This book narrates the parable of antibiotics, first perceived as revolutionising medical practice and then, in a staggering switch of medical discourse, singled out as causing, through microbial resistance, a potentially catastrophic medical risk. The book relates how this switch occurred by uncovering a complex story in which several actors played important roles, including microbiologists, physicians, biostatisticians, pharmacologists, journalists, journal editors, marketing communication experts, chief executives, politicians and bureaucrats. Naturally, the switch from treating antibiotics as the holy grail of medicine to considering them as a threat was not sudden. In particular, the book unveils the complicated story of how a social force (i.e., “REFORM”) tried to limit the “irrational” misuse of antibiotics, how their efforts were opposed by another social force (i.e., “RESISTANCE”) and how, eventually, the problem of antibiotic resistance became recognised as a serious medical problem. The narrative focuses on what happened in the United States of America. As the author explains in the introduction, the book does not provide a global history but a local one, chronicling how antibiotic resistance became a political issue in the USA, and how this political issue eventually turned global. This historical process took, according to the author’s reconstruction, several decades. The narrative of the book unfolds in a twisting way as in a good script, with the first chapters seemingly conveying the message that reform was objectively correct in seeking limitations of clear antibiotics misuse, and later chapters where the arguments of resistance are illustrated, nurturing the seed of doubt: whose conception of rational therapeutics was genuinely rational? With hindsight, the layman seems to have no choice but to side with reform. Today we know too much about antimicrobial resistance to underestimate the problem. But in the 1960s and 1970s the arguments in favour of reform were, if not objectionable, somehow counterweighted by those proposed by resistance. Only a simplistic reading of medical history would portray the clash between reform and resistance as a one-sided affair between a right faction only motivated by good reasons and a wrong faction spurred by purely ideological ones. The author succeeds in not banalising this important human story.

It would be a mistake to characterise resistance as a conservative social force. Undoubtedly pharmaceutical companies played an important role in thwarting reform. Already in the 1950s many scientists and doctors grew increasingly aware of the sleazy marketing practices of the pharmaceutical industry. Furthermore, its collusion with the publishing industry became a cause of serious concern: some medical journals were effectively co-opted, publishing clinical results based on the support of so called “testimonials” (i.e., putative clinical authorities) rather than rigorous clinical data, probably with the aim of creating “evidence” to be used by pharmaceutical companies in their attempts to corroborate the effectiveness of their products. Another objectionable practice was to experiment with combinations of drugs (viz., treatments containing different antibiotics – up to five together! – concocted sometimes with other drugs and substances, e.g, caffeine) with the principal aim of retaining patent rights when individual drugs’ licences had expired. Some pharmaceutical developments could have been even worse. One idea that took hold for a while was to dispense completely with diagnosis by immediately prescribing what was tentatively called “multimycetin”, i.e., a fictional combination of drugs designed to cure all infections. What was most absurd and alarming about this overoptimistic as well as naïve trend was the fact that it had already been demonstrated that the efficacy of combinations was limited to specific strains of the bacterial species under consideration, that is, in vitro efficacy was strain-dependent and not generalisable to the same type/species of bacteria. Reform considered these vicious and irrational trends hindrances in the quest for therapeutic rationalism. Eventually reform won the “battle” concerning “irrational” antibiotics: fixed-dose combinations were withdrew from the USA market in the early 1960s (to be duly found, in a further turn of the plot, in the pharmacies of developing countries years later). But reform did not win the “war” against the inappropriate use of antibiotics. On the contrary, in the 1960s and 1970s a backlash against reform ensued.

Many reasons explain this outcome. First of all, one implicit theme in the unfolding story concerns the spontaneous and misguided optimism of that period. One reason for such optimism was certainly the belief that the antibiotic — aka “wonder drug” –  epitomised the power of science to positively resolve social problems. This scientistic attitude, coupled with the unique optimism of the postwar period, were arguably major factors shaping the debate concerning the supposed risks of antibiotics. Secondly, the 1960s and 1970s were also characterised by the paucity of medical evidence. It was only in 1963 that microbiologists demonstrated that resistance to antibiotics could be transmitted via plasmids from one microbial species to another. But the clinical significance of this research remained unclear for years. Furthermore, the statistical link between overuse of antibiotics and increased resistance began to be studied in the same period and, again, the medical significance of this research remained obscure for years. Thirdly, and probably most interestingly, a clash of medical ideologies was lurking in the background to the extent that the terms of the debate between reform and resistance shifted to the characterisation of the very notion of rational therapeutics.

Reform characterised rational therapeutics as the pursuit of the medical ideal of seeking the right drug for the right patient in the right amount at the right time. This purist approach called for restraint in prescription, education of the physician and patient alike, a bigger role of the FDA in evaluating and arbitrating on the efficacy of drugs and the endorsement of the double blind clinical trial as the sole relevant method for determining the value of pharmaceutical products. But this view — so reasonable from the vantage point of contemporary evidence-based medicine — was far from universally endorsed. As a matter of fact, it was resisted by many different actors and social forces: clinicians who saw their fundamental freedom to prescribe curtailed by unnecessary federal “paternalistic” intervention, politicians who perceived the risks of an increasing socialisation of medicine, pharmaceutical companies that dreaded a substantial erosion to their right of enterprise etc. What is important to highlight is that reform was only proposing one “interpretation” of rational therapeutics. One argument of resistance was that the efficacy of drugs depends on the individual case, i.e., the unique nature of the patient’s organism; thus, the argument went, the results of controlled clinical trials should be considered largely irrelevant to ascertain whether the drug is efficacious in individual cases because clinical trials are based on statistical artefacts; this implies that the truly “rational” therapy should ultimately be founded on the historical basis provided by the judgments of generations of doctors. Another prominent argument in favour of resistance was pragmatic: given that the clinician works necessarily in a state of limited knowledge concerning the nature of the ailment affecting the patient, and given that it would be impossible to diminish this chronic ignorance through the acquisition of clinical and laboratory information – because of limited financial resources and limited technological capabilities — then the rational course of action is to give freedom to the physician to judge whether antibiotics should be used. The purist approach favoured by reform stigmatised the irrational use of antibiotics as a cure for the common cold, but the pragmatic approach favoured by resistance retorted that such use was eminently rational in a situation of persistent clinical and aetiological uncertainty (a conflict of clinical practices that perdures). Therefore, the clash between reform and resistance developed in the context of methodological debates concerning the epistemological significance of the double blind clinical trial, rapid advances in diagnostic techniques, the erosion of patients’ freedom to choose and clinicians’ freedom to prescribe and, generally, differing ideological sensibilities concerning the regulation of the drug market. Supported by some good arguments, resistance managed to withstand reform’s attempt to characterise rational therapeutics. However, their interpretation of the phenomenon of antibiotic resistance as an inflated scare eventually succumbed to the weight of evidence.

This remarkable book ultimately shows that antibiotic resistance is an issue of huge cultural import that spans many disciplinary areas and which cannot be completely understood in all its significance without understanding its history: it is surely necessary to know the molecular details of the biological processes through which microbes acquire resistance; but it is also necessary to understand the conflict between the various social forces that shaped the debate concerning the misuse, abuse and overuse of antibiotics. The book accomplishes this latter result formidably well.

© 2015  Davide Vecchi

Davide Vecchi, CFCUL, Faculty of Sciences, University of Lisbon, Portugal