It is no accident that Dubos developed his theories of microbial ecology, and his broader critique of the ‘mirage’ of modern medicine, within the context of his early work on bacterial resistance (Moberg 1996). Antimicrobials appear at first glance to be a technological fix par excellence, in the sense that they are a simple and effective technical solution to a complex problem with biological, social, political, and economic
determinants. Indeed, a recent article critiquing the pursuit of technological fixes in dementia cited antibiotics as the classic case of a technological fix with unintended consequences (Jongsma 2017).
One could in fact argue that the apparent success of antibiotics is in large part responsible for a broader faith in technological fixes in medicine in the developed world. In 1967, during an oft-cited speech before American public health officials at the White House, U.S. Surgeon General William H. Stewart declared that it was time to close the book on infectious diseases and turn attention towards chronic health problems (Garrett 1994, p. 33). Stewart’s optimistic claim reflects a perennial American faith in the power of biomedical science to conquer disease, but it is also evidence of a significant transformation in the burden of disease during the past century. In what is often referred to as the “epidemiologic transition,” the proportion of deaths caused by infectious disease in the United States (and other industrialized nations) declined precipitously (Omran 1983). In 1900, infectious disease was responsible for 797 deaths per 100,000 population; by 1980, this figure had dropped to 36 deaths per 100,000 population. As mortality from infectious disease climbed, death rates for heart disease, various cancers, stroke, and accidents held steady or increased. In a dramatic reversal, chronic diseases replaced infectious ones as the leading killers in the United States. In 1900, 40% of deaths in the U.S. were caused by the eleven major infectious diseases (pneumonia, influenza, and tuberculosis alone accounting for more than 25% of all deaths), 16% by the three major chronic diseases (heart disease, cancer, and stroke), and 4% by accidents; by 1973, only 6% of deaths were caused by infectious diseases, 58% by chronic diseases, and 9% by accidents (Armstrong 1999).
The social and institutional ramifications of the epidemiologic transition were profound. Deluged with dramatic stories of patients snatched from the brink of death by antibiotics such as streptomycin and penicillin (dubbed “yellow magic” by Reader’s Digest in 1943), Americans increasingly credited biomedical science for reducing the threat of infectious disease. This accelerated the transformation (or “narrowing”), underway since the early part of the century, of the focus of public health, from broad preventive measures towards clinical medicine, screening and the early detection of disease (Rosenkrantz 1974; Tomes 1998). This transformation was accompanied by changes in federal health expenditures as well: between 1950 and 1959, federal grants-in-aid declined from $45 million to $33 million, while funding for clinical and laboratory research jumped from $28 million in 1947 to $186 in 1957 (Fee 1994). The redirection of public and private funding from public health towards biomedical research would continue to accelerate into the 1980s, when it would be exacerbated by the dismantling of public health infrastructures in general under the pressure of Reagan-era budgetary constraints.
Even as much of the institutional apparatus for addressing infectious disease was being dismantled, the public and the medical profession increasingly mirrored Stewart’s optimism regarding the threat of infectious disease. As historian Nancy Tomes notes, “With the array of drugs and vaccines available by 1965, the need to guard against contact infection understandably relaxed. Americans quickly came to believe that with a few soon-to-be-cured exceptions, modern medicine and public health had ‘conquered’ epidemic disease. Young physicians in the 1960s were advised, ‘Don’t bother going into infectious diseases,’ and to concentrate on cancer or heart disease instead” (Tomes 1998, p. 254) Americans increasingly came to see infectious disease as a thing of the past, and they were bolstered in this confidence by the lack of significant epidemics of communicable disease – a confidence only briefly shaken by the HIV/AIDS epidemic, at least until the discovery of antiretroviral drugs.
Yet one can argue whether antibiotics truly ‘fixed’ the problem of infectious disease. As already noted, while they are often given full credit for the decline of infectious disease in Europe and North America, antibiotics were introduced after the majority of mortality declines that are more correctly attributed to rising standards of living, better nutrition, and basic public health preventive measures such as sanitation, vaccination, vector control, and provision of clean water (Szreter 1988; Cutler and Miller 2005). Moreover, social and economic
factors continue to be major determinants of infectious disease (Semenza 2016). Even in high-income countries with well-functioning health care systems and access to a full range of antibiotics, poverty, social marginalization, and food and water quality continue to play a significant role in the incidence of infectious disease (King 2003; Semenza 2010). It remains to be seen whether, from a population perspective, investment in additional antimicrobials is the most effective or efficient way to reduce the burden of infectious disease.
Whether or not antibiotics ‘fixed’ infectious disease, their introduction generated the unintended consequence of antimicrobial resistance. While it might seem logical that a ‘technological’ problem (antimicrobials) demands a ‘technological’ solution (more antimicrobials), as the other chapters in this volume illustrate, the causes of and solutions to antimicrobial resistance are more complicated. As with infectious disease, the proximate cause of antimicrobial resistance is biological – pathogens develop resistance under the selective pressure exerted by use of antimicrobials – but underlying this proximate cause is a range of more distal determinants. These include, among others:
Physician behavior – e.g., prescribing antibiotics for conditions caused by viruses (Sprenger 2015); engage in suboptimal practices such as use of monotherapy rather than combination therapy; and incorrect drug administration routes (Struelens 1998).
Patient behavior – e.g., failure to complete full course of treatment; and self-medication, particularly in countries where antimicrobials are available over the counter.
Poor hygiene, sanitation, and infection control in hospitals and other healthcare facilities, leading to cross-infection with multiple strains of bacteria (Aiello 2006; Struelens 1998).
Widespread use – including misuse and overuse – of antimicrobials in agriculture (Levy 2014; Ventola 2015).
Lack of development of new antimicrobials, which are less profitable than drugs for chronic conditions that are generally more expensive and used for much longer periods of time (Brown and Wright 2016).
Novel antibiotics will be introduced into the same social, political, and economic
contexts that have contributed to the development of antibiotic resistance in the first place. Addressing these contexts would require, among other interventions: changing the behavior of physicians and patients to encourage appropriate stewardship of antimicrobials; instituting and enforcing new sanitation and infection control protocols at healthcare facilities across the globe; reforming an agricultural system dependent upon cheap antibiotics; and changing the incentive structure of the pharmaceutical industry to ensure that need rather than profit drives drug research.
Faced with a wide and seemingly insurmountable range of determinants, focusing on the development of new lines of antimicrobials through targeted research grants and incentive programs is attractive. Yet such a narrow pursuit would, ultimately, amount to little more than layering technological fixes on prior technological fixes. As Dubos noted a half-century ago, “Granted the obvious usefulness of sanitary practices, immunological procedures, and antimicrobial drugs, it does not necessarily follow that destruction of microbes constitutes the only possible approach to the problem of infectious disease, nor necessarily the best”(Dubos 1996, p. 53).