From the outset of the study in April 2012, Children's Hospital of Philadelphia was in uncharted territory. So were the parents who consented to give their terminally ill offspring an experimental gene therapy for leukemia.
But the little children - 22 and counting - have shown them the way.
The first child, as the world learned a year ago, was Emily Whitehead of Philipsburg, Pa. She demonstrated that the bioengineered T cells can have catastrophic side effects, and pointed the way for her doctors to find an antidote drug. They also reduced the T cell dosage in children who followed her.
"She taught us that," said Children's oncologist Stephan Grupp. "We're learning a lot from every single patient."
Now a straight-A third grader, Emily and her parents, Tom and Kari, have become the poster family for the treatment, graciously sharing their experiences with the media, medical groups, and most of all, families battling childhood leukemia.
"Emily likes to take gifts to the kids in the hospital and tell them it's going to be OK," her father said. "But it's tough. Seven kids she played with in [the hospital] in Hershey or Philadelphia have died."
Acute lymphoblastic leukemia was a death sentence in the 1960s. Today, with potent chemotherapies, radiation, and bone marrow transplantation, more than 80 percent of the 3,000 children diagnosed annually in the United States are cured.
But the organ-damaging, growth-stunting, harrowing treatments take a lifelong toll.
The children in the T cell study have confirmed what the researchers theorized: Turbocharging the immune system is a better way. Although the T cells cause intense fevers, headaches, and nausea when they attack the leukemia, these effects last only a few days.
And then comes a wonderful new normal.
Tori Lee, 10, of Ocean Township, N.J., got her T cells in April.
"I don't know if it's going to be the cure. But her quality of life has been amazing," said her mother, Dana.
Rachel Weinstein, 7, of Maple Valley, Wash., got her T cells in July.
"I have not seen my daughter look this good and feel this good in a very long time," said her mother, Angelique. "For her to return to school is amazing. If not for this T cell trial, we'd have to have done another bone marrow transplant, and she'd have another year out of school."
Austin Schuetz, of Fall River, Wis., got his T cells in September.
"He feels great. He wears us out," his mother, Kim Schuetz, said. "He just started kindergarten. He picked up right where he left off."
But these medical pioneers are also teaching that it is far too soon to declare victory.
Two children relapsed after months in glorious remission. For unknown reasons, their engineered T cells died.
"We treated them again with more T cells," Grupp said. "In one child, it didn't work. In the other, it did."
The child with another reprieve is Maddie Major, 8, a precocious spitfire from La Plata, Md., whose Facebook fans are legion.
"None of us expected her to respond again," said her mother, Robyn Major. "We were blown away when it worked."
But Maddie's bone marrow, while again cancer-free, is not producing healthy cells, so she is back in intensive care at Children's, where she is recovering from a near-fatal infection and awaiting a marrow transplant from her father.
"Maddie has paved the way in many ways," said her mother, watching as her daughter pulled off a sticky pad, loosening an electric wire and setting off the heart monitor.
"Maddie, stop that!" her mother said. "The nurses keep looking in to see if your heart has stopped."
If Maddie has amazed everyone, so, too, has Logan Parker, 7, of Ocean Township, N.J. (Coincidentally, he goes to the same school as Tori Lee.)
Logan's cancer came back in July, but so far, only as a lesion beneath the skin of his forehead.
"They've never seen it before as a subcutaneous relapse, not in the bone and blood," said his father, Richard.
So far, radiation is keeping the cancer under control, but that, his father said matter-of-factly, is sure to change: "It's things that are outside our control. But Logan makes it easy for us. He's tough. His spirits are high."
That was apparent in Esquire Magazine's 80th-anniversary issue in October. The publication featured "80 accomplished, extraordinary men, one born in each year of Esquire's history."
Above a photo of the 7-year-old wearing an impish, megawatt smile, the magazine wrote: "In the near future, our immune system will be genetically supercharged to kill cancer. We will all be like Logan Parker."