ArgumentThis article uses four historical case studies to address epistemological issues related to the animal model of human diseases and its use in medical research on human diseases. The knowledge derived from animal models is widely assumed to be highly valid and predictive of reactions by human organisms. In this contribution, I use three significant historical cases of failure (ca. 1890, 1960, 2006), and a closer look at the emergence of the concept around 1860/70, to elucidate core assumptions related to (...) the specific practices of animal-human knowledge transfer, and to analyze the explanations provided by historical actors after each of the failures. Based on these examples, I argue that the epistemological status of the animal model changed from that of a helpful methodological tool for addressing specific questions, but with precarious validity, to an obligatory method for the production of strong knowledge on human diseases. As a result, there now exists a culture of biomedical research in human disease that, for more than a century, has taken the value of this methodological tool as self-evident, and more or less beyond question. (shrink)

This article compares the epistemic roles of theoretical models and model organisms in science, and specifically the role of non-human animal models in biomedicine. Much of the previous literature on this topic shares an assumption that animal models and theoretical models have a broadly similar epistemic role—that of indirect representation of a target through the study of a surrogate system. Recently, Levy and Currie have argued that model organism research and theoretical modelling differ in the justification of model-to-target inferences, such (...) that a unified account based on the widely accepted idea of modelling as indirect representation does not similarly apply to both. I defend a similar conclusion, but argue that the distinction between animal models and theoretical models does not always track a difference in the justification of model-to-target inferences. Case studies of the use of animal models in biomedicine are presented to illustrate this. However, Levy and Currie’s point can be argued for in a different way. I argue for the following distinction. Model organisms function as surrogate sources of evidence, from which results are transferred to their targets by empirical extrapolation. By contrast, theoretical modelling does not involve such an inductive step. Rather, theoretical models are used for drawing conclusions from what is already known or assumed about the target system. Codifying assumptions about the causal structure of the target in external representational media allows one to apply explicit inferential rules to reach conclusions that could not be reached with unaided cognition alone. (shrink)

Phenologists track the seasonal behavior of plants and animals in response to climatic change. During the second half of the twentieth century, phenologists developed a large-scale project to monitor the flowering time of the common lilac across the United States. By the 1960s, this approach offered a potential plant-based indicator of anthropogenic climate change, a biological signal amidst the emerging narrative of increasing levels of atmospheric carbon dioxide. As a tangible representation of changes in climate—warmer temperatures lead to earlier blooming—phenology (...) proved highly legible to scientists, politicians, and laypeople. Yet, as phenology gained broader repute in the 1960s, both in agricultural stations and as a component program of the International Biological Program, it struggled to align itself epistemically with the regnant disciplinary assumptions of mid-century ecology. Operating in the hinterlands between laboratory and field, biology and meteorology, ecological theory and agronomy practice, phenologists challenged prevailing notions of the model organism and what it meant to study biology in the field. Rebranding the discipline as a component of ecosystem modeling, scientists successfully brought phenology within the purview of mainstream ecology. In so doing, however, they obscured its climate-relevant meteorological character and stymied the development of a biological narrative of climate change. (shrink)

Many biologists appeal to the so-called Krogh principle when justifying their choice of experimental organisms. The principle states that “for a large number of problems there will be some animal of choice, or a few such animals, on which it can be most conveniently studied”. Despite its popularity, the principle is often critiqued for implying unwarranted generalizations from optimal models. We argue that the Krogh principle should be interpreted in relation to the historical and scientific contexts in which it has (...) been developed and used. We interpret the Krogh Principle as a heuristic, i.e., as a recommendation to approach biological problems through organisms where a specific trait or physiological mechanism is expected to be most distinctively displayed or most experimentally accessible. We designate these organisms “Krogh organisms.” We clarify the differences between uses of model organisms and non-standard Krogh organisms. Among these is the use of Krogh organisms as “negative models” in biomedical research, where organisms are chosen for their dissimilarity to human physiology. Importantly, the representational scope of Krogh organisms and the generalizability of their characteristics are not fixed or assumed but explored through experimental studies. Research on Krogh organisms is steeped in the comparative method characteristic of zoology and comparative physiology, in which studies of biological variation produce insights into general physiological constraints. Accordingly, we conclude that the Krogh principle exemplifies the advantages of studying biological variation as a strategy to produce generalizable insights. (shrink)

In the early 1990s, Microcebus murinus, a small primate endemic to Madagascar, emerged as a potential animal model for the study of aging and Alzheimer’s disease. This paper traces the use of the lesser mouse lemur in research on aging and associated neurodegenerative diseases, focusing on a basic material precondition that made this possible, namely, the conversion of a wild animal into an experimental organism that lives, breeds, and survives in the laboratory. It argues that the “old” mouse lemur model (...) can be considered as an eco-zootechnical acquisition. This is shown by examining how, since the early 1970s, French mouse lemur researchers have articulated colony productivity and viability with the influence of environmental factors on the demographics and physiology of the species. The appearance and maintenance of a growing number of old mouse lemurs in French research facilities are related to three developments: the application of the ecological notion of “social stress” to the understanding and management of the behavior of the captive population; the experimental demonstration that a variety of seasonal physiological changes in the species were influenced by the photoperiod; and the related attempt to accelerate aging in mouse lemurs through the manipulation of annual light conditions. (shrink)

Collections of living organisms are reservoirs of biological knowledge that operate across times and places. From the mid-20th century, scientific institutions dedicated to the cultivation of such collections have routinized and professionalized their care. But “care,” for these collections, is focused not just on individual organisms—instead, a principal aim of a curator is to maintain the integrity of a reproducing “strain,” “variety,” “line,” or “stock,” and the composition of a collection as a whole. This paper explores the forms, the material (...) dimensions, the temporalities, and the values of that care, to recover the conditions under which scientist-custodians maintain continuity of research over many decades. This paper does so by focusing on two rather different kinds of scientific collection: that of Drosophila fruit flies on the one hand, and plant seeds on the other. Their comparison is valuable because their vastly different needs and life cycles engender very different practices of care. Comparing the materialities, life cycles, needs, and values of these divergent collections helps to draw attention to the routine and the apparently mundane. First, the paper asks: what kinds of work go into managing such collections—that is, the day-to-day management and cultivation, surveillance, and administration of information? Second, it asks: how do these practices maintain the integrity of the strains and stocks, and the collections themselves? What kinds of value does this work create? Third, what are the future imaginaries that are rhetorically drawn into the funding strategies of these collections, and how do they envision future use, ownership, and control? (shrink)

The most conspicuous form of agricultural experiment is the field trial, and within the history of such trials, the arrival of the randomised control trial is considered revolutionary. Originating with R.A. Fisher within British agricultural science in the 1920s and 30s, the RCT has since become one of the most prodigiously used experimental techniques throughout the natural and social sciences. Philosophers of science have already scrutinised the epistemological uniqueness of RCTs, undermining their status as the ‘gold standard’ in experimental design. (...) The present paper introduces a historical case study from the origins of the RCT, uncovering the initially cool reception given to this method by agricultural scientists at the University of Cambridge and the National Institute of Agricultural Botany. Rather than giving further attention to the RCT, the paper focuses instead on a competitor method – the half-drill strip – which both predated the RCT and remained in wide use for at least a decade beyond the latter’s arrival. In telling this history, John Pickstone’s Ways of Knowing is adopted, as the most flexible, and productive way to write the history of science, particularly when sciences and scientists have to work across a number of different kinds of place. It is shown that those who resisted the RCT did so in order to preserve epistemic and social goals that randomisation would have otherwise run a tractor through. (shrink)