Talk of mechanisms is ubiquitous in biology, but the topic has received surprisingly little discussion. These sessions show a growing interest in the topic. In Part I, Jeff Ramsey will explore the relations between models and mechanisms in discoveries about protein folding. Lindley Darden will discuss reasoning strategies for constructing, evaluating, and revising hypothesized mechanisms in molecular biology. Larry Holmes will serve as commentator, drawing on his work on Hans Krebs's discussion of mechanisms in biochemistry. In Part II, Maria Jesus Santesmases will discuss mechanisms of enzyme action. George S. Levit will survey literature in both German and English on "mechanicism" and provide critiques. Stuart Glennan, whose work will be discussed by Levit, will serve as commentator for the session.

Organized by: Lindley Darden
Chair: Joan Straumanis, FIPSE, U.S. Dept. of Education

Jeffry L. Ramsey, Smith College
"Using the Molten Globule Model to Explore the Mechanism of Protein Folding"

Machamer, Darden and Craver (2000) distinguish mechanisms, mechanism schemas and mechanism sketches. In contrast to the first two categories, the last contains placeholders for "entites and activities [that] cannot (yet) be supplied or which contains gaps in its stages." In the study of folding, the so-called "molten globule" model is one of a variety of models that have been proposed as a way to fill in the protein folding sketch we currently possess. The model has come in and out of vogue. Here, I examine the history of the model with an eye towards uncovering how biochemists have argued that a molten globule is or is not a stable, productive intermediate entity in the overall folding process. In particular, I examine the interplay between separate theoretical and experimental lines of enquiry that have led scientists to alternately place the globule on and remove it from the list of possible intermediate structures.

Lindley Darden, University of Maryland
"Discovering Mechanisms in Molecular Biology: Construction, Evaluation, and Revision"

The discovery of mechanisms occurs in cycles of construction, evaluation and revision of hypothesized mechanism sketches and schemata. A new characterization of mechanisms by Machamer, Darden and Craver (Philosophy of Science, March 2000) points to hitherto unexplored aspects of mechanism discovery. Known types of entities and activities in a field provide conceptual resources during reasoning in schema construction. Incomplete sketches have their black boxes filled as research proceeds. Results from experimentation provide evidence for or against mechanism components. When an anomaly requires revision of a hypothesized mechanism schema, different entities and/or activities may be hypothesized to fulfill a functional role in the mechanism. This paper examines the reasoning in this on-going discovery process for mechanisms in molecular biology.

Frederick L. Holmes, Yale University

Commentary

Chair (Part II): TBA

Maria Jesus Santesmases, Instituo de Estudios Sociales Avanzados-Consejo Superior de Investigaciones CientÌficas
"Enzymes as mechanics: the role of enzyme action in the construction of molecular biology and in the survival of biochemical discourse"

The role of enzyme action in the construction of postwar molecular biology is based upon the existence of a discourse among biochemist on their instrumental action in life processes. It comes from the mechanistic view of life promoted among German Phisiologists from the mid-XIX century onwards. From Green (1945) until the decoding work (Kay, 2000), enzymes kept their central role as tools for research, after some decades during which they had been considered candidates for the chemical composition of the genes. However, as Kornberg (1989) put it, there has been not a life process in which enzymes are absent. Biochemists applied succesfully the concept of enzyme action to molecular biology: the mechanism of biological heredity included revisiting biochemist approach to molecular biology so as to include DNA in the whole mechanism of "life production". In the case of molecular biologists, it was exactly the opposite, as they finally accepted enzymes among the biopolymers which intervene in such "life production" mechanism.
A comparative approach to this problem of the mechanism of enzyme action of biochemists and molecular biologist may contribute to discuss how biological and chemical mechanisms of heredity have been constructed and reconstructed, constraint by the trends in biological thought and in research funding in postwar biomedical research in the US.

George S. Levit, Carl von Ossietzky University of Oldenburg
"Some Remarks on Contemporary Mechanicism"

We can distinct three basic "waves" of mechanic philosophy in the ocean of philosophical thinking. The classic Mechanicism was founded by Descartes; the second wave, stimulated by the discoveries in biology in the middle of 19th century, assumed that the problem of life can be completely solved by means of physics and chemistry. The third coming of mechanicism I associate with the school of Constructional Morphology which appeared in Germany in the late sixties and among some contemporary American philosophers. The international and interdisciplinary character of this trend (along with some historically important features) allow us to talk about a Renaissance of the mechanistic paradigm in science and philosophy. [After discussing the German School of Constructional Morphology, Dr. Levit will address "mechanism as a metaphor" and then critique Stuart Glennan's mechanistic theory of causality.]

Stuart Glennan, Butler University

Commentary