David and Goliath: The Triumph of the Underdog Read online

  That’s three remote misses.

  Losing a parent is not like having your house bombed or being set upon by a crazed mob. It’s worse. It’s not over in one terrible moment, and the injuries do not heal as quickly as a bruise or a wound. But what happens to children whose worst fear is realized—and then they discover that they are still standing? Couldn’t they also gain what Shuttlesworth and the Blitz remote misses gained—a self-confidence that is the very father and mother of courage?8

  “The officer who took Shuttlesworth to jail,” McWhorter writes of another of Shuttlesworth’s many run-ins with white authority, “struck him, kicked him in the shin, called him a monkey, and then goaded him, ‘Why don’t you hit me?’ Shuttlesworth replied, ‘Because I love you.’ He folded his arms and smiled the rest of the way to jail, where, forbidden to sing or pray, he took a nap.”

  8.

  The work that Freireich had done in stopping the bleeding was a breakthrough. It meant that children could now be kept alive long enough that the underlying cause of their illness could be treated. But leukemia was an even harder problem. Only a handful of drugs were known to be of any use at all against the disease. There were the cell-killing drugs 6-MP and methotrexate, and there was the steroid prednisone. But each was potentially severely toxic and could be given in limited doses only, and because it could be given in limited doses only, it could wipe out only some of a child’s cancer cells. The patient would get better for a week or so. Then the cells that had survived would start to multiply, and the cancer would come roaring back.

  “One of the consultants at the clinical center was a man named Max Wintrobe,” Freireich said. “He was world-famous because he wrote the first textbook of hematology, and he had written a review of the current state of the treatment of leukemia in children. I have a quotation from him that I show my students to this day. It says, ‘These drugs cause more harm than good because they just prolong the agony. The patients all die anyway. The drugs make them worse, so you shouldn’t use them.’ This was the world’s authority.”

  But Frei and Freireich and a companion group at the Roswell Park Memorial Institute in Buffalo led by James Holland became convinced that the medical orthodoxy had it backwards. If the drugs weren’t killing enough cancer cells, didn’t that mean that the children needed more aggressive treatment, not less? Why not combine 6-MP and methotrexate? They each attacked cancer cells in different ways. They were like the army and the navy. Maybe the cells that survived 6-MP would be killed by methotrexate. And what if they added prednisone into the mix? It could be the air force, bombing from the air while the other drugs attacked from the land and sea.

  Then Freireich stumbled across a fourth drug, one derived from the periwinkle plant. It was called vincristine. Someone from the drug company Eli Lilly brought it by the National Cancer Institute for researchers to study. No one knew much about it, but Freireich had a hunch that it might work against leukemia. “I had twenty-five kids dying,” he said. “I had nothing to offer them. My feeling was, I’ll try it. Why not? They’re going to die anyway.” Vincristine showed promise. Freireich and Frei tried it out on children who no longer responded to the other drugs, and several went into temporary remission. So Frei and Freireich went to the NCI’s research oversight board to ask for permission to test all four drugs together: army, navy, air force, marines.

  Cancer is now routinely treated with drug “cocktails,” complicated combinations of two or three or even four or five medications simultaneously. But in the early 1960s, it was unheard of. The drugs available to treat cancer in those years were considered just too dangerous. Even vincristine, Freireich’s prized new discovery, was utterly terrifying. Freireich learned that the hard way. “Did it have side effects? You bet,” he said. “It caused serious depression, neuropathies. The kids got paralyzed. When you get a toxic dose, you end up in coma. Of the first fourteen children we treated, one or two actually died. Their brains were totally fried.” Max Wintrobe 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 matched the infection with the most appropriate antibiotic. Antibiotics were never given in combination. You gave a second antibiotic only when the first one stopped working. “One of the first things Jay said to us was, no deal,” DeVita remembered. “These kids spike a fever, you treat them immediately, and you treat them with combinations of antibiotics, because they’re going to be dead in three hours if you don’t.” DeVita had an antibiotic that he had been told should never be administered in the spinal fluid. Freireich told him to give it to a patient—in the spinal fluid. “Freireich told us to do things,” DeVita said, “that we had been taught were heretical.

  “He was subject to so much criticism,” DeVita continued. “The clinical associates thought that what he was doing was completely nuts. He carried the weight of it. They would insult him—especially the guys from Harvard. They used to stand in the back of the room and heckle. He would say something, and they would say, ‘Sure, Jay, and I’m going to fly to the moon.’ It was awful, and Jay was there, all the time, hovering over you, looking at every lab test, going over every chart. God help you if you didn’t do something for one of his patients. He was ferocious. He would do things and say things that got him into trouble, or go to some meeting and insult someone and Frei would have to come in and smooth things over. Did he care what people thought of him? Maybe. But not enough to stop doing what he thought was right.10

  “How Jay did it,” he said finally, “I don’t know.”

  But we do know, don’t we? He had been through worse.

  In 1965, Freireich and Frei published “Progress and Perspectives in the Chemotherapy of Acute Leukemia” in Advances in Chemotherapy, announcing that they had developed a successful treatment for childhood leukemia.11 Today, the cure rate for this form of cancer is more than 90 percent. The number of children whose lives have been saved by the efforts of Freireich and Frei and the researchers who followed in their footsteps is in the many, many thousands.

  9.

  Does this mean that Freireich should be glad he had the childhood he had? The answer is plainly no. What he went through as a child no child should ever have to endure. Along the same lines, I asked every dyslexic I interviewed the question posed at the beginning of the previous chapter: Would they wish dyslexia on their own children? Every one of them said no. Grazer shuddered at the thought. Gary Cohn was horrified. David Boies has two boys who are both dyslexic, and watching them grow up in an environment where reading early and well counted for everything nearly broke his heart. Here were one of the top producers in Hollywood, one of the most powerful bankers on Wall Street, and one of the best trial lawyers in the country—all of whom recognized how central their dyslexia was to their success. Yet they also knew firsthand what the price of that success was—and they could not bring themselves to wish that same experience on their own children.

  But the question of what any of us would wish on our children is the wrong question, isn’t it? The right question is whether we as a society need people who have emerged from some kind of trauma—and the answer is that we plainly do. This is not a pleasant fact to contemplate. For every remote miss who becomes stronger, there are countless near misses who are crushed by what they have been through. There are times and places, however, when all of us depend on people who have been hardened by their experiences.12 Freireich had the courage to think the unthinkable. He experimented on children. He took them through pain no human being should ever have to go through. And he did it in no small part because he understood from his own childhood experience that it is possible to emerge from even the darkest hell healed and restored. Leukemia was a direct hit. He turned it into a remote miss.

  At one point, in the midst of his battle, Freireich realized that the standard method of monitoring the children’s cancer—taking a blood sample and counting the number of cancer cells under a microscope—wasn’t good enough. Blood was misleading. A child’s blood could look cancer free. But the disease could still be lurking in her bone marrow—which meant that you had to go through the painful process of gathering bone marrow samples, over and over again, month after month, until you were sure the cancer was gone. Max Wintrobe heard what Freireich was up to and tried to stop him. Freireich was torturing the patients, Wintrobe said. He was not wrong. His was the empathetic response. But it is also the response that would never have led to a cure.

  “We used to do bone marrows by grabbing their legs like this,” Freireich told me. He held one of his giant hands out, as if wrapped around a child’s tiny femur. “We’d stick the needle in without anesthesia. Why no anesthesia? Because they’d scream just as much when you gave them an anesthesia shot. It’s an eighteen- or nineteen-gauge needle straight into the shinbone, right below the knee. The kids are hysterical. The parents and nurses hold the kid down. We did that for every cycle. We needed to know if their bone marrow had recovered.”

  When he said the words “grabbing their legs like this,” an involuntary grimace passed across Freireich’s face, as if for a moment he could feel what an eighteen-gauge needle straight into the shinbone of a small child felt like, and as if the feeling of that pain would give him pause. But then, as quickly as it appeared, it was gone.

  10.

  When Jay Freireich was doing his medical training, he met a nurse named Haroldine Cunningham. He asked her out on a date. She said no. “All the young doctors were pretty aggressive,” she remembers. “He had a reputation for being very outspoken. He called a couple of times, and I didn’t go.” But one weekend, Cunningham went to visit her aunt in a suburb outside of Chicago—and the phone rang. It was Freireich. He had taken the train out from Chicago and was calling from the train station. “He said, ‘I’m here,’” she remembers. “He was very persistent.” This was the early 1950s. They have been married ever since.

  Freireich’s wife is as small as Freireich is enormous, a tiny woman with a deep and obvious reservoir of strength. “I see the man. I see his needs,” she said. He would come home from the hospital late at night, from the blood and the suffering, and she would be there. “She is the first person who ever loved me,” Freireich said simply. “She is my angel from heaven. She found me. I think she detected something in me that could be nourished. I defer to her in all things. She keeps me going every day.”

  Haroldine grew up poor as well. Her family lived in a tiny apartment outside Chicago. When she was twelve, she tried the bathroom door—and couldn’t get in. “My mother had locked the door,” she said. “I got the neighbor from downstairs, who was the landlord. He opened the window and got in. We called the hospital. She died there. You don’t really know when you’re twelve or thirteen years old what is going on, but I knew she was unhappy. My father was away, of course. He was not a terrific father.”

  She sat in the chair in her husband’s office, this woman who carved an island of calm out of the turbulence of her husband’s life. “You have to realize, of course, that love doesn’t always save people you want to save. Somebody asked me once, weren’t you angry? And I said, no, I wasn’t, I understood her misery.

  “There are things that either build you up or put you down. Jay and I have that in common.”

  1 When Freireich was completing his medical training, a distant relative died and left him six hundred dollars. “I had a patient, a used-car dealer who said he’d sell me a used car,” Freireich said. “It was a 1948 Pontiac. One night I was drunk and out partying with some girls, and I drove into the side of a brand-new Lincoln. I should have gone to jail for it, but the police came over and recognized me immediately as a county intern, so they said, ‘We’ll take care of it.’” This was what it was like being a doctor in those days. It is safe to say this doesn’t happen anymore.

  2 The twelve are George Washington, Thomas Jefferson, James Monroe, Andrew Jackson, Andrew Johnson, Rutherford Hayes, James Garfield, Grover Cleveland, Herbert Hoover, Gerald Ford, Bill Clinton, and Barack Obama.

/>   3 Brown begins with these haunting lines from Wordsworth, whose mother died when he was eight:

  She who was the heart

  And hinge of all our learnings and our loves:

  She left us destitute and, as we might,

  Trooping together.

  4 Or, as the English essayist Thomas De Quincey famously put it: “It is, or it is not, according to the nature of men, an advantage to be orphaned at an early age.”

  5 If you want to understand the full scientific context of the fight against leukemia, there is no better source than Siddhartha Mukherjee’s Pulitzer Prize–winning The Emperor of All Maladies: A Biography of Cancer. Mukherjee has a full chapter on the war on leukemia. It is well worth reading.

  6 In the 1960s, the daughter of the novelist Peter de Vries died of leukemia. He wrote a heartbreaking novel based on the experience called The Blood of the Lamb. De Vries writes:

  So we were back in the Children’s Pavilion, and there was again the familiar scene: the mothers with their nearly dead, the false face of mercy, the Slaughter of the Innocents. A girl with one leg came unsteadily down the hall between crutches, skillfully encouraged by nurses. Through the pane in a closed door a boy could be seen sitting up in bed, bleeding from everything in his head; a priest lounged alertly against the wall, ready to move in closer. In the next room a boy of five was having Methotrexate pumped into his skull, or, more accurately, was watching a group of mechanics gathered solemnly around the stalled machine. In the next a baby was sitting up watching a television set on which a panel show was in progress…Among the parents and children, flung together in a hell of prolonged farewell, wandered forever the ministering vampires from Laboratory, sucking samples from bones and veins to see how went with each the enemy that had marked them all. And the doctors in their butchers’ coats, who severed the limbs and gouged the brains and knifed the vitals where the demon variously dwelt, what did they think of these best fruits of ten million hours of dedicated toil? They hounded the culprit from organ to organ and joint to joint till nothing remained over which to practice their art: the art of prolonging sickness.