Book Review

Cancer: The evolutionary legacy

N Engl J Med 2000; 342:1762June 8, 2000

Article

Cancer: The evolutionary legacy
By Mel Greaves. 276 pp. New York, Oxford University Press, 2000. $27.50 ISBN: 0-19-262835-6

Cancer is often portrayed as a Darwinian struggle in which a progenitor cell evolves or progresses over a series of hurdles. A recent Medline search returned more than 7000 items on cancer and evolution and more than 27,000 on cancer and progression. However, evolution is a concept much easier to recognize than to define or apply. All living things evolve. The puzzle is which one of a number of plausible or seemingly improbable pathways is taken.

Recent advances allow increasingly fine dissections of the mechanisms underlying cancer. What causes a normal cell to become a killer? Although the final missteps are a natural focus, the development of cancer is contingent on remarkable chains of events. As in many disasters seen in retrospect, the final flaw is seldom the sole culprit. Greaves illuminates this deep evolutionary trail. Cancer: The Evolutionary Legacy is a thought-provoking perspective on cancer and evolution. It is a personal, high-spirited narrative by an experienced and knowledgeable cancer researcher and is written in a style similar to that of popular books on evolution. Because formal studies of evolution are often impenetrable, Greaves's unconventional approach succeeds remarkably. By clearing away the intellectual camouflage guarding evolution and cancer, Greaves makes the topic accessible to both general readers and specialists.

The thesis of this book is logical, but it differs from that of most books on cancer. In essence, Greaves argues that cancers are the ends of long, unbroken evolutionary chains that extend back billions of years. The lineage of a cancer cell has existed since the dawn of life. A journey through time does much to explain cancer and the value of studies of organisms such as yeasts, flies, and mice (which share with us much of this journey) in attempts to cure cancer. At both ends of a cancer lineage, single clones are selected for survival, expansion, invasion, and migration. In between is the harmony of metazoan life, where the behavior of individual cells is harnessed for the good of the whole. Millions of years of socialization are lost within a few decades of tumor progression.

The chain that connects this past and the present is DNA. The standard principles of evolution apply. DNA replication is inherently prone to error, and these errors provide new substrates for evolution or progression. Selection acts as a filter that determines which mutations persist. The complete history of a cancer cell includes the making and then the breaking of the genetic controls needed for multicellular life. Chance pervades the entire process because of the randomness of mutation, the ambiguities of selection, and the blindfold nature of evolution.

The author uses numerous persuasive examples to illustrate the concept of cancer within this framework of evolution. Germ-line mutations can prematurely start progression, whereas lifestyle alters the odds, highlighting nature–nurture mismatches. About a third of the book is devoted to epidemiology, with excellent expositions of prostate, breast, and cervical cancer. Tobacco and radiation are given their well-deserved roles as important environmental carcinogens.

Overall, Greaves does an excellent job of explaining and placing cancer within the broad framework of evolution. Cancer makes more sense in the light of evolution, and most cancer investigators would agree with the author's views and conclusions. Books such as this shed light on cancer by elegantly incorporating the unifying theme of evolution, but inevitably, studies of cancer will, in turn, shed light on the mysteries of evolution.

Darryl Shibata, M.D.
University of Southern California School of Medicine, Los Angeles, CA 90033