Reasoning in Biological Discoveries brings together a series of essays, which focus on one of the most heavily debated topics of scientific discovery. Collected together and richly illustrated, Darden's essays represent a groundbreaking foray into one of the major problems facing scientists and philosophers of science. Divided into three sections, the essays focus on broad themes, notably historical and philosophical issues at play in discussions of biological mechanism; and the problem of developing and refining reasoning strategies, including interfield relations and (...) anomaly resolution. Darden summarizes the philosophy of discovery and elaborates on the role that mechanisms play in biological discovery. Throughout the book, she uses historical case studies to extract advisory reasoning strategies for discovery. Examples in genetics, molecular biology, biochemistry, immunology, neuroscience and evolutionary biology reveal the process of discovery in action. (shrink)

The mechanistic perspective has dominated biological disciplines such as biochemistry, physiology, cell and molecular biology, and neuroscience, especially during the 20th century. The primary strategy is reductionist: organisms are to be decomposed into component parts and operations at multiple levels. Researchers adopting this perspective have generated an enormous body of information about the mechanisms of life at scales ranging from the whole organism down to genetic and other molecular operations.

There are two fundamentally distinct kinds of biological theorizing. "Formal biology" focuses on the relations, captured in formal laws, among mathematically abstracted properties of abstract objects. Population genetics and theoretical mathematical ecology, which are cases of formal biology, thus share methods and goals with theoretical physics. "Compositional biology," on the other hand, is concerned with articulating the concrete structure, mechanisms, and function, through developmental and evolutionary time, of material parts and wholes. Molecular genetics, biochemistry, developmental biology, (...) and physiology, which are examples of compositional biology, are in serious need of philosophical attention. For example, the very concept of a "part" is understudied in both philosophy of biology and philosophy of science. ;My dissertation is an attempt to clarify the distinction between formal biology and compositional biology and, in so doing, provide a clear philosophical analysis, with case studies, of compositional biology. Given the social, economic, and medical importance of compositional biology, understanding it is urgent. For my investigation, I draw on the philosophical fields of metaphysics and epistemology, as well as philosophy of biology and philosophy of science. I suggest new ways of thinking about some classic philosophy of science issues, such as modeling, laws of nature, abstraction, explanation, and confirmation. I hint at the relevance of my study of two kinds of biological theorizing to debates concerning the disunity of science. (shrink)

Recent advances in molecular genetics, plant physiology, and biochemistry have opened up the new biotechnology of herbicide resistant crops (HRCs). Herbicide resistant crops have been characterized as the solution for many environmental problems associated with modern crop production, being described as powerful tools for farmers that may increase production options. We are concerned that these releases are occurring in the absence of forethought about their impact on agroecosystems, the broader landscape, and the rural and urban economies and (...) cultures. Many of the benefits and risks associated with HRCs are not apparent to either the public, farmers, policy makers, or the scientific community. HRC technology raises moral issues in three areas: our duties toward the natural environment; our political and economic responsibilities to each other; and our communal character as one generation among many. We also need a rational basis on which to make evaluations of this new biotechnology. The technical aspects of their release require a logical guide to the ecological, environmental, and biological effects the release might have in sustainable agroecosystems. The initial step should include an assessment of the intrinsic qualities of the crop, the herbicide, and the resistance mechanisms. The second step should include an assessment of effects associated with population ecology, population genetics, environmental degradation, consumer health, and farm economic viability due to the resistant crop-herbicide pair. Herbicides have been used in crop production for nearly a half a century. There has been a tremendous increase in the use of these chemicals in that time. Society has seen the use of these chemicals not only help to feed many people, but also to bring costs not anticipated before the introduction of the chemicals. We need to draw on that long history of use and learn the lessons it can provide us as we approach the introduction and commercialization of the next generation of weed control technology, herbicide resistant crops. We also need to reflect on the lessons we missed during that half century because we spend more time imagining the possible benefits that would come from the technology than scrutinizing the possible harm. (shrink)

First the ‘Weismann barrier’ and later on Francis Crick’s ‘central dogma’ of molecular biology nourished the gene-centric paradigm of life, i.e., the conception of the gene/genome as a ‘central source’ from which hereditary specificity unidirectionally flows or radiates into cellular biochemistry and development. Today, due to advances in molecular genetics and epigenetics, such as the discovery of complex post-genomic and epigenetic processes in which genes are causally integrated, many theorists argue that a gene-centric conception of the (...) organism has become problematic. Here, we first explore the causal implications of the following two central dogma-related issues: (1) widespread reverse transcription—arguing for an extension from ‘DNA-genome’ to RNA-encompassing ‘NA-genome’ and, thus, from traditional DNA-centrism to a broader ‘NA-centrism’; and (2) the absence of a mechanism of reverse translation—arguing for the ‘structural primacy’ of NA-sequence over protein in cellular biochemistry. Secondly, we explore whether this latter conclusion can be extended to a ‘functional primacy’ of NA-sequence over protein in cellular biochemistry, which would imply a limited kind of ‘gene/NA-centrism’ confined to the subcellular level of NA/protein-based biochemistry. Finally, we explore the conditions—and their (non)fulfilment—for a more generalised form of gene-centrism extendable to higher levels of biological organisation. We conclude that the higher we go in the biological hierarchy, the more dubious gene-centric claims become. (shrink)

What is attention? How does it go wrong? Do attention deficits arise from genes or from the environment? Can we cure it with drugs or training? Are there disorders of attention other than deficit disorders? The past decade has seen a burgeoning of research on the subject of attention. This research has been facilitated by advances on several fronts: New methods are now available for viewing brain activity in real time, there is expanding information on the complexities of the (...) class='Hi'>biochemistry of neural activity, individual genes can be isolated and their functions identified, analysis of the component processes included under the broad umbrella of "attention" has become increasingly sophisticated, and ingenious methods have been devised for measuring typical and atypical development of these processes, from infancy into childhood, and then into adulthood. In this book, Kim Cornish and John Wilding are concerned with attention and its development, both typical and atypical, particularly in disorders with a known genetic etiology or assumed genetic linkage. Tremendous advances across seemingly diverse disciplines - molecular genetics, pediatric neurology, child psychiatry, developmental cognitive neuroscience, and education - have culminated in a wealth of new methods for elucidating disorders at multiple levels, possibly paving the way for new treatment options. Cornish and Wilding use three specific-yet-interlinking levels of analysis: genetic blueprint, the developing brain, and the behavioral-cognitive outcomes, as the basis for charting the attention profiles of six well-documented neurodevelopmental disorders: ADHD, autism, fragile X syndrome, Down syndrome, Williams syndrome, and 22q11 deletion syndrome. Their overarching aim in this book is to provide the most authoritative and extensive account to date of disorder-specific attention profiles and their development from infancy through adolescence. (shrink)

What is attention? How does it go wrong? Do attention deficits arise from genes or from the environment? Can we cure it with drugs or training? Are there disorders of attention other than deficit disorders? The past decade has seen a burgeoning of research on the subject of attention. This research has been facilitated by advances on several fronts: New methods are now available for viewing brain activity in real time, there is expanding information on the complexities of the (...) class='Hi'>biochemistry of neural activity, individual genes can be isolated and their functions identified, analysis of the component processes included under the broad umbrella of "attention" has become increasingly sophisticated, and ingenious methods have been devised for measuring typical and atypical development of these processes, from infancy into childhood, and then into adulthood. In this book, Kim Cornish and John Wilding are concerned with attention and its development, both typical and atypical, particularly in disorders with a known genetic etiology or assumed genetic linkage. Tremendous advances across seemingly diverse disciplines - molecular genetics, pediatric neurology, child psychiatry, developmental cognitive neuroscience, and education - have culminated in a wealth of new methods for elucidating disorders at multiple levels, possibly paving the way for new treatment options. Cornish and Wilding use three specific-yet-interlinking levels of analysis: genetic blueprint, the developing brain, and the behavioral-cognitive outcomes, as the basis for charting the attention profiles of six well-documented neurodevelopmental disorders: ADHD, autism, fragile X syndrome, Down syndrome, Williams syndrome, and 22q11 deletion syndrome. Their overarching aim in this book is to provide the most authoritative and extensive account to date of disorder-specific attention profiles and their development from infancy through adolescence. (shrink)

The concepts of hierarchical organization, genetic determinism and biological specificity have played a crucial role in biology as a modern experimental science since its beginnings in the nineteenth century. The idea of genetic information and genetic determination was at the basis of molecular biology that developed in the 1940s with macromolecules, viruses and prokaryotes as major objects of research often labelled “reductionist”. However, the concepts have been marginalized or rejected in some of the research that in the late 1960s (...) began to focus additionally on the molecularization of complex biological structures and functions using systems approaches. This paper challenges the view that ‘molecular reductionism’ has been successfully replaced by holism and a focus on the collective behaviour of cellular entities. It argues instead that there are more fertile replacements for molecular ‘reductionism’, in which genomics, embryology, biochemistry, and computer science intertwine and result in research that is as exact and causally predictive as earlier molecular biology. (shrink)

The concepts of hierarchical organization, genetic determinism and biological specificity have played a crucial role in biology as a modern experimental science since its beginnings in the nineteenth century. The idea of genetic information and genetic determination was at the basis of molecular biology that developed in the 1940s with macromolecules, viruses and prokaryotes as major objects of research often labelled “reductionist”. However, the concepts have been marginalized or rejected in some of the research that in the late 1960s (...) began to focus additionally on the molecularization of complex biological structures and functions using systems approaches. This paper challenges the view that ‘molecular reductionism’ has been successfully replaced by holism and a focus on the collective behaviour of cellular entities. It argues instead that there are more fertile replacements for molecular ‘reductionism’, in which genomics, embryology, biochemistry, and computer science intertwine and result in research that is as exact and causally predictive as earlier molecular biology. (shrink)

This paper investigated the part played by collaborative practices in chaneling the work of prominent biochemists into the development of molecular biology. The RNA collaborative network that emerged in the 1960s in France encompassed a continuum of activities that linked laboratories to policy-making centers. New institutional frameworks such as the DGRST committees were instrumental in establishing new patterns of funding, and in offering arenas for multidisciplinary debates and boundary assessment. It should be stressed however, that although this collaborative network (...) was based on centralized initiatives aimed at developing molecular biology as a new biological specialty, it operated above all as a nexus of practices. The main argument of this paper is that the central allocation of funds and resources, exemplified by the DGRST operation, actually enhanced the creation of a self-conscious community of biochemists turned molecular biologists by virtue of an increased circulation of tools, skills, and results that took place within the RNA network and a few analogous systems of exchange.Having hands on “things” viewed as identical for all practical purposes was a potent factor in changing the experimental systems and their meanings. Limited but shared means of doing helped to reduce uncertainties, change representations, and turn contingent decisions into meaningful choices. The collaborative enterprises then resulted in personal contacts and the transfer of skills and materials, which gradually incorporated the biochemical tools into systems producing facts relevant to molecular biology as defined by its early practitioners. In that sense, networking was a regulatory process that stabilized new research objects and acculturated French biochemists.The mere existence of such a collaborative network also changed the scale of the disciplining process. Collaborations may have been started for contingent motives, but multiple exchanges resulted in the emergence of a new collective, and amplified small displacements. Collaborations, however, worked both ways, and the RNA network may be viewed as an efficient “trading-post.” An unexpected outcome of the development of a conversion zone is the fact that, by the late 1960s, the former biochemists dominated the “new” world of molecular biology — both in terms of research habits, since interests in structural studies dominated the field, and in terms of institutional initiatives such as the creation of laboratories and institutes for molecular biology.As an example of the cognitive displacements achieved by the network, I have focused here on the stabilization of “messenger RNA” as a new biological entity. This process illustrates the role of “boundary objects” and other mediating innovations in the development of disciplinary structures. Students of science trained in the symbolic interactionism tradition have proposed that “boundary objects” enhance the multiple interactions between heterogeneous social worlds: they are robust enough to enhance unity, but plastic enough to be manipulated in different social and cultural contexts.81 Within the emerging network, messenger RNA was a weakly structured “genetic information carrier” in common use, but it could, at the same time, be a strongly structured “macromolecular structure” adapted to practical and local uses. Consequently, messenger RNA favored the association of groups of heterogeneous scientists with backgrounds and interests in medical biochemistry, genetics, physical chemistry, organic chemistry, and so forth. This contrast between general and local uses was also instrumental in integrating the manipulation of things and the negotiation of aims. In contrast to transfer RNAs, which in the French context remained objects for chemical (and mainly structural) studies, messenger RNA became a key component of the new culture of “genetic information”. Messenger RNA was a loose theoretical entity described as a “genetic information carrier” in the policy-making documents, while operational but tacit and more conflicting definitions prevailed at the bench. In other words, messenger RNA was not only a classical “boundary object” but also a “flag object,” which tightened the collaborative network by mediating between the DGRST offices and the laboratories. (shrink)

The desire to understand the mathematics of living systems is increasing. The widely held presupposition that the mathematics developed for modeling of physical systems as continuous functions can be extended to the discrete chemical reactions of genetic systems is viewed with skepticism. The skepticism is grounded in the issue of scientific invariance and the role of the International System of Units in representing the realities of the apodictic sciences. Various formal logics contribute to the theories of biochemistry and (...) class='Hi'>molecular biology and genetics. Various paths of extension are invoked in these formal logics in order to express the information of biological apodicticism. Symbolizing the appropriate notations for invariant relations and for biological extensions of relations is fundamental to the exact generating functions of discrete algebraic biology. Aspects of philosophical perspectives of the relation scientific number systems are contrasted. The deep distinction between physical motion and biological motion is expressed in terms the roles of Aristotelian causes. The interior motion within perplex numbers is contrasted with the exterior motion of physical systems. The need for a new mathematics for biology is suggested. (shrink)

To ensure their survival in natural habitats, plants must recognize and respond to a wide variety of insect herbivores. Aphids and other Hemiptera pose a particular challenge, because they cause relatively little direct tissue damage when inserting their slender stylets intercellularly to feed from the phloem sieve elements. Plant responses to this unusual feeding strategy almost certainly include recognition of aphid salivary components and the induction of phloem‐specific defenses. Due to the excellent genetic and genomic resources that are available for (...) Arabidopsis thaliana (Arabidopsis), this plant was chosen as a model system to study the metabolic and transcriptional responses to infestation by two aphids, Myzus persicae (green peach aphid, a broad generalist) and Brevicoryne brassicae (cabbage aphid, a crucifer‐feeding specialist). Future research on Arabidopsis–aphid interactions will lead to the identification of aphid‐specific elicitors, components of the defense‐signaling pathway, and additional metabolic responses that are induced by aphid infestation. BioEssays 29:871–883, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

An increasing number of non-model organisms are becoming accessible to genetic analysis in the field, as evolutionary biologists develop dense molecular genetic maps. Peichel et al.'s recent study[1] provides a microsatellite-based map for threespine stickleback fish (Gasterosteus aculeatus), and the first evidence for QTL affecting feeding morphology and defensive armor. This species has undergone rapid and parallel morphological and behavioral evolution, and there is now hope that some of the genes responsible for the divergence may soon be identified. BioEssays (...) 24:487-489, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

The discovery of RNA interference in 1998 has made a lasting impact on biological research. Identifying the regulatory role of small RNAs changed the modes of molecular biological inquiry as well as biologists' understanding of genetic regulation. This article examines the early years of small RNA biology's success story. I query which factors had to come together so that small RNA research came into life in the blink of an eye. I primarily look at scientific repertoires as facilitators of (...) rapid scientific change. I show that for a short period of time, between the years 1998 and 2002, different model organism communities, investigative strategies, technological innovations, and research interests could be successfully aligned to take small RNA research off the ground. I discuss how the keystone discoveries were situated in specific experimental traditions and what strategies were employed to establish these discoveries as more general phenomena. Providing thus a practice-based approach of rapid scientific change, I ask how to relate the change in propositional bits of scientific knowledge with changes in scientific practice. (shrink)

The autosomal recessive genetic disease, Fanconi anaemia, is perceived as another manifestation of defective cellular DNA repair, just as in the autosomal recessive disease Xeroderma pigmentosum. The biochemistry and cellular biology of Xeroderma pigmentosum have been convincingly elucidated, but the same has not been true for Fanconi anaemia. In this review we consider the pleiotropic nature of Fanconi anaemia, its clinical and cellular variability and its genetic heterogeneity. We take into account the wealth of experimental findings available and offer (...) a novel hypothesis involving feedback control of DNA replication during S phase of the cell cycle to explain the basic defect in the disease. (shrink)

The cellular machinery responsible for conveying proteins between the endoplasmic reticulum and the Golgi is being investigated using genetics and biochemistry. A role for vesicles in mediating protein traffic between the ER and the Golgi has been established by characterizing yeast mutants defective in this process, and by using recently developed cell‐free assays that measure ER to Golgi transport. These tools have also allowed the identification of several proteins crucial to intracellular protein trafficking. The characterization and possible functions (...) of several GTP‐binding proteins, peripheral membrane proteins, and an integral membrane protein during ER to Golgi transport are discussed here. (shrink)

Eukaryotic cells are able to mount several genetically complex cellular responses to DNA damage. The yeast Saccharomyces cerevisiae is a genetically well characterized organism that is also amenable to molecular and biochemical studies. Hence, this organism has provided a useful and informative model for dissecting the biochemistry and molecular biology of DNA repair in eukaryotes.

The basic premise of today's scientific medicine is that the ‘book of man’ is written in the language of the biological sciences, ultimately molecular genetics and biochemistry. The patient is a complex biological organism and disease is a deviation from the norm of somatic parameters. At the same time, many major contemporary diseases are reported to have psychosocial and environmental components in their etiology. Hence the challenge: how can a medical model be both scientific and conceptually well-suited (...) to today's disease burden? I argue that certain contemporary "postmodern" sciences support alternative, non-reductionist (self-organizational) premises. So doing, they offer an infrastructure for a medical model at once scientific and responsive to the diseases at hand. Keywords: biomedicine (biological medicine), natural science paradigm, Cartesian dualism, self-organization, postmodern sciences, self-referentiality CiteULike Connotea Del.icio.us What's this? (shrink)

Ludwik Fleck, Edmund Husserl : on the historicity of scientific knowledge -- Gaston Bachelard : the concept of "phenomenotechnique" -- Georges Canguilhem : epistemological history -- Pisum : Carl Correns's experiments on Xenia, 1896-99 -- Eudorina : Max Hartmann's experiments on biological regulation in protozoa, 1914-21 -- Ephestia : Alfred Kähn's experimental design for a developmental physiological -- Genetics, 1924-45 -- Tobacco mosaic virus : virus research at the Kaiser Wilhelm Institutes for Biochemistry and Biology, 1937-45 -- The (...) concept of the gene : molecular biological perspectives -- The liquid scintillation counter : traces of radioactivity -- The concept of information : the writings of François Jacob -- Intersections -- Preparations -- The economy of the scribble. (shrink)

Avery’s et al. ’s 1944 paper provides the first direct evidence of DNA having gene-like properties and marks the beginning of a new phase in early molecular genetics (with a strong focus on chemistry and DNA). The study of its reception shows that on the whole, Avery’s results were immediately appreciated and motivated new research on transformation, the chemical nature of DNA’s biological specificity and bacteria genetics. It shows, too, that initial problems of transferring transformation to other (...) systems and prominent criticism of its results nurtured skepticism. Avery’s experiment was downplayed and neglected particularly by many of those scientists who worked in the new fields of biochemical and biophysical genetics, genetic phage, and TMV research. This was not due to the fact that the implications of the paper could not be connected to generally accepted knowledge. Contrary to a widespread belief, the assumed uniformity of DNA as opposed to proteins was not used as an argument against the validity of Avery’s et al.’s finding. The indifference rather reflected, among other things, the disciplinary gap between the chemically oriented microbiologists and the old and new geneticists who remained committed to genetic and physical methods (in particular x-ray studies) and clung to the assumption that proteins were the sole carriers of biological specificity. The responses to Avery’s et al.’s paper show how different research interests in the areas between microbiology, genetics, and biochemistry interacted with the prejudices, dogmas, individual farsightedness or short-sightedness, and scientific authority during a pivotal period of early molecular biology. (shrink)

The multiple activities of the RecA protein in DNA metabolism have inspired over a decade of research in dozens of laboratories around the world. This effort has nevertheless failed to yield an understanding of the mechanism of several RecA protein‐mediated processes, the DNA strand exchange reactions prominent among them. The major factors impeding progress are the invalid constraints placed upon the problem by attempting to understand RecA protein‐mediated DNA strand exchange within the context of an inappropriate biological paradigm – namely, (...) homologous genetic recombination as a mechanism for generating genetic diversity. In this essay I summarize genetic and biochemical data demonstrating that RecA protein evolved as the central component of a recombinational DNA repair system, with the generation of genetic diversity being a sometimes useful byproduct, and review the major in vitro activities of RecA protein from a repair perspective. While models proposed for both recombination and recombinational repair often make use of DNA strand cleavage and transfer steps that appear to be quite similar, the molecular and thermodynamic requirements of the two processes are very different. The recombinational repair function provides a much more logical and informative framework for thinking about the biochemical properties of RecA and the strand exchange reactions it facilitates. (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)

Historians of biology have argued that much of the dynamics of experimental disciplines such as genetics or molecular biology can be understood from studying experimental systems and model organisms alone . Such accounts contrast sharply with more traditional philosophies of science which viewed scientific research essentially as a process of inventing and testing theories. I present a case from the history of biochemistry which can be viewed from both the experimental systems perspective and from the methodology of (...) theory testing. I argue that not only are the two perspectives fully compatible, but they are both necessary for a complete account of the research process. (shrink)

John Burdon Sanderson Haldane was a giant among men. He made major contributions to genetics, population biology, and evolutionary theory. He was at once comfortable in mathematics, chemistry, microbiology and animal physiology. But it was his belief in education that led to his preparing his popular essays for publication. In his own words: "Many scientific workers believe that they should confine their publications to learned journals. I think that the public has a right to know what is going on (...) inside the laboratories, for some of which it pays." So begins Haldane's collection of essays, perhaps the most public intellectual communicating science before the writings of Stephen Jay Gould. The first part of the volume emphasizes the important developments in biology and natural science in the first quarter of the century. As such, it provides a benchmark for studies of the next three quarters of the century. In an unusual introduction, Price takes the readers through their paces, discussing the situation then and now in vitamins, oxygen want, disease controls, and the rewards of science as such. This is followed by Haldane's views on society, art, religion and economy as seen through the eyes of a politically alert major scientist. The editor provides readers unfamiliar with Haldane with a carefully rendered chronology of a life that began in 1892 and that spanned much of the present century. Despite ideas on race, class and politics that have seen better times, Haldane was truly exceptional in translating the science of his time into ideas that "everyman" could readily grasp. His predictions on what science would achieve were on target far more often than not. But even his failed predictions are perhaps the most interesting of all. They throw into sharp relief the truly novel and revolutionary developments in science over the past 75 years. J.B.S. Haldane held many positions and received many honors during his lifetime. But for most of the period covered in this volume, he was the William Dunn Reader in Biochemistry at Cambridge University. He simultaneously served as Fellow of New College, in Oxford University's Horticultural Institute. Carl A. Price served until 1999 as professor IIof plant molecular biology in the Waksman Institute of Microbiology at Rutgers, the State University of New Jersey. He also served as the editor of Plant Molecular Biology Reporter from 1983 until 1997. This is the first volume in a new series on the history and theory of science. (shrink)

Several models of macromolecular arrangements in eukaryotic chromosomes have been proposed during the past fifteen years. Many of the models are consistent with physical and chemical data on the molecular components of chromosomes, and a few have the appearance of meeting the requirements for cytological organization in chromosomes. However, one of the most frustrating problems in developing a working model is to provide a scheme that fits genetic function while satisfying the structural parameters. This has not yet been achieved.Although (...) emphasis in this review has been placed on uninemic and polynemic models, alternatives, such as a bineme, for example, remain. It is clear, moreover, that the issue can be resolved only through continued efforts to make direct observations of chromosomes with light and electron microscopy coupled with the additional tools ofX-ray analysis and analytical biochemistry. A recent analysis byWray andStubblefield has led to a rather innovative model of the chromosome, and exemplifies the kind of approach needed to clarify the phenomenon. Furthermore, analyses of meiotic chromosomes may provide valuable insight for relating organization to genetic function . Of particular interest are mutation events as related to subchromatid organization, and the reorganization of chromosomal fibrils during early meiotic stages. At present, and as a generalization, the evidence points more strongly toward at least a binemic arrangement of chromosomal subunits than toward a uninemic one. (shrink)

High blood pressure is a disease of unknown cause. Family history of the disease indicates higher risk, but it is not known which genes are involved or how they interact with environmental influences to produce the disorder. Molecular biology offers an approach to problems that have not so far been solved by classical physiology or biochemistry. By analysing polymorphic variation in chromosome markers such as minisatellite sequences, or by restriction fragment polymorphism analysis of candidate genes, attempts are being (...) made to link genetic variations with hypertension. In genetically hypertensive rats, hypertension is associated with a polymorphism of the renin gene and with other loci on chromosomes 10 and 18. The role of these loci in human hypertension remains to be determined. Other genes such as sodium‐lithium countertransport may be involved. Environmental factors such as stress or salt intake could influence the rate or timing of expression of certain genes and thus result in hypertension. (shrink)

Until recently, sex determination in mammals has often been described as a male determination process, with male differentiation being the active and dominant pathway, and only in its absence is the passive female pathway followed. This picture has been challenged recently with the discovery that the gene encoding R-spondin1 is mutated in human patients with female-to-male sex reversal.((1)) These findings might place R-spondin1 in the exceptional position of being the female-determining gene in mammals. In this review, possible roles of R-spondin1 (...) during sex determination as well as questions arising from this study will be discussed. (shrink)

The central dogma of biology holds that genetic information normally flows from DNA to RNA to protein. As a consequence it has been generally assumed that genes generally code for proteins, and that proteins fulfil not only most structural and catalytic but also most regulatory functions, in all cells, from microbes to mammals. However, the latter may not be the case in complex organisms. A number of startling observations about the extent of non-protein-coding RNA (ncRNA) transcription in the higher eukaryotes (...) and the range of genetic and epigenetic phenomena that are RNA-directed suggests that the traditional view of the structure of genetic regulatory systems in animals and plants may be incorrect. ncRNA dominates the genomic output of the higher organisms and has been shown to control chromosome architecture, mRNA turnover and the developmental timing of protein expression, and may also regulate transcription and alternative splicing. This paper re-examines the available evidence and suggests a new framework for considering and understanding the genomic programming of biological complexity, autopoletic development and phenotypic variation. BioEssays 25:930-939,2003. (C) 2003 Wiley Periodicals, Inc. (shrink)