The long struggle to understand cancer
The Emperor of All Maladies: A Biography of Cancer. By Siddhartha Mukherjee. Scribner; 541 pages.
IT IS said that when the good burghers of Amsterdam were first presented with a rhinoceros—armoured, horned, three-toed, with a prehensile lip—spectators shook their heads in disbelief. Cancer provokes a similar bafflement. So protean are its forms and so varied its features that even specialist prognoses of aggressiveness, invasion and response to treatment have typically generated more exceptions than rules. Apparently identical cancers in two patients may behave so unlike as to appear utterly different diseases. Siddhartha Mukherjee’s “The Emperor of All Maladies” tells of the search for a “unifying theory” of cancer, the common attribute of all types of malignant cell growth that might reveal its cure.
The arc of this rich and engrossing book matches Mr Mukherjee’s personal evolution as an oncologist, beginning on the first day of his hospital residency. It seems that the diversity of this implacable, shape-shifting foe will defeat him. He is faced with dead-end discoveries, therapeutic disasters and revelations that lead only to more mysteries. But with the perceptiveness and patience of a true scientist he begins to weave these individual threads into a coherent and engrossing narrative.
The earliest references to cancer, in 2600BC or so by Imhotep, an ancient Egyptian physician, then by Hippocrates and Galen, were simple clinical descriptions: swelling, ulceration, death. These were attributed to “humours” or blockages of bile. In the mid-19th century, a pioneering German pathologist, Rudolf Virchow, identified one feature of cancers: that they represent an uncontrolled proliferation of cells. The cause may still have been a mystery, but the search began for cures.
Surgeons brandished the knife, cutting ever wider and deeper, but recurrence of the disease suggested that the operations had been too conservative, that even more extensive procedures stood more chance of cure. As the science of pathology advanced and leukaemias and lymphomas became recognised as cancers of blood cells, it became clear that the entire bone marrow or lymphatic system could not be extirpated (although some physicians tried). Chemotherapeutic drugs were used, singly and then in increasingly lethal combinations to try to destroy all abnormal cells. X-rays and other forms of radiation were known to kill cells and these were aimed at lymph glands near and distant, on sites of secondary cancer spread in bone and lung and brain.
Practitioners in each field claimed advances. Individual lives were saved. Scientific optimism after the second world war led a leading American oncologist, Sidney Farber, to talk in 1962 of the underlying “singularity” of cancer, and to postulate a “universal cure”. Screening programmes for breast and cervical cancer promised detection at an earlier stage, with improved outcomes. In 1985 American epidemiologists conducted a review of the benefits of these advances in diagnosis and treatment. In the previous year there had been 211 deaths and 448 new cancer cases diagnosed for every 100,000 Americans. When these were compared with the figures for 1962, it was evident that this war was not being won; cancer-related deaths had increased by 8.7%. Much of this could be traced back to the lung-cancer epidemic that had followed the surge in smoking in the 1950s, but the message was clear. More needed to be understood about cancer’s causes before true advances could be made on the curative front.
Scientists had not been idle, but the significance of their labours remained obscure. A virus had been found to cause a cancer in chickens. A rare eye tumour sometimes manifested itself in members of the same family. Certain occupations seemed to breed malignancy; chimney sweeps historically got cancer of the scrotum, dye manufacturers bladder cancer and wartime shipyard workers handling asbestos died from aggressive tumours of the membrane lining the chest. Radium, that source of X-rays used to treat some cancers, had induced fatal malignancies in Marie Curie and her fellow researchers. There was the explicit association between cigarettes and lung cancer, while the newest disease, AIDS, sometimes appeared as multiple malignant tumours called Kaposi’s sarcoma. What common process could be understood from these apparently unconnectable discoveries?
It was time to return to fundamentals. Instead of replicating to an organised plan and forming normal tissue, cancer cells multiply madly. They secrete compounds that induce a proliferation of blood vessels that feed their growth and allow them to infiltrate the walls of adjacent organs. These attributes are genetically programmed functions of normal cells that are intended to combat infection or repair injury. They are controlled by molecular triggers that switch on and off on demand. The common aspect of the apparently disparate causes of cancer is that they induced genetic damage, locking these switches full on. Chaotically multiplying, the abnormal cells mutate, evolving myriad new characteristics: resistance to chemotherapy or an ability to establish colonies in distant parts of the body. The unifying theory had been found.
No longer is the topography of cancer formless flesh, unbridled and invading, but a complex scaffold of cancer DNA that affords binding sites for molecular therapies to block or reset aberrant cellular switches. Twenty-four new drugs are already in use, targeting specific mutations of lung, breast, colon, prostate and blood-cell malignancies. Researchers have hundreds of others in trial. Surgery, radiotherapy and chemotherapy treatments advance constantly.
Cancer’s endless mutability, its ruthless adaptation to survive, is being matched by resourcefulness. The epitaph of the emperor of maladies has not been written quite yet, but his all-conquering domain is in perceptible retreat.
Full article and photo: http://www.economist.com/node/17413995