Oprah Winfrey admits she worried about embarrassing herself in The Immortal Life of Henrietta Lacks

It’s hard to imagine Oprah Winfrey being nervous. But the icon admits that taking on the starring role in HBO’s The Immortal Life of Henrietta Lacks was intimidating. “I was really anxious about this character,” says Winfrey. “The whole time I kept saying to [director] George C. Wolfe, ‘Don’t let me embarrass myself.'” All the worrying was for nothing: Winfrey gives a tour-de-force performance in Lacks, which premieres Saturday night at 8 p.m. on HBO, and will likely be a major contender in the awards races this year.

Adapted from the 2010 best-seller by journalist Rebecca Skloot, The Immortal Life of Henrietta Lacks tells of the titular Baltimore woman, played by Hamilton‘s Renée Elise Goldsberry, who unknowingly had her cells harvested after being treated for cervical cancer at Johns Hopkins in 1951. Though Lacks died that year, her cells, referred to as HeLa, became the backbone of the microbiology industry and are still vital components in the fight against diseases like cancer and AIDS — but Henrietta’s family was never told, nor were they given any money or credit for this contribution. The film, directed by Tony winner George C. Wolfe (Angels in America), pivots back and forth between flashbacks of Henrietta and modern day, as her grown daughter Deborah (Winfrey) and Skloot (Rose Byrne) piece together what happened. While the book is a family saga mixed with history and science, Wolfe centered the film on Deborah’s unrelenting quest to connect to her mother, who died when she was just a child. Explains Wolfe: “I instantly responded to Deborah. Not all of us have cells that revolutionized medicine, but we all want to know who our parents are.”

EW talked to Winfrey about this incredible performance, the legacy of HeLa, and why she’s acting more now.

ENTERTAINMENT WEEKLY: You optioned this book in 2010. What drew you to this?
OPRAH WINFREY: I lived in Baltimore as a reporter for eight years. I traveled the same streets that Henrietta walked on, her family. I’ve been in the neighborhood where Deborah lived. I was a real community engaged person in Baltimore. I never once in eight years heard the name HeLa or Henrietta Lacks. I couldn’t believe it. So I was like how is it possible that I, a student of African American history, lived in the community, never even heard of this person. If I haven’t heard of her then I’m sure there are lots of other people who haven’t heard. It’s in my nature to want to share stuff. Information. Croissants. Great pajamas. Juices. [Laughs.] Whatever I’ve found that I think you don’t know about, I wanna tell you about it!

Even though it’s a complicated story to try and get on film, I thought HBO was certainly the best place in the world to do it because they let you paint your dreams over there and really give you the freedom to create as you choose. George found the way in to tell the story that felt like it connected to the lives of the family in a way that wasn’t just about the science of it. I was quite frankly afraid of the science because science is like spinach — people don’t want to take it in, hard to convey it.

Did you always imagine playing Deborah?
Absolutely not. I had other people in mind. I had two really specific people in mind who I can’t tell you now because they would say, “Well why didn’t you call me, Oprah?” But I did say to [HBO Films President] Len Amato for five years that I had these other actresses in line to do it and he was like, “You should do it.” And then George said, “You have to do it.” I had wanted to work with George. George and I were trying to do a play on Broadway together. We were trying to do ‘night, Mother and it wasn’t working out. This was my opportunity to work with George. I pray it won’t be the last time because he’s a hoot and a holler to work for. He’s great as a therapist or a director! [Laughs]

It’s such a physical performance, especially with the manic episodes. How did you prepare for this? Did you meet with people with mania?
I dealt with some manic people. I actually went back and looked at some tapes of people. The thing about mania is it plays itself differently in every person. So I talked to her family members about how it showed up in her. They could see the acceleration start to happen in her eyes and in her movements. By the time she actually reaches the state where she’s’ breaking out in hives, she’s literally jumping from thought to thought to thought. So it’s a heightened way of being that I have no relatability to because I live in the cool, chill space. So I would meditate before going into that space. But I would do specific meditations to get myself to that peak to literally raise the blood pressure. There were a couple of those scenes where I thought, “I think I’ve raised my blood pressure so much that I think I need to sit down.”

The scene in the cabin where she’s recalling all the bad memories, I used my own stuff and other people’s stuff. Particularly in the scene in the slave cabin where she’s recalling her brother being beaten. One of my girls in my school grew up with an aunt who flogged her daily. So I actually sat down and talked with her about some of those stories and asked her if she would share them with me for this specific purpose of taking in the energy of that. I grew up abused by my grandmother but my grandmother wasn’t mean. My grandmother really loved me. It’s different when you grow up in a house with somebody who every day is out to get you.

On the day I was going to do that scene, I called one of my South African daughters who’s in school in the United States. I said, “I’m on my way to do this scene and obviously I have my own memories. Would you be willing to share with me?” So I was crying on the phone. As a result, we agreed to go into therapy for it. It was a big moment for us. Up until that time she was like, “No I’m not ready to talk about it. I’m not ready to deal with it.”

How were the Lacks family? Were they thrilled Oprah was playing Deborah? [Note: Some of Lacks’ relatives have publicly expressed displeasure at their portrayals in the book plus are seeking compensation for HeLa]
I would say that a majority of the family members, certainly the ones I had spoken to, are pleased and actually thrilled that this story is being told, being told by me, by HBO. This gives validation to the legacy of their grandmother and mother and aunt in a way that nothing could. One of the things I said to them is, “Look, when this movie is done, everyone is going to have their own memories of Deborah. Your memories are yours to cherish. I am here to represent the essence and in every way I can the spirit and energy of her. I am not her. I can’t be her. So in the end, when you judge it, it can’t be judged by, ‘Oh mama wouldn’t have done that.’ I’m just here to represent the essence of it.”

With Greenleaf, A Wrinkle in Time, and this, you’re acting more. Is that because the talk show is over?
It is not by design or strategy. It’s not like I said, “Oh gee I wanna do more acting.” If you see me in something else, it will because someone said, “Hey, Oprah, wanna do this?!”