The Emperor of All Maladies. Siddhartha Mukherjee

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СКАЧАТЬ Hampton’s surgery was rather conservative by comparison. He did not remove muscles, lymph nodes, or bone. He retained the notion of the en bloc removal of the organ from radical surgery, but stopped short of evacuating the entire pelvis or extirpating the urethra or the bladder. (A modification of this procedure is still used to remove localized prostate cancer, and it cures a substantial portion of patients with such tumors.)

      Harvey Cushing, Halsted’s student and chief surgical resident, concentrated on the brain. By the early 1900s, Cushing had found ingenious ways to surgically extract brain tumors, including the notorious glioblastomas—tumors so heavily crisscrossed with blood vessels that they could hemorrhage any minute, and meningiomas wrapped like sheaths around delicate and vital structures in the brain. Like Young, Cushing inherited Haslted’s intaglio surgical technique—“the slow separation of brain from tumor,¹⁸⁴ working now here, now there, leaving small, flattened pads of hot, wrung-out cotton to control oozing”—but not Halsted’s penchant for radical surgery. Indeed Cushing found radical operations on brain tumors not just difficult, but inconceivable: even if he desired it, a surgeon could not extirpate the entire organ.

      In 1933, at the Barnes Hospital¹⁸⁵ in St. Louis, yet another surgical innovator, Evarts Graham, pioneered an operation to remove a lung afflicted with cancer by piecing together prior operations that had been used to remove tubercular lungs. Graham, too, retained the essential spirit of Halstedian surgery: the meticulous excision of the organ en bloc and the cutting of wide margins around the tumor to prevent local recurrences. But he tried to sidestep its pitfalls. Resisting the temptation to excise more and more tissue—lymph nodes throughout the thorax, major blood vessels, or the adjacent fascia around the trachea and esophagus—he removed just the lung, keeping the specimen as intact as possible.

      Even so, obsessed with Halstedian theory and unable to see beyond its realm, surgeons sharply berated such attempts at nonradical surgery. A surgical procedure¹⁸⁶ that did not attempt to obliterate cancer from the body was pooh-poohed as a “makeshift operation.” To indulge in such makeshift operations was to succumb to the old flaw of “mistaken kindness” that a generation of surgeons had tried so diligently to banish.

       The Hard Tube and the Weak Light

      We have found in [¹⁸⁷X-rays] a cure for the malady.

      —Los Angeles Times, April 6, 1902

      By way of illustration¹⁸⁸ [of the destructive power of X-rays]¹⁸⁹ let us recall that nearly all pioneers in the medical X-ray laboratories in the United States died of cancers induced by the burns.

      —The Washington Post, 1945

      In late October 1895, a few months after Halsted had unveiled the radical mastectomy in Baltimore, Wilhelm Röntgen, a lecturer at the Würzburg Institute in Germany, was working with an electron tube—a vacuum tube that shot electrons from one electrode to another—when he noticed a strange leakage. The radiant energy was powerful and invisible, capable of penetrating layers of blackened cardboard and producing a white phosphorescent glow on a barium screen accidentally left on a bench in the room.

      Röntgen whisked his wife, Anna, into the lab and placed her hand between the source of his rays and a photographic plate. The rays penetrated through her hand and left a silhouette of her finger bones and her metallic wedding ring on the photographic plate—the inner anatomy of a hand seen as if through a magical lens. “I have seen my death,” Anna said—but her husband saw something else: a form of energy so powerful that it could pass through most living tissues. Röntgen called his form of light X-rays.

      At first, X-rays were thought to be an artificial quirk of energy produced by electron tubes. But in 1896, just a few months after Röntgen’s discovery, Henri Becquerel, the French chemist, who knew of Röntgen’s work, discovered that certain natural materials—uranium among them—autonomously emitted their own invisible rays with properties similar to those of X-rays. In Paris, friends of Becquerel’s, a young physicist-chemist couple named Pierre and Marie Curie, began to scour the natural world for even more powerful chemical sources of X-rays. Pierre and Marie (then Maria Skłodowska, a penniless Polish immigrant living in a garret in Paris) had met at the Sorbonne and been drawn to each other because of a common interest in magnetism. In the mid-1880s, Pierre Curie had used minuscule quartz crystals to craft an instrument called an electrometer, capable of measuring exquisitely small doses of energy. Using this device, Marie had shown that even tiny amounts of radiation emitted by uranium ores could be quantified. With their new measuring instrument for radioactivity, Marie and Pierre began hunting for new sources of X-rays. Another monumental journey of scientific discovery was thus launched with measurement.

      In a waste ore called pitchblende, a black sludge that came from the peaty forests of Joachimsthal in what is now the Czech Republic, the Curies found the first signal of a new element—an element many times more radioactive than uranium. The Curies set about distilling the boggy sludge to trap that potent radioactive source in its purest form. From several tons of pitchblende, four hundred tons of washing water, and hundreds of buckets of distilled sludge waste, they finally fished out one-tenth of a gram of the new element in 1902. The metal lay on the far edge of the periodic table, emitting X-rays with such feverish intensity that it glowered with a hypnotic blue light in the dark, consuming itself. Unstable, it was a strange chimera between matter and energy—matter decomposing into energy. Marie Curie called the new element radium, from the Greek word for “light.”

      Radium, by virtue of its potency, revealed a new and unexpected property of X-rays: they could not only carry radiant energy through human tissues, but also deposit energy deep inside tissues. Röntgen had been able to photograph his wife’s hand because of the first property: his X-rays had traversed through flesh and bone and left a shadow of the tissue on the film. Marie Curie’s hands, in contrast, bore the painful legacy of the second effect: having distilled pitchblende into a millionth part for week after week in the hunt for purer and purer radioactivity, the skin in her palm had begun to chafe and peel off in blackened layers, as if the tissue had been burnt from the inside. A few milligrams of radium left in a vial in Pierre’s pocket scorched through the heavy tweed of his waistcoat and left a permanent scar on his chest. One man who gave “magical” demonstrations¹⁹⁰ at a public fair with a leaky, unshielded radium machine developed swollen and blistered lips, and his cheeks and nails fell out. Radiation would eventually burn into Marie Curie’s bone marrow, leaving her permanently anemic.

      It would take biologists decades to fully decipher the mechanism that lay behind these effects, but the spectrum of damaged tissues—skin, lips, blood, gums, and nails—already provided an important clue: radium was attacking DNA. DNA is an inert molecule, 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 СКАЧАТЬ