Nancy Nersessian

Computational systems biologists create and manipulate computational models of biological systems, but they do not always have straightforward epistemic access to the content and behavioural profile of such models because of their length, coding idiosyncrasies, and formal complexity. This creates difficulties both for modellers in their research groups and for their bioscience collaborators who rely on these models. In this paper we introduce a new kind of visualization that was developed to address just this sort of epistemic opacity. The visualization is unusual in that it depicts the dynamics and structure of a computer model instead of that model’s target system, and because it is generated algorithmically. Using considerations from epistemology and aesthetics, we explore how this new kind of visualization increases scientific understanding of the content and function of computer models in systems biology to reduce epistemic opacity.

We have been studying cognition and learning in research laboratories in the field of biomedical engineering. Through our combining of ethnography and cognitive-historical analysis in studying these settings we have been led to understand these labs as comprising evolving distributed cognitive systems and as furnishing agentive learning environments. For this paper we develop the theme of 'models-in-action,' a variant of what Knorr Cetina has called 'knowledge-in-action.' Among the epistemically most salient objects in these labs are so called "model systems," which are designs that blend engineering with the study and use of biological systems for purposes of simulative model-based reasoning. We portray the prevalent design-orientation in this engineering specialty and how the prevailing activity of cell-culturing in these labs transitions into a design activity for the bio-medical engineers, leading them to work with 'wet' devices. We discuss how devices, 'wet' and 'dry,' situate model-based understandings and how they participate in model systems in these labs. Models tend to come in clusters or configurations, and the model systems in these labs are epistemically salient junctures of interlocking models. Model systems in these labs evolve thereby consolidating what we want to call a 'fabric of interlocking models,' which functions as point of stability and departure in these labs. We convey a taste of such a 'fabric' for a tissue-engineering lab. We conjecture that through this 'fabric' extended developments in technology and methodology have a 'situated' presence in the workings of these labs.

Modern integrative systems biology defines itself by the complexity of the problems it takes on through computational modeling and simulation. However in integrative systems biology computers do not solve problems alone. Problem solving depends as ever on human cognitive resources. Current philosophical accounts hint at their importance, but it remains to be understood what roles human cognition plays in computational modeling. In this paper we focus on practices through which modelers in systems biology use computational simulation and other tools to handle the cognitive complexity of their modeling problems so as to be able to make significant contributions to understanding, intervening in, and controlling complex biological systems. We thus show how cognition, especially processes of simulative mental modeling, is implicated centrally in processes of model-building. At the same time we suggest how the representational choices of what to model in systems biology are limited or constrained as a result. Such constraints help us both understand and rationalize the restricted form that problem solving takes in the field and why its results do not always measure up to expectations.

Building computational models of engineered exemplars, or prototypes, is a common practice in the bioengineering sciences. Computational models in this domain are often built in a patchwork fashion, drawing on data and bits of theory from many different domains, and in tandem with actual physical models, as the key objective is to engineer these prototypes of natural phenomena. Interestingly, such patchy model building, often combined with visualizations, whose format is open to a wide range of choice, leads to the discovery of new concepts and control structures. Two key questions are raised by this practice: how could discoveries arise from building external representations for which there is wide latitude in choice of the components from which they are built, and thus can be considered significantly arbitrary, and how could such discoveries allow engineering a real-world prototype system. To examine these questions, we present two case studies of discoveries that emerged from the building of such computational models in the bioengineering sciences. We then develop a process model that accounts for the discovery and transfer problems raised by both these cases, focusing on the process of building the model. Specifically, to account for the discovery problem, we propose that the process of building such models gradually leads to a close coupling between the modeler’s internal processes and the external dynamic model. To account for the transfer problem, we propose that the process of building the model leads to the creation of an enactive model that is generic, which closely enacts, and thus reveals, the way the system-level behavior of the engineered prototype emerges in time through the interaction of its parts. This enactive replication process leads to the model and the prototype forming a new class, which allows concepts and control structures developed for the computational model to be transfered to the real-world prototype. We argue that this account requires rethinking correspondence in engineering sciences as a plastic and enactive relation. A closer focus on the process of building models is required to develop a general account of this emerging approach to discovery.

Confronting any science studies or learning sciences researcher in the 21st century is the reality of interdisciplinary science. New hybrid fields1 collaboratively build new concepts, combine models from two or more disciplines and forge inter-reliant relationships among specialists with different skill sets to solve new problems. This paper emerges from our recognition that inescapable psychological factors, including identity dynamics, must be described and analyzed in order to better understand the social and cognitive practices specific to interdisciplinary science. In analysis of the foundations and opportunities for an...

Integrative systems biology is an emerging field that attempts to integrate computation, applied mathematics, engineering concepts and methods, and biological experimentation in order to model large-scale complex biochemical networks. The field is thus an important contemporary instance of an interdisciplinary approach to solving complex problems. Interdisciplinary science is a recent topic in the philosophy of science. Determining what is philosophically important and distinct about interdisciplinary practices requires detailed accounts of problem-solving practices that attempt to understand how specific practices address the challenges and constraints of interdisciplinary research in different contexts. In this paper we draw from our 5-year empirical ethnographic study of two systems biology labs and their collaborations with experimental biologists to analyze a significant problem-solving approach in ISB, which we call adaptive problem solving. ISB lacks much of the methodological and theoretical resources usually found in disciplines in the natural sciences, such as methodological frameworks that prescribe reliable model-building processes. Researchers in our labs compensate for the lack of these and for the complexity of their problems by using a range of heuristics and experimenting with multiple methods and concepts from the background fields available to them. Using these resources researchers search out good techniques and practices for transforming intractable problems into potentially solvable ones. The relative freedom lab directors grant their researchers to explore methodological options and find good practices that suit their problems is not only a response to the complex interdisciplinary nature of the specific problem, but also provides the field itself with an opportunity to discover more general methodological approaches and develop theories of biological systems. Such developments in turn can help to establish the field as an identifiably distinct and successful approach to understanding biological systems.

Cases where analogy has played a significant role in the formation of a new scientific concept are well-documented. Yet, how is it that genuinely new representations can be constructed from existing representations? It is argued that the process of ‘generic modeling’ enables abstraction of features common to both the domain of the source of the analogy and of the target phenomena. The analysis focuses on James Clerk Maxwell's construction of the electromagnetic field concept. The mathematical representation Maxwell constructed turned out to be a system of abstract laws that when applied to electromagnetic systems yield laws of a dynamical system that will not map back onto the mechanicals domains used in their construction.

Novel computational representations, such as simulation models of complex systems and video games for scientific discovery, are dramatically changing the way discoveries emerge in science and engineering. The cognitive roles played by such computational representations in discovery are not well understood. We present a theoretical analysis of the cognitive roles such representations play, based on an ethnographic study of the building of computational models in a systems biology laboratory. Specifically, we focus on a case of model-building by an engineer that led to a remarkable discovery in basic bioscience. Accounting for such discoveries requires a distributed cognition analysis, as DC focuses on the roles played by external representations in cognitive processes. However, DC analyses by and large have not examined scientific discovery, and they mostly focus on memory offloading, particularly how the use of existing external representations changes the nature of cognitive tasks. In contrast, we study discovery processes and argue that discoveries emerge from the processes of building the computational representation. The building process integrates manipulations in imagination and in the representation, creating a coupled cognitive system of model and modeler, where the model is incorporated into the modeler's imagination. This account extends DC significantly, and we present some of the theoretical and application implications of this extended account.

Integrative systems biology is among the most innovative fields of contemporary science, bringing together scientists from a range of diverse backgrounds and disciplines to tackle biological complexity through computational and mathematical modeling. The result is a plethora of problem-solving techniques, theoretical perspectives, lab-structures and organizations, and identity labels that have made it difficult for commentators to pin down precisely what systems biology is, philosophically or sociologically. In this paper, through the ethnographic investigation of two ISB laboratories, we explore the particular structural features of ISB thinking and organization and its relations to other disciplines that necessitate cognitive innovation at all levels from lab PI’s to individual researchers. We find that systems biologists face numerous constraints that make the production of models far from straight-forward, while at the same time they inhabit largely unstructured task environments in comparison to other fields. We refer to these environments as adaptive problem spaces. These environments they handle by relying substantially on the flexibility and affordances of model-based reasoning to integrate these various constraints and find novel adaptive solutions. Ultimately what is driving this innovation is a determination to construct new cognitive niches in the form of functional model building frameworks that integrate systems biology within the biological sciences. The result is an industry of diverse and different innovative practices and solutions to the problem of modeling complex, large-scale biological systems

There are several key ingredients common to the various forms of model-based reasoning considered in this book. The term ‘model’ comprises both internal and external representations. The models are intended as interpretations of target physical systems, processes, phenomena, or situations and are retrieved or constructed on the basis of potentially satisfying salient constraints of the target domain. The book’s contributors are researchers active in the area of creative reasoning in science and technology.