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SEEING THE PAST OR TELLING THE FUTURE?
On the Origins of Pandemics and the Phylogeny of Viral Expertise
It is so difficult to find the beginning. Or, better: it is difficult to begin at the beginning. And not try to go further back.
LUDWIG WITTGENSTEIN, On Certainty
Gene Segment PB2. Biological function: Encodes a protein that slices open a host cellâs mRNA (messenger RNA), producing a short primer used to begin the process of viral transcription. In human influenza viruses, PB2 also interacts with the host cellâs mitochondria, inhibiting the cellâs natural immune response. The biological pathway for this second function is unknown. Pathographic function: Examines a key biological or scientific narrative about the origins of influenza pandemics. This segment slices opens our pathography of the 2009 H1N1 pandemic by first defining its protagonistâthe H1N1 virus itselfâand depicting how a âpandemicâ becomes a pandemic in the first place. An exploration of the production of genetic phylogenies, this segment is the primer that begins our exploration of viral expertise and the production of knowledge during the 2009 pandemic. Knowledge about a virusâs genetic lineage is interpreted and used differently by virologists and epidemiology to carry out different tasks.
On Origins
In late March 2009, a new strain of the Influenza A (H1N1) virus began to unfurl out of a remote region in Mexico. It seemed to many as if the developing pandemic might be the denouement of a harrowing story that public health workers had been telling and retelling for decades. Epidemiologists and virologists working on viruses have been sounding warning sirens about the potential for another lethalâand globalâoutbreak of infectious disease since the discovery of HIV/AIDS in the early eighties. Sporadic admonitions related to the collective weakness of our pandemic preparedness highlighted the very real threat posed by such emergent or ânovelâ viruses. These forewarnings only intensified after the 2003 SARS epidemic and in the wake of increasingly frequent outbreaks of âbird fluâ in East Asia beginning in 1997. For a brief moment in the spring of 2009, then, it appeared as if all the past predictions about the epidemic future were finally coming to pass.
But were they?
And perhaps more importantly, how would we know?
Answering this all too urgent question would ultimately rely upon an understanding of what a novel Influenza A virus is in the first place, where the term ânovelâ is used to indicate not only biological or genetic variance but also a particular viral strainâs potential for causing a deadly pandemic in an immunologically naĂŻve population.1 But how does the public health community come to a conclusion about whether or not a virus is both novel and dangerous enough to warrant attention and formulation of an aggressive global response? How do virologists and epidemiologists tell the difference between routine changes in seasonal influenza and modifications that could presage a killer pandemic?
Such questions are never easy to answer, but they pose a particularly thorny set of problems during a potential crisis situation as it is developing, when the speed and accuracy of decision-making matter more than ever. Throughout my fieldwork during the 2009 H1N1 pandemic, I discovered that the answers revolved almost entirely around a complex set of relationships and exchanges among evolutionary virologists, epidemiologists, and the influenza viruses that they study. As a social scientist caught up in the puzzle of determining the severity of the 2009 Influenza A (H1N1) virus, I found all the myriad social and professional exchanges vexing to trace. Mapping out the connections between people and places necessitated an almost continuous rethinking of how we experience and embody our social and professional connections through time in an increasingly digital age. The experts I encountered thought about themselves and their work in association not only with other people, places, and institutions, but also in terms of a complicated and mutating relationship to the past and the future.
By late summer 2010, as I began to write the pathography of the pandemic, I realized I was entangled in my own temporal dilemma. The WHO had officially declared the global pandemic over, and yet I discovered that I still had far less perspective on events than any thoughtful scholar attempting to write a âfactually accurateâ account might desire or require of herself. I choseâperhaps artificiallyâto begin my initial examination of the 2009 H1N1 pandemic through an analysis of the biology of the virus. Biology and genetics might seem a peculiar place to begin any investigation of the historical origins of a particular virus or pandemic, but it becomes far more appropriate to the task at hand once one considers how the spread of a particular strain of influenza virus becomes labeled as a âpandemicâ in the first place. In retrospect, beginning within the realm of the scientific laboratory also seemed like a good choice primarily because examining the biology of the virus, explaining H1N1 through its virology and genetic makeup, would be âeasierâ than examining its social, political, and economic aspects. It would delineate what I meant when I referred to H1N1; in effect, it would ground my pathography by defining my protagonist (and public healthâs antagonist)âthe object at the very center of the 2009 pandemic.
Once I began the painstaking process of reviewing scientific articles, re-interviewing virologists and epidemiologists, and going through my copious field notes, however, I realized almost immediately that I had been horrifically naĂŻve in my initial assumptions. The biological beginnings of the 2009 A (H1N1) influenza virus are anything but simple. In fact, the biologicalâor scientificâstory is one of the trickiest narratives about the H1N1 virus, or the resulting pandemic, to recount or analyze. It is, if you will, an always mutating or drifting narrative. As any virologist can tell you, viruses are forever in flux.
Any attempt to retell the tale of the 2009 pandemic, whether beginning from the history of influenza pandemics, or from the threat of avian influenza, or from global funding for international influenza surveillance networks, or from the social and political aspects of decision-making during a pandemic, eventually leads back to biologyâto the genetic sequence of the virusâand converges upon the moment that the virus first became âknownâ or understandable. A virusâs unique genetic sequence is often conceptualized as a kind of scientific Rosetta Stone, essential not only for an accurate reading of a virusâs present (or sudden presence on the global stage), but for working out its evolutionary past and predicting its epidemic future. From an evolutionary virology standpoint, the genetic sequence of an influenza virus is integral to answering the central question: Where did this virus come from and how does it work? And yet, as any evolutionary virologist will tell you, the predictive qualities of phylogenetic trees (or the evolutionary âlineageâ charts of viruses) are deficient. Still, from the standpoint of epidemiology or public health, the genetic sequence provides crucial information about a virusâs virulence, its severity, its transmissibility. For epidemiologists, genetic phylogeny is seen as âgood enoughâ to serve as the foundation for scientific âbest guessesâ regarding a novel influenza virusâs pandemic potential.
In this chapter, I am interested in how phylogenic trees of the H1N1 virus became central to the enactment of virological expertise as well as to the decision-making process of epidemiologists during the 2009 pandemic. From an anthropological perspective, then, genetic phylogeny is key to understanding how the social comes to insert itself into the biological and back again, or how human culture invades viral cultures and vice versa. The story of a pandemic or a particular influenza virus cannot simply be told from the singular perspective of science, or history, or epidemiology, or culture. A virusâs genetic lineage is much more complicated than that; it refuses any simple explanation of its being in the world, just as it defies any traditional methods of taxonomy. Here I utilize the sequencing of influenza viruses and their resulting genetic phylogeny treesâor evolutionary treesâas an anthropological lens. In what follows, I trace the ways in which speculation about a future deadly influenza pandemic shaped not only the direction of scientific research on influenza viruses, but also helped to formulate the possible ways in which virologists and epidemiologists conceptualized the pandemic in March 2009. Our historical âpandemic pastâ was used not only to anticipate the epidemiological future or to influence action in the present, but helped to create the network of experts working on influenza. I take seriously the ways in which the various experts I interacted with were âtacking back and forth between the past, present and futureâ (Adams, Murphy, and Clarke 2009, 255) in their attempts to make better decisions about which actions to take in March 2009, a moment when it was still highly uncertain whether or not the H1N1 virus would develop into a deadly influenza pandemic. The routine practice of genetically mapping influenza viruses not only highlights biological connections among viruses through time and space, but also produces and reifies larger social structures. Genetic information is exchanged rapidly and widely among participants in the scientific network. The resultant network of information collected, analyzed, and shared is both representative and generative of the superorganism that is global public health. The playful idea of a resultant âphylogenyâ of viral expertise is my attempt to highlight all the complex relationships that develop between scientists, farmers, public health institutions, and even the viruses themselves, or what the scientists themselves often referred to as âalliancesâ between âpartners.â In this framing, viruses and their genetic phylogeny trees are both derivative and constructive of biological and social relationships.
In the end, I suggest, the evolutionary tree of a virus is often âreadâ by virologists and epidemiologists as a type of kinship chart; by reading a phylogenic tree, one can arguably be said to know the origin story of a particular virus. But what stands outâespecially in the process of discovering, analyzing, and naming a virusâis not the biological heritage of a particular viral strain, or its relationships to places, people and other objectsâbut its centrality to the âenactment of expertiseâ (Carr 2010), the assessment of risk, and the emergence of the global public health network. Nodes in the global public health network are fashioned through work done on the influenza virus, so it should also not be all that surprising if those same interpersonal and institutional relationships ultimately reflect certain characteristics of the phylogenic trees crafted through the process of sequencing, analyzing, and sharing genetic information. This chapter ultimately examines not only how a pandemic becomes a pandemic in the first place, but also how human cultures and viral cultures intersect to produce expertise.
A Brief History of Flu Research and Pandemic Planning
When an unusual late-season outbreak of an influenza-like illness hit central Mexico in March 2009, it is no surprise that epidemiologists who responded to the growing epidemic instantaneously thought of influenza. In many ways, since pandemic planning efforts began in 2003, epidemiologists had never stopped thinking of it. Public health experts were primed to respond to the beginnings of a new influenza pandemic. After the 2009 virus was subtyped as a descendant of the infamous 1918 H1N1 strain, influenza experts immediately began to worry that it might be the start of âthe next big oneâ for which they had all been preparing. Hence there is no way to talk about the 2009 H1N1 pandemic without recourse to both the 1918 H1N1 pandemic and the more recent predictions of a potential H5N1 pandemic. This is a pathography of the 2009 pandemic, but it is alsoâof necessityâa story about the interrelationship between the past and future that often drives decision-making in the present moment.
Whenever I asked about the history of scientific research on influenza, when it began or how Influenza A came to be at the center of a global surveillance program, virologists or epidemiologists had to pause to think. Despite a renewed sense of urgency, which began after 9/11 in the wake of the anthrax attacks that same fall, research on potentially hazardous microbes such as influenza had already been ongoing for decades. For the âflu people,â sometimes also referred to as âflu guysâ since the majority of people who specialize in influenza are male, flu research already seemed ubiquitous. It is their natural milieu, and hence it is hard for them to put an exact date on its beginnings. The history of influenza itself is no less elusive. Medical historians have identified outbreaks of an influenza-like disease in historical records dating as far back as Greece in 412 BC. The first medical description of an outbreak of influenza was recorded in Philadelphia as early as 1793 (Oldstone 1998, 179). But the events which form the backbone of this pathography span the more recent history of the field of influenza virology.
It is not at all spurious to argue that everything began in 1918. A pandemic of H1N1 Influenza A virus that year impelled what has now become almost a centuryâs worth of intense scientific study on a single infectious disease agent. During the deadly 1918 pandemic, which lasted approximately eighteen months, it is estimated that between twenty and forty million people died worldwide as a result of the flu. As millions of people fell ill and died in record numbers, an animal husbandry inspector working for the US government noticed that swine on farms were falling prey to a disease with a similar set of symptoms. Over a decade of subsequent research on porcine influenza provided scientists with concrete evidence that influenza is caused by a virus (and not a bacterium, as had been suspected). Even so, the influenza virus was not isolated and confirmed in a laboratory using Kochâs postulates2 until 1932 (Potter 2001), during a relatively minor epidemic of influenza subsequent to the 1918 pandemic. During that epidemic, researchers at Wellcome Laboratories in London who became infected with influenza noticed that ferrets in their research facility also fell ill,3 and quickly confirmed that influenza was transmitted via virus (Oldstone 1998, 181). In essence, this single event marks the official start of modern influenza virology.
For the following two decades, laboratory research on influenza progressed slowly. In 1941, the HA and NA surface proteins were first described, and their usefulness as markers for detecting and tracking influenza viruses was immediately recognized (Artenstein 2010, 194). The discovery of the roles of these surface proteins in invading a host cell also helped to advance the biological understanding of how influenza functioned. At the same time, beginning in 1940 and continuing throughout the 1950s, MacFarlane Burnet, an Australian scientist, made significant progress in the use of chicken embryos for research on influenza. He established the practice of cultivating influenza viruses in eggs (Oldstone 1998, 182)âa technological advance that made it possible not only to grow large amounts of the virus for scientific study and diagnostic assays, but also enabled the development of influenza vaccines.4
Given that World War I had precipitated the deadliest influenza pandemic in memory, the United States had influenza near the top of its list of concerns as it approached World War II. Preparations for that war included the establishment of a Commission on Influenza (Artenstein 2010, 198), which would be instrumental in the development of effective vaccines. World War II also inaugurated the practice of mass vaccination campaigns among US soldiers, thereby providing virologists and epidemiologists with their first chance to study vaccine effectiveness in a large population. The Commission on Influenza financed a bevy of scientific research over the three decades of its existence, and spurred broader advancements in research on other viral pathogens. By 1957, when another pandemic of influenza spread around the globe, virologists and epidemiologists were equipped with far better methods and equipment (Artenstein 2010, 200), marking the beginnings of modern virological analysis of Influenza A. Since then, laboratory work on influenza has progressed apace, increasingly reliant upon new techniques in genetic sequencing and analysis, and focused on unpacking the virusâs origins, understanding its ecological environment, and decoding its biological processes and functioning inside host cells. With the establishment of the WHOâs Global Influenza Surveillance Network (GISN)5 in 1952, and the networkâs expansion over the ensuing decades, laboratory research on influenza continues to receive a generous amount of international attention and funding.
The history of scientific research on the influenza virus is, of course, deeply intertwined with that of pandemic planning. Did advances in v...