was”). Their happy reunion is cut short when Kane suddenly falls ill, and on the way to a hospital, is grabbed—along with Lena—by shadowy governmental forces. Awakening in “Area X,” Lena learns the horrifying, and baffling, truth: Kane was part of the most recent expedition into the “Shimmer,” a rapidly expanding hot zone (think of it as a biodome made out of that rainbow-swirling stuff) whose cause and constitution is unknown. He’s the only one to have ever returned.

Desperate to find out what happened to her beloved (in an effort to possibly save him), as well as curious about the spreading-without-remorse Shimmer, Lena joins the multicultural team prepping for another run into the region. That squad is comprised of physicist Josie (Tessa Thompson), paramedic Anya (Gina Rodriguez), magnetic fields expert Cass (Tuva Novotny), and operation leader Dr. Ventress (Jennifer Jason Leigh), all of whom are, in some way, damaged, and in search of escape and/or healing. They’re also, obviously, all women, which—despite the fact that these characters define themselves, first and foremost, as scientists—lends the proceedings a distinct feminist vitality that eventually proves essential to the film’s mother-of-unholy-invention conclusion.

Garland’s actresses employ confident exteriors to mask increasingly uncontrollable internal tumult, and they’re led by a captivating Portman, whose turn (as with the story itself) is well-defined and lucid, even as it operates on the edge of intriguing obliqueness. What they find inside the Shimmer is a lush swampy wilderness where cell signals can’t escape, compasses don’t work, time seems to move at a bizarre pace (almost immediately, the women can’t recall setting up their camp), and different strains of flowers are sprouting from shared stems. Oh yes, and there are other things lurking in the Shimmer as well: big, unnatural creatures that thrash, growl and cry out in the voices of their victims.

Interspersed amidst this primary action are flashbacks to Lena’s bedroom, where she’s seen with both Kane and Daniel (David Gyasi), a colleague with whom she had an (now-regretted) affair. These interludes are visions of convergence and separation, of conception and ruin—concepts that are also ever-present in the Shimmer, where mutations are plentiful, especially the closer the team gets to the lighthouse. As Lena and company proceed deeper into this environment, what they discover is corruption and madness, both within their group dynamics and within themselves—and everything around them.

A journey into an alien heart of darkness, Annihilation feels like it’s been fashioned from gene-splicing Francis Ford Coppola’s Apocalypse Now with John Carpenter’s The Thing (especially in a pool-set scene of blooming monstrousness) and, also, Stanley Kubrick’s 2001, the latter’s spiritual influence coming to the fore during a finale of such prolonged, mesmerizing surrealism that it made my eyes burn—mainly because I didn’t want to blink, lest I miss a moment of its insanity. Like Geoff Barrow and Ben Salisbury’s score, which alternates between acoustic guitar and unearthly tonal arrangements, Garland’s climax is simultaneously elegant and bone-chilling. That’s just like Lena’s account of the Shimmer, which she describes, after being asked if it was nightmarish, as “dreamlike…sometimes it was beautiful.” Via psychedelic visuals, slow-motion sequences, and a bevy of evocative cinematographic compositions, Garland establishes an atmosphere of unshakeable waking-reverie dread, and moreover, formally conveys his fascination with the question of what, ultimately, defines existence.

Without spoiling any of his (uniformly gripping) narrative surprises, the answer to that query, it turns out, has to do with the inherent relationship between division and replication, be it with regard to our cells, our desires, our relationships or life itself. Annihilation is a portrait of nature, and human nature, as fundamentally trapped in an endless cycle of self-destruction and evolution, and the way those warring forces, for good and bad—if such distinctions even apply here—define us, and everything else in the universe. A sci-fi mystery that slowly turns into a beguiling adventure, and then metamorphizes into a sublime freak-out the likes of which audiences have rarely seen, Garland’s film tackles Big Issues with a suspensefulness and aesthetic splendor that’s nothing short of astonishing.

Big-budget sci-fi doesn’t come much more incisive, exhilarating and mind-blowing than this.