relatedness as well as circumstantial evidence, the mycobacteria probably emerged from the soil to find a niche first infesting, then infecting various mammals and birds. M. bovis is the most common animal pathogen, afflicting a diverse array of mammals, including ruminants and primates. Webb in his 1932 historical overview of tuberculosis speculated that the tuberculosis germ was first systematically introduced into humankind when humans domesticated cattle around 5000 B.C. (1). Indeed, modern genetic analysis indicates an extremely high degree of DNA homology between M. bovis and M. tuberculosis, indicating that they are virtually the same species (2). Thus, it is reasonable to infer that the parent strain M. bovis—which does have limited invasive and disease-producing capacity within humans—has undergone subtle host adaptation within the human body to become the tubercle bacillus. In this process, the microbe has developed these unique traits: (i) its only significant natural reservoir is humans, (ii) it has substantially diminished virulence for most animal species other than humans, and (iii) it has developed a survival-transmission strategy that is unparalleled among the mycobacteria: airborne human-to-human spread.

Skeletal artifacts indicate that tuberculosis has afflicted humankind since at least 3000–5000 B.C. From the Hippocratic writings and the work of Galen we infer that tuberculosis, referred to then as "phthisis" (translation: "I am wasting") was highly prevalent in the Greco–Roman era. For the past 500 years, tuberculosis has been pandemic in Europe and North America; at its apex in the 17th–18th centuries, the "White Plague" took the lives of 1 in 5 adults. In the 100 years from 1850–1950, it is estimated that one billion persons died of tuberculosis.

Certainly one of the most meaningful achievements of modern medicine has been the development of curative therapy for this ancient scourge. Although it is a bacterium, the tuberculosis bacillus is highly resistant to the conventional antibiotics, such as penicillin or sulfa, which were developed in the 1930s and 1940s. Selman Waksman, a specialist in soil biology at Rutgers, while screening microbes recovered from the earth, came upon a substance elaborated by one of them with substantial activity against the tubercle bacillus in 1943–1944; this compound, streptomycin, was pressed rapidly into clinical use, with initial reports of its efficacy appearing in 1945 (3). Although useful in ameliorating disease manifestations, streptomycin alone was not sufficient to cure most cases. Microbiologists soon recognized that, while most bacilli in a population of M. tuberculosis were susceptible to the drug (they were killed rapidly by concentrations of the medication readily achievable in tissue), some mutant offspring were present that were resistant to the drug's effects. When streptomycin was given alone, it killed the vulnerable population but left behind the resistant mutants,

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