|Page 2 of 2 <|
Chronicling a modern plague
It's time to welcome a new star in the constellation of great doctor-writers. With this fat, enthralling, juicy, scholarly, wonderfully written history of cancer, Siddhartha Mukherjee - a cancer physician and researcher at Columbia University - vaults into that exalted company, inviting comparison to the late physician and historian Lewis Thomas and the late paleontologist and historian of science Stephen Jay Gould. Calling his book a biography of cancer, Mukherjee opens "The Emperor of All Maladies" with the disease's first mentions - in the musings of Imhotep, an Egyptian physician who lived 4,600 years ago, and in the case of Queen Atossa of Persia, who, according to Herodotus, ordered a Greek slave to cut off her tumorous breast and lived.
But cancer remained relatively rare until the early 20th century, when a steady rise in life expectancy propelled this disease of aging cells to its current position as the second-leading cause of death (a ranking it had assumed by 1940). Most of the book's action takes place during the past 100 years, as Mukherjee traces the recent stunning transformations in our scientific and societal image of cancer - from a death sentence, to a mysterious foe to be bludgeoned with radical surgery and chemotherapy, to a rallying cry for activists in a politically fueled war, and ultimately to an array of separate, endlessly resourceful diseases, distortions of normal human biology that must be understood at the cellular level before they can be vanquished. "It lives desperately, inventively, fiercely, territorially, cannily, and defensively - at times, as if teaching us how to survive," Mukherjee writes.
And what a story - full of quixotic characters, therapeutic triumphs and setbacks with all the hubris and pathos of Greek tragedy. There's William Halsted, the obsessive, cocaine- and morphine-addicted surgeon whose disfiguring operation, the radical mastectomy, turned out to be needlessly aggressive for early breast cancer and useless for tumors that had spread, yet was inflicted on 500,000 women between 1891 and 1981. There's chemotherapist Sidney Farber and socialite Mary Lasker, a dynamic duo who invented the modern marketing of a disease as a social and political cause. Lasker, a masterful lobbyist, helped launch and fund the National Cancer Institute in the 1950s, leading over the ensuing decades to the development of curative chemotherapy for some cancers and culminating with President Nixon's declaration of a national war on cancer in 1971. It was the perfect Cold War metaphor at a time when the United States, its military stalemated in Vietnam, was preoccupied with societal decay from within.
And there's the astonishing recent history of breast cancer treatment: the gradual eclipse of surgery by chemotherapy, radiation therapy and especially by drugs such as tamoxifen and Herceptin that target proteins on or inside cancer cells to help shut off their growth. Against those signs of biologically based progress, recall (as Mukherjee does, to devastating effect) the misplaced hope during the 1980s and 1990s that high-dose chemotherapy combined with bone marrow transplantation would cure the disease. On the strength of dazzling research results from South Africa that turned out to be fraudulent, thousands of women underwent a life-threatening, prohibitively expensive therapy that offered no improvement over standard treatments and actually caused second cancers or precancerous conditions in 5 to 10 percent of recipients.
In 1986, epidemiologists John Bailar and Elaine Smith published a devastating progress report on the war on cancer. Despite 35 years of intense effort, they wrote in a medical journal, there was no evidence of "much overall effect on the most fundamental measure of clinical outcome - death." But meanwhile, a parallel scientific and political drama had been unfolding concerning efforts to prevent cancer by attacking its environmental causes. Its central events - the unexpected discovery of the link between cigarette smoking and lung cancer by twin studies in 1950; the tobacco industry's decades-long campaign of denial, deceit and obfuscation; the courage of surgeon general Luther Terry in releasing his bombshell 1964 report on the dangers of smoking; a tide of anti-tobacco lawsuits; and in recent decades, a steady decline in U.S. smoking rates - are riveting both for their public health impact and for their importance in focusing more resources on cancer prevention.
As researchers identified other external triggers of cancer development - a liver virus, a stomach bacterium, exposure to X-rays, even sunbathing - they also explored the sequence of genetic events that such environmental factors set off deep inside normal cells. Mukherjee recounts how, during the 1970s and '80s, researchers elucidated "a unitary cause" of cancer - describing how a healthy cell gradually accumulates mutations in certain key genes regulating its growth and behavior, until it becomes insensitive to signals and instructions from the cells around it and is able to survive, attract a blood supply, reproduce and spread its progeny seemingly without limits. Advances in understanding this sequence of events on a molecular level have slowly begun to yield targeted therapies - at least two dozen so far - that deserve, for the first time, the overworked nickname "magic bullet." Gleevec, the prototype medicine in this group, is a pill with almost no side effects that turned a particular type of leukemia from a universally fatal disease to one that most patients keep in check, living essentially a normal life.
Yet some cancers develop resistance to these new agents. Overall cancer mortality is down - it declined 15 percent between 1990 and 2005 because of better prevention, better screening and therapeutic advances - but there's no end to this war. Mukherjee quotes Lewis Carroll's Red Queen: "It takes all the running you can do, to keep in the same place."
My one criticism of this otherwise impeccable book is that Mukherjee scarcely mentions the role of pharmaceutical companies in directing the course of the search for new cancer medicines, sometimes steering away from promising but untested new directions in favor of incremental variations on a tired theme. The only exceptions are his descriptions of how Genentech nearly pulled the plug on Herceptin, and how Novartis almost buried Gleevec. One wonders how many other blockbuster therapies are languishing in vials on laboratory shelves.
Along with poets and philosophers - Plato, Hippocrates, Kafka, Blake - Mukherjee's patients (bearing pseudonyms) make touching cameo appearances in these pages, as does the doctor himself. My favorite of these was his description of the birth of his daughter in 2005, in a delivery room not far from his hospital's cancer wards. "I was gowned and gloved like a surgeon . . . a long syringe in my hands, poised to harvest the maroon gush of blood cells from the umbilical cord," he recalls. "Part of me was the father, but the other part an oncologist." Used for a bone marrow transplant, the stem cells in his baby's umbilical cord blood might, he knew, save a patient's life.