The Emperor of All Maladies. Siddhartha Mukherjee

      That winter of 1948, a severe and dismal chill descended on Boston. Snowstorms broke out, bringing Farber’s clinic to a standstill. The narrow asphalt road out to Longwood Avenue was piled with heaps of muddy sleet, and the basement tunnels, poorly heated even in the fall, were now freezing. Daily injections of antifolates became impossible, and Farber’s team backed down to three times a week. In February, when the storms abated, the daily injections started again.

      Meanwhile, news of Farber’s experience with childhood leukemia was beginning to spread, and a slow train of children began to arrive at his clinic. And case by case, an incredible pattern emerged: the antifolates could drive leukemia cell counts down, occasionally even resulting in their complete disappearance—at least for a while. There were other remissions as dramatic as Sandler’s. Two boys treated with aminopterin⁹¹ returned to school. Another child, a two-and-a-half-year-old⁹² girl, started to “play and run about” after seven months of lying in bed. The normalcy of blood almost restored a flickering, momentary normalcy to the childhood.

      But there was always the same catch. After a few months of remission, the cancer would inevitably relapse, ultimately flinging aside even the most potent of Yella’s drugs. The cells would return in the bone marrow, then burst out into the blood, and even the most active antifolates would not keep their growth down. Robert Sandler died in 1948, having responded for a few months.

      Yet the remissions, even if temporary, were still genuine remissions—and historic. By April 1948, there was just enough data⁹³ to put together a preliminary paper for the New England Journal of Medicine. The team had treated sixteen patients. Of the sixteen, ten had responded. And five children—about one-third of the initial group—remained alive four or even six months after their diagnosis. In leukemia, six months of survival was an eternity.

      Farber’s paper, published on June 3, 1948, was seven pages long, jam-packed with tables, figures, microscope photographs, laboratory values, and blood counts. Its language was starched, formal, detached, and scientific. Yet, like all great medical papers, it was a page-turner. And like all good novels, it was timeless: to read it today is to be pitched behind the scenes into the tumultuous life of the Boston clinic, its patients hanging on for life as Farber and his assistants scrambled to find new drugs for a dreadful disease that kept flickering away and returning. It was a plot with a beginning, a middle, and, unfortunately, an end.

      The paper was received, as one scientist recalls, “with skepticism, disbelief, and outrage.”⁹⁴ But for Farber, the study carried a tantalizing message: cancer, even in its most aggressive form, had been treated with a medicine, a chemical. In six months between 1947 and 1948, Farber thus saw a door open—briefly, seductively—then close tightly shut again. And through that doorway, he glimpsed an incandescent possibility. The disappearance of an aggressive systemic cancer via a chemical drug was virtually unprecedented in the history of cancer. In the summer of 1948, when one of Farber’s assistants performed a bone marrow biopsy on a leukemic child after treatment with aminopterin, the assistant could not believe the results. “The bone marrow looked so normal,”⁹⁵ he wrote, “that one could dream of a cure.”

      And so Farber did dream. He dreamed of malignant cells being killed by specific anticancer drugs, and of normal cells regenerating and reclaiming their physiological spaces; of a whole gamut of such systemic antagonists to decimate malignant cells; of curing leukemia with chemicals, then applying his experience with chemicals and leukemia to more common cancers. He was throwing down a gauntlet for cancer medicine. It was then up to an entire generation of doctors and scientists to pick it up.

       A Private Plague

      We reveal ourselves⁹⁶ in the metaphors we choose for depicting the cosmos in miniature.

      —Stephen Jay Gould

      Thus, for 3,000 years and more⁹⁷, this disease has been known to the medical profession. And for 3,000 years and more, humanity has been knocking at the door of the medical profession for a “cure.”

      —Fortune, March 1937

      Now it is cancer’s turn⁹⁸ to be the disease that doesn’t knock before it enters.

      —Susan Sontag, Illness as Metaphor

      We tend to think of cancer as a “modern” illness because its metaphors are so modern. It is a disease of overproduction, of fulminant growth—growth unstoppable, growth tipped into the abyss of no control. Modern biology encourages us to imagine the cell as a molecular machine. Cancer is that machine unable to quench its initial command (to grow) and thus transformed into an indestructible, self-propelled automaton.

      The notion of cancer as an affliction that belongs paradigmatically to the twentieth century is reminiscent, as Susan Sontag argued so powerfully in her book Illness as Metaphor, of another disease once considered emblematic of another era: tuberculosis in the nineteenth century. Both diseases, as Sontag pointedly noted, were similarly “obscene—in the original meaning of that word: ill-omened, abominable, repugnant to the senses.” Both drain vitality; both stretch out the encounter with death; in both cases, dying, even more than death, defines the illness.

      But despite such parallels, tuberculosis belongs to another century. TB (or consumption) was Victorian romanticism brought to its pathological extreme—febrile, unrelenting, breathless, and obsessive. It was a disease of poets: John Keats involuting silently⁹⁹ toward death in a small room overlooking the Spanish Steps in Rome, or Byron, an obsessive romantic, who fantasized about dying of the disease to impress his mistresses. “Death and disease are often beautiful,¹⁰⁰ like . . . the hectic glow of consumption,” Thoreau wrote in 1852. In Thomas Mann’s The Magic Mountain, this “hectic glow” releases a feverish creative force in its victims—a clarifying, edifying, cathartic force that, too, appears to be charged with the essence of its era.

      Cancer, in contrast, is riddled with more contemporary images. The cancer cell is a desperate individualist, “in every possible sense, a nonconformist,”¹⁰¹ as the surgeon-writer Sherwin Nuland wrote. The word metastasis, used to describe the migration of cancer from one site to another, is a curious mix of meta and stasis—“beyond stillness” in Latin—an unmoored, partially unstable state that captures the peculiar instability of modernity. If consumption once killed its victims by pathological evisceration (the tuberculosis bacillus gradually hollows out the lung), then cancer asphyxiates us by filling bodies with too many cells; it is consumption in its alternate meaning—the pathology of excess. Cancer is an expansionist disease; it invades through tissues, sets up colonies in hostile landscapes, seeking “sanctuary” in one organ and then immigrating to another. It lives desperately, inventively, fiercely, territorially, cannily, and defensively—at times, as if teaching us how to survive. To confront cancer is to encounter a parallel species, one perhaps more adapted to survival than even we are.

      This image—of cancer as our desperate, malevolent, contemporary doppelgänger—is so haunting because it is at least partly true. A cancer cell is an astonishing perversion of the normal cell. Cancer is a phenomenally successful invader and colonizer in part because it exploits the very features that make us successful as a species or as an organism.

      Like the normal cell, the cancer cell relies on growth in the most basic, elemental