For more than 50 years, Frank Herbert’s bestselling science-fiction novel “Dune” was a puzzle no one in show business seemed able to solve. Published in 1965, the book had inspired a shelf full of sequels and prequels — along with scores of imitators — yet it defied every attempt to turn it into a blockbuster film or TV series.

In the 1970s, beloved avant-garde filmmaker Alejandro Jodorowsky spent two years and millions of dollars developing a movie and never shot a single frame. David Lynch tried next, but the resulting film, released in 1984, was a personal and box-office catastrophe. The story’s vastness and exoticism proved as perilous to storytellers as the fictional planet Arrakis, whose hostile deserts inspired the franchise’s name.

When the HBO series “Dune: Prophecy” was announced, in 2019, its prospects seemed just as murky. Indeed, the production struggled to find its footing. By the premiere, it will have seen four showrunners, three lead directors and high-level cast changes — not to mention a pandemic and two crippling industry strikes.

But then in 2021, French Canadian filmmaker Denis Villeneuve, who was set to direct the pilot, released Part 1 of his two-part adaptation of “Dune.” Critics were ecstatic, and the film grossed over $400 million worldwide. Suddenly a “Dune” franchise looked viable. Villeneuve’s team had offered a blueprint for other creators to work from, tonally, aesthetically and narratively. (The studios behind the film, Legendary and Warner, which owns HBO, are also behind the series.)

Perhaps more important, there was now a huge audience that had never read Herbert’s famously dense novels but had become invested in the story and characters. The resounding critical and financial success of “Dune: Part Two,” released in February, indicates viewers are still invested in the franchise.

“I think Denis really unlocked this universe for people in a way that was relatable,” said Alison Schapker, a “Westworld” veteran who took over as the sole showrunner of “Dune: Prophecy” in 2022. “He grounded it. We wanted to tell a story that takes place in that universe.”

Starring Emily Watson, Olivia Williams and Travis Fimmel, the HBO series, debuting Nov. 17, is a prequel, set 10,000 years before the Villeneuve films and inspired by “Sisterhood of Dune,” written by Herbert’s son Brian and Kevin J. Anderson. The show tells the origin story of the veiled female religious order called the Bene Gesserit, familiar from the movies, which uses supernatural powers to wield influence in an intergalactic empire.

The look of the show resembles that of the films, with its imposing architecture and elaborate costumes. Fans of the movies will also recognize some of the names, including the Harkonnen family, the primary villains in “Dune,” and the Atreides family, the “Dune” protagonists, whose rivalry reaches back millenniums.

The right ingredients are there. One major exception, though, is Villeneuve, who wound up stepping away entirely. A remaining question for HBO, then, is whether the storytelling team it finally chose can find that same elusive alchemy. Can the series avoid the mistakes of several other big fantasy franchises lately and not get bogged down in its own arcana?

Watson, who plays Valya Harkonnen, the leader of the mystic sisterhood, seemed to think so. “Dune: Prophecy” is ultimately about something rather straightforward, she said — “a really bad-ass, big, bold girl who is a properly complex grown-up.”

With a twist, of course: “She sort of wants to control human destiny.”

For all its Byzantine trappings, “Dune” has long been one of the world’s most popular science-fiction novels, having sold around 20 million copies to date. Its appeal has always been due partly to the many ways in which its high-fantasy world of interplanetary travel and giant sandworms has, with its themes of religion, politics and ecological destruction, resonated with the real world.

The original novel — and Villeneuve’s two-part adaptation — concerns a futuristic society governed rigidly by several aristocratic families who control a life-extending and ability-enhancing drug known as spice, found only on Arrakis. The HBO prequel rewinds to a time soon after the conclusion of a war between humanity and “thinking machines,” which ended with a near-universal ban on advanced computers, robots and artificial intelligence.

Williams, who plays Valya’s sister, Tula, said she could relate. She has two daughters. “Every bloody day, I’m having a one-on-one battle with AI in our house, trying to get a kid off a machine,” she said, laughing, in a joint video call with Watson.

But the story relates to more than smartphones. Neither actress had read the books before taking the job, but its poignancy was obvious. “The whole idea of forging a path and conquering the universe is an age-old thing,” Watson said. “For ‘spice,’ read ‘oil,’ read ‘energy.’ And there’s religion, and there’s conflict over land.”

Williams added, “For the Bene Gesserit, read “the Cult of the Virgin Queen,’” referring to Queen Elizabeth I of Britain, who never married. “What women get up to when they don’t have a husband has been a source of fascination for generations.”

Schapker came to the series with a deeper emotional connection to Herbert’s original novel, stretching back long before she was asked to take over as showrunner. She described “Dune” as a book that she had “almost, like, a sense-memory of reading.”

“I can picture myself on my bed,” she added. “I can see the cover.”

She later became “obsessed,” she said, with the 2013 Frank Pavich documentary “Jodorowsky’s Dune,” about Jodorowsky’s failed adaptation. Despite that failure, Jodorowsky’s efforts — the tome-like script, the designs, the thousands of storyboard sketches — filtered into films his collaborators and fans worked on, like “Star Wars,” “Alien” and “The Terminator.”

Schapker was enchanted by the thought of “Dune” “inspiring that much love and creativity,” she said. It was part of what drew her to this TV series: her own chance to play in that sandbox.

The series had its own journey to get to Schapker. From the start, “Dune: Prophecy,” originally titled “Dune: The Sisterhood,” was meant to share personnel. In addition to Villeneuve’s role directing the pilot, one of the movies’ screenwriters, Jon Spaihts, was announced as showrunner. After some criticism that a series about a sisterhood was led by an all-male creative team, producers hired Dana Calvo (“Narcos,” “Good Girls Revolt”) as a showrunner.

But by the end of 2019, Spaihts had left — to focus on the film, an HBO spokesperson said — and Calvo left shortly after. (Spaihts, who remains an executive producer of the show, could not be reached for comment; Calvo declined to comment.) In the summer of 2021, writer Diane Ademu-John (“The Originals,” “Empire”) was made showrunner, eventually joined by Schapker. But in late 2022, Ademu-John left her role, making Schapker the sole showrunner.

(An HBO spokesperson said Ademu-John left because of other commitments; Ademu-John, who remains an executive producer and is credited as a developer, could not be reached for comment.)

Then Villeneuve departed — the first movie was a huge success, and he decided to focus solely on the sequel. Producers hired the Emmy-winning director of “Chernobyl,” Johan Renck, to shoot the first two episodes, but by early 2023, he too had left. In an interview with The Playlist, he said that the “the original idea of the story” had “completely changed course,” adding in an email this month that he had been “aiming for something with a similar uniqueness and idiosyncrasy in the sci-fi universe” to Lynch’s film, now beloved by many cinephiles. (An HBO spokesperson said only that Renck had decided to pursue other projects.)

The production, which had already begun shooting in Budapest, Hungary, went on hiatus. When it restarted, Anna Foerster, who had worked on “Westworld,” was the new lead director. After all the changes and strike delays, the production had only six months to shoot in order to meet everyone’s schedule.

Faced with the pressure of a compressed production calendar, Schapker drew on her experience with fast-moving schedules on network series like “Alias” and “Lost.” The process was helped, she said, by the fact that Ademu-John had already put in motion much of what would become “Dune: Prophecy.” “A lot of world-building and characterization and story was there,” she said.

Throughout the process, the creators (including writer-producer Jordan Goldberg, whom Schapker described as her “partner”) had two main priorities. The first was to recapture what audiences loved about the Villeneuve movies while still telling their own story. “We’re not building this in lock step,” Schapker explained.

The second goal was to make sure that even as the story traversed worlds far from the Bene Gesserit’s center of power, women remained at the center of the action. While there are central male roles, too, like Fimmel’s character, Desmond Hart, a grizzled soldier with haunting eyes and a mysterious past involving a sandworm, Schapker wanted to follow the Herberts’ lead in crafting characters and storylines that are “predicated on women shaping that universe along with men,” she said. That extended to staffing the show.

“The idea that we would put together a team that reflected that behind the scenes? Resounding yes,” she added.

Whatever the staffing or intentions, the end result had to be comprehensible, relatable. For Watson and Williams, who started together at the Royal Shakespeare Company and had little experience anchoring a story with spaceships and superpowers, the series had to speak to something more than sci-fi esoterica. In search of real-world grounding, the actresses sought inspiration together at the National Portrait Gallery in London, where they studied paintings of 16th-century Tudor queens.

For her part, Williams said she had taken the role because Tula was the type of character she so rarely got to play. “Middle-aged women who want to rule the universe don’t come along that often,” she said.