Perspectives in Biology and Medicine

Perspectives in Biology and Medicine 44.1 (2001) 1-16

Bacteriophage Therapy for Bacterial Infections: rekindling a memory from the pre-antibiotics era

Karen Ho *

Introduction

What was the attitude of man toward these new perils, the nature of which he barely grasped? Danger from the wild beasts was a physical reality which man could face and combat, but infectious diseases confronted him with the unknown. Man's complete helplessness against sudden epidemics which killed wives, husbands, children and friends made these epidemics seem supernatural, as though sent by Providence. . . . Disease was looked upon as the striking arm of Providence, the punishment of sin and immorality. Even when, with the progress of science, we acquired full knowledge of the disease-producing germs, the fatalistic attitude toward infectious disease still remained. Although modified in some degree this belief was still part of our consciousness until the time of the discovery of penicillin. (Sokoloff 1949, p. 253)

This dramatic account of the seemingly indomitable power of bacteria and the exultant confidence that antibiotics would stem the tide of illness and death from bacterial infections was written by a physician in 1949, when the power of antibiotics was just beginning to be realized. In the decades to follow, [End Page 1] the worldwide success of antibiotics in combating infections from septicemia to syphilis certainly validated the hailing of antibiotics as "miracle drugs" (p. 255).

In recent years, however, the increasing incidence of antibiotic-resistant bacterial strains has raised the deadly specter of bacterial infections from the pre-antibiotics era. Although resistance has been recognized since the 1940s, the discovery that resistant organisms could transfer the genetic information for resistance to other species, as well as the global emergence of multi-drug-resistant organisms, have increased the concern that infectious diseases will again be a lethal threat to public health (Tenover and Hughes 1996). In the United States alone, Streptococcus pneumoniae is responsible for 3,000 cases of meningitis, 50,000 cases of bacteremia, 500,000 cases of pneumonia and 7 million cases of otitis media each year. In the pre-antibiotics era, 75 percent of the cases of bacteremic pneumonia were fatal; after the advent of penicillin treatment in the 1940s, childhood mortality alone decreased by 97 percent (Dowell et al. 2000). In the late 1980s, however, the Centers for Disease Control reported that in some areas, the success of penicillin treatment had dropped by 20 to 30 percent due to either intermediately or highly resistant pneumococcal isolates and that a significant percentage of other isolates was resistant to three or more other antibiotics. By 1994, 40 percent of the isolates were susceptible only to vancomycin (Jernigan and Cetron 1996).

The challenge of multi-drug-resistant bacteria has rekindled interest in another memory from the pre-antibiotics era: bacteriophage therapy for bacterial infections. In the 1910s, British microbiologist and physician Frederick Twort (1915) and French-Canadian scientist Felix d'Herelle (1917) independently discovered bacteriophages, or bacterial viruses. While studying bacteria isolated from the stools of a patient with severe bacillary dysentery in 1916, d'Herelle noticed that one sample of bacteria would repeatedly become clear while the others grew turbid from bacterial proliferation. He recalls that the observation "led me to consider the question of a virus pathogenic for the man or the animal" and "offered the suggestion that the dissolving principle might be a virus pathogenic for the bacterium" (d'Herelle 1926, p. 4). He noted that "the dissolving principle actually regenerated in the course of the action" and that "the principle was condensed in the form of actual particles. . . . It is to this principle that I have given the name Bacteriophage and the phenomenon of bacterial solution caused by it being termed Bacteriophagy" (p. 5).

D'Herelle and his colleagues would subsequently administer bacteriophages (which in 1922 he hypothesized to be living "parasites" of bacteria) to patients with a variety of bacterial infections, which spawned a flurry of publications describing both fantastic successes of treatment as well as dismal failures. As a result of his...