Like dysfunctional family members, genetically flawed microorganisms can wreak havoc far beyond what would be expected from their inherent weaknesses - or so goes one of the theories put forward by University of California at San Diego biologist Christopher Wills in Yellow Fever, Black Goddess.

The book's main focus is the evolutionary interplay between hosts and the microorganisms that cause disease. Although Wills tries repeatedly throughout the text to describe eloquently third-world slums, shantytowns, and cultures in various states of disarray - and occasionally succeeds in vividly portraying these epidemic playgrounds - the book's real meat is his evidence for, and speculations on, the role evolution and changing environments play in outbreaks of disease.

He jumps straight in, beginning with the disease that struck terror in the hearts of medieval citizenry, and whose cultural memory lingers on in the name we apply to any serious disease outbreak: plague. Children jumping rope in the streets still pay homage to the historic killer when they chant: "In sixteen-sixty-five, no one was left alive; in sixteen-sixty-six, London was burned to sticks."

All of this attention is focused on a dysfunctional weakling of a microbe, Wills contends. Yersinia pestis, which causes plague, is one of just ten members of the genus Yersinia, only three of which are known to be pathogenic in animals. What distinguishes pestis from its more worthy cousins, Wills contends, is its unique genetic flaws. Pestis cannot swim freely; instead it drifts passively through bodily currents, and its metabolism has been so crippled that it can no longer survive outside a host. Its poor-man's version of the Krebs cycle - that biopathway charged with producing high-energy phosphates and amino-acid building blocks - is crippled at a key step in its molecular pathway. To make up for its faulty design, the microbe must turn to its host for these key compounds. Most troubling to its victims, according to Wills, is the apparent inability of pestis to invade human cells, leaving it to wander outside of the apparent safety of host cells.

This clumsiness would seem to doom the bacteria to a swift demise at the hands of the host's immune system. But of course history argues otherwise. Wills explains that the microbe captures a plasmid containing a gene for a protease, which destroys proteins on the surface of circulating phagocytes, pestis's immunologic opponents. Thus shielded, the bacteria are free to multiply within the host.

Wills's insistence that pestis - and its unfortunate hosts - are in some way "evolutionarily challenged" seems tenuous at this point, since the protection conferred by the phagocyte-dulling protease would seem to be an evolutionary boost, rather than a liability. But no matter. The story is getting intriguing.

The next stop is the flea, which forms the key link in the sequence of events that decimated medieval populations. These insects pick up the plaque bacilli from the blood of a victim. The bacilli skirt the flea's defenses just as they do human defenses, and immediately produce a protein that clots the blood the flea has just ingested. Unable to digest its meal, the flea grows more desperate, moving swiftly from person to person to quench its appetite. Our flawed protagonist - which seems more resourceful and well-adjusted as the story progresses - is the big winner, of course, as it quickly infects the human population.

A brief interlude follows in which Wills tracks a recent outbreak of disease in India, and asks the question: Was it plague? He recounts spotty epidemiologic evidence, hurried field work performed in the face of a potential outbreak of the age-old nemesis, and cultural conditions that made it very difficult to collect, store, and accurately measure telltale blood samples. The point of the chapter seems to be to reveal the frailties of modern epidemiology. It succeeds in this, but contributes essentially nothing to the central thesis of the book, serving instead as a mildly irritating distraction. These wanderings appear frequently throughout the book, sometimes adding a personal zest (as in the anecdote that describes his uncle's bout of malaria during World War II), but often drawing the reader's attention away from the evolutionary arguments. In each instance, thankfully, Wills soon pushes on to more interesting material.

Wills traces similar evidence for the inferiority of microbes that cause cholera, malaria, syphilis, and AIDS. But the inferiority argument lies in the roots of the broader case Wills makes in his final chapters - that selective pressures, in the form of pathogenic microbes, have driven the huge genetic diversity that characterizes the living world. "Is all our mind-numbing genetic complexity . . . [protective against] the penumbra of diseases that surround us?" he asks.

Wills cites the example of "herd immunity," known to ranchers and farmers who understand empirically that not all animals in a herd need to be vaccinated against a particular disease. If the majority are protected, then a still-susceptible but uninfected animal will likely be separated from another infected animal by its shielded cohorts. Wills argues that our genetic heritage confers herd immunity, as molecular and cellular variations foil the attempts of specific microbes to infect some subgroups of the population.

Here Wills interjects another of his asides, this one an account of his personal battle with Heliobacter, the stomach-dwelling bacteria that were recently found to cause ulcers. Heliobacter binds more strongly to the carbohydrates dotting the surface of blood cells in people with blood type O, a category that lamentably includes Wills. His wife and daughter, blessed with blood type B antigens, remained free of infection. Wills argues that it is this sort of pressure from a vast array of ancient and present-day microbes - ranging over the planet's entire complement of species - that has driven the enormous biological complexity that surrounds us.

This argument brings one back to the question of plagues, since according to this view, humanity's herd immunity should muffle such outbreaks. But not so, says Wills, in an unconvincing bit of hand-waving. "With plagues, all bets are off," he offers. Peculiar ecological conditions that allow a plague organism such as Yersinium pestis to take root and multiply soon disappear, leaving a reduced population to resume its struggle with more mundane pathogens.

Wills is clearly on to something here, but it often seems as if he has cast his net too widely, allowing it to settle outside the reach of his theories. Nevertheless, this is a thought-provoking book with plenty of insights into the evolutionary and cultural impacts of a wide variety of pests.

Is it too much to suppose that before the Great Fire (of London, in 1666) there was some kind of focus of the plague, perhaps lurking in the sewage-filled alleys and tottering houses of Pudding Lane or nearby Thames Street with its rotting wharves? If there was such a focus, then it was somehow activated every decade or two, spreading its effects out to the rest of the towns of England . . . [Perhaps it was a group of rats] swarming in a small piece of the medieval world that had lasted beyond its time. . . .

"The Delicate Balance Between Life and Death" - chapter 1 of Yellow Fever, Black Goddess, courtesy of the Washington Post Web site, which has also reviewed the book. Other reviews may be read at The Net Net and The New England Journal of Medicine.

Soundprint's Deadly Evolution Book List - a short list of required reading for aficionados of emerging diseases.

Bi 199: Plagues Term Projects - a half dozen plague-related Web pages created by first-year students at the University of Oregon. The illustrations are good and the bibliographies include some useful Web sites.

Plagues Since the Roman Empire - outlines what the plague bacillus has been up to over the last 2,000 years. The site is part of the Impact of Insects on Human History site.

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