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c h a p t e r o n e The Advent of Type-Specific Antipneumococcal Serotherapy The first twenty-two years of antipneumococcal serotherapy’s evolution were hardly auspicious. By 1897, while the treatment of diphtheria through the neutralization of its toxin with antitoxin was being hailed as the crowning glory of laboratory science, the existence of a pneumococcal toxin itself was called into question .1 Internationally, various researchers advocated their own antipneumococcal antibody sources—cows, ponies, donkeys, and convalescing humans to name a few—with varying degrees of success. Opinion in the United States was mixed, overall, as scientists at the turn of the century judged whether or not this was to be yet “another marvelous gift of science to the closing decade of the nineteenth century.”2 One practitioner felt so strongly about the “curative e¤ect” of serotherapy that he stated he would consider himself culpable if he did not treat a case of pneumonia with serum.3 Another, viewing the potential elimination of the old man’s “friend” through the lens of contemporary Social Darwinism, even wondered aloud whether in some respects such a longed-for therapeutic was indeed a “boon to humanity,” given that it entailed “the prolongation of life under conditions which, when nature has marked the limit, would be purely artificial.”4 To others , though, the best that could be said of serum was that it was harmless. In a review of the literature comprising 535 cases collected from dozens of small series by 1904, the prominent Philadelphia clinician James Anders revealed the standards of contemporary clinical proof in concluding: “A suªciently extensive trial of antipneumococcal sera has been made to determine with a reasonable degree of accuracy their eªciency, and the results, as a whole, fail to carry conviction.”5 For the remainder of the decade, little would occur to change this conviction.6 However, in 1913 a new era in antipneumococcal serotherapy would commence in America, grounded in a redefinition of the pneumococci themselves and in the emergence of an equally novel institution constructed for the facilita- tion of bench-to-bedside research. In Germany, Fred Neufeld had found that a given antiserum generated through the immunization of a horse with a particular strain of pneumococcus was protective upon being administered to mice against certain pneumococcal strains but failed to save the mice from others. This suggested the subdivision of the pneumococci into serological subgroups in which only members of the same subgroup, by definition, could be recognized and countered by the same antiserum. At the same time, this hinted at the possibility of a more rational clinical use of serum.7 In the United States, the Hospital of the Rockefeller Institute had been opened in 1910 with the explicit goal of its serving as a model for the clinical application of scientific medicine. Its first director, Rufus Cole, would remark of the hospital ’s mission: “In building the hospital it has not been the purpose to merely add a number of beds to the hospital facilities of greater New York. The idea has been rather to equip a hospital for a small number of patients, in such a way that the most modern methods in treatment and diagnosis could be carried out.”8 Applying the “intensive method” to the study and treatment of selected diseases, Cole hoped in particular to bring the benefits of the laboratory to the bedside of the patient . Nearly forty years old, Cole had been a disciple of William Welch at Johns Hopkins before being chosen for the Rockefeller post. One year previously, he had visited Neufeld’s lab and had been fascinated by the potential for progress against such an impassive foe as the pneumococcus.9 In choosing “those diseases . . . in which the need for improved knowledge and better therapeutics seem most urgent , or in which the chances for new discoveries and improving the methods of treatment seem greatest,”10 pneumonia seemed an ideal candidate. Cole attracted such scientists as Alphonse Dochez and Oswald Avery to the problem, and by 1913 Dochez could report that the seemingly homogeneous pneumococci could in fact be divided into four groups (or “types,” as they would come to be called).11 Strains included among types I and II, comprising nearly two-thirds of all pneumococcal isolates found and studied at the time, could be di¤erentiated by serological means (via agglutination reactions, characterized by the clumping of the organisms by antiserum...

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