The Emperor of All Maladies. Siddhartha Mukherjee

      When Farber entered the world of cancer in 1947, the public outcry of the past decade had dissipated. Cancer had again become a politically silent illness. In the airy wards of the Children’s Hospital, doctors and patients fought their private battles against cancer. In the tunnels downstairs, Farber fought an even more private battle with his chemicals and experiments.

      This isolation was key to Farber’s early success. Insulated from the spotlights of public scrutiny, he worked on a small, obscure piece of the puzzle. Leukemia was an orphan disease, abandoned by internists, who had no drugs to offer for it, and by surgeons, who could not possibly operate on blood. “Leukemia,” as one physician put it⁶⁵, “in some senses, had not [even] been cancer before World War II.” The illness lived on the borderlands of illnesses, a pariah lurking between disciplines and departments—not unlike Farber himself.

      If leukemia “belonged” anywhere⁶⁶, it was within hematology, the study of normal blood. If a cure for it was to be found, Farber reasoned, it would be found by studying blood. If he could uncover how normal blood cells were generated, he might stumble backward into a way to block the growth of abnormal leukemic cells. His strategy, then, was to approach the disease from the normal to the abnormal—to confront cancer in reverse.

      Much of what Farber knew about normal blood he had learned from George Minot. A thin, balding aristocrat with pale, intense eyes, Minot ran a laboratory in a colonnaded, brick-and-stone structure off Harrison Avenue in Boston, just a few miles down the road from the sprawling hospital complex on Longwood Avenue that included Children’s Hospital. Like many hematologists at Harvard, Farber had trained briefly with Minot in the 1920s before joining the staff at Children’s.

      Every decade has a unique hematological riddle, and for Minot’s era, that riddle was pernicious anemia. Anemia is the deficiency of red blood cells—and its most common form arises from a lack of iron, a crucial nutrient used to build red blood cells. But pernicious anemia, the rare variant that Minot studied, was not caused by iron deficiency (indeed, its name derives from its intransigence to the standard treatment of anemia with iron). By feeding patients increasingly macabre concoctions—half a pound of chicken liver⁶⁷, half-cooked hamburgers, raw hog stomach, and even once the regurgitated gastric juices⁶⁸ of one of his students (spiced up with butter, lemon, and parsley⁶⁹)—Minot and his team of researchers⁷⁰ conclusively demonstrated in 1926⁷¹ that pernicious anemia was caused by the lack of a critical micronutrient, a single molecule later identified as vitamin B12. In 1934, Minot and two of his colleagues⁷² won the Nobel Prize for this pathbreaking work. Minot had shown that replacing a single molecule could restore the normalcy of blood in this complex hematological disease. Blood was an organ whose activity could be turned on and off by molecular switches.

      There was another form of nutritional anemia that Minot’s group had not tackled, an anemia just as “pernicious”—although in the moral sense of that word. Eight thousand miles away, in the cloth mills of Bombay⁷³ (owned by English traders and managed by their cutthroat local middlemen), wages had been driven to such low levels that the mill workers lived in abject poverty, malnourished and without medical care. When English physicians tested these mill workers in the 1920s to study the effects of this chronic malnutrition, they discovered that many of them, particularly women after childbirth, were severely anemic. (This was yet another colonial fascination: to create the conditions of misery in a population, then subject it to social or medical experimentation.)

      In 1928, a young English physician named Lucy Wills,⁷⁴ freshly out of the London School of Medicine for Women, traveled on a grant to Bombay to study this anemia. Wills was an exotic among hematologists, an adventurous woman driven by a powerful curiosity about blood willing to travel to a faraway country to solve a mysterious anemia on a whim. She knew of Minot’s work. But unlike Minot’s anemia, she found that the anemia in Bombay couldn’t be reversed by Minot’s concoctions or by vitamin B12. Astonishingly, she found she could cure it with Marmite, the dark, yeasty spread then popular among health fanatics in England and Australia. Wills could not determine the key chemical nutrient of Marmite. She called it the Wills factor⁷⁵.

      Wills factor turned out to be folic acid, or folate, a vitamin-like substance found in fruits and vegetables (and amply in Marmite). When cells divide, they need to make copies of DNA—the chemical that carries all the genetic information in a cell. Folic acid is a crucial building block for DNA and is thus vital for cell division. Since blood cells are produced by arguably the most fearsome rate of cell division in the human body—more than 300 billion cells a day—the genesis of blood is particularly dependent on folic acid. In its absence (in men and women starved of vegetables, as in Bombay) the production of new blood cells in the bone marrow halts. Millions of half-matured cells spew out, piling up like half-finished goods bottlenecked in an assembly line. The bone marrow becomes a dysfunctional mill, a malnourished biological factory oddly reminiscent of the cloth factories of Bombay.