David and Goliath: Underdogs, Misfits, and the Art of Battling Giants

thought the humane approach was not to use any drugs at all. Freireich and Frei wanted to use four, all at once. Frei went before the NCI advisory board to ask for approval. He got nowhere.
    “There was a senior hematologist on the board by the name of Dr. Carl Moore, who happened to be a friend of my father’s from St. Louis,” Frei remembered years later. “I had always considered him a friend, too. But my presentation struck him as being outrageous. He didn’t deal in pediatric diseases like childhood leukemia, so he talked about Hodgkin’s disease in adults. He said that if you have a patient who has widespread Hodgkin’s disease, then it’s best to tell that patient to go to Florida and enjoy life. If patients are having too many symptoms from their Hodgkin’s disease, you treat them with a little X-ray or possibly a little nitrogen mustard, but give the smallest dose possible. Anything more aggressive than that is unethical, and giving four drugs at a time is unconscionable.”
    Frei and Freireich were desperate. They went to their boss, Gordon Zubrod. Zubrod had been through the wars with Freireich over the platelets controversy. He had only reluctantly approved the vincristine experiment. He was responsible for what happened on the second floor. If somehow things didn’t go well, he would be the one hauled before a congressional committee. Can you imagine? Two renegade researchers are giving experimental and highly toxic cocktails of drugs to four- and five-year-olds at a government laboratory. He had grave reservations. But Frei and Freireich persisted. Actually, Frei persisted; Freireich isn’t the kind of person who can be trusted with a delicate negotiation. “I couldn’t have done anything without Tom,” Freireich admitted. “Frei is the inverse of me. He is deliberate and very humane.” Yes, the drugs were all poisons, Frei argued. But they were poisonous in different ways, which meant that if you were careful with the dosages—and if you were aggressive enough in the way you treated the side effects—the children could be kept alive. Zubrod gave in. “It was crazy,” Freireich said. “But smart and correct. I thought about it and I knew it would work. It was like the platelets. It had to work!”
    The trial was called the VAMP regimen. Some of the clinical associates—the junior doctors assisting on the ward—refused to take part. They thought Freireich was insane. “I had to do it all myself,” Freireich said. “I had to order the drugs. I had to mix them. I had to inject them. I had to do the blood counts. I had to measure the bleeding. I had to do the bone marrows. I had to count the slides.” There were thirteen children in the initial round of the trial. The first was a young girl. Freireich started her off with a dose that turned out to be too high, and she almost died. He sat with her for hours. He kept her going with antibiotics and respirators. She pulled through, only to die later when her cancer returned. But Frei and Freireich were learning. They tinkered with the protocol and moved on to patient number two. Her name was Janice. She recovered, as did the next child and the next child. It was a start.
    The only problem was that the cancer wasn’t gone. A handful of malignant cells was still lurking. One bout of chemotherapy wouldn’t be enough, they realized. So they started up another round. Would the disease return? It did. They needed to try again. “We gave them three treatments,” Freireich said. “Twelve of the thirteen relapsed. So I decided, there’s only one way to do this. We are going to continue treating them every month—for a year.” 9
    “If people thought I was crazy before, now they thought I was completely crazy,” Freireich went on. “These were children who seemed completely normal, in complete remission, walking around, playing football, and I was going to put them in the hospital again and make them sick again. No platelets. No white cells. Hemorrhage. Infection.” VAMP wiped out the children’s immune system. They were defenseless. For their parents, it was agony. In order to have a chance at life—they were told—their child had to be brought savagely and repeatedly to the brink of death.
    Freireich threw himself into the task, using every ounce of his energy and audacity to keep his patients alive. In those days, when a patient developed a fever, the physician took a blood culture, and when the results came back, the doctor