Eurasian settlers were newly being exposed. A corollary consequence of thousands of years of H. sapiens exposure to infected animals is that the natural selection of surviving humans led to a population safeguarded by induced immunity to the prevailing bacteria and other infectious agents and other pathogens. But when unexposed indigenous populations crossed paths with those who had become immunologically protected, for example, during the Age of Discovery between the 15th and 18th centuries, some vulnerable island populations were totally exterminated, and at least 90% of several Native American populations were wiped out following contact, particularly, with immune-shielded European travelers [15].
The quintessential downside to the positive forces of agriculture and domestication, abetted by a continuously increasing population, as described later in this chapter, was the onset of warfare: the mass killing of one or more groups of human beings by other human beings. The bright side of the developing cradle of civilization has been characterized by the development of written language and by feats of human ingenuity, improving health, and rising prosperity. But the dark side created the formation of armies, the advancement of weapons, and the virtually endless practice of war and death.
Evolution of TB
TB is the largest cause of adult deaths from any single infectious disease, and ranks among the top 10 causes of death worldwide. According to the latest (2017) World Health Organization Global Tuberculosis Report, “The TB epidemic is larger than previously estimated reflecting new surveillance and survey data from India.” Specifically,
In 2016 there were an estimated 10.4 million new (incident) TB cases worldwide, of which 6.2 million (59.5%) were among men, 3.2 million (30.5%) among women, and 1.0 million (10%) among children. People living with human immunodeficiency virus (HIV) accounted for 1.0 million (10%) of all new TB cases.
Furthermore,
In 2016, there were an estimated 490,000 new cases of multidrug-resistant TB and an additional 110,000 people with rifampicin-resistant TB who were also newly eligible for multidrug-resistant TB treatment.
Lastly,
there were an estimated 1.3 million TB deaths in 2016, and an additional 0.4 million deaths resulting from TB disease among people living with HIV. [16]
Early Observations
TB has traditionally been considered a disease of “antiquity.” And as far back as 460 BCE, the Hippocratic Corpus included reference to TB, or whatever symptom-complex was referenced at the time; moreover, the Corpus warned physicians to avoid caring for such patients when seriously ill, because their high mortality rates were damaging to their professional reputations [17]. For centuries thereafter, arguments raged over whether TB was caused by miasmas, atmospheric imbalances, heredity constitutional defects, contagion, or even divine intervention. In 1720, an English physician, Benjamin Martin, postulated that TB was caused by “wonderfully minute living creatures,” and he believed that getting too close to “consumptives” would “draw in part of the breath he emits from the lungs,” which could transmit the disease [18]. But then nearly another century went by overflowing with supposition and mystery.
In the early 1800s, an important first start leading to an accurate diagnosis of TB was made by René T. H. Laennec, the “Father of Pulmonary Disease” and inventor of the stethoscope. In his studies on the pathologic findings of hundreds of autopsies, Laennec made the “inspired deduction” that the morphologic similarities among the abundant pulmonary abnormalities – including neighboring infiltrations and cavities as well as all the various extrapulmonary lesions – were caused by a single disease, which he called “phthisis” [19]. Not long afterward, Johann Schönlein of Berlin demonstrated that “the tubercle was the fundamental pathologic lesion” in all organs affected by the disease, which he therefore designated as “TB” [19]. Getting even closer to an answer, in 1865 Jean-Antoine Villemin, a French military surgeon, proved by transmitting pathologic material from victims of TB to a variety of experimental animals that TB was a communicable infectious disease [20, 21]. Villemin should have received far more attention to this seminal observation than he had hoped for, but the Franco-Prussian War intervened.
Finally, it was left for Robert Koch (Fig. 1), physician-scientist in Berlin, Germany, to author “one of the most definitive pronouncements in medical history” [22] on March 24, 1882. Like his great rival Louis Pasteur, Koch was already famous for his studies on the pathogenesis and life cycle of anthrax, a common and important disease of domestic and wild animals that occasionally strikes humans. Most accounts affirm that this was Koch’s maiden exposition and he started by fumbling with his notes and was obviously nervous. But after he got going, no one cared
because slowly and methodically he convinced his spellbound audience that a bacterium, which he had invented a novel way of staining so that it could be seen under a microscope, which he had succeeded for the first time ever in growing on artificial culture medium, and which he had then used to infect laboratory animals and reproduce the identical disorder, caused the most important disease of mankind of all time – TB. [22]
Seventeen days after Koch’s brilliant presentation, incredibly fast compared with current publishing norms, a seminal article announcing his discovery appeared in a major medical journal [23]. The news spread quickly. Many physicians were greatly impressed but, as expected, skeptics wanted to be certain. Koch became instantly famous, as illustrated in Figure 1. Kaiser Wilhelm I appointed him Professor and an Imperial Privy Councilor, upped his salary and research support, and added more laboratory assistants [24].
But there remained a nagging uncertainty about TB itself: was it one disease or two? Koch and other specialists knew with certainty that TB occurred in both cattle as well as humans, but no one at the time could be sure whether 2 different species of Mycobacterium were involved. Koch believed – wrongly – “that bovine disease posed no threat to humans” [22]. In 1896, Smith [25] showed “sharp differences” between M. tuberculosis and M. bovis, including their staining characteristics, morphology, and manifestations in infants and children. Five years later (1901), Koch [26] was still trivializing the public importance of M. bovis as an agent of disease; he wrote, “if such a susceptibility really exists,… (it) is but a very rare occurrence.”
Fig. 1. An engraving depicting German Bacteriologist Robert Koch (1843–1910) as the new Saint George after he isolated the bacillus of tuberculosis. Original publication: The Review of Reviews, London. English language version of an original image published in the satirical magazine Ulk in Berlin, 1890. Photo by Hulton Archive/Getty Images, with permission.
Koch waffled about the virulence of M. bovis,