Integrabiotics: Past, Present, and Future of Antibiotic Resistance and Antivirulence

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There have been no new antibiotic classes of drugs since 1987, and by some estimates, antibiotic resistance will eclipse cancer in terms of mortality by 2050. Antibiotic resistance (ABR) is, arguably, on par with climate change as a threat to humanity. The simple explanation for how this happened is selective pressure: humans developed and overused—misused—antibiotics, and, bacteria evolved resistance mechanisms. The relationships between humans and bacteria was constructed as antibiotic—us against them, them against us. Consequently, the solution to bacterial infection became the problem. While a causal model is relatively simple, the history and subtilties of the actors, processes and networks involved in this phenomenon is confoundingly expansive and nuanced. To face resistance, we must address the complexity of this problem, and, likewise, approach the mitigations and possible solutions with an appreciation of how we got here. We coin the term Integrabiotic as a guiding principle to meet and overcome the problem of ABR in sustainable ways. Integrabiotic denotes the incorporation—the integration— of human and non-human life. Simultaneously, we stress the prefix to draw attention to our purposeful integration of humanistic research methods with science, social science, and engineering to stem the tide of antibiotic resistance.

Integrabiotics expand and delimit the ways we think about the relationship between humans, microbes, and the technologies and structures that mediate them. It takes as its fundamental premise that the operant logic of antibiosis, arguably in force since the implementation of antisepsis during the late ninteenth century and aggressively inflected during the post-Penicillin era of the mid- twentieth, is unsustainable. To do so, we need to think carefully, collaboratively, and differently about the way the constellation of language and ideas surrounding antibiotic are used, precisely and imprecisely; how they are over and underextended; how they circulate between academic, industrial, clinical, and vernacular discursive registers. This kind of work is not without precedent, biomedical researchers and humanists have independently and on occasion collaboratively signaled that complexities, gaps, and limitations of terms like virulence and pathogen exist (Langford et al 2019; Taussat et al 2014; Méthot and Alizon 2014; Casadevall and Pirofski 2009)

We follow such work as a point of departure, to more broadly consider the language, history and communication of antibiosis and its present and future mitigations, such as antivirulence. Considering that virulence is not an essential property belonging to pathogens, but rather a possible outcome of the dynamic relationship between a host and pathogen, has implications for ecological, epidemiological, and even pharmacological research and treatment. Indeed, we would hypothesize that the historical framing of virulence as a property of pathogens—rather than as a contextual relation (Méthotab & Samuel Alizonc 2014)—drew attention away from ecological perspectives of disease toward pathogenically targeted (molecular and cellular) frames and therapies, which in turn, catalyzed resistance. We propose to tease out the language, history, and narratives of antibiotics by having an engineer, a social scientist, and a humanist fully immerse in each other’s disciplines, methods, and sources to examine ABR and alternative therapies. In short, this project seeks to produce a traffic of ideas between different disciplines and then reflexively analyze that traffic.

We hypothesize that such a project can facilitate a productive and preemptive way to enable the development of novel therapeutic strategies, improved communication of risk, and improved community engagement with the problem. Integrabiotics, consequentially, looks to the culture, research, and practice of science and biomedicine as dynamic structures and in a dynamic way.

IAAR Seminar

This project emerged from the Humanities Center/Research Future funded “Interdisciplinary Approaches to Antibiotic Resistance” (IAAR). Among the productive dialogue and ideas, a tangible outcome that emerged is an article in progress for a forthcoming special issue of the journal Antibiotics, “Antibiotic Alternatives: Virulence Factors Produced by Pathogenic Bacteria,” guest edited by Angela Brown. The introductory article for this issue in preparation, “A Natural and Synthetic History of Virulence,” traces the origin of the term and its use relative to different points in the history of infectious disease. The second phase of the IAAR group—Integrabiotics— takes this article’s narrow topic as a point of departure and expands outwards to see its broader entanglements in the discourse of academic publication, clinical practice, and culture at large. We require a Humanities Lab grant to fund a more intensive research project lead by three faculty members from the IAAR group. We aim to continue the seminar in its current form, if funded by a CORE grant, as a larger protracted conversation where the smaller Integrabiotics group can present its specific line of inquiry in light of a continued reading group on the topic. Participants include those from the IAAR group: Vassie Ware, Kelly Austin, and Dena Davis. We will seek, and hope to attract, additional participants across campus in departments including English, Biological Sciences, Sociology, Psychology, and faculty from the College of Health.

This Humanities lab grant will provide the labor infrastructure to pursue the broader aims of the project. Course releases will allow PIs to immerse in and traffic between each other’s disciplines, focusing on ABR and antivirulence as specific objects of inquiry, and produce tangible outcomes (articles, conference presentations, social media, course development) that derive from this experimental integration. This scaffolding will also allow other supporting elements to solidify and expand the work done from IAAR in three ways: 1) have an afterlife beyond this specific grant; 2) include and train students more effectively in its core work; 3) bring in experts on the topics (ABR/virulence) and multi/interdisciplinary collaborative work more broadly.

Investigators

Lorenzo Servitje, English/Health, Medicine, and Society. Professor Servitje researches the relationship between medicine and culture as represented in literature, film, media, and professional publications. He has written one monograph on the metaphorical militarization of medicine and is currently writing a second on the history and culture of antibiotic resistance.

Angela Brown, Chemical & Biomolecular Engineering. Professor Brown leads the Brown Lab, which employs an “antivirulence” approach for the identification of novel therapeutic options against bacterial infections. The Brown Lab is also focused on developing improved delivery systems for antibiotics and enhanced detection strategies, to reduce the misuse/overuse of antibiotics.

Sharon Friedman, Science and Environmental Writing. Professor Friedman has been involved in translating scientific information into lay language for almost all of her career. He research has centered on environmental and health-related risk issues and on how they are communicated to the public. She has conducted research on mass media coverage of such risk issues as the Three Mile Island, Chernobyl and Fukushima nuclear accidents, Alar, radon, dioxin, electromagnetic fields, nanotechnology and hydraulic fracturing.

Project Plan

This project has three components, corresponding to the three different investigators and their respective discipline and expertise, that follow something like a narrative trajectory: how we came to need and conceptualize antivirulence (Servitje); the experimentation and engineering of specific materials and methods for its implementation (Brown); and, how the present research is and will be understood and communicated across disciplines and to lay audiences (Friedman). We hypothesize that collaborative, multidisciplinary exchange can benefit individuals and groups as they work toward new knowledge, understandings, and implementations in the study of ABR.

PIs will reciprocally cycle as observers and participants in each other’s work. We envision this taking the following form: Professor Servitje’s research on the cultural history and representation of antibiotic resistance would be observed and interrogated by Professor Friedman’s content and risk analysis and would inform the framing and language of Professor Brown’s antivirulence experiments. Professor Friedman’s examinations of the current language surrounding antibiotic resistance and virulence deployed in risk analysis publications will be analyzed by Professor Servitje’s rhetorical, literary, and cultural contextualized reading and used to modify Professor Brown’s communication of her work. Professor Brown would work with Professor Friedman to “translate” her research output for improved public awareness and with Professor Servitje to understand and incorporate the historical and cultural context of the problem.

Workflow

  1. Theoretical grounding on interdisciplinary method: The three PIs, along with their graduate and undergraduate students, will meet regularly throughout the funding period in a collaborative lab setting. The group will begin by reading the case studies and theoretical work on interdisciplinary observation and collaboration from science and technology studies and health humanities (Latour 1987; Macnaughton and Carel 2016; Willis and Waddington 2019) to ground the meetings that follow.

    2. Interdisciplinary application and exchange of ideas and methods After laying this groundwork, during each meeting, one of the attendees will discuss their current research, as it relates to ABR. After the presentation, a significant amount of time will be devoted to a question/answer and discussion session, in which investigators in all fields will consider the problem from multiple angles. We anticipate that this may initially be difficult, as methodology is often approached intuitively rather than intentionally. However, this is one of the larger aims of the group beyond the specific topic—to reflect and refine method. Participants will inquire about the tools and processes used by researchers in each field, resulting in an enhanced understanding of how the problem is approached by others, as well as a more thoughtful approach to their own methodologies.

  2. Documentation of and reflection on topic and process: utilizing undergraduate HMS and Art, Architecture, and Design students, we will create a written and visual archive of meetings, to serve as material for research and communication of our work to the larger IAAR group and to a broader public (which might look something like this image produced by an artist sitting in on a similar group seen in this image). We will also use this material, with consultation of the graduate and undergraduate students, to develop the most engaging topics for course moments. These specific exchanges will also serve as opportunities to design a first- year co-taught seminar by the PIs.