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The Enemy Within

Julie Parsonnet

Plague Time: How Stealth Infections Cause Cancers, Heart Disease, and Other Deadly Ailments. Paul W. Ewald. vi + 288 pp. The Free Press, 2000. $25.

We are outnumbered by the enemy: not the enemy without, but the enemy within. Human beings are walking, talking ecosystems, replete with more microbes than human cells. These organisms interact with and enter our cells. They use us as food, getting energy from our metabolic work. They protect themselves from hostile competitors by concealing themselves in human hideaways.

For those readers naive enough to believe that the microbes we harbor are there for our benefit, Paul Ewald's book Plague Time could be eye-opening. By incorporating evolutionary theory into microbial and human biology, Ewald brings essential principles to the fore. In a clear manner, he explains the natural selection that underlies the ebb and flow of new and old infections within human beings. Although many have understood the human body to be a battleground for a microbial "survival of the fittest," Ewald dissects and elaborates on this theme. In doing so, he not only describes how the best bugs win, but also reveals how understanding the process can help us fight back. But this illumination comes at an expense: Theories are supported by incomplete and sometimes inaccurate portraits of specific infectious agents. Moreover, the interplay between our many microbial colonizers is never mentioned. Those in the field will take particular umbrage at the imprecise and hyperbolic way in which infectious diseases are presented to a lay audience.

Ewald is an original thinker. Moreover, his desire to inform people of our evolving relationship with microbes is ultimately of paramount importance. But in trying to impress the reader with the overwhelming significance of human-microbial cross talk, he simply overwhelms. He takes on too many thorny topics—from preventing bioterrorism, to designing the perfect HIV vaccine, to eliminating antimicrobial resistance—and in doing too much, makes errors and overstatements. These errors range from minor (calling the systemic illness typhoid fever a diarrheal disease) to disquieting (his claim that "less than 5% of all cancers are known to be caused without any assistance from infectious organisms" simply cannot be given credence—except, perhaps, by the Tobacco Institute).

The many misstatements are compounded by odd omissions and exaggerations. Every disease is not "a mix of environmental and genetic factors." In fact, some diseases are strictly genetic—that the driving forces for the mutations thousands of years ago were infectious does little to mitigate the real diseases that afflict us today. Ewald calls it miraculous that a vaccine for yellow fever contaminated with live hepatitis B virus did not result in chronic hepatitis or liver cancer in the adults to whom it was administered; in making this statement, he ignores the fact that the chronic forms of infection that lead to these serious sequelae occur chiefly in people who were infected in infancy and only very rarely in those infected as adults. It is neither fair nor accurate to say that the hands of doctors and nurses cause most hospital infections. There are few citations; in the absence of rigorous documentation, it is hard to avoid the suspicion that facts are being molded to fit preconceived hypotheses.

Ewald chastises researchers for lagging in their efforts to seek infection behind chronic diseases. However, a relatively large cadre of individual researchers is extremely interested in this field—a fact evidenced by the rapid pace with which infections in chronic disease are being uncovered. Yet the field remains challenging simply because we don't know how to study it. We are particularly at a loss to identify organisms that perpetrate hit-and-run diseases (those that cause irreparable damage and disappear or cause an autoimmune-type response). Even infections that directly cause chronic disease can be thorny to identify because they may be extremely common (human papillomavirus, Chlamydia pneumoniae or Helicobacter pylori) or virtually universal (Epstein-Barr virus). If "everyone" has them, Ewald's suggestion that scientists chase down individual anecdotal responses to antibiotics is unlikely to be fruitful.

In February of this year, the code for the human genome was officially unveiled. Some felt disappointed that the number of human genes did not far exceed the number of worm genes. However, Stephen Jay Gould rightly noted that this gene counting is short-sighted (The New York Times, Feb. 19). Humans are more complex than worms. If we don't have many more genes, then we must assume that the actual workings of these genes and the interactions among them are much more complicated than we had previously anticipated. The same can be said of our life with the microbial world: It is not simple and cannot be reduced to simple relationships. Ewald's goal of documenting our complex relationship with the microbial world is a great one. But I wish he would rewrite his book. Its exciting and important arguments are obscured by its overly broad sweep, its lack of focus on proved associations and its inadequate documentation of his more interesting points.—Julie Parsonnet, Infectious Diseases and Geographic Medicine, Stanford University School of Medicine

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