In an instant classic paper ; 2002: 179–182) biologist Yuri Lazebnik deplores the poor effectiveness of the approach adopted by biologists to understand and “fix” biological systems. Lazebnik suggests that to remedy this state of things biologist should take inspiration from the approach used by engineers to design, understand, and troubleshoot technological systems. In the present paper I substantiate Lazebnik’s analysis by concretely showing how to apply the engineering approach to biological problems. I use an actual example of electronic circuit (...) troubleshooting to ground the thesis that, in engineering, the crucial phases of any non-trivial troubleshooting process are aimed at generating a mechanistic explanation of the functioning of the system, which makes extensive recourse to problem-driven qualitative reasoning possibly based on cognitive artifacts applied to systems that are known to have been designed for function. To show how to translate these findings into biological practice I consider a concrete example of biological model building and “troubleshooting”, aimed at the identification of a “fix” for the human immune system in presence of progressing cancer, autoimmune disease, and transplant rejection. The result is a novel immune system model—the danger model with regulatory cells— and new, original hypotheses concerning the development, prophylaxis, and therapy of these unwanted biological processes. Based on the manifest efficacy of the proposed approach, I suggest a refocusing of the activity of theoretical biologists along the engineering-inspired lines illustrated in the paper. (shrink)

The importation of computational methods into biology is generating novel methodological strategies for managing complexity which philosophers are only just starting to explore and elaborate. This paper aims to enrich our understanding of methodology in integrative systems biology, which is developing novel epistemic and cognitive strategies for managing complex problem-solving tasks. We illustrate this through developing a case study of a bimodal researcher from our ethnographic investigation of two systems biology research labs. The researcher constructed models of metabolic and cell-signaling (...) pathways by conducting her own wet-lab experimentation while building simulation models. We show how this coupling of experiment and simulation enabled her to build and validate her models and also triangulate and localize errors and uncertainties in them. This method can be contrasted with the unimodal modeling strategy in systems biology which relies more on mathematical or algorithmic methods to reduce complexity. We discuss the relative affordances and limitations of these strategies, which represent distinct opinions in the field about how to handle the investigation of complex biological systems. (shrink)

Scientific knowledge production is currently affected by the dissemination of data on an unprecedented scale. Technologies for the automated production and sharing of vast amounts of data have changed the way in which data are handled and interpreted in several scientific domains, most notably molecular biology and biomedicine. In these fields, the activity of data gathering has become increasingly technology-driven, with machines such as next generation genome sequencers and mass spectrometers generating billions of data points within hours, and with little (...) need for human supervision. Given the relative ease and low costs with which datasets can be produced (that is, once a laboratory has been able to afford .. (shrink)

Evo-Devo exhibits a plurality of scientific “cultures” of practice and theory. When are the cultures acting—individually or collectively—in ways that actually move research forward, empirically, theoretically, and ethically? When do they become imperialistic, in the sense of excluding and subordinating other cultures? This chapter identifies six cultures – three /styles/ (mathematical modeling, mechanism, and history) and three /paradigms/ (adaptationism, structuralism, and cladism). The key assumptions standing behind, under, or within each of these cultures are explored. Characterizing the internal structure of (...) the cultures is necessary for understanding how they collaborate or compete, and how they are fragmented or integrated, in the rich interdisciplinary /trading zone/ (Galison 1997) of Evo-Devo. Evo-Devo is an important example of how science can progress through a radical plurality of perspectives and cultures. (shrink)