Pneumonia Before Antibiotics: Therapeutic Evolution and Evaluation in Twentieth-Century America

PART I: SEROTHERAPY AND THE RISE OF THE SPECIFIC, 1891 – 1930

p a r t i serotherapy and the rise of the specific, 1891–1930 “Pneumonia,” wrote two clinicians on the eve of antipneumococcal serotherapy in 1890, “is a representative disease.”1 From the standpoints of nosology (the classification of disease) and diagnosis, the tempo and mode of change regarding pneumonia as a disease entity over the past two millennia certainly does serve in many respects as a type for the evolution of disease concepts more broadly. From the time of the Hippocratic corpus through the nineteenth century, while the acute chills and painful cough experienced by “peripneumonia” patients were well characterized, the disease’s broad dichotomization into pleurisy (a¤ecting the lining around the lungs) and pneumonia (a¤ecting the lungs themselves) by Anton Maria Valsalva and Giovanni Battista Morgagni in the eighteenth century constituted virtually the only attempts to place such nosology on a firmer anatomic basis. With the rise of European hospital medicine in the nineteenth century, however, René-T.-H. Laennec in Paris and Carl von Rokitansky in Vienna would correlate the antemortem symptoms and signs of pneumonia with its postmortem pathology. And the predictive capacities of the physical signs of pneumonia—based first on manual percussion (introduced by Leopold Auenbrügger in 1761) and then on auscultation through use of the stethoscope (introduced by Laennec in 1819)—could soon serve as paradigmatic examples of the power of the tools used to reveal them.2 With respect to changing notions of pathophysiology and consequent therapeutics, however, pneumonia would serve even more faithfully as a representative type, epitomizing the evolving “therapeutic perspective” throughout the nineteenth century in particular. As the two London clinicians cited above continued: Discussions as to the nature and results of inflammation have chosen it for their chief illustration, and the e¤ect of antiphlogistic treatment has been condemned or approved upon its evidence. When depletion was most in vogue it was to the lung in inflammation that its methods were most relentlessly applied. When the wisdom of bloodletting began to be questioned, it was resolved to test its eªcacy by appealing to the results obtained in pneumonia; and, coming to later times, when disease was first recognized as consisting in an orderly succession of phenomena , it was again with pneumonia that the crucial experiment was made of leaving inflammation to its own course.3 In America, pneumonia likewise served as a test case for clinicians to implement their changing therapeutic rationales throughout the century, from the vogue of heroic bloodletting in the early decades of the century, through the anti-heroic reaction and the increasing attention paid to the physiological support of the presumably depleted patient by the end of the 1860s.4 With the advent of the Golden Age of Microbiology ushered in by Louis Pasteur and Robert Koch and their colleagues in the 1870s and 1880s, such opportunities would continue to present themselves. The gram-positive diplococcal pneumococcus would—after much negotiation—be established as the primary etiological agent of pneumonia by the end of the 1880s, during the same time that immunology as a field came into being.5 In 1884 Elie Metchniko¤ had revealed the role of the amoeboid cellular phagocyte (from the Greek phagos, “to eat”) in mediating immunity, initially demonstrated by the response of the phagocytic cells of the water flea to a fungal infection.6 By 1888, George Nuttall, in Carl Flügge’s lab in Göttingen , had revealed the in vitro activity of humoral (cell-free) factors as well, initially through demonstrating their destruction of anthrax bacilli.7 And if the late 1870s and early 1880s had marked the onset of the discovery of infectious agents of disease, the late 1880s and early 1890s witnessed the onset of the medical attack on such pathogens through applied humoral immunology. By 1890, Emil von Behring and Shibusaburo Kitasato , in Robert Koch’s lab in Berlin, had confirmed in vivo the activity of the humoral agents (soon to be termed “antitoxins,” a class of what would come to be known as “antibodies”), demonstrating that their passive transfer into laboratory animals was protective against diphtheria and tetanus toxins.8 Such passive serotherapy, or the administration of serum obtained from animals already rendered immune to a given toxin or microorgan10 Serotherapy, 1891–1930 ism, could thus be contrasted with active vaccination, in which the intention would be to stimulate the recipient’s...