Antibiotics: the epitome of a wonder drug
BMJ 2007; 334 doi: https://doi.org/10.1136/bmj.39021.640255.94 (Published 04 January 2007) Cite this as: BMJ 2007;334:s6
Antibiotics can truly be considered the epitome of the 20th century's “wonder drugs.” This term was widely used in the 1950s, even in official documents, expressing the enthusiasm of patients, doctors, and policy makers for drugs that transformed once mortally feared bacterial infections into curable conditions.
Penicillin is the iconic antibiotic. Its introduction into clinical practice was widely celebrated and was the culmination of individual achievements, long running trends in science, and a supportive environment. In 1929 Alexander Fleming, at St Mary's Hospital Medical School in London, reported his observation that the culture medium on which a penicillium mould had grown attacked certain bacteria. However, chemists and bacteriologists, then working largely separately, failed to isolate the active substance in the mould juice. Only in 1940 was the isolation achieved, at Oxford, where Howard Florey had created a multidisciplinary team. The team's efforts were sustained by the interest and talent of, among others, Ernst Chain, a German refugee, and Norman Heatley, who developed key techniques for growing the mould and isolating the drug. But the financial support of the Rockefeller Foundation in the United States and the Medical Research Council in the United Kingdom was also crucial, as were the need created by the outbreak of war and the remarkable properties of penicillin itself. This confluence of factors led rapidly to laboratory scale production and the demonstration of penicillin's clinical potential.
Cheap production, mass protection
When British industry, under the pressure of German bombing and with little experience in sterile fermentation, failed to take up penicillin with enthusiasm, Florey and Heatley flew to the US to seek help. There they found expertise in chemical production by fermentation and in growing organisms in deep tanks, even aerobic ones. This expertise made cheap mass production possible.
From the time of the Allies' invasion of Italy, soldiers were protected by penicillin not just from infected wounds but also from the effects of sexually transmitted diseases. Compared with the previous long and risky treatment for syphilis, penicillin provided a swift and effective cure. This would prove a critical benefit in Europe during the early postwar years, when a syphilis epidemic threatened the occupying armies and the impoverished former Axis countries alike. Syphilis might then have proved the threat to Europe that AIDS would later pose in Africa, but penicillin stopped the epidemic decisively.
However, antibiotics had wider consequences than strictly medical ones. The new drugs underpinned a surge in the use of health services in the postwar years. Fast throughput in general practice was possible because antibiotics could be swiftly administered or prescribed after a short consultation. Surgeons undertook more complex operations on patients now protected from infection.
The end of a duty?
Even more profound were the moral consequences of the use of the drugs. Until the mid-1930s prevention rather than cure had been the general means of control of most infections. Injunctions to the healthy were complemented by a moral disdain for those who lapsed and then succumbed to disease. The introduction of antibiotics in the 1940s converted illness into a strictly technical problem. In richer countries the avoidance of “germs” gradually ceased to be a duty. The immunologist Frank Macfarlane Burnet expressed a then widespread (if eventually misplaced) hope in his Natural History of Infectious Disease that the mid-20th century represented a revolution in human history—the “virtual elimination of infectious disease as a significant factor in social life.”1
Undoubtedly, other factors also drove the transition in the health of richer nations. Better nutrition and housing were probably among the most important, but there were also technological innovations. The synthetic sulphonamides, developed in the 1930s, predated the antibiotics derived from natural organisms. They provided the first general solution to many bacterial infections. Nevertheless, bacteria quickly developed resistance to them, many people suffered severe side effects, and their spectrum of action was not great by later standards. For instance, they could not be used to treat syphilis, which was soon easily addressed with penicillin. Penicillin offered greater clinical benefits, particularly important in wartime.
The broader category of antibiotics soon developed. Their name had been claimed as early as 1942, when—following quickly on the isolation of penicillin—other new antibacterial drugs were derived from fungi and streptomyces. Selman Waksman, a soil microbiologist at Rutgers University, chose the word to describe those substances “inhibiting the growth or the metabolic activities of bacteria and other micro-organisms by a chemical substance of microbial origin.”2
Genomic advances
Antibiotics developed rapidly after the second world war, but since the early 1960s few fundamentally new families of antibiotics have been introduced, and at the beginning of the 21st century 14 million people a year die of infectious disease. From the mid-1990s multiply resistant staphylococci and resistant pneumococci have caused widespread anxiety across a world that seemed at imminent risk of the emergence of bacteria that were resistant to all known antibiotics. Resistance has become a public health issue worldwide.
The contemporaneous emergence of genomics gave rise, initially, to the prospect of the selection of many completely new antibiotics through a series of new technologies. The sequencing of bacterial genomes, understanding of the molecular basis of pathogenicity and protein expression, and combinatorial chemistry would, it was hoped, generate huge libraries of potential agents for screening. Such advances have not yet yielded large numbers of new drugs, and the popularity of antibacterial vaccines to combat such diseases as pneumonia has once again emphasised prevention rather than cure. Two generations after the introduction of antibiotics can we see—in the renewed concern for cleanliness in hospitals and greater reluctance to use antibiotics in the community—the revival of the hygienic and perhaps even the moral disciplines that predated the antibiotic revolution?
Footnotes
Publication of this online supplement is made possible by an educational grant from AstraZeneca
Competing interests: RB is the author of Penicillin: Triumph and Tragedy, to be published this year by Oxford University Press, and is curating a new exhibition at the Science Museum, London, on the history of penicillin. He has been paid fees by GlaxoSmithKline and AstraZeneca for speaking on the history of antibiotics to their employees and consultants and had been paid a fee by the Wellcome Trust for writing on the topic of penicillin.