The Emperor of All Maladies. Siddhartha Mukherjee
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Название: The Emperor of All Maladies
Автор: Siddhartha Mukherjee
Издательство: HarperCollins
Жанр: Прочая образовательная литература
isbn: 9780007435814
isbn:
Farber was ecstatic, but impatient305. “The enthusiasm . . . of these new friends of chemotherapy is refreshing and seems to be on a genuine foundation,” he wrote to Lasker in 1955. “It nevertheless seems frightfully slow. It sometimes becomes monotonous to see more and more men brought into the program go through the joys of discovering America.”
Farber had, meanwhile, stepped up his own drug-discovery efforts in Boston. In the 1940s, the soil microbiologist Selman Waksman had systematically scoured the world of soil bacteria and purified a diverse series of antibiotics. (Like the Penicillium mold, which produces penicillin, bacteria also produce antibiotics to wage chemical warfare on other microbes.) One such antibiotic came from a rod-shaped microbe306 called Actinomyces. Waksman called it actinomycin D307. An enormous molecule shaped like an ancient Greek statue, with a small, headless torso and two extended wings, actinomycin D was later found to work by binding and damaging DNA. It potently killed bacterial cells—but unfortunately it also killed human cells, limiting its use as an antibacterial agent.
But a cellular poison could always excite an oncologist. In the summer of 1954, Farber persuaded Waksman to send him a number of antibiotics, including actinomycin D, to repurpose them as antitumor agents by testing the drugs on a series of mouse tumors. Actinomycin D, Farber found, was remarkably effective in mice. Just a few doses melted away many mouse cancers, including leukemias, lymphomas, and breast cancers. “One hesitates to call them ‘cures,’ ” Farber wrote expectantly, “but it is hard to classify them otherwise.”
Energized by the animal “cures,” in 1955 he launched a series of trials to evaluate the efficacy of the drug in humans. Actinomycin D had no effect on leukemias in children. Undeterred, Farber unleashed the drug on 275 children with a diverse range of cancers: lymphomas, kidney sarcomas, muscle sarcomas, and neuroblastic tumors. The trial was a pharmacist’s nightmare. Actinomycin D was so toxic that it had to be heavily diluted in saline; if even minute amounts leaked out of the veins, then the skin around the leak would necrose and turn black. In children with small veins, the drug was often given through an intravenous line inserted into the scalp.
The one form of cancer that responded in these early trials was Wilms’ tumor, a rare variant of kidney cancer. Often detected in very young children, Wilms’ tumor was typically treated by surgical removal of the affected kidney. Surgical removal was followed by X-ray radiation to the affected kidney bed. But not all Wilms’ cases could be treated using local therapy. In a fraction of cases, by the time the tumor was detected, it had already metastasized, usually to the lungs. Recalcitrant to treatment there, Wilms’ tumors were usually bombarded with X-rays and assorted drugs but with little hopes of a sustained response.
Farber found that actinomycin D, administered intravenously, potently inhibited the growth of these lung metastases, often producing remissions that lasted months. Intrigued, he pressed further. If X-rays and actinomycin D could both attack Wilms’ metastases independently, what if the agents could be combined? In 1958, he set a young radiologist couple named Giulio D’Angio and Audrey Evans and an oncologist named Donald Pinkel to work on the project. Within months, the team had confirmed that X-rays and actinomycin D were remarkably synergistic, each multiplying the toxic effect of the other. Children with metastatic cancer treated with the combined regimen often responded briskly. “In about three weeks lungs previously riddled with308 Wilms’ tumor metastasis cleared completely,” D’Angio recalled. “Imagine the excitement of those days when one could say for the first time with justifiable confidence, ‘We can fix that.’ ”
The enthusiasm generated by these findings was infectious. Although combination X-ray and chemotherapy did not always produce long-term cures, Wilms’ tumor was the first metastatic solid tumor to respond to chemotherapy. Farber had achieved his long-sought leap from the world of liquid cancers to solid tumors.
By the late 1950s, Farber was bristling with a fiery brand of optimism. Yet visitors to the Jimmy Fund clinic in the mid-1950s might have witnessed a more nuanced and complex reality. For Sonja Goldstein309, whose two-year-old son, David, was treated with chemotherapy for Wilms’ tumor in 1956, the clinic seemed perpetually suspended between two poles—both “wonderful and tragic . . . unspeakably depressing and indescribably hopeful.” On entering the cancer ward, Goldstein would write later, “I sense an undercurrent of excitement, a feeling (persistent despite repeated frustrations) of being on the verge of discovery, which makes me almost hopeful.
“We enter a large hall decorated with a cardboard train along one wall. Half way down the ward is an authentic-looking stop sign, which can flash green, red, and amber lights. The train’s engine can be climbed into and the bell pulled. At the other end of the ward is a life-size gasoline pump, registering amount sold and price. . . . My first impression is one of overweening activity, almost snake pit-like in its intensity.”
It was a snake-pit—only of cancer, a seething, immersed box coiled with illness, hope, and desperation. A girl named Jenny, about four years old, played with a new set of crayons in the corner. Her mother, an attractive, easily excitable woman, kept Jenny in constant sight, holding her child with the clawlike intensity of her gaze as Jenny stooped to pick up the colors. No activity was innocent here; anything might be a sign, a symptom, a portent. Jenny, Goldstein realized, “has leukemia and is currently in the hospital because she developed jaundice. Her eyeballs are still yellow”—presaging fulminant liver failure. She, like many of the ward’s inhabitants, was relatively oblivious to the meaning of her illness. Jenny’s only concern was an aluminum teakettle to which she was deeply attached.
“Sitting in a go-cart in the hall is a little girl, who, I think at first, has been given a black eye. . . . Lucy, a 2-year old, suffers from a form of cancer that spreads to the area behind the eye and causes hemorrhaging there. She is not a very attractive child, and wails almost incessantly that first day. So does Debbie, an angelic-looking 4-year old whose face is white and frowning with suffering. She has the same type of tumor as Lucy—a neuroblastoma. Alone in a room lies Teddy. It takes many days before I venture inside it, for, skeleton-thin and blinded, Teddy has a monstrosity for a face. His tumor, starting behind the ear, has engulfed one side of his head and obliterated his normal features. He is fed through a tube in the nostril, and is fully conscious.”
Throughout the ward were little inventions and improvisations, often devised by Farber himself. Since the children were usually too exhausted to walk, tiny wooden go-carts were scattered about the room so that the patients could move around with relative freedom. IV poles for chemotherapy were strung up on the carts to allow chemo to be given at all times during the day. “To me,” Goldstein wrote, “one of the most pathetic sights of all that I have seen is the little go-cart, with the little child, leg or arm tightly bandaged to hold needle in vein, and a tall IV pole with its burette. The combined effect is that of a boat with mast but no sail, helplessly drifting alone in a rough, СКАЧАТЬ