20 December 2009
Book Review: The Social Construction of Disease: From Scrapie to Prion
Kiheung Kim’s The Social Construction of Disease: From Scrapie to Prion is a remarkable and elegant work that examines the history of the discovery of the prion, pathological entities found to be resistant to radiation treatment and later discovered to be proteins. Building upon approaches common in the sociology of scientific knowledge, Kim organizes his sociologically informed history of medicine by analyzing the ways scrapie and (later) prion researchers organized and conducted their experiments and framed their hypotheses. He argues that disease cannot be isolated from its social circumstances and that it is furthermore shaped by that context. Thus, words like “scrapie” bring with them historical ambiguities that cannot be neglected by historians, and in part arise from the various disease theories that exist in given moments. Scientists and physicians have typically negotiated with such uncertainty by forming consensus about the definition of disease entities. Kim’s study, which begins by examining the history of scrapie research in the context of the modern biomedicine, examines “the relations between scientific practices and wider social transformations” associated with the development of scientific knowledge.
Scrapie had an enormous impact on British Agriculture throughout the eighteenth and nineteenth centuries. With the establishment of the veterinary profession in the twentieth century, researchers began investigating the disease. Early proposals included the suggestion that it was caused by a parasite, but in this period in which the germ theory and Koch’s postulates were still under negotiation, the parasite theory found little support. It did, however, establish one of the important facts of the disease: namely that the incubation period of the disease was long. At the same time, scrapie research began to be institutionalized in Britain. The formation of the Animal Diseases Research Association (1921) and the Moredun Institute in Edinburgh (1926) established two players, although both took only a partial interest in scrapie. At the Moredun Institute a disastrous vaccine experiment in sheep with louping-ill led to a dramatic loss of animals, which developed signs of scrapie some three years following the otherwise successful vaccination. Concern about how scrapie had spread to the sheep led to several important observations at Moredune, including that whatever the agent of scrapie was, it was resistant to formalin, formaldehyde, autoclave treatment, and ultraviolet light. It was these factors that led to the first controversy in scrapie research – the question of whether the disease was genetic or spread by some infectious agent.
This question largely defined research on scrapie in the period between 1960 and 1980. In two subsequent chapters, Kim discusses the experiments of two groups in Britain who reached vastly different conclusions. One group at Moredun led by Alan Dickinson observed that there was variation in the incubation period in laboratory mice. They hypothesized that these differences were genetic in origin, and they eventually observed a single gene that exerted enormous “influence in the pathological development of scrapie in mice” and was determinative over the length of the incubation period. They proposed that the reasons for this selective influence was the interaction of a hypothetical agent – termed virino – comprised of proteins that utilized the host’s genetic material for self-reproduction. As Kim writes, “the virino hypothesis” was exciting because it served to “explain a number of the anomalous pathological and biochemical properties of the scrapie agent” (p. 46) including its camouflage in the organism and transcription, both presumably mediated by host protein. But the virino hypothesis had severe problems. A second group at the Institute for Research on Animal Diseases and led by Tikvah Alper, a radiologist at the Hammersmith Hospital, demonstrated that the infectious agent was much smaller than any known virus, suggesting that the agent might not possess any genetic information. They furthermore noted that large doses of radiation had little effect on the infectiousness of the material, and that the agent was practically resistant to deactivation by UV light. The ultimate result of these divergent studies was a controversy in the scrapie community – one that was resolved in an interesting if non-scientific way.
Scientific consensus usually arises from a convergence of factors, many of which have little bearing on the scientific facts in dispute. This particular controversy was as much a clash between individuals as it was between “two distinctive experimental systems” with their “own intrinsic standard of measurement, criteria of evaluation and interpretation” (p. 70-71). The two groups, now in competition with one another, were furthermore organized around wholly different management ethos. The group at the Institute for Research on Animal Diseases adopted a competitive even commercial entrepreneurialism, and tended to defend their techniques and specialties; whereas, the group at Moredun focused their attention on the pathogenesis of scrapie. In the end, an external administrative body – the Agricultural Research Council – resolved the dispute in highly political terms in favor of the Moredune group. In consequence, the radiological research at the Institute became marginalized and eventually lost funding. The resolution in favor of the Moredun group ultimately captures the conservativism of scientific discovery: the Moredun group’s conclusions were simply more aligned with the views of the wider British scientific community.
While the debate about the etiology of scrapie was raging in the United Kingdom, research on the condition only came to the attention of researchers in the United States with the advent of the concept of “unconventional slow viruses” of which scrapie was seen as a particularly good experimental model. Beyond these diseases, attention to scrapie had been confined to rare conditions of similar pathology in other organisms, especially a human disease called Kuru discovered among the indigenous peoples of Papua New Guinea. One American researcher, William Hadlow, had briefly worked at the Institute for Research on Animal Diseases in the 1950s, and had then observed the common pathology of scrapie and Kuru brains. This observation was seen by many medical scientists in the United States as a confirmation that researchers were dealing with a new type of viruses. It was this line of inquiry that was pursed at the Rocky Mountain Laboratory in Montana and under the guidance of Carl Eklund, Hadlow’s onetime mentor. Other institutions in the United States soon joined the fray, including the Laboratory of Central Nervous System Studies at the National Institutes of Health, which was focused on Kuru, the Institute for Basic Research in Developmental Disabilities, and the Department of Veterinary Science at the University of Wisconsin. Whereas British researchers were interested in scrapie purely, researchers in the United States were interested in a more uncertain and hazy group of viruses. The clash of cultures, according to Kim, was thus between agricultural interests and the science of virology. It was the Americans who would deliver the most controversial turn to the study of the diseases, but the new hypothesis would do little to support virology.
Throughout the mid-to-late 1970s, Stanley Prusiner, a neurologist based in San Francisco, began examining the chemical composition of the infectious agent of scrapie. Based upon his biochemical research (chiefly centrifugation), Prusiner identified through a partial purification a specific cluster of homogenate that contained the active agent. In subsequent experiments, Prusiner’s group selectively treated the homogenate with enzymes that broke down proteins or nucleic acids. These studies demonstrated conclusively that proteins were necessary for transmission of the disease, and also that nucleic acids were not necessary for infectivity. Prusiner published these findings in Science in 1982 and adopted the name “prion” to describe small protein based infectious particles that caused diseases like scrapie and Kuru. Prusiner’s research substantially challenged all prevailing theories of the disease – from the genetic to the slow virus hypotheses.
Prion skeptics hated the hypothesis and were not appeased by Prusiner’s various confirmatory experiments and explanations. Even his award of a Nobel Prize in 1997 failed to mollify criticism, which was sustained for two decades. Kim concludes that the ultimate basis of the tension between prion proponents and skeptics was the social and material basis of their science and assumptions. Prion skeptics tended to be housed in supportive environments that adhered to generalist programs of biological research. By contrast, proponents of the prion theory tended to be embedded in competitive and often soft money environments, making the demands for both innovative and specialist research larger. As biomedicine in the 1980s and 1990s became increasingly commericialized and standardized, medicine also became increasingly molecularized. In this new neoliberal world with its molecular bias, the specialist biochemist – individualist and product oriented – won out over an older social order based upon a model of social conformity. Prusiner’s success partly derived from the fact that his group was at the forefront of these large scale social, political, and economic changes. His scientific collaborative networks stretched deeply into the influential circles that granted short-term funding and institutional support. In the new climate, Prusiner’s style of science was simply in tune with the times.
In sum, Kim’s book is not only a triumph of empirical and theoretical rigor, but it also contains a story that will fascinate readers. The work can be regarded as an excellent marriage between methods native to the sociology of science and historical analysis. Although the “prion” hypothesis remains contentious even to this day, Kim makes clear in his work that much of the controversy surrounding the science of the prion arose from institutional assumptions and the embedded nature of scientific actors. Science accordingly was less the object of dispute than its interpretation. The interpretation was contingent and negotiated. The science was open-ended. Doubt and possibility thus triumphed over certainty.