The sweeping chronicle of cancer that premieres this week on PBS has strong Philadelphia connections.
Cancer: The Emperor of All Maladies is famed documentarian Ken Burns' three-part, six-hour film adaptation of the Pulitzer Prize-winning, best-selling book. On Wednesday, the third and final episode prominently features a breakthrough immunotherapy being developed at the University of Pennsylvania and Children's Hospital of Philadelphia in partnership with pharmaceutical giant Novartis.
Another local tie is Barak Goodman, the award-winning director of the documentary. He grew up in the Philadelphia suburbs, and his parents are emeritus professors at Penn - Joan Goodman in education, Frank Goodman at the law school.
But Goodman and his production team had to be persuaded by author Siddhartha Mukherjee that the Philadelphia research, led by Penn gene-therapy pioneer Carl June, should be showcased.
"The decision to go to Philadelphia had nothing to do with my coming from there," Goodman said in a phone interview. "Sid impressed on us the importance of this trial. He said what Carl was doing was truly groundbreaking."
"It's enormously promising," Mukherjee, an oncologist at Columbia University Medical Center, said in a separate interview. "It's gone through the tough tests already. Some patients are already in long remissions."
Finding a way to harness the body's immune defenses has long been a holy grail of cancer research. It has proved to be monumentally difficult, largely because the immune system is tolerant of malignancy. After all, cancer cells are just mutated versions of the ones the immune system innately protects.
Breakthroughs in immunotherapy are so recent the field is conspicuously absent from Mukherjee's book, published in 2010.
But almost half of the final episode of the PBS film is devoted to it.
"We very much wanted to take the film all the way to today. We didn't want to stop with Sid's book - nor did Sid," Goodman said. "I think we first realized what was going on with immunotherapy when we went to the ASCO [American Society of Clinical Oncology] annual conference in Chicago three years ago. This subject was dominant. It was clear this was for real. It wasn't just a flash in the pan."
"We had to modify the script to keep up with the pace of discovery," said Mukherjee, who adds commentary throughout the film.
The final episode, "Finding the Achilles' Heel," includes the University of Texas immunologist whose novel strategy for taking molecular brakes off the immune system led to the approval of the drug Yervoy for melanoma in 2011. Two more "checkpoint inhibitors" have since been approved, with more in the pipeline.
There was another part of the behind-the-script debate that initially weighed against the Philadelphia connection.
Emily Whitehead of Philipsburg, Pa., the first child to receive the immunotherapy at Children's in 2012, was an international media sensation when her story became public.
And no wonder. The adorable 7-year-old pixie, out of treatment options for her leukemia and weeks from death, got the immunotherapy - which triggered a lethal immune overreaction. Doctors threw the medical version of a Hail Mary pass, giving her a brand-new immune-modulating rheumatoid arthritis drug. It saved her, and, from then on, became a vital part of the immunotherapy protocol.
Three weeks after her near-death experience, Emily was cancer-free.
"We knew about Emily's story, but we wanted to stay away from it because it wasn't ours," Goodman said. "Every other case study in the film was one we found."
Goodman changed his mind when he met Emily - who will celebrate three years in remission next month - and her parents, Tom and Kari. Besides being articulate and cooperative, the couple had photos and videos.
"The Whiteheads were great," Goodman said.
Like the book, the documentary presents the story of cancer as a never-ending cycle of excitement about the latest "cure," followed by the letdown that cancer is, as one researcher says, "evolution at hyperspeed," ceaselessly powerful and adaptable. Cancer has been able to evade even revolutionary targeted therapies such as Herceptin and Gleevec, which disrupt specific molecules needed for malignant growth and spread.
The filmmakers strive not to oversell immunotherapy, while suggesting that only a weapon as adaptable as cancer can conquer it.
"That weapon, many scientists believe, is the human immune system," the narrator intones.
"The history of cancer is full of these moments of exuberance and, then, a crash," Goodman said. "But [immunotherapy] really seems to have legs."
Mukherjee has the last word as the film ends: "If the cancer cell is evolving, then so are we."
"THE EMPEROR OF ALL MALADIES"
9 to 11 p.m. Monday through Wednesday on WHYY (Channel 12).
Monday: "Magic Bullets" The first episode follows the centuries-long search for a "cure" for cancer, centering on the story of Boston Children's Hospital pediatrician Sidney Farber, the father of modern chemotherapy. His pioneering work against childhood leukemia in the late 1940s galvanized a "war on cancer" - one that continually showed the elusive nature of cures. Interwoven with Farber's tale is the contemporary story of a 14-month-old diagnosed with acute lymphoblastic leukemia.
Tuesday: "The Blind Men and the Elephant" After President Richard Nixon's declaration of the "war on cancer" in 1971, rapid progress is made in understanding the essential nature of the cancer cell, leading to the revolutionary discovery of the genetic basis of cancer. Still, few novel therapies become available until the late 1990s, with the advent of more precise, molecularly targeted therapies. The science history is intertwined with the contemporary story of an oncologist diagnosed with breast cancer.
Wednesday: "Finding the Achilles' Heel" Buoyant optimism over "targeted" therapies gives way to the recognition that cancer is even more complex than imagined. Amid calls for a new focus on prevention and early detection, scientists make headway in harnessing the immune system against cancer. The film follows two experimental immunotherapy patients - Doug Rogers, a NASCAR mechanic with advanced melanoma, and Emily Whitehead, a 7-year-old with leukemia.