Bugs, Drugs, Documents.

Post,Reflections May 30, 2016 2:31 am
Electron micrograph images of E.coli/ Courtesy: http://www.ottawasun.com/2016/01/05/what-is-mcr-1-doctors-find-new-superbug-gene-in-ottawaoneplan

Electron micrograph image of E.coli/ Source: http://www.ottawasun.com/2016/01/05/what-is-mcr-1-doctors-find-new-superbug-gene-in-ottawaoneplan


What a fortnight it’s been for (anti)microbials! A fortnight presaging an emergent summer of action, discontent and alarm.

First up, there’s the final report from the Review on Antimicrobial Resistance, a body commissioned by the British Government to delve into the “global problem of antimicrobial resistance (AMR) and propose concrete actions to tackle it internationally”. Released on May 19th, 2016, the final report’s warnings couldn’t be starker: if things carry on as they are with the uptake of antimicrobials and a simultaneous diminishment in the new development of antibiotics, then by 2050, 10 million—yes, that’s correct, ten million—people will die each year from primary and secondary microbial infections.

The Review is headed by Jim O’Neill, the economist known for conceptualising the rising emergence of the BRIC economies. O’Neill, a former chairman of Goldman Sachs, is “an unorthodox choice to lead an international commission on drug-resistant infections”, as this piece in The Atlantic points out. In the foreword to the Review’s final report, O’Neill describes how money and time are deliberately, and inextricably, tied to an emergent biomedical crisis: 2050 is the year by which the BRIC nations are supposed to have “emerged”; 10 million is the expected rate of fatalities in human lives globally by then; and a $100 trillion is the expected cost of “lost global production” from now till 2050 as a result of proliferative antimicrobial resistance. This resistance, the report argues, transcends infectious diseases. It also includes conditions emerging from cancer treatment, and complications from routine surgical procedures such as organ transplants and caesarean sections.

These are confounding and catastrophic scenarios. They are also sober reminders that the terrain of antibiotics and resistance is a complex and riddled one. Here life-forms (human, microbial, recalcitrant) are in perpetual, evolutionary competition. The development and use of antimicrobial-pharmaceuticals is a story of everyday, technoscientific faith-based use (for human health and agricultural growth), of corporate financial speculation in the (un)profitability of drug-development, and of planetary biopolitical alarm that cannot be contained by the logics of sovereign borders. This terrain generates horizonal futures, entwining forms of waiting for technoscientific “fixes” against the spectre of “superbugs”; of hoping via performative-expertise for which the Review’s report stands as an exemplar; and of a scramble for knowledge and action that demonstrates a mode of doing. This past fortnight has given us much to think of this tripartite emergence of futures:

I. Hoping:

What does this final report from the Review on Antimicrobial Resistance perform? As the most current expert-articulation of the state-of-affairs in antibiotic resistance, it provides warnings, offers a roadmap for action, and charts a vision of the future where evolutionary struggle between biological life-forms may be culturally trammelled through resources, quarantines, and knowledge. The report, as prognostication, is also an artefact of hoping. Set against the dire tolls of antibiotic failure on life and value that are predicted for the middle decades of the 21st century, this final treatise offers visions of salvation amidst the emergent ruins of antibiotics. First, it calls for a lowering of demand of antibiotics through: an overhaul in awareness campaigns globally; improvements in hygiene and sanitation to prevent infections; reduction of antimicrobial-use in agriculture as growth-promotants and better stewardship of environmental runoff from manufactories, farms and hospitals; better surveillance of antimicrobial consumption via precision techniques that include cloud-computing and ‘big data’ analyses into which lower-income countries are enjoined to “leapfrog”; promotion of cutting-edge diagnostic tools for “optimal treatments” that prevent the empirical misuse of unnecessary antibiotics; the deployment of alternatives to antimicrobials such as phage-therapeutics, lysins, probiotics, immune-stimulation, etc. for treating infections; and better recognition and pay for a larger corps of specialists in infectious diseases and microbiology.

Second, the report calls for “defeating” infections already resistant to extant antimicrobial agents through business-models that bring together governments, the private pharmaceutical industry, and NGOs: this would involve the establishment of a ‘Global Innovation Fund’ that encourages research in “early-stage ‘blue-sky’ science” that lacks the incentives of financial profitability; newer models of drug-development, market-entry rewards, and acquisitions of these pharma products through government guarantees; an overhaul towards business-friendly regulations, patenting regimes, clinical-trial protocols, and supply-chains of drugs to make it “attractive” for commercial drug developers to pool resources into drugs that have short evolutionary shelf-lives; and the maintenance of existing arsenals of older antibiotics through stocking, judicious dosage, and more research into the “pharmacokinetics (PK) and pharmacodynamics (PD) of antibiotics” to better understand their metabolism in the body.

Tackling drug-resistant infections globally: final report and recommendations of the Review on Antimicrobial Resistance (May 2016)

Info-graphic source: “Tackling drug-resistant infections globally”: final report and recommendations of the Review on Antimicrobial Resistance (May 2016)

Third, the report lays out a global strategy to combat a crises of planetary proportions: it calls for the active participation of G-20, G-7, and various UN bodies; it deconstructs the costs of its own proposals, and offers mechanisms to fund them, as a preemptive measure to combat pathogens that traverse borders; and it argues for national interventions that would have planetary ramifications and subsequent national payoffs. Finally, the report hopes against hope that a statistic will not come to pass: “By 2050, the death toll could be a staggering one person every three seconds if AMR is not tackled now.” This is both a warning and a vision of a future performed into being.

The report is an enjoinment to a new mode of living—one where the faith in antimicrobials is trammelled not only by the ongoing collapse in the efficacy of these wonder agents, or a technoeconomic hunt for redress, but also a new order of living the everyday with these drugs responsibly. For, in this vision, the personal is the planetary.

II. Waiting:

A future performed into being is not one divorced from reality. The same week this final report was published, apocalyptic news broke. “Infection Raises Specter of Superbugs Resistant to All Antibiotics”, blared a headline in The New York Times. “A dreaded superbug found for the first time in a U.S. woman”, warned CNN. Others followed, in the same vein. Basing themselves on a scientific article—titled “Escherichia coli Harboring mcr-1 and blaCTX-M on a Novel IncF Plasmid: First report of mcr-1 in the USA”—published in the journal Antimicrobial Agents and Chemotherapy, these news reports not only urge alarm, or gesture at the popular consumption of scientific data. They also stand as signposts that periodically emerge to distil the ongoing experience of contemporary bio-cultures where mutant life-forms are proliferative, and various spectres haunt the public imagination in the increasing absence of efficacious chemical weapons or borders. How is life to be lived with insecurity, and what must be awaited next, when infections are untreatable, antibiotics of last resort are failing, and microbes far away are very close (the mcr-1 was first reported late last November in China’s agricultural and meat industry)? The scientific article in question is authored by a team at the Walter Reed National Military Medical Centre, and emerged from a case of a woman in Pennsylvania harbouring a urinary tract infection due to a strain of E. Coli with “plasmid-borne colistin resistance gene, mcr-1” that, as the article warns at the very beginning, “heralds the emergence of truly pan-drug resistant bacteria”.

Two facts, if one cuts through the spectrality of the superbug, emerge: first, Colistin-resistance is really bad news, because Colistin—an old drug that’s itself nephrotoxic and rarely used—is a “treatment of last resort” antibiotic “held in reserve to treat especially dangerous infections that are resistant to a class of drugs called carbapenems. If carbapenem-resistant bacteria, called CRE, also pick up resistance to colistin, they will be unstoppable”. Second, as this piece in ArsTechnica argues, this case of the Pennsylvania mcr-1 is a plasmid-resistance gene that can be easily shared between neighbours, unlike colistin resistance genes on bacterial chromosomes that aren’t shareable. It is only a matter of time, within this terrain of waiting, where the mcr-1 travels to CRE pathogens and other bacterial populations and species that are, themselves, already resistant to other treatments-of-last-resort antibiotics. That horizontal gene transfer would herald the arrival of what the director of the Centres for Disease Control and Prevention (CDC) has called “nightmare superbugs”, against which the “medicine cabinet is empty”. Why? Because in addition to biological and antimicrobial-induced evolution, as this report in Nature reminds us, “The US Food and Drug Administration has approved about half a dozen new antibiotics in the past two years, and about 30 more are in the pipeline. But most are similar to existing drugs and may not work any better. The most recently discovered class of antibiotics, lipopeptides, was identified in the late 1980s”.

Time, money, and biomechanics have bequeathed recalcitrant lives, and the payback is now.

III. Doing:

But waiting is not without action. There is ongoing, inter-agency effort in the United States to address outbreaks such as the Pennsylvania mcr-1 E. coli and the drug-resistant Elizabethkingia outbreak in April across Illinois, Michigan and Wisconsin. When outbreaks are becoming the norm, waiting involves mobilising efforts to observe, isolate, research, and communicate findings of cases such as the mcr-1 E. coli and their transmission to other pathogenic species. For instance, it was through the Multidrug-resistant Organism Repository and Surveillance Network (MRSN) at the Walter Reed Institute of Research that this recent case of mcr-1 E. coli was communicated across departments of defence, health and human services, and agriculture, suggesting the operations of the 2015 National Action Plan to Combat Antibiotic-Resistant Bacteria—a policy of the Obama administration that envisages the diagnostics, therapeutics, surveillance, and innovations necessary to address an emergent crisis across human and zoonotic populations.

Which brings me to the third development this fortnight—the ultimate scramble to know. On Friday, May 13, 2016 the White House launched the National Microbiome Initiative (NMI). The NMI marshals an array of federal agencies, and public as well as private stakeholders, aiming “to advance understanding of microbiomes in order to aid in the development of useful applications in areas such as health care, food production, and environmental restoration”. The NMI is a massive exploratory effort towards the microbial world, taking the multitude of biological life-forms seriously in the earth, the sky, humans, animals, oceans, etc. Ed Yong, over at The Atlantic, has a great piece on the initiative, and describes the NMI evocatively as an effort where “America has decided to point half a billion microscopes at the planet, and look through them”. Everything and anything is a potential source of knowledge, and through that knowing, of action—the bacterial communities affecting soils, atmospherics, and oceans, the toxic microbes resident in built environments, the gut-microbes now being shown to affect all kinds of dispositions, etc.

The NMI is pledged $121 million by federal agencies, while over a hundred universities, foundations, etc. have been roped in to provide another $400 million for the effort. Yong is partially right to claim that this initiative is anti-“narcissistic” because it moves beyond the contemporary fascination with the human microbiome; instead, the NMI acknowledges that biologies are multiple and, majorly, microbial. I say he’s partially correct because the NMI is, itself, justified on the basis of generating knowledge of microbial life-forms for useful applications in human worlds; this use-value is reminiscent of bioprospecting, historical and ongoing—a scramble to know and, thereby, control biological phenomena for profit that is limited to a few. Nevertheless, the NMI, at this moment, is being conceived as an epistemic resource: it will support fundamental research and aid interdisciplinary conversations viz. microbial life-forms; it will design “platforms” for the sharing of research of normal, pathological or promising microbiologies; and it will recruit “citizen scientists” for contribution to our knowledge of diversely-situated microbial communities. As a site of pure potentiality, the NMI promises a remarkable inter-action between life-forms.

Looking back, this past fortnight may well stand as a watershed moment. Everything’s connected: an expert report that acknowledges the profound effects of antibiotics resistance and the limits of expertise in the face of evolving and experimental futures; a mutant bacterial strain that realises the apocalyptic fears of many and presages an endless deferral of survival and struggle; and a multisited/multimodal initiative for knowledge and action that aims to take seriously the role that microbial communities play in their troubled imbrications with our engineered worlds.

Courtesy: Nadav Kander/Flowers Gallery (http://www.flowersgallery.com/shop/view/nadav-kander-dust)

Courtesy: Nadav Kander/Flowers Gallery (http://www.flowersgallery.com/shop/view/nadav-kander-dust)

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