The Emperor of All Maladies. Siddhartha Mukherjee
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exquisitely resistant to most chemical reactions, for its job is to maintain the stability of genetic information. But X-rays can shatter strands of DNA or generate toxic chemicals that corrode DNA. Cells respond to this damage by dying or, more often, by ceasing to divide. X-rays thus preferentially kill the most rapidly proliferating cells in the body, cells in the skin, nails, gums, and blood.
This ability of X-rays to selectively kill rapidly dividing cells did not go unnoticed—especially by cancer researchers. In 1896, barely a year after Röntgen191 had discovered his X-rays, a twenty-one-year-old Chicago medical student, Emil Grubbe, had the inspired notion of using X-rays to treat cancer. Flamboyant, adventurous, and fiercely inventive, Grubbe had worked in a factory in Chicago that produced vacuum X-ray tubes, and he had built a crude version of a tube for his own experiments. Having encountered X-ray-exposed factory workers with peeling skin and nails—his own hands had also become chapped and swollen from repeated exposures—Grubbe quickly extended the logic of this cell death to tumors.
On March 29, 1896, in a tube factory on Halsted Street (the name bears no connection to Halsted the surgeon) in Chicago, Grubbe began to bombard Rose Lee, an elderly woman with breast cancer, with radiation using an improvised X-ray tube. Lee’s cancer had relapsed after a mastectomy, and the tumor had exploded into a painful mass in her breast. She had been referred to Grubbe as a last-ditch measure, more to satisfy his experimental curiosity than to provide any clinical benefit. Grubbe looked through the factory for something to cover the rest of the breast, and finding no sheet of metal, wrapped Lee’s chest in some tinfoil that he found in the bottom of a Chinese tea box. He irradiated her cancer every night for eighteen consecutive days. The treatment was painful—but somewhat successful. The tumor in Lee’s breast ulcerated, tightened, and shrank, producing the first documented local response in the history of X-ray therapy. A few months after the initial treatment, though, Lee became dizzy and nauseated. The cancer had metastasized to her spine, brain, and liver, and she died shortly after. Grubbe had stumbled on another important observation: X-rays could only be used to treat cancer locally, with little effect on tumors that had already metastasized.*
Inspired by the response, even if it had been temporary, Grubbe began using X-ray therapy to treat scores of other patients with local tumors. A new branch of cancer medicine, radiation oncology, was born, with X-ray clinics mushrooming up in Europe and America. By the early 1900s, less than a decade after Röntgen’s discovery, doctors waxed ecstatic about the possibility of curing cancer with radiation. “I believe this treatment is an absolute cure192 for all forms of cancer,” a Chicago physician noted in 1901. “I do not know what its limitations are.”
With the Curies’ discovery of radium in 1902, surgeons could beam thousandfold more powerful bursts of energy on tumors. Conferences and societies on high-dose radiation therapy were organized in a flurry of excitement. Radium was infused into gold wires and stitched directly into tumors, to produce even higher local doses of X-rays. Surgeons implanted radon pellets into abdominal tumors. By the 1930s and ’40s, America had a national surplus of radium, so much so that it was being advertised for sale to laypeople193 in the back pages of journals. Vacuum-tube technology advanced in parallel; by the mid-1950s variants of these tubes could deliver blisteringly high doses of X-ray energy into cancerous tissues.
Radiation therapy catapulted cancer medicine into its atomic age—an age replete with both promise and peril. Certainly, the vocabulary, the images, and the metaphors bore the potent symbolism of atomic power unleashed on cancer. There were “cyclotrons” and “supervoltage rays” and “linear accelerators” and “neutron beams.” One man was asked to think of his X-ray therapy as “millions of tiny bullets of energy.”194 Another account of a radiation treatment is imbued with the thrill and horror of a space journey: “The patient is put on a stretcher195 that is placed in the oxygen chamber. As a team of six doctors, nurses, and technicians hover at chamber-side, the radiologist maneuvers a betatron into position. After slamming shut a hatch at the end of the chamber, technicians force oxygen in. After fifteen minutes under full pressure . . . the radiologist turns on the betatron and shoots radiation at the tumor. Following treatment, the patient is decompressed in deep-sea-diver fashion and taken to the recovery room.”
Stuffed into chambers, herded in and out of hatches, hovered upon, monitored through closed-circuit television, pressurized, oxygenated, decompressed, and sent back to a room to recover, patients weathered the onslaught of radiation therapy as if it were an invisible benediction.
And for certain forms of cancer, it was a benediction. Like surgery, radiation was remarkably effective at obliterating locally confined cancers. Breast tumors were pulverized with X-rays. Lymphoma lumps melted away. One woman with a brain tumor196 woke up from her yearlong coma to watch a basketball game in her hospital room.
But like surgery, radiation medicine also struggled against its inherent limits. Emil Grubbe had already encountered the first of these limits with his earliest experimental treatments: since X-rays could only be directed locally, radiation was of limited use for cancers that had metastasized.* One could double and quadruple the doses of radiant energy, but this did not translate into more cures. Instead, indiscriminate irradiation left patients scarred, blinded, and scalded by doses that had far exceeded tolerability.
The second limit was far more insidious: radiation produced cancers. The very effect of X-rays killing rapidly dividing cells—DNA damage—also created cancer-causing mutations in genes. In the 1910s, soon after the Curies had discovered radium, a New Jersey corporation called U.S. Radium began to mix radium with paint to create a product called Undark—radium-infused paint that emitted a greenish white light at night. Although aware of the many injurious effects of radium, U.S. Radium promoted Undark for clock dials, boasting of glow-in-the-dark watches. Watch painting was a precise and artisanal craft, and young women with nimble, steady hands were commonly employed. These women were encouraged to use the paint without precautions, and to frequently lick the brushes with their tongues to produce sharp lettering on watches.
Radium workers soon began to complain of jaw pain, fatigue, and skin and tooth problems. In the late 1920s, medical investigations revealed that the bones in their jaws had necrosed, their tongues had been scarred by irradiation, and many had become chronically anemic (a sign of severe bone marrow damage). Some women, tested with radioactivity counters, were found to be glowing with radioactivity. Over the next decades, dozens of radium-induced tumors sprouted in these radium-exposed workers—sarcomas and leukemias, and bone, tongue, neck, and jaw tumors. In 1927, a group of five severely afflicted women in New Jersey—collectively termed “Radium girls”197 by the media—sued U.S. Radium. None of them had yet developed cancers; they were suffering from the more acute effects of radium toxicity—jaw, skin, and tooth necrosis. A year later, the case was settled out of court with a compensation of $10,000 each to the girls, and $600 per year to cover living and medical expenses. The “compensation” was not widely collected. Many of the Radium girls, too weak even to raise their hands to take an oath in court, died of leukemia and other cancers soon after their case was settled.
Marie Curie died of leukemia198 in July 1934. Emil Grubbe, who had been exposed to somewhat weaker X-rays, also succumbed to the deadly late effects of chronic radiation. By the mid-1940s, Grubbe’s fingers had been amputated199 one by one to remove necrotic and gangrenous bones, and his face was cut up in repeated operations to remove radiation-induced tumors and premalignant warts. In 1960, at the age of eighty-five, he died in Chicago, with multiple forms of cancer that had spread throughout his body.