Oprah Winfrey became obsessed with Henrietta Lacks’ story along with the rest of the world in 2010, but she never intended to star in HBO’s movie version, The Immortal Life of Henrietta Lacks (Saturday, 8 ET/PT).

“For years, I was like, ‘I don’t want to do it. I don’t want to take this on. I just want to be a producer,’” says Winfrey, from her home in Montecito, Calif.

But she ended up taking a lead role as Lacks’ daughter Deborah, after optioning  the rights to produce a film based on the 2010 bestseller. .  The book chronicles how the African-American Baltimore cancer patient died in 1951, not knowing her tumor cells were harvested by researchers at Johns Hopkins Hospital. Henrietta’s cells, knowns as HeLa, were later duplicated into “immortal” cell lines used by scientists for medical testing all over the world.

Author Rebecca Skloot’s nearly 400-page tome proved difficult to adapt. The non-fiction work weaves together the story of Lacks’ descendants, many of whom couldn’t afford health insurance despite their mother’s medical contributions; HeLa’s effect on sprawling scientific breakthroughs, from the polio vaccine to cancer research; and the ethical repercussions of sampling body tissue without patients’ consent.

Early on, “there were some versions (of the script) where it was mostly science, and I was falling asleep,” Winfrey says. “We know, obviously, that getting people to digest science is a very difficult thing. Like, ‘Yes, you will enjoy spinach with a broccoli sauce.’ Being able to put it in a form where it is accessible and actually meaningful was the challenge.”

And hey, Skloot gets it. “It took me 11 years to turn it into a book,” says the author, who had to persuade the Lacks family to trust her after they’d been burned by others hoping to profit from their story. (The family remains divided on the HBO film.)

Winfrey’s tune changed when director George C. Wolfe (Nights in Rodanthe) signed on and rewrote the script to focus on Deborah and her quest to learn about what actually happened to her mother inside the then-segregated walls of Johns Hopkins.

“The biotech industry was born on the use of Henrietta Lacks’ cells,” Wolfe says. “HeLa is this incredible medical phenomenon. And then a few blocks away, there was a family that knew nothing about it.”

Rose Byrne (who “failed” biology and was a “miserable” science student) signed on to play Skloot, whose work “encompasses a lot of things: the line between science and ethics, race in America, the history of African-Americans,” she says. “It’s a perspective from a young white journalist and an…