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Brief Tragedies

Paul Ewald, Gregory Cochran

Cancer: The Evolutionary Legacy. Mel Greaves. x + 276 pp. Oxford University Press, 2000. $27.50.

Lifestyle, genetics, chemical carcinogens, radiation or pathogens? At one level Mel Greaves's Cancer: The Evolutionary Legacy sorts through the evidence to assess the influence of these factors on the development of cancer. Not surprisingly, he finds that each plays a role, and much of his effort involves clarification of what, when and where. But at another level his engaging tour of the world of cancer diverges from the rest of the books on the subject. He draws together the mechanistic insights from cell biology, immunology and molecular biology with the process that is responsible for generating all of this clockwork: evolution by natural selection. As such, this is the first book on cancer that unites insights from the entire spectrum of biology. It's also fun to read. As a tour guide, Greaves is clever but not snooty, deep but still accessible.

Molecular mug shotClick to Enlarge Image

G. Evelyn Hutchinson's "evolutionary play" is transformed by Greaves into innumerable short plays within an immeasurably long play. The long play has the world as its ecological theater and a seemingly eternal duration. It explains the intricately regulated and defended mammalian body as the legacy of a process of refinement that traces its organization with unbroken continuity back to beginning of life on earth. For each short play, the ecological theater is the individual and the immediate environment of that individual; each of these plays begins and ends within a lifetime, snuffing itself out with a metastatic finale the geological instant after it begins.

Greaves has identified the important actors, but we think that he has overlooked something important in the script, something about infectious causation of cancer. He is quite correct in writing that "infection . . . isn't sufficient to cause cancer." The processes of cancer involve leading roles and supporting casts. He notes that knocking down all of the barriers that protect the body against cancer is an extremely improbable event for a given lineage of cells; and he proposes that it is this improbability that protects us against cancer. Undoubtedly he is correct in this assertion. But those cancer-causing viruses that we understand fairly well typically knock down two or more of the barriers against cancers. The most oncogenic of the human papillomaviruses, for example, frees its host cells from regulatory shackles by producing proteins that knock out the cell's p53 and retinoblastoma proteins, inhibiting the cell's ability to stop its own division and its self-destruct mechanism. By this manipulation the virus is able to replicate along with its host cell, while keeping itself fairly well hidden from immunologic surveillance. With two or three of the barriers to cancer knocked down, the probability of generating cancer in those cells is tremendously increased.

Now comes the subtle but crucial step in logic that Greaves missed. Natural selection acting in the long play will undoubtedly favor additional protective barriers to guard against cancers caused by infection, because these barriers are needed to counter the tremendous head start that infection affords in the evolution toward cancer. As Greaves notes, current estimates indicate that infections are known to play a causal role in about 15 percent of all human cancers. Whether pathogens play a role in most of the remaining 85 percent is now being debated, but the 15 percent figure indicates that additional protective barriers would be necessary to combat cancers caused by infection. These layers of protection should overprotect against cancer wanna-bes that, acting without the aid of an infectious agent, have to break through all of the barriers. This logic leads to the conclusion that infectious agents will tend to be lead actors in the cancer plays.

This conclusion is quite different from Greaves's general conclusion, which incriminates lifestyles more than pathogens. It is also more encouraging, because the medical track record against pathogens has been relatively good—vaccines can be generated and transmission routes can be blocked. Greaves especially should like this twist, because he ends his book apologetically by being drawn to . . . Nah, we won't spoil the ending for you.

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