and that cagA+ strains signal human gastric cells differently from cagA− strains, and affect gastric physiology in markedly different ways than in the absence of H. pylori. This work led to a general model for the persistence of co-evolved organisms, based on the presence of a Nash equilibrium, and also for the relationship of persisting microbes to cancer, and age-related mortality. Beginning in 1996, he hypothesized that H. pylori strains might have benefit to humans as well as costs. Despite considerable and ongoing skepticism by the community of H. pylori investigators, Blaser and his colleagues progressively developed a body of research that provided evidence that gastric colonization by this organism provided protection against the esophageal diseases of gastroesophageal reflux disease (GERD), Barrett's esophagus, and esophageal adenocarcinoma, work that has since been confirmed by independent investigators. His work has suggested a benefit of H. pylori against such early life illnesses as childhood diarrhea and asthma. This work is consistent with the hypothesis that H. pylori is an ancient, universal inhabitant of the human stomach that has been disappearing as a result of 20th century changes in socio-economic status, including the use of antibiotics and that this loss has health consequences, not only good (less gastric cancer), but bad as well (more esophageal disease and cancer, and more childhood-onset allergic asthma and hay fever). In 1998, Blaser created the term acagia, to indicate a susceptibility for esophageal diseases in persons not carrying cagA+ H. pylori strains. Since then, acagia has come to reflect the rise in other diseases associated with the loss of cagA+ H. pylori, and may become a metaphor for the disappearance of members of the human microbiome that have symbiotic roles. In 2009, with Stanley Falkow, he hypothesized that human microecology is rapidly changing with potentially substantial consequences. He envisioned a step-wise (generational) diminution in microbial diversity, especially in early life to explain the epidemic rise of such diseases as childhood-onset asthma and obesity. Blaser has proposed that greater understanding of our indigenous (and progressively disappearing) microbiota can lead to improvements in human health. He has proposed that the routine use (and overuse) of antibiotics in young children may be causing collateral damage, with extinctions of our ancient microbiota at critical stages of early life. This scenario may be contributing to the risk of epidemic metabolic, immunologic, and neurodevelopmental disorders. Studies in mice have contributed strong support to these