Model organisms became an indispensable part of experimental systems in molecular developmental and cell biology, constructed to investigate physiological and pathological processes. They are thought to play a crucial role for the elucidation of gene function, complementing the sequencing of the genomes of humans and other organisms. Accordingly, historians and philosophers paid considerable attention to various issues concerning this aspect of experimental biology. With respect to the representational features of model organisms, that is, their status as models, the (...) main focus was on generalization of phenomena investigated in such experimental systems. Model organisms have been said to be models for other organisms or a higher taxon. This, however, presupposes a representation of the phenomenon in question. I will argue that prior to generalization, model organisms allow researchers to built generative material models of phenomena – structures, processes or the mechanisms that explain them – through their integration in experimental set-ups that carve out the phenomena from the whole organism and thus represent them. I will use the history of zebrafish biology to show how model organism systems, from around 1970 on, were developed to construct material models of molecular mechanisms explaining developmental or physiological processes. (shrink)

Chelicerates (scorpions, horseshoe crabs, spiders, mites and ticks) are the second largest group of arthropods and are of immense importance for fundamental and applied science. They occupy a basal phylogenetic position within the phylum Arthropoda, and are of crucial significance for understanding the evolution of various arthropod lineages. Chelicerates are vectors of human diseases, such as ticks, and major agricultural pests, such as spider mites, thus this group is also of importance for both medicine and agriculture. The developmental genetics (...) of chelicerates is poorly understood and a challenge for the future progress for many aspects of chelicerate biology is the development of a model organism for this group. Toward this end, we are developing a chelicerate genetic model: the two‐spotted spider mite Tetranychus urticae. T. urticae has the smallest genome of any arthropod determined so far (75 Mbp, 60% of the size of the Drosophila genome), undergoes rapid development and is easy to maintain in the laboratory. These features make T. urticae a promising reference organism for the economically important, poorly studied and species‐rich chelicerate lineage. BioEssays 29:489–496, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Understanding in vivo regeneration of complex structures offers a fascinating perspective for translation into medical applications. Unfortunately, mammals in general lack large‐scale regenerative capacity, whereas planarians, newts or Hydra can regenerate complete body parts. Such organisms are, however, poorly annotated because of the lack of sequence information. This leads to limited access for molecular biological investigations. In the last decade, high throughput technologies and new methods enabling the effective generation of transgenic animals have rapidly evolved. These developments have allowed the (...) extensive use of niche model organisms as part of a trend towards the accessibility of a greater panel of model species for scientific research. The case study that follows provides an insight into the impact of high throughput techniques on the landscape of models of regeneration. The cases presented here give evidence of alternative stem cell maintenance pathways, the identification of new protein families and new stem cell markers. (shrink)

This article critically examines one of the most prevalent metaphors in modern biology, namely the machine conception of the organism (MCO). Although the fundamental differences between organisms and machines make the MCO an inadequate metaphor for conceptualizing living systems, many biologists and philosophers continue to draw upon the MCO or tacitly accept it as the standard model of the organism. This paper analyses the specific difficulties that arise when the MCO is invoked in the study of development (...) and evolution. In developmental biology the MCO underlies a logically incoherent model of ontogeny, the genetic program, which serves to legitimate three problematic theses about development: genetic animism, neo-preformationism, and developmental computability. In evolutionary biology the MCO is responsible for grounding unwarranted theoretical appeals to the concept of design as well as to the interpretation of natural selection as an engineer, which promote a distorted understanding of the process and products of evolutionary change. Overall, it is argued that, despite its heuristic value, the MCO today is impeding rather than enabling further progress in our comprehension of living systems. (shrink)

Although the interdisciplinary nature of contemporary biological sciences has been addressed by philosophers, historians, and sociologists of science, the different ways in which engineering concepts and methods have been applied in biology have been somewhat neglected. We examine - using the mechanistic philosophy of science as an analytic springboard - the transfer of network methods from engineering to biology through the cases of two biology laboratories operating at the California Institute of Technology. The two laboratories study gene regulatory networks, but (...) in remarkably different ways. The research strategy of the Davidson lab fits squarely into the traditional mechanist philosophy in its aim to decompose and reconstruct, in detail, gene regulatory networks of a chosen model organism. In contrast, the Elowitz lab constructs minimal models that do not attempt to represent any particular naturally evolved genetic circuits. Instead, it studies the principles of gene regulation through a template-based approach that is applicable to any kinds of networks, whether biological or not. We call for the mechanists to consider whether the latter approach can be accommodated by the mechanistic approach, and what kinds of modifications it would imply for the mechanistic paradigm of explanation, if it were to address modelling more generally. (shrink)

This paper aims to identify the key characteristics of model organisms that make them a specific type of model within the contemporary life sciences: in particular, we argue that the term “model organism” does not apply to all organisms used for the purposes of experimental research. We explore the differences between experimental and model organisms in terms of their material and epistemic features, and argue that it is essential to distinguish between their representational scope and (...) representational target. We also examine the characteristics of the communities who use these two types of models, including their research goals, disciplinary affiliations, and preferred practices to show how these have contributed to the conceptualization of a model organism. We conclude that model organisms are a specific subgroup of organisms that have been standardized to fit an integrative and comparative mode of research, and that it must be clearly distinguished from the broader class of experimental organisms. In addition, we argue that model organisms are the key components of a unique and distinctively biological way of doing research using models.Keywords: Experimental organism; Genetics; Model organism; Modeling; Philosophy of biology; Representation. (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)

Invertebrate genetic models with their tractable neuromuscular systems are effective vehicles for the study of human nerve and muscle disorders. This is exemplified by insights made into spinal muscular atrophy (SMA) using the fruit fly Drosophila melanogaster and the nematode worm Caenorhabditis elegans. For speed and economy, these invertebrates offer convenient, whole‐organism platforms for genetic screening as well as RNA interference (RNAi) and chemical library screens, permitting the rapid testing of hypotheses related to disease mechanisms and the exploration of (...) new therapeutic routes and drug candidates. Here, we discuss recent developments encompassing synaptic physiology, RNA processing, and screening of compound and genome‐scale RNAi libraries, showcasing the importance of invertebrate SMA models.Editor's suggested further reading in BioEssays: SMN and Gemins: ‘We are family’... or are we? Abstract. (shrink)

Insight into animal biology and development provided by classical genetic analysis of the model organism Drosophila melanogaster was an incentive to develop advanced genetic tools for this insect. But genetic systems for the over one million other known insect species are largely undeveloped. With increasing information about insect genomes resulting from next generation sequencing, RNA interference is now the method of choice for reverse genetics, although it is constrained by the means of delivery of interfering RNA. A (...) recent advance to ensure sustained delivery with minimal experimental intervention or trauma to the insect is to exploit commensal bacteria for symbiont‐mediated RNA interference. This technology not only offers an efficient means for RNA interference in insects in laboratory conditions, but also has potential for use in the control of human disease vectors, agricultural pests and pathogens of beneficial insects. (shrink)

Stalk‐eyed flies of the family Diopsidae exhibit a unique form of hypercephaly, which has evolved under both natural and sexual selection. Male hypercephaly is used by female diopsids as an indicator of male quality. By choosing to mate with males expressing the most‐exaggerated hypercephaly, females can benefit both from the enhanced fertility of these males and the transmission of other heritable advantages to their offspring. Stalk‐eyed flies are close relatives of the model organism, Drosophila melanogaster. We have shown (...) that similar genetic and cellular mechanisms regulate the initial development of the head capsule in fruitflies and diopsids. The great diversity of stalk‐eyed fly species, exhibiting varying degrees of hypercephaly and sexual dimorphism, constitutes a major advantage for comparative studies of their development and evolution. BioEssays 29: 300–307, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

ArgumentWe examine the criteria used to validate the use of nonhuman organisms in North-American alcohol addiction research from the 1950s to the present day. We argue that this field, where the similarities between behaviors in humans and non-humans are particularly difficult to assess, has addressed questions of model validity by transforming the situatedness of non-human organisms into an experimental tool. We demonstrate that model validity does not hinge on the standardization of one type of organism in isolation, (...) as often the case with genetic model organisms. Rather, organisms are viewed as necessarily situated: they cannot be understood as a model for human behavior in isolation from their environmental conditions. Hence the environment itself is standardized as part of the modeling process; and model validity is assessed with reference to the environmental conditions under which organisms are studied. (shrink)

Caenorhabditis elegans is a tiny worm that has become the focus of a large number of worldwide research projects examining its genetics, development, neuroscience, and behavior. Recently several groups of investigators have begun to tie together the behavior of the organism and the underlying genes, neural circuits, and molecular processes implemented in those circuits. Behavior is quintessentially organismal—it is the organism as a whole that moves and mates—but the explanations are devised at the molecular and neurocircuit levels, (...) and tested in populations using protocols that span many levels of aggregation. Following a brief review of the main relevant features of C. elegans, I describe some of these circuits, and then discuss two contrasting approaches in behavioral genetics and neural network analysis of the worm. Finally, I outline the rudiments of a “field and focus” explanation model using the two contrasting approaches. (shrink)

In the multidisciplinary field of developmental cognitive neuroscience, statistical associations between levels of description play an increasingly important role. One example of such associations is the observation of correlations between relatively common gene variants and individual differences in behavior. It is perhaps surprising that such associations can be detected despite the remoteness of these levels of description, and the fact that behavior is the outcome of an extended developmental process involving interaction of the whole organism with a variable environment. (...) Given that they have been detected, how do such associations inform cognitive-level theories? To investigate this question, we employed a multiscale computational model of development, using a sample domain drawn from the field of language acquisition. The model comprised an artificial neural network model of past-tense acquisition trained using the backpropagation learning algorithm, extended to incorporate population modeling and genetic algorithms. It included five levels of description—four internal: genetic, network, neurocomputation, behavior; and one external: environment. Since the mechanistic assumptions of the model were known and its operation was relatively transparent, we could evaluate whether cross-level associations gave an accurate picture of causal processes. We established that associations could be detected between artificial genes and behavioral variation, even under polygenic assumptions of a many-to-one relationship between genes and neurocomputational parameters, and when an experience-dependent developmental process interceded between the action of genes and the emergence of behavior. We evaluated these associations with respect to their specificity, to their developmental stability, and to their replicability, as well as considering issues of missing heritability and gene–environment interactions. We argue that gene–behavior associations can inform cognitive theory with respect to effect size, specificity, and timing. The model demonstrates a means by which researchers can undertake multiscale modeling with respect to cognition and develop highly specific and complex hypotheses across multiple levels of description. (shrink)

Mathematics and logic are indispensable in science, yet how they are deployed and why they are so effective, especially in the natural sciences, is poorly understood. In this paper, I focus on the how by analysing Jean Piaget’s application of mathematics to the empirical content of psychological experiment; however, I do not lose sight of the application’s wider implications on the why. In a case study, I set out how Piaget drew on the stock of mathematical structures to model (...) psychological content, namely, the operations of thought involved in reasoning. In particular, I show how operations of thought form structured wholes that initially resisted modelling by either lattices or groups but could be modelled adequately by modifications of these mathematical structures. Piaget coined the term ‘grouping’ for the modified structure, and I conclude that it represents a non-canonical application of mathematics to the empirical content of experimental psychology. I also touch on the role external factors played in Piaget’s development of the grouping. According to the genetic epistemology conceived by Piaget, the origin of intelligence lies in the biological organism and develops in stages over time, and, via the grouping, Piaget established a genetic relationship between two stages of reasoning. I show how this relationship explains why mathematics and logic fit the psychological content of reasoning whilst simultaneously making their successful deployment in the natural sciences more mysterious. Finally, I turn to the explanation Piaget envisaged for the unreasonable effectiveness of mathematics in the natural sciences and consider some consequences for naturalism and Pythagoreanism. (shrink)

The book considers biology in parallel with philosophical structuralism in order to argue that notions of form in the organism are analogous to similar ideas in structuralist philosophy and literary theory. This analogy is then used to shed light on debates among biological scientists from the turn of the 19th century to the present day, including Cuvier, Geoffroy Saint-Hilaire, Dawkins, Crick, Goodwin, Rosen and West-Eberhard. The book critiques the endorsement of genetic manipulation and bioengineering as keys to solving agricultural (...) and environmental problems, suggesting that alternative models have been marginalized in the promotion of this discourse. Drawing from the work of philosophers including Cassirer, Saussure, Jakobson and Foucault the book ultimately argues that methods based on agroecology, supported by molecular applications (such as marker-assisted selection, MAS), can both advance agricultural development and remain focused on the whole organism. (shrink)

Genes are gained and lost over the course of evolution. A recent study found that over 1,800 new genes have appeared during primate evolution and that an unexpectedly high proportion of these genes are expressed in the human brain. But what are the molecular functions of newly evolved genes and what is their impact on an organism's fitness? The acquisition of new genes may provide a rich source of genetic diversity that fuels evolutionary innovation. Although gene manipulation experiments are (...) not feasible in humans, studies in model organisms, such as Drosophila melanogaster, have shown that new genes can quickly become integrated into genetic networks and become essential for survival or fertility. Future studies of new genes, especially chimeric genes, and their functions will help determine the role of genetic novelty in the adaptation and diversification of species. (shrink)

Predicting the phenotype of an organism from its genotype is a central question in genetics. Most importantly, we would like to find out if the perturbation of a single gene may be the cause of a disease. However, our current ability to predict the phenotypic effects of perturbations of individual genes is limited. Network models of genes are one tool for tackling this problem. In a recent study, (Lee et al.) it has been shown that network models covering (...) the majority of genes of an organism can be used for accurately predicting phenotypic effects of gene perturbations in multicellular organisms. BioEssays 30:707–710, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

The functions of the Bloom syndrome helicase and its orthologs are well characterized in mitotic DNA damage repair, but their roles within the context of meiotic recombination are less clear. In meiotic recombination, multiple repair pathways are used to repair meiotic DSBs, and current studies suggest that BLM may regulate the use of these pathways. Based on literature from Saccharomyces cerevisiae, Arabidopsis thaliana, Mus musculus, Drosophila melanogaster, and Caenorhabditis elegans, we present a unified model for a critical meiotic role (...) of BLM and its orthologs. In this model, BLM and its orthologs utilize helicase activity to regulate the use of various pathways in meiotic recombination by continuously disassembling recombination intermediates. This unwinding activity provides the meiotic program with a steady pool of early recombination substrates, increasing the probability for a DSB to be processed by the appropriate pathway. As a result of BLM activity, crossovers are properly placed throughout the genome, promoting proper chromosomal disjunction at the end of meiosis. This unified model can be used to further refine the complex role of BLM and its orthologs in meiotic recombination. In meiotic recombination, Blm utilizes its helicase activity to disassemble early recombination intermediates, thereby retaining a pool of recombination sites from which some can be selected to enter the Class I crossover pathway while simultaneously promoting SDSA and preventing the use of the Class II pathway. (shrink)

Spatial evolutionary game theory explains how cooperative traits can survive the intense competition in biological systems. If the spatial distribution allows cooperators to interact with each other frequently, the benefits of cooperation will outweigh the losses due to exploitation by selfish organisms. However, for a cooperative behavior to get established in a system, it needs to be found initially in a sufficiently large cluster to allow a high frequency of intracooperator interactions. Since mutations are rare events, this poses the question (...) of how cooperation can arise in a biological system in the first place. We present a simple model which captures two concepts from genetics that can explain how evolution overcomes the emergence problem. The first concept is, often in nature, a gene may not express its phenotype except under specific environmental conditions, rendering it to be a “silent” gene. The second key idea is that a neutral gene, one that does not harm or improve an organism’s survival chances, can still spread through a population if it is physically near to another gene that is positively selected. Through these two ideas, our model offers a possible solution to the fundamental problem of emergence of cooperation in biological systems. (shrink)

ArgumentThis paper brings together the history of risk and the history of DNA repair, a biological phenomenon that emerged as a research field in between molecular biology, genetics, and radiation research in the 1960s. The case of xeroderma pigmentosum (XP), an inherited hypersensitivity to UV light and, hence, a disposition to skin cancer will be the starting point to argue that, in the 1970s and 1980s, DNA repair became entangled in the creation of new models of the human body (...) at risk – what is here conceptually referred to as the vulnerability aspect of body history – and new attempts at cancer prevention and enhancement of the body associated with the new flourishing research areas of antimutagenesis and anticarcinogenesis. The aim will be to demonstrate that DNA repair created special attempts at disease prevention: molecular enhancement, seeking to identify means to increase the self-repair abilities of the body at the molecular level. Prevention in this sense meant enhancing the body's ability to cope with the environmental hazards of an already toxic world. This strategy has recently been adopted by the beauty industry, which introduced DNA care as a new target for skin care research and anti-aging formulas. (shrink)

Epithelial development dictates the shape of an organism. The metamorphic development of a Drosophila leg precursor into an adult leg is a well‐defined example of epithelial morphogenesis that can be analyzed from the perspectives of genetics and molecular and cell biology. The steroid hormone 20‐hydroxyecdysone induces and regulates the entire process. Mutants affecting Drosophila leg morphogenesis characteristically have short thick legs (the malformed phenotype) resulting from a failure to execute normal cell shape changes at a specific stage of (...) development. Mutations that cause the malformed phenotype have already led to the identification and cloning of genes encoding transcription factors, a transmembrane serine protease presumably required for modification of the apical extracellular matrix, and components of the contractile cytoskeleton and adherens junctions. All of these products are required for the execution of normal changes in leg cell shape. (shrink)

Many natural and biological phenomena can be depicted as networks. Theoretical and empirical analyses of networks have become prevalent. I discuss theoretical biases involved in the delineation of biological networks. The network perspective is shown to dissolve the distinction between regulatory architecture and regulatory state, consistent with the theoretical impossibility of distinguishing a priori between “program” and “data”. The evolutionary significance of the dynamics of trans-generational and inter-organism regulatory networks is explored and implications are presented for understanding the evolution (...) of the biological categories development-heredity; plasticity-evolvability; and epigenetic-genetic. (shrink)

The complete sequencing of the genome of the fruit fly Drosophila melanogaster offers the prospect of detailed functional analysis of the extensive gene families in this genetic model organism. Comprehensive functional analysis of family members is facilitated by access to a robust, stable and inducible expression system in a fly cell line. Here we show how the Schneider S2 cell line, derived from the Drosophila embryo, provides such an expression system, with the bonus that radioligand binding studies, second (...) messenger assays, ion imaging, patch‐clamp electrophysiology and gene silencing can readily be applied. Drosophila is also ideal for the study of new control strategies for insect pests since the receptors and ion channels that many new animal health drugs and crop protection chemicals target can be expressed in this cell line. In addition, many useful orthologues of human disease genes are emerging from the Drosophila genome and the study of their functions and interactions is another area for postgenome applications of S2 cell lines. BioEssays 24:1066–1073, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

Since the practice turn, the role technologies play in the production of scientific knowledge has become a prominent topic in science studies. Much existing scholarship, however, either limits technology to merely mechanical instrumentation or uses the term for a wide variety of items. This article argues that technologies in scientific practice can be understood as a result of past scientific knowledge becoming sedimented in materials, like model organisms, synthetic reagents or mechanical instruments, through the routine use of these materials (...) in subsequent research practice. The proposed theoretical interpretation of technology is examined through a case where a model organism—Drosophila melanogaster—acted as a technology for investigating a contested biological effect of a mechanical instrument: Hermann J. Muller’s experiments on X-ray mutagenicity in the 1920s. The article reconstructs how Muller employed two synthetic Drosophila stocks as tests for measuring X-rays’ capacity to cause genetic aberration. It argues that past scientific knowledge sedimented in the Drosophila stocks influenced Muller’s perception of X-ray-induced mutation. It further describes how Muller’s concept of X-ray mutagenicity sedimented through the adoption of X-ray machines as a ready-made resource for producing mutants by other geneticists, for instance George Beadle and Edward Tatum in their experiments on Neurospora crassa, despite ongoing disputes surrounding Muller’s conclusions. Technological sedimentation is proposed as a potential explanation why sedimentation and disputation may often coexist in the history of science. (shrink)

Amphioxus represents the most basally divergent group in chordates and probably the best extant proxy to the ancestor of all chordates including vertebrates. The amphioxus, or lancelets, are benthic filter feeding marine animals and their interest as a model in research is due to their phylogenetic position and their anatomical and genetic stasis throughout their evolutionary history. From the first works in the 19th century to the present day, enormous progress is made mainly favored by technical development at different (...) levels, from spawning induction and husbandry techniques, through techniques for studies of gene function or of the role of different signalling pathways through embryonic development, to functional genomics techniques. Together, these advances foretell a plethora of interesting developments in the world of research with the amphioxus model. Here, the author review the discovery and development of amphioxus as a superb model organism in evolutionary and evolutionary‐developmental biology. (shrink)

Arabidopsis thaliana (Thale cress, Arabidopsis) is an ideal model organism for the molecular genetic analysis of many plant processes. The availability of a complete physical map would greatly facilitate the gene cloning steps in these studies. The small genome size of Arabidopsis makes the construction of such a map a feasible goal. One of the approaches to construct an overlapping library of the Arabidopsis genome takes advantage of the many mapped markers and the availability of Arabidopsis yeast artificial (...) chromosome (YAC) libraries. Mapped molecular markers are used to identify corresponding YAC clones and thereby place them on the genetic map. Subsequently, these YAC clones provide the framework for directed walking experiments aimed at closing the gaps between the YAC contigs. Adopting this strategy, YAC clones comprising about 10% of the genome have been assigned to the top halves of Arabidopsis chromosomes 4 and 5. Extensive walking experiments in a 10 cM interval of chromosome 4 have resulted in two contiguous regions in the megabase size range. (shrink)

Conrad Hal Waddington was a British developmental biologist who mainly worked in Cambridge and Edinburgh, but spent the late 1930s with Morgan in California learning about Drosophila. He was the first person to realize that development depended on the then unknown activities of genes, and he needed an appropriate model organism. His major experimental contributions were to show how mutation analysis could be used to investigate developmental mechanisms in Drosophila, and to explore how developmental mutation could drive evolution, (...) his other deep interest. Waddington was, however, predominantly a thinker, and set out to provide a coherent framework for understanding the genetic bases of embryogenesis and evolution, developing his ideas in many books. Perhaps his best-known concept is the epigenetic landscape: here a ball rolls down a complex valley, making path choices. The rolling ball represents a cell’s development over time, while the topography represents the changing regulatory environment that controls these choices. In its later forms, the role of each feature in the landscape was controlled by the effects of sets of interacting genes, an idea underpinning contemporary approaches to systems biology. Waddington was the first developmental geneticist and probably the most important developmental biologist of the pre-molecular age. (shrink)

Background: Olfactory cues directly link the environment to gene expression. Two types of olfactory cues, food odors and social odors, alter genetically predisposed hormone-mediated activity in the mammalian brain. Methods: The honeybee is a model organism for understanding the epigenetic link from food odors and social odors to neural networks of the mammalian brain, which ultimately determine human behavior. Results: Pertinent aspects that extend the honeybee model to human behavior include bottom-up followed by top-down gene, cell, tissue, (...) organ, organ-system, and organism reciprocity; neurophysiological effects of food odors and of sexually dimorphic, species-specific social odors; a model of motor function required for social selection that precedes sexual selection; and hormonal effects that link current neuroscience to social science affects on the development of animal behavior. Conclusion: As the psychological influence of food odors and social orders is examined in detail, the socioaffective nature of olfactory cues on the biologically based development of sexual preferences across all species that sexually reproduce becomes clearer Keywords: behavior; development; evolution; odors; food; social; sexual; epigenetic; olfaction; pheromones; hormones; environment; animal; affect; effect; neuroscience (Published: 15 March 2012) Citation: Socioaffective Neuroscience & Psychology 2012, 2 : 17338 - DOI: 10.3402/snp.v2i0.17338. (shrink)

Glial cells play a central role in the development and function of complex nervous systems. Drosophila is an excellent model organism for the study of mechanisms underlying neural development, and recent attention has been focused on the differentiation and function of glial cells. We now have a nearly complete description of glial cell organization in the embryo, which enables a systematic genetic analysis of glial cell development. Most glia arise from neural stem cells that originate in the neurogenic (...) ectoderm. The bifurcation of glial and neuronal fates is under the control of the glial promoting factor glial cells missing. Differentiation is propagated through the regulation of several transcription factors. Genes have been discovered affecting the terminal differentiation of glia, including the promotion glial–neuronal interactions and the formation of the blood–nerve barrier. Other roles of glia are being explored, including their requirement for axon guidance, neuronal survival, and signaling. BioEssays 23:877–887, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Tobacco mosaic virus has served as a model organism for pathbreaking work in plant pathology, virology, biochemistry and applied genetics for more than a century. We were intrigued by a photograph published in Phytopathology in 1934 showing that Tabasco pepper plants responded to TMV infection with localized necrotic lesions, followed by abscission of the inoculated leaves. This dramatic outcome of a biological response to infection observed by Francis O. Holmes, a virologist at the Rockefeller Institute for Medical (...) Research, was used to score plants for resistance to TMV infection. Our objective was to gain a better understanding of early to mid-twentieth century ideas of genetic resistance to viruses in crop plants. We investigated Holmes’ observation as a practical exercise in reworking an experiment, having been inspired by Pamela Smith’s innovative Making and Knowing Project. We had a great deal of difficulty replicating Holmes’ experiment, finding that biological materials and experimental customs change over time, in ways that ideas do not. Using complementary tools plus careful study and interpretation of the original text and figures, we were able to rework, yet only partially replicate, this experiment. Reading peer-reviewed manuscripts that cited Holmes’ 1934 report provided an additional level of insight into the interpretation and replication of this work in the decades that followed. From this, we touch on how experimental reworking can inform our strategies to address the reproducibility “crisis” in twenty-first century science. (shrink)

In a military-sponsored research project begun during the Second World War, inmates of the Stateville Penitentiary in Illinois were infected with malaria and treated with experimental drugs that sometimes had vicious side effects. They were made into reservoirs for the disease and they provided a food supply for the mosquito cultures. They acted as secretaries and technicians, recording data on one another, administering malarious mosquito bites and experimental drugs to one another, and helping decide who was admitted to the project (...) and who became eligible for early parole as a result of his participation. Thus, the prisoners were not simply research subjects; they were deeply constitutive of the research project. Because a prisoner’s time on the project was counted as part of his sentence, and because serving on the project could shorten one’s sentence, the project must be seen as simultaneously serving the functions of research and punishment. Michel Foucault wrote about such ‘mixed mechanisms’ in his Discipline and punish. His shining example of such a ‘transparent’ and subtle style of punishment was the panopticon, Jeremy Bentham’s architectural invention of prison cellblocks arrayed around a central guard tower. Stateville prison was designed on Bentham’s model; Foucault featured it in his own discussion. This paper, then, explores the power relations in this highly idiosyncratic experimental system, in which the various roles of model organism, reagent, and technician are all occupied by sentient beings who move among them fluidly. This, I argue, created an environment in the Stateville hospital wing more panoptic than that in the cellblocks. Research and punishment were completely interpenetrating, and mutually reinforcing. (shrink)

The genetically manipulated organism crisis demonstrated that technological development based solely on the law of the marketplace and State protection against serious risks to health and safety is no longer a warrant of ethical acceptability. In the first part of our paper, we critique the implicitly individualist social-acceptance model for State regulation of technology and recommend an interdisciplinary approach for comprehensive analysis of the impacts and ethical acceptability of technologies. In the second part, we present a framework for (...) the analysis of impacts and acceptability, devised—with the goal of supporting the development of specific nanotechnological applications—by a team of researchers from various disciplines. At the conceptual level, this analytic framework is intended to make explicit those various operations required in preparing a judgement about the acceptability of technologies that have been implicit in the classical analysis of toxicological risk. On a practical level, we present a reflective tool that makes it possible to take into account all the dimensions involved and understand the reasons invoked in determining impacts, assessing them, and arriving at a judgement about acceptability. (shrink)

Abstract.Since the gene splicing debates of the 1980s, the public has been exposed to an ongoing sequence of genetic and reproductive technologies. Many issue areas have outcomes that lose track of people's inner values or engender opposing religious viewpoints defying final resolution. This essay relocates the discussion of what is an acceptable application from the individual to the societal level, examining technologies that stand to address large numbers of people and thus call for policy resolution, rather than individual fiat, in (...) their application. A major source of guidance is the “Genetic Frontiers” series of professional dialogues and conferences held by the National Conference for Community and Justice from 2002 to 2004. Genetic testing, human gene therapy, genetic engineering of plants and animals, and stem cell technology are examined. While differences in perspective on the beginning of life persist, a stepwise approach to the examination of genetic testing reveals areas of general agreement. Stewardship of life, human co‐creativity with the divine, and social justice help define the bounds of application of genetic engineering and therapy; compassionate care plays a major role in establishing stem cell policy. Active, sustained dialogue is a useful resource for enabling sharing of religious values and crystallization of policies. (shrink)

In a military-sponsored research project begun during the Second World War, inmates of the Stateville Penitentiary in Illinois were infected with malaria and treated with experimental drugs that sometimes had vicious side effects. They were made into reservoirs for the disease and they provided a food supply for the mosquito cultures. They acted as secretaries and technicians, recording data on one another, administering malarious mosquito bites and experimental drugs to one another, and helping decide who was admitted to the project (...) and who became eligible for early parole as a result of his participation. Thus, the prisoners were not simply research subjects; they were deeply constitutive of the research project. Because a prisoners time on the project was counted as part of his sentence, and because serving on the project could shorten ones sentence, the project must be seen as simultaneously serving the functions of research and punishment. Michel Foucault wrote about such mixed mechanisms in his Discipline and punish. His shining example of such a transparent and subtle style of punishment was the panopticon, Jeremy Benthams architectural invention of prison cellblocks arrayed around a central guard tower. Stateville prison was designed on Benthams model; Foucault featured it in his own discussion. This paper, then, explores the power relations in this highly idiosyncratic experimental system, in which the various roles of model organism, reagent, and technician are all occupied by sentient beings who move among them fluidly. This, I argue, created an environment in the Stateville hospital wing more panoptic than that in the cellblocks. Research and punishment were completely interpenetrating, and mutually reinforcing. (shrink)

Combining genetic algorithms that produce complex, fluid, biomorphic shapes with probabilistic systems that incorporate randomness, the designers attempt to mimic adaptive systems in natural evolution in order to arrive at intelligent design solutions. The design processes are said to be interactive and sensitive to varying conditions, behaving like an exceptionally perceptive and adaptive organism during an evolutionary process (Somol 2004: 8687); this process can be compared to the recent attempt by the architectural avant-garde to move beyond the semiotic interests (...) of deconstructionism and tap into the authority of the natural sciences. In some sense, an analogy can be drawn to natural evolution. In the natural world, adaptation and change result from an iterative progress, from one generation to the next, driven by mutation, recombination, and the survival of the fittest in the sense of selection. Following the model of nature in architecture, as proposed by some proponents of parametricism, should not be expected to make buildings more precisely adapted to particular circumstances and optimally functional. Evolutionary theory is used in contemporary architecture as a form of legitimization. It can also cast light on ethical issues, not reducing the human mind's creative intelligence to some sort of genetic determinism, developing in the free market of social choice. Therefore, searching for better ways of managing resources should be at the core of an adaptive concept of architecture. (shrink)

The estrangement between genetic scientists and theologians originating in the 1960s is reflected in novel combinations of human thought (subject) and genes (investigational object), paralleling each other through the universal process known in chaos theory as self-similarity. The clash and recombination of genes and knowledge captures what Philip Hefner refers to as irony, one of four voices he suggests transmit the knowledge and arguments of the religion-and-science debate. When viewed along a tangent connecting irony to leadership, journal dissemination, and the (...) activities of the "public intellectual" and the public at large, the sequence of voices is shown to resemble the passage of genetic information from DNA to mRNA, tRNA, and protein, and from cell nucleus to surrounding environment. In this light, Hefner's inquiry into the voices of Zygon is bound up with the very subject matter Zygon covers. (shrink)

This article offers a historical analysis of the relationship between the practice of participant-observation among American sociologists and Erving Goffman’s dramaturgical model of the self. He was a social scientist who privileged ethnography in the field over the laboratory experiment, the survey questionnaire, or the mental test. His goal was a natural history of communication among humans. Rather than rely upon standardizing technologies for measurement, Goffman tried to obtain accurate recordings of human behavior through secretive observations. During the 1950s, (...) he conducted three major studies as a participant-observer, disguised from those studied through insincere performances. As originally presented, his dramaturgical theory did not draw upon the theater as the governing metaphor, but rather the confidence game. It is suggested that Goffman’s writings exemplify what Gerd Gigerenzer calls the tools-to-theories heuristic. Goffman’s depiction of the confidence man’s behavior closely mirrored how he and his fellow sociologists described the practice of participant-observation. Both were represented as embedded and attentive yet coolly detached observers skilled at playing different roles as the situation necessitated. The similarities between his own professional behavior and the activities of the confidence man may have suggested to Goffman the latter as a model for human nature. (shrink)

Graphical AbstractThe sea anemone Nematostella vectensis has developed into a model organism for studying genome evolution and animal development.

Our understanding of biological processes in humans is often based on examination of analogous processes in other organisms. The nematode worm Caenorhabditis elegans has been a particularly valuable model, leading to Nobel prize winning discoveries in development and genetics. Until recently, however, the worm has not been widely used as a model to study transcription due to the lack of a comprehensive catalogue of its RNA transcripts. A recent study by Chen et al. uses next‐generation sequencing to (...) address this issue, mapping the transcription initiation sites in C. elegans and finding many unexpected similarities between the transcription of enhancers and promoters in the worm and mammalian genomes. As well as providing a valuable resource for researchers in the C. elegans community, these findings raise the possibility of using the worm as a model to investigate some key, current questions about transcriptional regulation that remain technically challenging in more complex organisms. (shrink)

Controversies about optimality models and adaptationist methodologies have animated the discussions of evolutionary theory in recent years. The sociobiologists, following the lead of E. O. Wilson, have argued that if Darwinian natural selection can be reliably expected to produce the best possible type of organism - one that optimizes the value of its genetic contribution to future generations - then evolution becomes a powerfully predictive theory as well as an explanatory one. The enthusiastic claims of the sociobiologists for the (...) predictability and applicability that the optimalist approach engenders have been met with severe criticism by Richard C. Lewontin, Stephen Jay Gould, and other biologists and philosophers of biology. These original essays take up both sides of the controversy over the role of optimality models in evolutionary biology, providing a refreshingly insightful and balanced discussion of optimality issues by an interdisciplinary group of leading philosophers of biology, biologists, psychologists, anthropologists, and an economist. They focus on the current state of adaptationist and optimalist methodology in evolutionary theory, and on the possibility of extending such methodology to the human sciences, especially those of psychology and anthropology. Introduction / John Dupre -- Part 1. Methodological questions. Simple models of complex phenomena: the case of cultural evolution / Peter J. Richerson and Robert Boyd -- Natural selection and the null hypothesis / John Beatty -- Why not the best? / Philip Kitcher -- Part 2. Evolution and optimality. What is adaptationism? / Elliot Sober -- How to model evolution / John Maynard Smith -- Comments on Maynard Smith’s "How to Model Evolution" / Elliot Sober -- Reply to Sober / John Maynard Smith -- The shape of optimality / Richard C. Lewontin -- Part 3. Applications. Evolutionary ecology and the optimality assumption / John M. Emlen -- Optimality theory and behavior / John E.R. Staddon -- Part 4. Applications to human behavior. Optimization theory in anthropology: applications and critiques / Eric Alden Smith -- Evolution of a mesh between principles of the mind and regularities of the world / Roger N. Shepard -- From evolution to behavior: evolutionary psychology as the missing link / Leda Cosmides and John Tooby -- On the emotions as guarantors of threats and promises / Jack Hirschleifer -- Human kinds / John Dupre. (shrink)

A comparative method of studying the biological bases of personality compares human trait dimensions with likely animal models in terms of genetic determination and common biological correlates. The approach is applied to the trait of sensation seeking, which is defined on the human level by a questionnaire, reports of experience, and observations of behavior, and on the animal level by general activity, behavior in novel situations, and certain types of naturalistic behavior in animal colonies. Moderately high genetic determination has been (...) found for human sensation seeking, and marked strain differences in rodents have been found in open-field behavior that may be related to basic differences in brain neurochemistry. Agonistic and sociable behaviors in both animals and humans and the trait measure of sensation seeking in humans have been related to certain common biological correlates such as gonadal hormones, monoamine oxidase (MAO), and augmenting of the cortical evoked potential.The monoamine systems in the rodent brain are involved in general activity, exploratory behavior, emotionality, socialization, dominance, sexual and consummately behaviors, and intracranial self-stimulation. Preliminary studies have related norepinephrine and enzymes involved in its production and degradation to human sensation seeking. A model is suggested that relates mood, behavioral activity, sociability, and clinical states to activity of the central catecholamine neurotransmitters and to neuroregulators and other transmitters that act in opposite ways on behavior or stabilize activity in the arousal systems. Stimulation and behavioral activity act on the catecholamine systems in a brain–behavior feedback loop. At optimal levels of catecholamine systems activity (CSA) mood is positive and activity and sociability are adaptive. At very low or very high levels of CSA mood is dysphoric, activity is restricted or stereotyped, and the organism is unsocial or aggressively antisocial. Novelty, in the absence of threat, may be rewarding through activation of noradrenergic neurons. (shrink)

Community databases have become crucial to the collection, ordering and retrieval of data gathered on model organisms, as well as to the ways in which these data are interpreted and used across a range of research contexts. This paper analyses the impact of community databases on research practices in model organism biology by focusing on the history and current use of four community databases: FlyBase, Mouse Genome Informatics, WormBase and The Arabidopsis Information Resource. We discuss the standards (...) used by the curators of these databases for what counts as reliable evidence, acceptable terminology, appropriate experimental set-ups and adequate materials (e.g., specimens). On the one hand, these choices are informed by the collaborative research ethos characterising most model organism communities. On the other hand, the deployment of these standards in databases reinforces this ethos and gives it concrete and precise instantiations by shaping the skills, practices, values and background knowledge required of the database users. We conclude that the increasing reliance on community databases as vehicles to circulate data is having a major impact on how researchers conduct and communicate their research, which affects how they understand the biology of model organisms and its relation to the biology of other species. (shrink)

This study focuses on the concept of a 'model organism' in the biomedical sciences through an historical and philosophical examination of research with the nematode Caenorhabditis elegans. I explore the choice of C. elegans in the mid-1960s, showing a rich context existed within which the organism was selected as the focus for a molecular biological research program, including an experimental life prior to Sydney Brenner's work. I argue that this choice can be seen as an obvious outcome (...) of what was a complex search procedure, and that the success of the 'worm project' depended not only on organismal choice but also on the conceptual and institutional framework at the Laboratory of Molecular Biology in Cambridge within which it was pursued. Examination of C. elegans work in the late 1960s through the early 1980s illuminates several additional theses. Although development and behavior were the general areas of interest for the project, the original goals and proposed methodology were extremely vague. As the project evolved, which investigations proved to be tractable using the worm depended not only on which methodologies were fruitful but also on the interests and skills of early workers. Much of the power of C. elegans as a model organism can be traced historically to the investment of resources which resulted in an unprecedented, complete description of the organism, and represented a return to a more naturalistic biological tradition. In light of the historical study, I develop a philosophical analysis of C. elegans as a model organism through exploration of the three kinds of modeling with the worm: modeling of structures, processes, and information. I expand the notion of a descriptive model, arguing that C. elegans is best understood as a prototype of the metazoa, and that C. elegans as a model organism has been not only heuristically valuable, but also essential to this research project particularly in its pre-explanatory stages. I conclude by suggesting that more investigation of descriptive prototypes such as those in the worm project must be done to capture important aspects of the biomedical sciences that will be neglected if explanatory models are the sole focus in the philosophy of science. (shrink)

How to use a model organism to study phenotypic integration and constraints on evolution.

Drawing on models of communication due to Lewis and Skyrms, I contrast sender-receiver systems as they appear within and between organisms, and as they function in the bridging of space and time. Within the organism, memory can be seen as the sending of messages over time, communication between stages as opposed to spatial parts. Psychological memory and genetic memory are compared with respect to their relations to a sender-receiver model. Some puzzles about “genetic information” can be resolved by (...) seeing the genome as a cell-level memory with no sender. (shrink)

In this paper it is analyzed from the informational perspective the relation between mind and body, an ancient philosophic issue defined as a problem, which still did not receive up to date an adequate solution. By introducing/using the concept of information, it is shown that this concept includes two facets, one of them referring to the common communications and another one referring to a hidden/structuring matter-related information, effectively acting in the human body and in the living systems, which determines the (...) dynamic inter-change of information between specific structures of the organism by electric/electronic/chemical agents and genetic/epigenetic processes. It is shown that the maintenance of body, permanently and obligatory depending on the external matter (foods, air, water) resources, needed to provide both the structuring/restructuring basic material and energy, determines the necessary existence of an info-managing system, administrating the internal mechano-chemical/physical processes. As a natural consequence, such a system should organize and assure own survival by an effective informational operability to detect the external food resources, to select the appropriate interest information and to decide as a function of circumstances. One important component in such an informational system is memory, allowing to dispose of the reference informational data for analysis/comparison and the selection between good and bad binary possible decisions. The memory receives and stores therefore signals from external reality and from the body itself, referring to the emotional reaction, digestion status, creation, and inherited predilections, within specific info-neural communication circuits between the brain and body execution/sensitive organs, the human body appearing as an integrated info-matter self-managed dynamic system. The specific body components memorize information with different degrees of info-integration: short/long-term integration, emotive/action reaction, info-abilities, culminating with the integration in the chromosomal structures by epigenetic processes. The new acquired information is transgenerationally transmissible, and is manifested as new traits, showing the adaptation capability of the human and close relation between mind and body. Analyzing the results of such a mind-body informational model in comparison with the earlier assumed/proposed/asserted archaic, Greek and Occidental philosophies, which represent only partial aspects of this relation, it is shown that this informational model, elaborated in terms of information on the basis of scientific reasons and arguments, constitutes a general, realist, and coherent model of the mind-body relation, able to integrate and/or explain most of the others. (shrink)

One might be inclined to assume, given the mouse donning its cover, that the behavior of interest in Nicole Nelson's book Model Behavior (2018) is that of organisms like mice that are widely used as “stand-ins” for investigating the causes of human behavior. Instead, Nelson's ethnographic study focuses on the strategies adopted by a community of rodent behavioral researchers to identify and respond to epistemic challenges they face in using mice as models to understand the causes of disordered human (...) behaviors associated with mental illness. Although Nelson never explicitly describes the knowledge production activities in which her behavioral geneticist research subjects engage as “exemplary”, the question of whether or not these activities constitute “model behavior(s)”—generalizable norms for engaging in scientific research—is one of the many thought-provoking questions raised by her book. As a philosopher of science interested in this question, I take it up here. (shrink)