Book Review

摘要

By the 1940s, it had been inferred that dozens of chemicals caused cancer in people or had been shown to do so in experimental animals. These chemicals came from a bewildering array of structural classes, including polycyclic hydrocarbons, aromatic amines, and others. A seminal paper authored in 1947 by Elizabeth C. Miller (1920–87) and James  A. Miller (1915–2000) provided the first clue to an underlying common mechanism for the biological activities of chemical carcinogens. They observed that feeding rats a carcinogenic dye resulted in a chemical bond between a metabolite of the carcinogen and liver proteins. Over the next twenty-five years, this extraordinary scientific team of husband and wife ‘discovered and developed the important unifying concept that most carcinogenic and mutagenic chemicals are not carcinogenic or mutagenic per se but that these compounds must undergo metabolism to reactive electrophilic metabolites that exert their effects by covalently binding to critical sites on cellular macromolecules (DNA, RNA, and protein).’ In addition to its importance as one of the foundations of modern cancer biology, this unifying concept has had broad societal implications for how we identify cancer-causing chemicals and how we protect people from them. The Millers’ discovery is so widely accepted that it is often cited without attribution and they have received relatively little recognition for their contributions outside the field of cancer research. Robert G. McKinnell has recently published an excellent biography of James and Elizabeth Miller, motivated in part by his desire ‘that the Millers should be recognised by the myriads of ordinary people whose lives have been impacted for the better.’