The Emperor of All Maladies: A Biography of Cancer

by Siddhartha Mukherjee

For studies on chronic and complex human diseases such as cancer, Hill suggested, the traditional understanding of causality needed to be broadened and revised. If lung cancer would not fit into Koch’s straitjacket, then the jacket needed to be loosened. Hill acknowledged epidemiology’s infernal methodological struggle with causation—this was not an experimental discipline at its core—but he rose beyond it. At least in the case of lung cancer and smoking, he argued, the association possessed several additional features: It was strong: the increased risk of cancer was nearly five- or tenfold in smokers. It was consistent: Doll and Hill’s study, and Wynder and Graham’s study, performed in vastly different contexts on vastly different populations, had come up with the same link. It was specific: tobacco was linked to lung cancer—precisely the site where tobacco smoke enters the body. It was temporal: Doll and Hill had found that the longer one smoked, the greater the increase in risk. It possessed a “biological gradient”: the more one smoked in quantity, the greater the risk for lung cancer. It was plausible: a mechanistic link between an inhaled carcinogen and a malignant change in the lung was not implausible. It was coherent; it was backed by experimental evidence: the epidemiological findings and the laboratory findings, such as Graham’s tar-painting experiments in mice, were concordant. It behaved similarly in analogous situations: smoking had been correlated with lung c...