First Author

Microbial infections are often likened to warfare — either the microbe or the host prevails. But persistent infections represent an equilibrium between host and microbe. On page 843, Martin Blaser, an infectious-disease specialist at New York University School of Medicine, presents a dynamic, multi-scale model of cooperation to explain how an equilibrium can be sustained between a microbe and its host. He tells Nature that this model could help determine microbial responses to modernization.

How, as a physician, did you come to model persistent-infection dynamics?

At a 1990 conference, a hot topic was how Helicobacter pylori, a microbe that persists in the human stomach, increases the host's inflammation response. I postulated that, for it to persist for a lifetime, H. pylori must trigger an equal and opposite cellular response to avoid excessive inflammation that could ultimately destroy its niche. My co-author, Denise Kirschner, and I showed that only a negative feedback of co-evolved signals — whereby bacterial-induced inflammation prompts the host to alter the environment such that the bacteria signal less — could allow the cycle to persist.

Your work reconciles evolutionary theory with game theory. How does this work?

In classical evolutionary theory, everything is based on competition because it's assumed that, in a cooperative situation, 'cheaters' would usurp resources and the system would fail. But cooperation exists, so I wanted to determine how it fits into the model. About six months ago, I came across game theory's Nash equilibrium concept, which can be summed up as 'if you cheat, you lose'. I realized that persistence relies on creating a system that would be disadvantageous to either a bacterial or host cheater.

How has the rise of civilization affected pathogen success?

Population size has been very important. Evolutionarily, small host-population size selects for microbes that are symbiotic or cause disease only late in life. Bigger populations can tolerate greater virulence, as is evidenced by the HIV pandemic.

What effect has modernization had?

H. pylori causes ulcers and stomach cancer later in life, but also protects against reflux and oesophageal diseases early in life. Owing to increased antibiotic use, however, organisms such as H. pylori are disappearing. We're thus more exposed to virulent organisms at a time when our microbiological defences, evolved over millions of years, are possibly being depleted.