This paper is devoted to an examination of the discovery, characterization, and analysis of the functions of microRNAs, which also serves as a vehicle for demonstrating the importance of exploratory experimentation in current (post-genomic) molecular biology. The material on microRNAs is important in its own right: it provides important insight into the extreme complexity of regulatory networks involving components made of DNA, RNA, and protein. These networks play a central role in regulating development of multicellular organisms and illustrate the importance (...) of epigenetic as well as genetic systems in evolution and development. The examination of these matters yields principled arguments for the historicity of the functions of key biological molecules and for the indispensability of exploratory experimentation in contemporary molecular biology as well as some insight into the complex interplay between exploratory experimentation and hypothesis-driven science. This latter result is not only important for philosophy of science, but also of practical importance for the evaluation of grant proposals, although the elaboration of this latter claim must be left for another occasion. (shrink)

Textbook descriptions of the foundations of Genetics give the impression that besides Mendel’s no other research on heredity took place during the nineteenth century. However, the publication of the Origin of Species in 1859, and the criticism that it received, placed the study of heredity at the centre of biological thought. Consequently, Herbert Spencer, Charles Darwin himself, Francis Galton, William Keith Brooks, Carl von Nägeli, August Weismann, and Hugo de Vries attempted to develop theories of heredity under an evolutionary perspective, (...) and they were all influenced by each other in various ways. Nonetheless, only Nägeli became aware of Mendel’s experimental work; it has also been questioned whether Mendel even had the intention to develop a theory of heredity. In this article, a short presentation of these theories is made, based on the original writings. The major aim of this article is to suggest that Mendel was definitely not the only one studying heredity before 1900, if he even did this, as may be inferred by textbooks. Although his work had a major impact after 1900, it had no impact during the latter half of the nineteenth century when an active community of students of heredity emerged. Thus, textbooks should not only present the work of Mendel, but also provide a wider view of the actual history and a depiction of science as a social process. (shrink)

In this paper I respond to Wim van der Steen''s arguments against the supposed current overemphasis on norms ofcoherence andinterdisciplinary integration in biology. On the normative level, I argue that these aremiddle-range norms which, although they may be misapplied in short-term attempts to solve (temporarily?) intractable problems, play a guiding role in the longer-term treatment of biological problems. This stance is supported by a case study of apartial success story, the development of the one gene — one enzyme hypothesis. As (...) that case shows, thegoal of coherent interdisciplinary integration not only provides guidance for research, but also provides the standard for recognizingfailed integrations of the sort that van der Steen criticizes. (shrink)

Summary In 1979, Robert C. Olby published an article titled ?Mendel no Mendelian??, in which he questioned commonly held views that Gregor Mendel (1822?1884) laid the foundations for modern genetics. According to Olby, and other historians of science who have since followed him, Mendel worked within the tradition of so-called hybridists, who were interested in the evolutionary role of hybrids rather than in laws of inheritance. We propose instead to view the hybridist tradition as an experimental programme characterized by a (...) dynamic development that inadvertently led to a focus on the inheritance of individual traits. Through a careful analysis of publications on hybridization by Carl Linnaeus (1707?1778), Joseph Gottlieb Koelreuter (1733?1806), Carl Friedrich Gärtner (1772?1850), and finally Mendel himself, we will show that this development consisted in repeated reclassifications of hybrids to accommodate anomalies, which in the end allowed Mendel to draw analogies between whole organisms, individual traits, and ?elements? contained in reproductive cells. Mendel's achievement was a product of normal science, and yet a revolutionary step forward. This also explains why, in 1900, when the report he gave on his experiments was ?rediscovered?, Mendel could be read as a ?Mendelian? (shrink)

In this study we have examined the reception of Mendelism in France from 1900 to 1940, and the place of some of the extra-Mendelian traditions of research that contributed to the development of genetics in France after World War II.

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)

The discovery and ongoing investigation of microRNAs suggest important conceptual and methodological lessons for philosophers and historians of biology. This paper provides an account of miRNA research and the shift from viewing these tiny regulatory entities as minor curiosities to seeing them as major players in the post-transcriptional regulation of genes. Conceptually, the study of miRNAs is part of a broader change in understandings of genetic regulation, in which simple switch-like mechanisms were reinterpreted as aspects of complex cellular and genome-wide (...) processes. Among them are the activities of small RNAs, previously regarded as non-functional. Methodologically, the miRNA story suggests new ways of characterizing biological research that should prove helpful to philosophers of science who seek to develop more pluralistic, pragmatic models of scientific inquiry. miRNA research displays iterative movements between multiple modes of investigation that include not only the proposal and testing of hypotheses but also exploratory, technology-oriented and question-driven modes of research. As an exemplary story of scientific discovery and development, the miRNA case illustrates transitions from genetics to genomics and systems biology, and it shows how diverse configurations of research practice are related to major scientific advances. (shrink)