Philosophers of science diverge on the question what drives the growth of scientific knowledge. Most of the twentieth century was dominated by the notion that theories propel that growth whereas experiments play secondary roles of operating within the theoretical framework or testing theoretical predictions. New experimentalism, a school of thought pioneered by Ian Hacking in the early 1980s, challenged this view by arguing that theory-free exploratory experimentation may in many cases effectively probe nature and potentially spawn higher evidence-based theories. Because (...) theories are often powerless to envisage workings of complex biological systems, theory-independent experimentation is common in the life sciences. Some such experiments are triggered by compelling observation, others are prompted by innovative techniques or instruments, whereas different investigations query big data to identify regularities and underlying organizing principles. A distinct fourth type of experiments is motivated by a major question. Here I describe two question-guided experimental discoveries in biochemistry: the cyclic adenosine monophosphate mediator of hormone action and the ubiquitin-mediated system of protein degradation. Lacking underlying theories, antecedent data bases, or new techniques, the sole guides of the two discoveries were respective substantial questions. Both research projects were similarly instigated by theory-free exploratory experimentation and continued in alternating phases of results-based interim working hypotheses, their examination by experiment, provisional hypotheses again, and so on. These two cases designate theory-free, question-guided, stepwise biochemical investigations as a distinct subtype of the new experimentalism mode of scientific enquiry. (shrink)

This article on the epistemology of computational models stems from an analysis of the Gaia hypothesis (GH). It begins with James Kirchner’s criticisms of the central computational model of GH: Daisyworld. Among other things, the model has been criticized for being too abstract, describing fictional entities (fictive daisies on an imaginary planet) and trying to answer counterfactual (what-if) questions (how would a planet look like if life had no influence on it?). For these reasons the model has been considered not (...) testable and therefore not legitimate in science, and in any case not very interesting since it explores non actual issues. This criticism implicitly assumes that science should only be involved in the making of models that are ‘‘actual’’ (by opposition to what-if) and ‘‘specific’’ (by opposition to abstract). I challenge both of these criticisms in this article. First by showing that although the testability—understood as the comparison of model output with empirical data—is an important procedure for explanatory models, there are plenty of models that are not testable. The fact that these are not testable (in this restricted sense) has nothing to do with their being ‘‘abstract’’ or ‘‘what-if’’ but with their being predictive models. Secondly, I argue that ‘‘abstract’’ and ‘‘what-if’’ models aim at (respectable) epistemic purposes distinct from those pursued by ‘‘actual and specific models’’. Abstract models are used to propose how-possibly explanation or to pursue theorizing. What-if models are used to attribute causal or explanatory power to a variable of interest. The fact that they aim at different epistemic goals entails that it may not be accurate to consider the choice between different kinds of model as a ‘‘strategy‘‘. (shrink)

This article on the epistemology of computational models stems from an analysis of the Gaïa hypothesis. It begins with James Kirchner’s criticisms of the central computational model of GH: Daisyworld. Among other things, the model has been criticized for being too abstract, describing fictional entities and trying to answer counterfactual questions. For these reasons the model has been considered not testable and therefore not legitimate in science, and in any case not very interesting since it explores non actual issues. This (...) criticism implicitly assumes that science should only be involved in the making of models that are “actual” and “specific”. I challenge both of these criticisms in this article. First by showing that although the testability—understood as the comparison of model output with empirical data—is an important procedure for explanatory models, there are plenty of models that are not testable. The fact that these are not testable has nothing to do with their being “abstract” or “what-if” but with their being predictive models. Secondly, I argue that “abstract” and “what-if” models aim at epistemic purposes distinct from those pursued by “actual and specific models”. Abstract models are used to propose how-possibly explanation or to pursue theorizing. What-if models are used to attribute causal or explanatory power to a variable of interest. The fact that they aim at different epistemic goals entails that it may not be accurate to consider the choice between different kinds of model as a “strategy“. (shrink)

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in (...) this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined. (shrink)