Waking up from antibiotic sleep

Antibiotics and Public Health, CA. 1950S

To understand how far-reaching an event in the history of public health was the arrival of antibiotics, we must recall that the formation known as public health originated to battle infectious diseases. In the early 19^th century context of industrialisation, peasants abandoned their farms to work in factories. The rural exodus quickly led to densely populated shanty towns which lacked even the most basic sanitary infrastructure. Cholera, typhoid fever, tuberculosis, whooping cough and pneumonia spread quickly – and soon confronted officials with the challenge of infection prevention and control. ¹ The discovery of the antibacterial quality of the penicillium mold ² and the subsequent large-scale production of the first ‘antibiotics’ (prepared by Chain and Florey) marked a major step in the history of these prevention efforts. Although, by around 1945, when penicillin became generally available and a century’s worth of sanitary measures had already markedly reduced death rates, bacterial infections were still an important cause of mortality.

The arrival of antibiotics changed this significantly: if, in 1945, bacterial meningitis was almost certainly a death sentence, it had become a controllable disease only a few years later. The enthusiasm surrounding antibiotics – the drug was widely celebrated in newspaper and magazine reports – was enormous, and to contemporaries, it seemed as if the discovery of antibiotics could lead to a marked reduction in death from infections. ³ ‘One can think of the middle of the twentieth century’, F. Macfarlane Burnett wrote in 1953, ‘as the end of one of the most important social revolutions in history – the virtual elimination of infectious disease as a significant factor in social life’. ⁴

Therefore, in the 1950s, it seemed as if antibiotics had relieved public health experts of the challenge that had once been constitutive of their field – the challenge of preventing bacterial infections. Although viral pathogens had certainly not disappeared, infectious diseases seemed now a minor risk, and so the public health profession began to turn towards what now seemed the next big challenge: chronic diseases. ⁵

Antibiotics and Public Health, ca. 1980s to 2000s

In the 1980s, reports about the emergence of multiple drug resistant (MDR) bacteria and the ‘return of infectious disease’ troubled the optimism once engendered by antibiotics – and forced public health experts to reconsider the question of infections. The problem of resistance was not new. From the start, biologists were aware that the mass production of antibiotics might select for antibiotic-resistant strains. Penicillin was first administered to patients in 1940, and the first observations of penicillin-resistant bacteria were already made in 1941.^6,7 However, concerns raised about resistance were usually dismissed with confidence that new antibiotics would soon be discovered: physicians and drug researchers could always outsmart bacteria. ⁸ The seriousness of the threat of antibiotic resistance became apparent only in the mid-1990s, partly through reports about MDR tuberculosis in the wake of the HIV epidemic and partly through continuing research on horizontal gene transfer (HGT) among bacteria, which provided new understandings of the problem of resistance: it became apparent that the assumption that only bacteria exposed to antibiotics could acquire resistance was erroneous. On the contrary, bacteria with antibiotic resistance genes could easily export them to bacterial populations never before exposed to antibiotics – and these could share them further.^9–11 Sadly, hospitals, where patients with various debilities often receive multiple classes of antibiotics, are an ideal setting for the amplification and spread of antibiotic resistance.

By the late 1990s or early 2000s, antibiotics had thus produced their own kind of public health emergency: the rise of serious infections due to antibiotic-resistant bacteria. ¹²

Antibiotics and Public Health, ca. 2000s Onwards

In the early 2000s, the discovery that thousands of little-known and barely studied bacterial species live in and on the human body, coupled with the observation that these bacteria cumulatively are a critical part of human physiology, gave rise to a new branch of biology – microbiome research.^13–16

In the decade since its inception, microbiome research – which is itself building on the insights of decades of symbiosis research in plants and animals – has provided substantial evidence that the old conception of genomic autonomy, according to which one organism is the result of one genome only, is not adequate. For example, many aspects of normal human physiology – from immune defences to digestion, from behaviour to metabolism – don’t function properly in the absence of genes that don’t belong, strictly speaking, to humans but rather to bacteria. Quite literally, humans are part of a metaorganism that is composed of many different species and even phyla.^17,18

And antibiotics?

If viewed from a microbial perspective, the current broad-spectrum antibiotics most commonly in use resemble a carpet-bombing of the complex microbiota on which we depend. They not only suppress or destroy potential pathogens, but also many of the symbiotic microbiota on which human physiology is contingent. The effect on health and wellbeing can be significant. ¹⁹ For example, an increasing number of epidemiological as well as experimental studies have shown correlation of antibiotic exposure with the development of allergies, ²⁰ inflammatory bowel disease, ²¹ asthma, ²² obesity,^23,24 coeliac disease, ²⁵ type 1 and type 2 diabetes,^26,27 and even neurological and psychiatric disorders, from autism to depression, from Parkinson’s to anxiety disorders. ²⁸

Another line of evidence supporting a link between antibiotic usage and disease is that the start of the current epidemics of allergies, asthma, obesity and type 1 diabetes, which can be traced back to the late 1940s, that is, to the time when antibiotics entered medical practice. The observation that mothers pass on their microbiota to their offspring, and that mothers who have, due to antibiotic use, a diminished microbiome transmit a diminished microbiota, provides at least a partial explanation as to how quickly and suddenly these epidemics emerged. ²⁹

Microbiome research thus reconfigures the relation between antibiotics and public health. Before the emergence of this new field of research, public health experts largely understood antibiotics as a weapon in the human fight against pathogens (here the human, there the microbes). The new challenge is to understand our microbiota as essential partners and to consider that antibiotic disruption of the multi-species community of which we are a part may lead to disease.

Could it be that chronic diseases to which public health experts turned in the 1950s have been – and are being – fuelled by antibiotics?

Waking up from Antibiotic Sleep

The story of antibiotics is often told as a victory of human inventiveness over nature, as a major step in the technical liberation of humans from the dangers of the natural world to which prior generations were exposed. ⁱ Arguably, modernist beliefs that separate humans and our technology on the one hand from nature on the other have silently organised medical as well as agricultural use of antibacterial drugs, since penicillin was discovered. We believe that it is time to wake up from this ‘antibiotic sleep’.

In our view, we need to recognise that antibiotics are not totally beneficent, without turning our back to their often life-saving use. For microbiologists and anthropologists, this means persuading a broadly ‘germophobic’ public to view our world quite differently, to accept that our microbiome is an essential part of us, vital to our health, that needs to be nourished, or at the least only minimally assaulted. For drug developers, this means inventing precision antibiotics that are lethal, exclusively for a specific disease-causing microbe but not for the symbionts critical for human wellbeing. For physicians, this means liberating the vocabulary of medicine from the warfare metaphors – the ‘fight’ against microbes – used since the germ theories of Pasteur and Koch, and to find ways to preserve the multi-species consortia called the human organism. For public health experts, this means giving up the one-sided view of microbes as pathogens and learning to think about humans in microbial terms.

If we speak about human health, we had better include our microbes.