My aim in this article is to introduce readers to the topic of exploratory experimentation and briefly explain how the three articles that follow, by Richard Burian, Kevin Elliott, and Maureen O'Malley, advance our understanding of the nature and significance of exploratory research. I suggest that the distinction between exploratory and theory-driven experimentation is multidimensional and that some of the dimensions are continuums. I point out that exploratory experiments are typically theory-informed even if they are not theory-driven. I also distinguish (...) between research programs and experiments. Research programs that are largely exploratory, such as the ones discussed in these case studies, can involve both exploratory and theory-driven experimentation. (shrink)

This paper argues that the consensus physicalist antireductionism in the philosophy of biology cannot accommodate the research strategy or indeed the recent findings of molecular developmental biology. After describing Wolperts programmatic claims on its behalf, and recent work by Gehring and others to identify the molecular determinants of development, the paper attempts to identify the relationship between evolutionary and developmental biology by reconciling two apparently conflicting accounts of bio-function – Wrights and Nagels (as elaborated by Cummins). Finally, the paper seeks (...) a way of defending the two central theses of physicalist antireductionism in the light of the research program of molecular developmental biology, by sharply reducing their metaphysical force. (shrink)

In reworking a variety of biological concepts, Developmental Systems Theory (DST) has made frequent use of parity of reasoning. We have done this to show, for instance, that factors that have similar sorts of impact on a developing organism tend nevertheless to be invested with quite different causal importance. We have made similar arguments about evolutionary processes. Together, these analyses have allowed DST not only to cut through some age-old muddles about the nature of development, but also to effect a (...) long-delayed reintegration of development into evolutionary theory. Our penchant for causal symmetry, however (or 'causal democracy', as it has recently been termed), has sometimes been misunderstood. This paper shows that causal symmetry is neither a platitude about multiple influences nor a denial of useful distinctions, but a powerful way of exposing hidden assumptions and opening up traditional formulations to fruitful change. (shrink)

The concept of mechanism is analyzed in terms of entities and activities, organized such that they are productive of regular changes. Examples show how mechanisms work in neurobiology and molecular biology. Thinking in terms of mechanisms provides a new framework for addressing many traditional philosophical issues: causality, laws, explanation, reduction, and scientific change.

The linear sequence specification of a gene product is not provided by the target DNA sequence alone but by the mechanisms of gene expressions. The main actors of these mechanisms, proteins and functional RNAs, relay environmental information to the genome with important consequences to sequence selection and processing. This `postgenomic' reality has implications for our understandings of development not as predetermined by genes but as an epigenetic process. Critics of genetic determinism have long argued that the activity of `genes' and (...) hence their contribution to the phenotype depends on intra- and extraorganismal `environmental' elements. As will be shown here, even the mere physical existence of a `gene' is dependent on its phenotypic context. (shrink)

We outline three very different concepts of the gene—instrumental, nominal, and postgenomic. The instrumental gene has a critical role in the construction and interpretation of experiments in which the relationship between genotype and phenotype is explored via hybridization between organisms or directly between nucleic acid molecules. It also plays an important theoretical role in the foundations of disciplines such as quantitative genetics and population genetics. The nominal gene is a critical practical tool, allowing stable communication between bioscientists in a wide (...) range of fields grounded in well-defined sequences of nucleotides, but this concept does not embody major theoretical insights into genome structure or function. The post-genomic gene embodies the continuing project of understanding how genome structure supports genome function, but with a deflationary picture of the gene as a structural unit. This final concept of the gene poses a significant challenge to conventional assumptions about the relationship between genome structure and function, and between genotype and phenotype. (shrink)

In this paper I offer an analysis of causation based upon a theory of mechanisms-complex systems whose internal parts interact to produce a system's external behavior. I argue that all but the fundamental laws of physics can be explained by reference to mechanisms. Mechanisms provide an epistemologically unproblematic way to explain the necessity which is often taken to distinguish laws from other generalizations. This account of necessity leads to a theory of causation according to which events are causally related when (...) there is a mechanism that connects them. I present reasons why the lack of an account of fundamental physical causation does not undermine the mechanical account. (shrink)

Explanations in the life sciences frequently involve presenting a model of the mechanism taken to be responsible for a given phenomenon. Such explanations depart in numerous ways from nomological explanations commonly presented in philosophy of science. This paper focuses on three sorts of differences. First, scientists who develop mechanistic explanations are not limited to linguistic representations and logical inference; they frequently employ diagrams to characterize mechanisms and simulations to reason about them. Thus, the epistemic resources for presenting mechanistic explanations are (...) considerably richer than those suggested by a nomological framework. Second, the fact that mechanisms involve organized systems of component parts and operations provides direction to both the discovery and testing of mechanistic explanations. Finally, models of mechanisms are developed for specific exemplars and are not represented in terms of universally quantified statements. Generalization involves investigating both the similarity of new exemplars to those already studied and the variations between them. (shrink)

After the discovery of the structure of DNA in 1953, scientists working in molecular biology embraced reductionism—the theory that all complex systems can be understood in terms of their components. Reductionism, however, has been widely resisted by both nonmolecular biologists and scientists working outside the field of biology. Many of these antireductionists, nevertheless, embrace the notion of physicalism—the idea that all biological processes are physical in nature. How, Alexander Rosenberg asks, can these self-proclaimed physicalists also be antireductionists? With clarity and (...) wit, Darwinian Reductionism navigates this difficult and seemingly intractable dualism with convincing analysis and timely evidence. In the spirit of the few distinguished biologists who accept reductionism—E. O. Wilson, Francis Crick, Jacques Monod, James Watson, and Richard Dawkins—Rosenberg provides a philosophically sophisticated defense of reductionism and applies it to molecular developmental biology and the theory of natural selection, ultimately proving that the physicalist must also be a reductionist. (shrink)

The paper argues against the central dogma and its interpretation by C. Kenneth Waters and Alex Rosenberg. I argue that certain phenomena in the regulation of gene expression provide a break with the central dogma, according to which sequence specificity for a gene product must be template derived. My thesis of 'molecular epigenesis' with its three classes of phenomena, sequence 'activation', 'selection', and 'creation', is exemplified by processes such as transcriptional activation, alternative cis- and trans-splicing, and RNA editing. It argues (...) that other molecular resources share the causal role of genes; the sequence specificity for the linear sequence of any gene product is distributed between the coding sequence, cis-acting sequences, trans-acting factors, environmental signals, and the contingent history of the cell (thesis of distributed causal specificity). I conclude that the central dogma has unnecessarily restricted genetic research to the sequencing of protein-coding genes, unilinear pathway analyses, and the focus on exclusive specificity. (shrink)

The paper describes the change from molecular genetics to postgenomic biology. It focuses on phenomena in the regulation of gene expression that provide a break with the central dogma, according to which sequence specificity for a gene product must be template derived. In its place we find what is called here ‘constitutive molecular epigenesis’. Its three classes of phenomena, which I call sequence ‘activation’, ‘selection’ and ‘creation’, are exemplified by processes such as transcriptional activation, alternative cis- and trans-splicing, and RNA (...) editing. These phenomena support the following main theses of the paper: 1. Other molecular resources share the causal role of ‘genes’: the ‘causal specificity’ for the linear sequence of any gene product is distributed between the coding sequence, cis-acting sequences, trans-acting factors, environmental signals, and the contingent history of the cell (the cellular code) (thesis of distributed causal specificity). 2. These multiple and overlapping processing and targeting mechanisms amplify the repertoire of RNA and protein products specified through the eukaryotic genome, expanding the possibilities specified by the literal code of DNA (thesis of genetic underdeterminism). 3. These mechanisms of gene expression change the focus of postgenomic research from single molecules and their molecular, biochemical and intrinsic function to their cellular, constituent, component or contextual function due to their recruitment and organization in complex cellular networks. In other words, all agents involved in the regulation of gene expression, including DNA, must interact with other agents to achieve full specificity, which is imposed by regulated recruitment and combinatorial control (theses of regulated recruitment and of system analysis). I conclude from these three main theses that the complexity of higher organisms lies not in its number of genes but in the flexibility, versatility and reactivity of its whole genome. (shrink)

Current knowledge about the variety and complexity of the processes that allow regulated gene expression in living organisms calls for a new understanding of genes. A ‘postgenomic’ understanding of genes as entities constituted during genome expression is outlined and illustrated with specific examples that formed part of a survey research instrument developed by two of the authors for an ongoing empirical study of conceptual change in contemporary biology.

The existence claim of a "genetic program" encoded in the DNA molecule which controls biological processes such as development has been examined. Sources of belief in such an entity are found in the rhetoric of Mendelian genetics, in the informationist speculations of Schrodinger and Delbruck, and in the instrumental efficacy found in the use of certain viral, and molecular genetic techniques. In examining specific research models, it is found that attempts at tracking the source of biological control always leads back (...) to the complex state of a cell as a whole, the organizational structure of which is not itself encoded in the DNA. It is argued that the "genetic program" is not an existing biological entity and its philosophical and heuristic status is challenged. (shrink)