This article argues that the basic account of mechanism and mechanistic explanation, involving sequential execution of qualitatively characterized operations, is itself insufficient to explain biological phenomena such as the capacity of living organisms to maintain themselves as systems distinct from their environment. This capacity depends on cyclic organization, including positive and negative feedback loops, which can generate complex dynamics. Understanding cyclically organized mechanisms with complex dynamics requires coordinating research directed at decomposing mechanisms into parts and operations with research using computational (...) models to recompose mechanisms and determine their dynamic behavior. This coordinated endeavor yields dynamic mechanistic explanations. (shrink)

Developing models of biological mechanisms, such as those involved in respiration in cells, often requires collaborative effort drawing upon techniques developed and information generated in different disciplines. Biochemists in the early decades of the 20th century uncovered all but the most elusive chemical operations involved in cellular respiration, but were unable to align the reaction pathways with particular structures in the cell. During the period 1940-1965 cell biology was emerging as a new discipline and made distinctive contributions to understanding the (...) role of the mitochondrion and its component parts in cellular respiration. In particular, by developing techniques for localizing enzymes or enzyme systems in specific cellular components, cell biologists provided crucial information about the organized structures in which the biochemical reactions occurred. Although the idea that biochemical operations are intimately related to and depend on cell structures was at odds with the then-dominant emphasis on systems of soluble enzymes in biochemistry, a reconceptualization of energetic processes in the 1960s and 1970s made it clear why cell structure was critical to the biochemical account. This paper examines how numerous excursions between biochemistry and cell biology contributed a new understanding of the mechanism of cellular respiration. (shrink)

Paul Boyer shared a Nobel Prize in 1997 for his work on the mechanism of ATP synthase. His earlier work, though (which contributed indirectly to his triumph), included major errors, both experimental and theoretical. Two benchmark cases offer insight into how scientists err and how they deal with error. Boyer's work also parallels and illustrates the emergence of bioenergetics in the second half of the twentieth century, rivaling achievements in evolution and molecular biology.

In the 1950s–60s biochemists searched intensively for a series of high-energy molecules in the cell. Although we now believe that these molecules do not exist, biochemists claimed to have isolated or identified them on at least sixteen occasions. The episode parallels the familiar eighteenth-century case of phlogiston, in illustrating how error is not simply the loss of facts but, instead, must be actively constructed. In addition, the debates surrounding each case demonstrate how revolutionary-scale disagreement is sometimes resolved by differentiating or (...) partitioning empirical domains, rather than by replacement of one theory by another. (shrink)

Reductionism encompasses a set of ontological, epistemological, and methodological claims about the relation of different scientific domains. The basic question of reduction is whether the properties, concepts, explanations, or methods from one scientific domain (typically at higher levels of organization) can be deduced from or explained by the properties, concepts, explanations, or methods from another domain of science (typically one about lower levels of organization). Reduction is germane to a variety of issues in philosophy of science, including the structure of (...) scientific theories, the relations between different scientific disciplines, the nature of explanation, the diversity of methodology, and the very idea of theoretical progress, as well as to numerous topics in metaphysics and philosophy of mind, such as emergence, mereology, and supervenience. (shrink)

Most philosophical accounts of emergence are incompatible with reduction. Most scientists regard a system property as emergent relative to properties of the system's parts if it depends upon their mode of organization--a view consistent with reduction. Emergence can be analyzed as a failure of aggregativity--a state in which "the whole is nothing more than the sum of its parts." Aggregativity requires four conditions, giving tools for analyzing modes of organization. Differently met for different decompositions of the system, and in different (...) degrees, these conditions provide powerful evaluation criteria for choosing decompositions, and heuristics for detecting biases of vulgar reductionisms. This analysis of emergence is compatible with reduction. (shrink)

Mitchell's formulation of the chemiosmotic theory of oxidative phosphorylation in 1961 lacked any experimental support for its three central postulates. The path by which Mitchell reached this theory is explored. A major factor was the role of Mitchell's philosophical system conceived in his student days at Cambridge. This system appears to have become a tacit influence on his work in the sense that Polanyi understood all knowledge to be generated by an interaction between tacit and explicit knowing. Early in his (...) life Mitchell had evolved a simple philosophy based on fluctoids, fluctids and statids which was developed in a thesis submitted for the Ph.D. at the University of Cambridge, England. This aspect of his work was rejected by the examiners and became a tacit element in his intellectual development. It is argued from his various publications that this philosophy can be traced as an underlying theme behind much of Mitchell's theoretical writing in the 50's leading, through his notion of vectorial metabolism, to the formulation and amplification of the chemiosmotic theory in the sixties. This philosophy formed the basis for Mitchell of his understanding of biological systems and gave him his unique approach to cell biology. (shrink)

Diagrams make it possible to present scientific facts in more abstract and generalized form. While some detail is lost, simplified and accessible knowledge is gained. E. B. Wilson's work in cytology provides a case study of changing uses of diagrams and accompanying abstraction. In his early work, Wilson presented his data in photographs, which he saw as coming closest to “fact.” As he gained confidence in his interpretations, and as he sought to provide a generalized textbook account of cell development, (...) he relied on increasingly abstract diagrams. In addition, he came to see that highly abstract and even schematic drawings could provide more than pictures directly from life. (shrink)

Proponents of mechanistic explanation all acknowledge the importance of organization. But they have also tended to emphasize specificity with respect to parts and operations in mechanisms. We argue that in understanding one important mode of organization—patterns of causal connectivity—a successful explanatory strategy abstracts from the specifics of the mechanism and invokes tools such as those of graph theory to explain how mechanisms with a particular mode of connectivity will behave. We discuss the connection between organization, abstraction, and mechanistic explanation and (...) illustrate our claims by looking at an example from recent research on so-called network motifs. (shrink)

A historical and critical analysis of the concept of the gene that attempts to provide new perspectives and metaphors for the transformation of biology and its philosophy.

Ideas about heredity and evolution are undergoing a revolutionary change. New findings in molecular biology challenge the gene-centered version of Darwinian theory according to which adaptation occurs only through natural selection of chance DNA variations. In Evolution in Four Dimensions, Eva Jablonka and Marion Lamb argue that there is more to heredity than genes. They trace four "dimensions" in evolution -- four inheritance systems that play a role in evolution: genetic, epigenetic, behavioral, and symbolic. These systems, they argue, can all (...) provide variations on which natural selection can act. Evolution in Four Dimensions offers a richer, more complex view of evolution than the gene-based, one-dimensional view held by many today. The new synthesis advanced by Jablonka and Lamb makes clear that induced and acquired changes also play a role in evolution.After discussing each of the four inheritance systems in detail, Jablonka and Lamb "put Humpty Dumpty together again" by showing how all of these systems interact. They consider how each may have originated and guided evolutionary history and they discuss the social and philosophical implications of the four-dimensional view of evolution. Each chapter ends with a dialogue in which the authors engage the contrarieties of the fictional "I.M.," or Ifcha Mistabra -- Aramaic for "the opposite conjecture" -- refining their arguments against I.M.'s vigorous counterarguments. The lucid and accessible text is accompanied by artist-physician Anna Zeligowski's lively drawings, which humorously and effectively illustrate the authors' points. (shrink)

This book offers a philosophy for error-prone humans trying to understand messy systems in the real world.