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)

Philosophers have committed sins while studying science, it is said – philosophy of science focused on physics to the detriment of biology, reconstructed idealizations of scientific episodes rather than attending to historical details, and focused on theories and concepts to the detriment of experiments. Recent generations of philosophers of science have tried to atone for these sins, and by the 1980s the exculpation was in full swing. Marcel Weber’s Philosophy of Experimental Biology is a zenith mea culpa for philosophy of (...) science: it carefully describes several historical examples from twentieth century biology to address both ‘old’ philosophical topics, like reductionism, inference, and realism, and ‘new’ topics, like discovery, models, and norms. Biology, experiments, history – at last, philosophy of science, free of sin. (shrink)

Recent work on gene concepts has been influenced by recognition of the extent to which RNA transcripts from a given DNA sequence yield different products in different cellular environments. These transcripts are altered in many ways and yield many products based, somehow, on the sequence of nucleotides in the DNA. I focus on alternative splicing of RNA transcripts (which often yields distinct proteins from the same raw transcript) and on 'gene sharing', in which a single gene produces distinct proteins with (...) the exact same amino acid sequence. These are instances of molecular pleiotropy, in which distinct molecules are derived from a single putative gene. In such cases the cellular and external environments play major roles in determining which protein is produced. Where there is molecular pleiotropy, alternative gene concepts are naturally deployed; molecular epigenesis (revision of sequence-based information by altering molecular conformations or by action of non-informational molecules) plays a major role in orderly development. These results show that gene concepts in molecular biology do, and should, have both structural and functional components. They also show the need for a plurality of gene concepts and reveal fundamental difficulties in stabilizing gene concepts solely by reference to nucleotide sequence. (shrink)

Philosophers now treat the relationship between classical genetics and molecular biology as a paradigm of nonreduction and this example is playing an increasingly prominent role in debates about the reducibility of theories in other sciences. This paper shows that the anti-reductionist consensus about genetics will not withstand serious scrutiny. In addition to defusing the main anti-reductionist objections, this critical analysis uncovers tell-tale signs of a significant reduction in progress. It also identifies philosophical issues relevant to gaining a better understanding of (...) what is now happening in genetics and of what we might expect to happen in other sciences. (shrink)

Philosophy of Experimental Biology explores some central philosophical issues concerning scientific research in experimental biology, including genetics, biochemistry, molecular biology, developmental biology, neurobiology, and microbiology. It seeks to make sense of the explanatory strategies, concepts, ways of reasoning, approaches to discovery and problem solving, tools, models and experimental systems deployed by scientific life science researchers and also integrates developments in historical scholarship, in particular the New Experimentalism. It concludes that historical explanations of scientific change that are based on local laboratory (...) practice need to be supplemented with an account of the epistemic norms and standards that are operative in science. This book should be of interest to philosophers and historians of science as well as to scientists. (shrink)

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)

Radically new or unexpected findings in a science demand an openness to new concepts and styles of explanation. The time is more than ripe for asking ourselves what we have learned from the research program of comparative genomics. Where not long ago the human genome was expected to reveal a close association of complexity with the quantitative expansion of the roster of unique genes, more recent findings, especially in relation to comparisons between human and chimp, have raised the bracing possibility (...) that when it comes to complexity, it may be that `less is more'. But `less is more' is not the only observation or inference that follows from the data. The idea of `progressive detachment' will be introduced and set forth as the most perspicuous conceptual resource for unifying and interpreting the overall findings from comparative genomics to date. (shrink)

The historian Raphael Falk has described the gene as a ‘concept in tension’ (Falk 2000) – an idea pulled this way and that by the differing demands of different kinds of biological work. Several authors have suggested that in the light of contemporary molecular biology ‘gene’ is no more than a handy term which acquires a specific meaning only in a specific scientific context in which it occurs. Hence the best way to answer the question ‘what is a gene’, and (...) the only way to provide a truly philosophical answer to that question is to outline the diversity of conceptions of the gene and the reasons for this diversity. In this essay we draw on the extensive literature in the history of biology to explain how the concept has changed over time in response to the changing demands of the biosciences . Finally, we outline some of the conceptions of the gene current today. The seeds of change are implicit in many of those current conceptions and the future of the gene concept looks set to be at as turbulent as the past. (shrink)

Splicing is an efficient and precise mechanism that removes noncoding regions from a single primary RNA transcript. Cutting and rejoining of the segments occurs on nascent RNA. Trans-splicing between small specialized RNAs and a primary transcript has been known in some organisms but recent papers show that trans-splicing between two RNA molecules containing different coding regions is the normal mode in a Drosophila gene.1-3 The mod(mdg4) gene produces 26 different mRNAs encoding as many protein isoforms. The differences lie in alternative (...) 3′ exons encoded by different transcriptional units and spliced to the 5′ common region by a surprising trans-splicing mechanism. BioEssays 24:988–991, 2002. © 2002 Wiley-Periodicals, Inc. (shrink)