Neat Science in a Messy World: The Global Impact of Human Behavior on Phage Therapy, Past and Present

Abstract

The scientific potential of bacteriophage (phage) therapy is gaining recognition in the global fight against antimicrobial resistance (AMR). However, phages are not well understood by the general population in the West and this is a major barrier to phage therapy. This piece takes an interdisciplinary approach to public “acceptability,” highlighting the significant impact that human behavior has had on the development of bacteriophage science to date, before addressing what current human factors might impact on the future exploitation of this scientific field. It argues that the history and status of phage therapy are not identical across the world, and that more understanding of different cultural attitudes in different places is essential. In addition, it argues that from a Western perspective, human issues relating to phage therapy make this science particularly susceptible to media hype and misunderstanding. Further study of the human dimensions is, therefore, crucial in any future development of phage therapy as a response to AMR.

Introduction

The need to tackle antimicrobial resistance (AMR) through interdisciplinary interagency cooperation, taking into account human behavioral as well as scientific factors, is widely recognized. As the World Health Organization stated in 2018, “AMR is an increasingly serious threat to global public health that requires action across all government sectors and society”.¹ A further example of the global compass of the fight against AMR is the recent Wellcome Trust meeting that was hosted jointly with the Ghanaian, Thai, and U.K. governments, the World Bank, and the UN Foundation (in Akraa, November 2018), which highlighted our need for a sustained international effort against AMR. Within the United Kingdom, research funding bodies have also stressed the need not only for worldwide scientific cooperation but also for interdisciplinary research, with their 2016 cross-council initiative grounded in the rationale that:

It is clear that AMR is a hugely complex problem with a range of influences, driven by human activity as much as by biological mechanisms. Biomedical and clinical expertise alone cannot tackle AMR and globally co-operative, interdisciplinary approaches are needed to tackle the challenge.²

Breaking down barriers, whether national or disciplinary, and finding solutions that rely upon innovative collaborations, is increasingly recognized to be crucial in efforts to overcome AMR.

Bacteriophage therapy, the practice of using phages to target disease-causing bacteria and, therefore, treat infection, is gaining increasing scientific credibility as a potential alternative or supplement to antibacterial chemotherapy.³ In their 2015 review, Oliveira et al. argue that of the six identifiable barriers to phage therapy, two important but often overlooked aspects are “regulatory acceptance” and “lack of public awareness.” Although most current research focuses on the scientific aspects of bacteriophage therapy, a greater understanding of the human factors that might impinge upon this promising field's ability to achieve its full potential is a particularly acute issue, and one that we seek to address here. Lack of public awareness, we contend, is, in fact, one aspect of the complex issue of public “acceptability.” In this, the human beings involved in a particular therapy need not only have a passive understanding of key facts, but also have confidence in—and a sense of acceptance of—the efficacy of a treatment. As controversy surrounding the measles, mumps, and rubella (MMR) vaccine has demonstrated in an extreme form, once public misinformation takes hold, it is extremely difficult to counter, and residual cultural fears can be long lasting.⁴ In the case under discussion here, it is not only the members of the general public who lack understanding, but even medical practitioners in the West are largely unaware of bacteriophages, and this may represent a very substantial obstacle to their exploitation.⁵ In some cases, medical practitioners are aware of phages but are negatively predisposed to them. These opinions largely stem from a lack of inclusion within current medical teaching practices.

In any discussion of phage therapy, and particularly one focusing on the impacts and influences of human behavior on this science, it is important to note that the history and status of phage therapy are not identical across the world. To fully explore the subjective human forces at play in this scientific arena, this article highlights some of the key distinctions in our perceptions of phage therapy in different parts of the world. Focusing particularly on Western perspectives, it also draws out the ways in which scientific developments have been influenced either by individual human actors or by bigger cultural issues. Here, “culture” is understood as the “codes of meaning” by which particular groups of humans share understandings of the world. As Kroeber and Kluckhohn argued in 1952,

Culture consists of patterns, explicit and implicit, of and for behaviour acquired and transmitted by symbols, constituting the distinctive achievements of human groups, including their embodiment in artifacts; the essential core of culture consists of traditional (i.e., historically derived and selected) ideas and especially their attached values; culture systems may, on the one hand, be considered as products of action, on the other, as conditional elements of future action. (p. 181)⁶

In other words, cultures reflect both traditional and current attitudes, and also play a role in actively influencing the future responses and behaviors of particular groups of people. Moreover, as work within the discipline of cultural studies has long shown us, the distinct, sometimes conflicting, views of different groups of people do not exist in isolation from each other. On the contrary, cultural differences often create group identity and a sense of belonging. This is relevant to the case of phage therapy because it highlights the fact that we cannot assume that the successful acceptance of phage therapy in some cultural contexts will necessarily translate into acceptance in others. This article identifies the different attitudes toward phage therapy that are embedded in different cultural groups around the world, and finishes by beginning to outline how these differences might be anticipated to impact upon “acceptability” in the West. This article, therefore, addresses an important factor within the numerous calls for action on AMR that have highlighted the importance of a concerted effort at a global scale. Our exploration of this subject is grounded in the argument that the world is not a uniform blank slate onto which phage therapy can be simply inscribed. On the contrary, if phage therapy is to achieve its full potential as a complement or alternative to antimicrobials, we need to understand the human factors—different in different places—that might impact upon it.

This piece is underpinned by three inter-related questions to begin to establish the first foundation blocks upon which public “acceptability” of phage therapy in the West might be built: (1) what role has human behavior played in the development of phage therapy to date, (2) how has this varied in different cultural contexts, and different parts of the world, and (3) what lessons can we learn from this about the potential for human factors to impact upon the future implementation of phage therapy? We include “human behavioral factors” ranging in scale from the actions of key individuals, right up to the large-scale human-led geopolitical processes of war and interstate conflict. Although the discussion follows a broadly chronological structure, it is important to note that the objective here is not to attempt to establish a comprehensive historical account of the history of phage therapy. Rather, it is to identify and synthesize key patterns relating to the impacts of human behavior on phage therapy across the trajectory of its development. To this end, the methodological approach will center upon the close textual analysis of selected pre-existing studies, and their contextualization in relation to both the wider historical and political climate. In other words, this piece tries to look beneath the historical facts of phage therapy to identify the human influences, assumptions, and judgments that have directed and sometimes constrained the scientific trajectory.

Human Factors in the Early Stage of Phage Therapy Research

Although the majority of academic studies of phages published to date have—understandably—focused on the scientific challenges presented by this field, a small minority have also addressed, or at least alluded to, the impacts of human behavior.^7–9 Indeed, since the discovery of phages ∼100 years ago, the story of their development has been considerably more complex than might at first be thought. From a Western perspective, the trajectory of phage therapy-focused research and trials involving phages is often perceived in terms of a simple bell curve: an initial growth period from the 1920s to 1940s, followed by a decisive decline as broad-spectrum antibiotics established a monopoly on treating bacterial infections. Phage therapy after this date, according to the dominant Western narrative, was concentrated in specific countries such as USSR, Poland, and France, and outside of these places the emphasis in phage research shifted to using phages to understand genetics and molecular biology.¹⁰ Although the practice of phage therapy was pushed into near obsolescence in the Western world, the discourse continues; in recent times there has been a resurgence of interest, largely driven by the threat of AMR, and this growing need for novel antimicrobials. This resurgence has motivated numerous academic research groups and companies worldwide to carry out studies relating to the future applicability of bacteriophage therapy.

However, looking beneath the simple narrative of rise, fall, and possible resurgence in the West, we can unpick a considerably more complex picture. Presenting bacteriophage therapy as something that was merely “replaced” by a more effective scientific development is perhaps to underestimate what Summers describes as “[the] curious history” of bacteriophages.⁷ As Summers' historical overview points out, despite the pivotal importance of “reason, evidence, and logic” in post-Enlightenment science, the development of phage therapy has been “rich with politics, personal feuds, and unrecognized conflicts” from its very outset.⁷ It is to an analysis of these human behavioral factors, drawn from Summers and from other key works, that this study will first turn, before moving on to sketch out some broader observations about the current cultural climate for phage therapy.

Key individuals

Summers⁷ lays out in detail the history of the discovery of bacteriophages by Frederick Twort and Felix D'Herelle, scientists working in different countries (United Kingdon and France, respectively), and who independently discovered bacteriophages in 1915 and 1917. It is not the intention of this piece to repeat this now familiar story, but rather to highlight the impact of human, nonscientific, factors within it, and to link them to the perspectives of other scholars. From the very start, Summers' historical account highlights the human factors at play by characterizing the early stages of phage development in oppositional terms, stating that “two camps” could be identified. Felix D'Herelle was, according to Summers, “the French-Canadian autodidact who first recognized phage in line with our current conception of the nature of viruses.”⁷ In contrast, Frederick Twort was a “quirky British microbiologist who observed ‘transmissible glassy transformation’ of bacteria but failed to follow up on his original observations.”⁷ Summers continues to argue that human factors were key to the drama that played out, telling us that Twort's early work was developed and defended “by an unlikely surrogate, the Nobelist Jules Bordet,” and that the powerful antagonism between Bordet and D'Herelle fuelled a decade long dispute, in which the scientific became entangled in the personal.¹¹ As other scholars have documented, Twort's individual circumstances in the form of lack of institutional backing and enlistment in the Royal Army Medical Corps during World War 1 (WW1)¹² hindered the progression of his work, and Bordet continued to contest D'Herelle's view of the nature of bacteriophage. It took the development of electron microscopy in 1930s for the viral conception of the phage to be vindicated.¹³ This finally allowed the suppression of Bordet's alternative theory that the killing effect of bacteria was due to induced lytic enzymes, and this human rivalry was laid to rest.

Subsequently, D'Herelle carried out research in the United States until 1934 when he left for the USSR, motivated in no small part by a desire to experience the socialist society being constructed there,¹⁴ and helped to establish the bacteriophage institute in Tbilissi (now Eliava Institute, Tbilissi, Georgia).

During this period, a number of small-scale trials continued to be carried out, scattered across a diverse range of places including Egypt (Compton, 1929), Sudan (Riding, 1930), France (des Essarts), the United States, and the United Kingdom. However, it was the impact of human behavior on a scale and influence far beyond that of key individuals, in the form of the advent of the WW2, that represented the next decisive fork in the path of phage development.

War

Looking closely at Summers' piece, we can detect a number of ways in which WW2 precipitated the alignment of expertise relating to phage therapy with Eastern Europe and USSR, reinforcing Western perceptions of this science as something “foreign.” In very practical terms, for instance, WW2 disrupted transport flows, and key journals on their way to the United States from Germany had to be stored in Switzerland for the duration of the conflict. In this way, important research into phages after the invention of the electron microscope that was put into the public domain through publication became less widely available than would otherwise have been the case.⁷ Such blockages to the circulation of research consolidated the polarization, which did not occur along Allied/Axis lines, but whereby in broad terms Western countries focused their efforts on early antibiotics, whereas the USSR, and to a lesser extent Germany, continued to invest in phage therapy as well as in antibiotics. More fundamentally, in a number of ways, WW2 could be said to have reinforced the association of phage therapy with war, and more importantly with its foes, in the Western cultural imaginary. A seminal moment in the discovery of phages had occurred in WW1 through D'Herelle's study of an outbreak of hemorrhagic dysentery occurred in a dragoon squadron resting in Maisons-Laffitte near the city of Paris.^14,15

This early link between phage therapy and war would be consolidated by a very different conflict some 20 years later, when the conditions of WW2 created conditions in which phage therapy was again called upon on a substantial scale, in this case to treat wound infections and gastrointestinal illnesses among the Soviet military. According to Abedon et al., while the Allies focused exclusively on their increasingly effective antibiotic research, in the former Eastern bloc phage therapy gained prominence in military medicine, and active phage research was done at the request of the army. Writing in the popular science journal, “Science First Hand,” Dabizheva et al. add a triumphalist narrative to the association between phage therapy and war, going as far as to claim that phage therapy played a crucial role in the Russian victory in the notorious Battle of Stalingrad, when an underground laboratory was established to manufacture phages to protect Russian troops from the outbreak of cholera that had struck the German army.¹⁶

Although the veracity of this account is difficult to assess, it is relevant to note the underlying resonance within this narrative, again associating phage therapy with war in the Eastern bloc. Indeed, the Georgian military's recourse to phage therapy to treat soldiers as recently as in the 1991 and 1992 battles in Abkhazia, and later in the 2008 dispute between Russia and Georgia, could only solidify such an association in the Western mindset.

The picture of this early stage of phage development that emerges above, extracted through the close textual analysis of existing key sources including those of Summers, Abedon et al., and others, is one in which human behavior can be seen to have had a significant impact. From factors surrounding the careers and behaviors of influential individuals to the far-reaching human-induced conflict of war, the fortunes of phage therapy were strongly affected by factors outside of the purely scientific realm. The resulting pattern was of strongly uneven development and application of phage therapy across the world, with much greater expertise in Russia and the former Eastern bloc, and indifference or even suspicion elsewhere.

Key individuals in the postwar period

In fact, the pattern of large scale human processes, primarily involving geopolitical disputes, punctuated by the intervention of particular key figures, continued to have a strong impact on the development of bacteriophage therapy throughout the second half of the 20th century. Indeed, the interconnected nature of these influences was to be particularly evident nearly 20 years after the end of WW2, personified by Gunther Stent. In his introduction to the textbook, Molecular Biology of Bacterial Viruses (1963),¹⁷ which was at the time a must-read text for students in the field, Stent's description of phage therapy is far from objective. Quoting at length from the text, Summers describes this as “perhaps the most telling, most detailed and most influential nail in the coffin of phage therapy.” He goes on to point out that “Stent manages to undermine phage therapy in three key ways completely unrelated to scientific evidence.”⁷ Although it would be repetitive to re-cite at length here, Summers' points can be summarized as follows.

First Stent casts doubt on the scientific credibility of phage therapy's advocates. Second, he demonstrates allegiance with the dominant political climate of his own cultural and historical moment, highlighting links between phage therapy and the German and Japanese armies. Within the context of Cold War tension and McCarthyist paranoia about communist sympathizers, as Summers points out, this was tantamount to labeling such science “unAmerican.”⁷ Finally, Stent implies that “phage therapy was consigned to the backward and the primitive regions of the globe.” Again, Summers' analysis is pertinent, highlighting Stent's positioning of phage therapy as “outside the narrative of progress and scientific triumph that is conventionally told about Western medicine” (Summers⁷, italics added). In this way, Stent's piece highlights the way in which cultures position certain beliefs and attributes as either “inside” or “in opposition” to their own sense of cultural identity, referred to in the early stages of this discussion.

In fact, although Summers' analysis of Stent's highly partisan stance is astute, he does not draw out the very personal individual roots that were very likely to have anchored Stent's position. Scratching beneath the surface of Stent's own life story, we can identify the enduring impact of WW2 on Stent himself. Stent was a Berlin-born Jew who had fled Nazi Germany and emigrated to the United States in 1940 when he was just 14 years old. As he recounts in his memoir “Nazis, Women, and Molecular Biology: Memoirs of a Lucky Self-hater” (1988),¹⁸ he returned to Berlin as a scientific consultant of the American military, shortly after the war. He describes his real motivation in this trip as needing to free himself from a recurring nightmare by returning to his homeland in triumph before going back to the United States to pursue his scientific career.

If WW2 marked a decisive moment in which attitudes toward phage therapy split alongside East/West lines as already argued, then it is little wonder that the work of a scientist who was personally affected by the conflict should bear enduring marks of this legacy. In so decisively casting phage therapy as “foreign,” “distant,” and perhaps even in some ways a threat, Stent was aligning himself with the dominant geopolitical frame of his adopted homeland, yet this personal story was not evident to the generation of microbiologists studying his must-read textbook. A contemporary review of Molecular Biology of Bacterial Viruses described it as “required reading for every student entering experimental biology,” in which “the student will sense the smell and the rattle of the laboratory.”¹⁹

Moreover, stepping even further away from the principles of scientific rationality and objectivity, it is interesting to note that Stent's chapter also draws upon a fictional representation of phage therapy—in this case the novel Arrowsmith, published in 1925 and subsequently awarded the Pulitzer prize—to add weight to his implicit claim that phage therapy had been tried but reached its natural limits and failed.⁷ In this fictional text, the doctor protagonist battles an epidemic in the West Indies, turning to phages as his main hope of treatment. Stent's judgment is that “though Lewis wrote Arrowsmith as early as 1924, he allowed his hero to reach what subsequent developments showed to be a most sensible decision: in spite of twenty years' intensive work, bacteriophages never became a successful medical tool” (Stent cited in Summers⁷). Very tellingly, neither in Stent's citation of this text nor in Summers' analysis of it, is the fictional status of this text acknowledged. Stent's use of a fictional story means that his own common sense, if teleological, perspective remains unchecked.^*

Stent's authoritative dismissal of phage therapy, then, riddled with personal and geopolitical biases, provides us with yet another example of the subjective human factors that have impacted significantly on the development of phage therapy by way of influencing the minds of a generation of scientific and medical researchers.

The Current Era: Improving the Flow of Knowledge and Overcoming Obstacles

Turning to recent literature, it is clear that there have been a number of attempts to overcome the East/West split in Western perceptions of phage therapy, and to shift the blockages in the flow of information and understanding that were solidified by WW2 and the Cold War. Recognizing the uneven development of phage therapy around the world, a particularly helpful and systematic article by Abedon et al.⁸ outlines in depth the development and status of phages in different countries to provide a synthesized timeline and état present of phage therapy. In the systematic analysis of France, Poland, the United States, Georgia, and Russia, what becomes clear is that the Western perspective of research and practice in the field of phage therapy has tended to be very reductive.

As Abedon et al. argue, “there is much more in the literature than has generally been realized” (p. 82).⁸ Despite being uncommon in the West, phage therapy, we learn, continues to be widely used in Russia, with manufacturing now taken over by the pharmacological company Microgen and “a wide variety of their phage preparations are available in pharmacies as well as online” (p. 74). Dabezheva et al. supplement this with the information that more than a billion packages of phage treatments are issued per year in Russia, and that so normalized is phage therapy in this cultural context that it comprises part of the Soviet astronauts' health regimen. Similarly, the Eliava Institute in Georgia, established since 1934, is an internationally renowned center of excellence, and it is interesting to note that it is a growing destination for small-scale health tourism. Another notable center of expertise is the Hirsfield Institute in Wroclaw, Poland, that was established in 1954, and that has reported high cure rates among the thousands of patients treated.^8,20

Since 2005, Poland has had a phage therapy center dedicated to antibiotic resistance and difficult-to-treat infections, so focusing on infections for which few alternatives exist. The status of Poland within the EU makes this a particularly significant case: as Abedon et al. note, this means its work is now being carried out within Western regulatory frameworks (p. 70).⁸ It, therefore, may be particularly well placed to undermine Western perspectives that phage therapy is not a viable form of treatment. Recent phage therapy work in the United States, including that in the longstanding Pittsburgh center, and the more recently San Diego center, is well placed to make a similar contribution.

What, then, are the remaining barriers to phage therapy in Western perceptions?

Language barriers

Perhaps crucially in any analysis of the human factors impacting upon bacteriophage therapy is the matter of language barriers, a recurring theme relating to the sharing of knowledge and expertise around phage therapy. Less dramatic than any story of personal feuds or large-scale international conflicts, language barriers continue to be insidious and stubborn obstacles to the free flow of information, normalized, perhaps, to the extent of being “hidden in plain sight.” Of the story of phage development in Russia, for instance, Abedon et al. summarize that this has been “long, inaccessible to the non-Russian speaker, and has not been subject to the same kind of scrutiny as has the Georgian experience” (p. 74).

Similarly, referring more broadly to the interrelated history of phage development in Georgia and the USSR, Abedon et al. clarify that “there has been little primary publication in English language journals.” In this very specific cultural context, it seems that this is at least partially related to the factors already outlined relating to the geopolitical context: “due to the intense secrecy behind the Iron Curtain surrounding militarily applicable sciences” (p. 73). In fact, “phage research funded by the military was deemed to be a state secret, thereby hindering publication” (p. 74). However, it seems that language barriers have also been in existence much closer to home, and entirely independent of the Cold War split. Abedon et al. reveal that “much of the extensive French research has also been largely ignored due to language barriers.” Indeed, unlike most other Western countries, phage therapy continued in France after WW2 “with some vigor until the early 90s,” and yet much of this expertise has not been widely drawn upon, even in neighboring countries, in the West. The Pasteur Institute, for instance, continued making phage cocktails in what could be described as “an individualized, essentially artisan-like” way up until the mid-1990s.⁸

However, as Abedon et al. go on to explain, “this individualized approach did not lend itself to double-blind study establishing proof,” and perceptions of success remained anecdotal. In the tightening up of regulation in the public health care system that occurred in the wake of the AIDS crisis in the blood supply, such individualized artisan-style treatments became less feasible.⁸ Even now, in fact, superficial analysis of popular media sources suggests that although phage therapy is no longer routinely accepted or even widely known about in France, neither is it portrayed in quite such alarmist terms as in the Anglophone world.^† As Abedon et al. argue, drawing attention overtly to the obfuscatory impact of language barriers, “although France is clearly a Western country, most of the reviews [in English] of phage therapy have not mentioned the continuation of phage therapy in France” (p. 67).⁸ Slightly shifting in focus, Abedon et al. conclude by attributing the language barriers obscuring phage therapy to be not universal, but particular to the English language community: “phage therapy has a long history, though for most of the history this approach has been neglected by the English-speaking Western world.”

It is perhaps important to note, then, that the uneven flow of information around the world cannot merely be attributed to military secrecy, or to geopolitical enmity. Within the English-speaking world, it is also perhaps caused by the inability to reach out beyond the easily accessible to fully realize the richness of research that is in existence. Again, scientific knowledge could be said to have been constrained by the imaginary boundaries that different culture groups draw around themselves, often unconsciously, to establish “here” and “there,” “us” and “them.”

Pre-existing cultural frameworks and metaphors

Finally, we need to ask whether our dominant perception of phage therapy in the West, the simple bell curve—rise and fall—and possible resurgence— mentioned in the early stages of this discussion, inversely correlated to the fortunes of antibiotics, sits so comfortably within the Western mindset because of the way in which it draws upon a pre-existing cultural framework. In this case, that pre-existing framework could be said to be that of the Bildungsroman narrative, as we will explore in more detail hereunder.

de Lorenzo²¹ argues that “we use metaphors all the time in science and that is useful as long as they serve their purpose well and we are aware of them. But it is a serious mistake to identify uncritically the thing and the metaphors employed to bring the thing to mind” [italics added]. In other words, using a pre-existing cultural idea as a point of comparison can be helpful to facilitate our understanding of difficult or abstract concepts, but it is a mistake to forget that we are doing so. Further useful perspectives on the use of metaphor in science can be found in Stephanie Fishel's The Microbial State,²² and in Brigitte Nerlich's blog,²³ in which the ideologically loaded nature of metaphors in biological sciences is discussed.

Both Fishel and Nerlich highlight that the use of metaphors in relation to science not only entails a simplification of complex ideas into something more easily understood, but also involves a transfer of meaning between the two fields involved. Some of this transfer of meaning may exceed that originally intended, as attributes of the comparator concept become unwittingly associated with the original concept. Nerlich identifies the use of ideologically loaded capitalist metaphors in relation to biology, for instance, whereas Fishel, like Susan Sontag before her, concentrates on metaphors of war. In both cases, the metaphors used can be seen to alter perceptions of the science that they are applied to, beyond the intentions of the original comparison.

In the case of phage therapy, we have already seen the strong association of this science with war, and with the Eastern bloc, and the way in which the science of phage therapy itself became connoted with value-laden judgments as something “foreign,” “distant,” and incompatible with Western science.⁷ However, it is to Abedon et al.'s piece that it is most helpful to return to unpick the most influential ways in which pre-existing metaphorical cultural frameworks underpin Western perceptions of the potential of phage therapy.

In Abedon et al.'s account, the broad history of phage science is outlined in terms of “an early enthusiastic period” before the WW1 where claims were “excessive and unrealistic,” followed by “a period of declining enthusiasm” in much of the Western world, before the widespread “displacement by antibiotics after WW2” (p. 66).⁸ This depiction of the early stages of phage therapy is, therefore, simplified down to a unified and coherent process, and one that is attributed to human characteristics: scientists were not objective, rational, and dispassionate, but “enthusiastic” and “excessive.” There was a period of neglect and decline (obscurity), followed by “rediscovery” in the 1980s; the growing momentum of the 1990s was succeeded by the “maturing” of the field in the 2000s. This conceptual framework, presumably entirely unwittingly, seems to bear remarkable similarities to some powerful cultural norms from the outset: the “bildungsroman,” or “coming of age” narrative, is the cultural frame, so influential in Western culture, in which an enthusiastic young self-ventures out into the world, gathers experience, is troubled by a conflict or obstacles that must be overcome, and eventually matures.

Presenting the development of bacteriophage in these terms, therefore, seems to attest to a critical framework, implicitly inflected by the rich cultural patterns around us, which will lead to a “happily ever after,” a positive ending in which the (now old and wise) science of phage therapy will find its deserved niche within the contemporary scientific context. This framework seems to humanize the development of both phage therapy and the phages themselves. The danger here, perhaps, is not only the way in which the multiple complex threads of the development of phage therapy are ignored, but that it may lead to easy assumptions about the future: that is to say, the inevitability of a “happily ever after” ending for phage therapy, which would underestimate the power of the remaining cultural barriers and human influences.

Concluding Thoughts: The Future Cultural Outlook for Phage Therapy

Bacteriophage therapy is increasingly recognized to have the scientific potential to make a serious contribution to the global AMR crisis. However, this piece has highlighted some of the ways in which human cultural factors have had a significant impact on the fortunes of phage therapy—particularly in the West—over the course of the last century. Acknowledging the role played to date by factors far beyond the purely scientific paves the way for us to recognize the need for much greater understanding of the possible impact of human factors on phage therapy's ability to achieve its full potential in future. As Loc-Carillo and Abedon argue:

The Western medical establishment's unfamiliarity with phages, as antibacterial agents, may be phage therapy's greatest challenge. [….] Phages as ‘viruses' could be misinterpreted by the general public as being in some manner equivalent to viral pathogens that cause human disease. So far, however, public resistance has not materialized, and it is perhaps fortunate that bacterial viruses are known, instead, as phages.²⁴

The lack of phage knowledge among both the general public and, in fact, the medical establishment, in the West, might suggest the status quo to be an information vacuum that—in the context of growing concern about AMR—could simply be filled with relevant facts about the value of phage therapy. However, we need to recognize that the matter is considerably more complex. Although Loc-Carillo et al. conclude by saying that it is fortunate that phages are known as phages rather than viruses, in fact, an analysis of the available public information sources suggests that this is not the case. A simple survey of the materials most readily available to the public shows that the term “virus” is used almost ubiquitously in public-facing explanations of what phages are.^‡ This is significant because the concept of the virus is heavily loaded with negative cultural associations. Etymologically, the word virus denotes something toxic, harmful in Latin, and viruses have long been a noteworthy feature of both literary and cultural studies. Often, depictions of viruses are tied up in societal concerns about other matters: for example, the threat of bodily invasion by a virus seems to be frequently scaled up in the public imaginary to generate fears of the breakdown of the wider “social body.”²⁵

In recent years, fears of the consequences of communicable illnesses in a globalized world have led to particularly fearful reporting of outbreaks of anthrax, Ebola, bird flu, swine flu, SARS, Zika, etc. in news media, and similarly, the rise of “killer zombie” films and “outbreak narratives,” both attest to the widespread cultural anxiety around viral epidemics.²⁵ What is significant here, then, is that we recognize first that bacteriophage therapy is very unlikely to remain separate from cultural understandings of viruses and second that these understandings are already strongly inflected with negative connotations. As the controversy surrounding the MMR vaccine demonstrated, once a sense of fear and mistrust of medical information has occurred, it is extremely difficult for the medical establishment to rectify this.

Indeed, referring specifically to the case of phages, Hausler, himself a scientific journalist by trade, states that the history of phage therapy has all the elements of a good story, which means that it is more likely to get substantial media attention. In fact, as Hausler points out, the tendency of such reporting is to adopt a tone of “hype” and he sounds a particular note of caution in this case: “I would argue that phage therapy is especially vulnerable to such damage [caused by ‘hyped up’ journalistic reporting] to its reputation due to its ‘exotic’ history.” Hausler is referring here, of course, to the association of phage therapy with the “foreign” and the “distant,” as well as the “military,” which we have already outlined. In other words, Hausler is emphasizing that the story of the development of phage therapy not only means that it has the necessary ingredients to generate substantial public interest, but also that it is at serious risk of becoming the subject of damaging and inaccurate sensationalism.

How, then, can we mitigate against this cultural backdrop to ensure that phage therapy can achieve its full scientific potential? First, it is our contention here that rather than assuming that implementing bacteriophage therapy across the world where it is not currently common will be a simple matter once the scientific procedures and expertise are in place, then, and that a simple “factual” information campaign might be sufficient to inform the public, we advocate much greater pre-emptive reflection. It is the argument of the authors here that alongside the continued work to tackle the scientific barriers to bacteriophage therapy, we must give much greater thought to the cultural and human barriers. For phage therapy to achieve its full potential, to make a real contribution to the AMR crisis, we need to work to develop a favorable cultural terrain in which phage therapy will be accepted in all parts of the world. If, as Summers argues, “understanding the […] extra-scientific aspects of its [phage therapy's] history can help explain the tortuous course of phage therapy over the past century,” we need to also note of them to begin to understand the potential human barriers to the future of this therapy. The next phase of this project will entail undertaking a qualitative review of current awareness of phages among the general public, as well as further study of dominant cultural representations of viruses as they are expressed in the popular media. Ultimately, once greater understanding of the current cultural context has been established, it is our intention to draw upon the concept of “good bacteria” as promoted so successfully in relation to yoghurt, and to devise a public health campaign linking phage therapy with a notion of “good viruses.”

Authorship Confirmation Statement

This article derives from a project conceived and designed jointly by E.H.J. and M.C. The article was drafted and then reworked by E.H.J. after detailed review by M.C. A.L. reviewed the draft on several occasions and provided critical input into the direction and shape of the piece. All coauthors have reviewed and approved of the article before submission.

Author Disclosure Statement

No competing financial interests exist.