Motile bacteria respond to environmental cues to move to more favorable locations. The components of the chemotaxis signal transduction systems that mediate these responses are highly conserved among prokaryotes including both eubacterial and archael species. The best‐studied system is that found in Escherichia coli. Attractant and repellant chemicals are sensed through their interactions with transmembrane chemoreceptor proteins that are localized in multimeric assemblies at one or both cell poles together with a histidine protein kinase, CheA, an SH3‐like adaptor protein, (...) CheW, and a phosphoprotein phosphatase, CheZ. These multimeric protein assemblies act to control the level of phosphorylation of a response regulator, CheY, which dictates flagellar motion. Bacterial chemotaxis is one of the most‐understood signal transduction systems, and many biochemical and structural details of this system have been elucidated. This is an exciting field of study because the depth of knowledge now allows the detailed molecular mechanisms of transmembrane signaling and signal processing to be investigated. BioEssays 28:9–22, 2006. © 2005 Wiley Periodicals, Inc. (shrink)

Chemotaxis and thermotaxis in Caenorhabditis elegans are based on the chemical senses (smell and taste) and the thermal sense, respectively, which are important for the life of the animal. Laser ablation experiments have allowed identification of sensory neurons and some interneurons required for these senses. Many mutants that exhibit various abnormalies have been isolated and analyzed. These studies have predicted novel signaling pathways whose components include a putative odorant specific transmembrane receptor (ODR‐10) and a cyclic nucleotide‐gated channel (TAX‐4/TAX‐2) functioning (...) in taste and thermosensation as well as in smell. The emerging picture of the mechanisms of sensory transduction in C. elegans seems to be basically similar to what is known of visual and olfactory sensory transduction in vertebrates. Thus, molecular and cellular analyses of chemotaxis and thermotaxis in C. elegans have proved useful and will continue to provide significant implications for the molecular basis of sensory systems in higher animals. (shrink)

Chemotaxis in bacteria is an excellent model for signal transduction processes. In Agrobacterium tumefaciens, the causative agent of crown gall tumour on wounded plants, it is a vital part of the organism's biology. A chromosomally‐determined chemotaxis system causes the bacterium to be attracted into the rhizosphere by chemoattractants in plant exudates. By interfacing with this system, the multifunctional products of two Tiplasmid encoded genes, virA and virG, allow the sensing of specific wound phenolics such as acetosyringone. This attracts (...) Ti‐plasmid harbouring A. tumefaciens to wound sites, where the higher acetosyringone concentrations lead to virA and virG‐mediated induction of the vir‐genes. The products of the induced genes, act in concert to effect transfer of the T‐DNA to the plant cell. (shrink)

Streamer F mutants have been found to be useful tools for studying the pathway of signal transduction leading to chemotactic cell movement. The primary defect in these mutants is in the structural gene for the cyclic GMP specific phosphodiesterase. This defect allows a larger and prolonged peak of cyclic GMP to be formed in response to the chemotactic stimulus, cyclic AMP. This characteristic aberrant pattern of cyclic GMP accumulation in the streamer F mutants has been correlated with similar patterns of (...) changes in the influx of calcium from the medium, myosin II association with the cytoskeleton, myosin phosphorylation and a decrease in speed of movement of the amoebae. From these studies a sequence of events can be deduced that leads from cell surface cyclic AMP stimulation to cell polarization prior to movement of the amoebae in response to the chemotactic stimulus. (shrink)

Bacterial chemotaxis is often considered to be a textbook example of the rudimentary semiotic process. As such, it gives an excellent opportunity to better understand both semiosis and biology. Our study reviews this phenomenon in the light of up-to-date scientific knowledge to answer the most basic semiotic questions: what is the sign? What types of signs are there? What is the meaning understood on the molecular level, and by what means can it grow with time? As a case study, (...) the bacterial chemotaxis toward glucose in E. coli species is chosen, and the semiotic framework of Charles Sanders Peirce applied. The analyses provide us with the following results: the sign, in its ultimate nature, is a general process. Bacterial chemotaxis can be understood in terms of Peircean type, symbol, and argument. The meaning on the molecular level is entirely pragmatic and, in this case, reduced to a bacterial response to glucose. A sign can grow through sign generalization, the emergence of different sign categories, the integration of these categories in functional cycles, and the introduction of contextuality. The sign of bacterial chemotaxis extends from the cell signaling pathways up to the population level. The presented results advance our knowledge of sign processing in the context of semiotic evolution. (shrink)

Upon first reading, the beginning of Chapter 2 of Difference and Repetition, with its talk of ―contemplative souls‖ and ―larval subjects,‖ seems something of a bizarre biological panpsychism. Actually it does defend a sort of biological panpsychism, but by defining the kind of psyche Deleuze is talking about, I‘ll show here how we can remove the bizarreness from that concept. First, I will sketch Deleuze‘s treatment of ―larval subjects,‖ then show how Deleuze‘s discourse can be articulated with Evan Thompson‘s biologically (...) based intervention into cognitive science, the ―mind in life‖ or ―enaction‖ position. Then I will then show how each in turn fits with contemporary biological work on E. coli chemotaxis (movement in response to changes in environment). (shrink)

In this paper, we develop a 3D-individual-based model to understand effect of various small-scale mechanisms in phytoplankton cells, on the cellular aggregation process. These mechanisms are: spatial interactions between cells due to their chemosensory abilities, a molecular diffusion and a demographical process. The latter is considered as a branching process with a density-dependent death rate to take into account the local competition on resources. We implement the IBM and simulate various scenarios under real parameter values for phytoplankton cells. To quantify (...) the effects of the different processes quoted above on the spatial and temporal distribution of phytoplankton, we used two spatial statistics: the Clark–Evans index and the group belonging percentage. Our simulation study highlights the role of the branching process with a weak-to-medium competition in reinforcing the aggregating structure that forms from attraction mechanisms, and shows by contrast that aggregations cannot form when competition is high. (shrink)

Our defence against microbes depends largely on the ability of neutrophils to migrate from the blood stream to sites of infection. Although the ability of animal cells to move may be primitive, and also fundamental for a number of phenomena in biology, the cellular mechanism by which neutrophils are able to move rapidly towards the infection remains an enigma. Even though the structures of the receptors involved have been sequenced and many of the molecules involved in neutrophil adherence and traction (...) identified, the essential mechanisms that control and regulate the neutrophil motor remain obscure. Here, an outline of the fundamental inadequacies in our current understanding is given, along with some recent developments that promise to produce some significant advances. (shrink)

A very rapid cellular event that follows chemotactic stimulation of leucocyte and cellular slime mould amoebae is a massive polymerization of G to F actin and its association with the cytoskeleton. In the cellular slime moulds this event occurs within 3–5 sec of cell surface binding of chemoattractants. It is correlated with rapid pseudopodium extension and may be a cell orientation mechanism. Curiously, before an amoebae moves away in the direction of its new pseudopodium it rounds up or “cringes” for (...) 10–20 sec, an event correlated with a massive actin depolymerization. Transduction of the chemotactic signal involves Ca2+ release from internal stores by inositol trisphosphate. (shrink)

Biological regulation is what allows an organism to handle the effects of a perturbation, modulating its own constitutive dynamics in response to particular changes in internal and external conditions. With the central focus of analysis on the case of minimal living systems, we argue that regulation consists in a specific form of second-order control, exerted over the core regime of production and maintenance of the components that actually put together the organism. The main argument is that regulation requires a distinctive (...) architecture of functional relationships, and specifically the action of a dedicated subsystem whose activity is dynamically decoupled from that of the constitutive regime. We distinguish between two major ways in which control mechanisms contribute to the maintenance of a biological organisation in response to internal and external perturbations: dynamic stability and regulation. Based on this distinction an explicit definition and a set of organisational requirements for regulation are provided, and thoroughly illustrated through the examples of bacterial chemotaxis and the lac-operon. The analysis enables us to mark out the differences between regulation and closely related concepts such as feedback, robustness and homeostasis. (shrink)

I consider three explanatory strategies from recent systems biology that are driven by mathematics as much as mechanistic detail. Analysis of differential equations drives the first strategy; topological analysis of network motifs drives the second; mathematical theorems from control engineering drive the third. I also distinguish three abstraction types: aggregations, which simplify by condensing information; generalizations, which simplify by generalizing information; and structurations, which simplify by contextualizing information. Using a common explanandum as reference point—namely, the robust perfect adaptation of (...) class='Hi'>chemotaxis in Escherichia coli—I argue that each strategy invokes a different combination of abstraction types and that each targets its abstractions to different mechanistic details. (shrink)

Gene regulatory networks are intensively studied in biology. One of the main aims of these studies is to gain an understanding of how the structure of genetic networks relates to specific functions such as chemotaxis and the circadian clock. Scientists have examined this question by using model organisms such as Drosophila and mathematical models. In the last years, synthetic models—engineered genetic networks—have become more and more important in the exploration of gene regulation. What is the potential of this new (...) approach in the investigation of gene network structures? How do synthetic models relate to model organisms and mathematical models? (shrink)

Organismic agency is often understood as the capacity to produce goal-directed behavior. This paper proposes a new way of modelling agency, namely as a naturalized deliberation. Deliberative action is not directed towards a particular goal, but involves a process of weighing multiple goals and a choice for a particular combination of these. The underlying causal model is symmetry breaking, where the organism breaks symmetries present in the selective environment. Deliberation is illustrated though the phenomena of mate choice and bacterial (...) class='Hi'>chemotaxis. (shrink)

Computation and philosophy intersect three times in this essay. Computation is considered as an object, as a method, and as a model used in a certain line of philosophical inquiry concerning the relation of mind to matter. As object, the question considered is whether computation and related notions of mental representation constitute the best ways to conceive of how physical systems give rise to mental properties. As method and model, the computational techniques of artificial life and embodied evolutionary connectionism are (...) used to conduct prosthetically enhanced thought experiments concerning the evolvability of mental representations. Central to this essay is a discussion of the computer simulation and evolution of three‐dimensional synthetic animals with neural network controllers. The minimally cognitive behavior of finding food by exhibiting positive chemotaxis is simulated with swimming and walking creatures. These simulations form the basis of a discussion of the evolutionary and neurocomputational bases of the incremental emergence of more complex forms of cognition. Other related work has been used to attack computational and representational theories of cognition. In contrast, I argue that the proper understanding of the evolutionary emergence of minimally cognitive behaviors is computational and representational through and through. (shrink)

Computation and philosophy intersect three times in this essay. Computation is considered as an object, as a method, and as a model used in a certain line of philosophical inquiry concerning the relation of mind to matter. As object, the question considered is whether computation and related notions of mental representation constitute the best ways to conceive of how physical systems give rise to mental properties. As method and model, the computational techniques of artificial life and embodied evolutionary connectionism are (...) used to conduct prosthetically enhanced thought experiments concerning the evolvability of mental representations. Central to this essay is a discussion of the computer simulation and evolution of three-dimensional synthetic animals with neural network controllers. The minimally cognitive behavior of finding food by exhibit- ing positive chemotaxis is simulated with swimming and walking creatures. These simulations form the basis of a discussion of the evolutionary and neurocomputa- tional bases of the incremental emergence of more complex forms of cognition. Other related work has been used to attack computational and representational theories of cognition. In contrast, I argue that the proper understanding of the evolutionary emergence of minimally cognitive behaviors is computational and representational through and through. (shrink)

Movement of leukocytes from peripheral blood into tissues, also called leukocyte extravasation, is absolutely essential for immunity in higher organisms. Over the past decade, our understanding of the molecular mechanisms involved in white blood cell extravasation during both normal immune surveillance and the generation of protective immune responses has taken a great leap forward with the discovery of the chemokine gene superfamily. Chemokines are low-molecular-weight cytokines whose major collective biological activity appears to be that of chemotaxis of both specific (...) and overlapping subsets of leukocytes. They are therefore likely to play a critical role in the directed movement of leukocytes from the bloodstream into tissue. These molecules are almost exclusively secreted and act as extracellular messengers for the immune system. However, emerging data also show that various members of the chemokine gene superfamily exert other biological effects outside the immune system. All nucleated cells and all tissues examined to date are capable of expressing at least some chemokines, and it seems likely therefore that by the time all the chemokines are identified, and all their biological functions elucidated, we will find that, as a family, these molecules perform an extracellular messenger role in all tissues and systems of the body. BioEssays 1999;21:17–28. © 1999 John Wiley & Sons, Inc. (shrink)

Philosophers of biology, along with everyone else, generally perceive life to fall into two broad categories, the microbes and macrobes, and then pay most of their attention to the latter. ‘Macrobe’ is the word we propose for larger life forms, and we use it as part of an argument for microbial equality. We suggest that taking more notice of microbes – the dominant life form on the planet, both now and throughout evolutionary history – will transform some of the philosophy (...) of biology’s standard ideas on ontology, evolution, taxonomy and biodiversity. We set out a number of recent developments in microbiology – including biofilm formation, chemotaxis, quorum sensing and gene transfer – that highlight microbial capacities for cooperation and communication and break down conventional thinking that microbes are solely or primarily single-celled organisms. These insights also bring new perspectives to the levels of selection debate, as well as to discussions of the evolution and nature of multicellularity, and to neo-Darwinian understandings of evolutionary mechanisms. We show how these revisions lead to further complications for microbial classification and the philosophies of systematics and biodiversity. Incorporating microbial insights into the philosophy of biology will challenge many of its assumptions, but also give greater scope and depth to its investigations. (shrink)

We advance an account that grounds cognition, specifically decision-making, in an activity all organisms as autonomous systems must perform to keep themselves viable—controlling their production mechanisms. Production mechanisms, as we characterize them, perform activities such as procuring resources from their environment, putting these resources to use to construct and repair the organism's body and moving through the environment. Given the variable nature of the environment and the continual degradation of the organism, these production mechanisms must be regulated by control mechanisms (...) that select when a production is required and how it should be carried out. To operate on production mechanisms, control mechanisms need to procure information through measurement processes and evaluate possible actions. They are making decisions. In all organisms, these decisions are made by multiple different control mechanisms that are organized not hierarchically but heterarchically. In many cases, they employ internal models of features of the environment with which the organism must deal. Cognition, in the form of decision-making, is thus fundamental to living systems which must control their production mechanisms. (shrink)

Teleological theories are often dismissed in the study of animal behaviour, because of both the anthropomorphic element, and the paradox of retro-causation. Instead, emergent properties of animal systems, such as those which drive behaviour and decision making, are generally deemed to be non-purposeful. Nonetheless, organisms’ interactions with the environment, including sensory processing, have long been subject to biological study, and the resulting models include Jakob von Uexküll’s functional circle (part of his ‘Umwelt Theory’). The functional circle is modelled on an (...) assumption of three- dimensional space containing matter and energy, and one-dimensional, linear time. Moreover, the function of such models relies upon feedback within biological systems, and generally assume that the functional feedback loops close. I argue that this is impossible, because a feedback loop cannot go back intime to close itself, and so whilst it may approximate closure in space, it does not close in the dimension of time. To address this problem, I propose a conceptual model where time is treated as having a three- dimensional structure, and is measured in terms of past, future, and subjective present, termed the ‘period,’ ‘present’ and ‘phase,’ respectively. Space and matter, meanwhile, occur as a two- dimensional intersect, in which three-dimensional emergent properties which occur ion time are embedded. The model relies on functional helices rather than circles, and the loops of each helix (unlike circular loops) never achieve closure. I explain how this therefore results in a biological system, based on both feedback and anticipatory probabilities, which is both autopoietic and teleological. I also provide examples of how the concept can be applied, using foraging behaviour as an example. I further propose the theoretical origin of such a system is ‘timing’ and ‘rhythm,’ both of which I argue have their origins in single cellular organisms’ chemotaxis and the associated gradient descent search. (shrink)

Free swimming cells of the ciliated protozoan Tetrahymena are attracted to certain chemicals by chemokinesis. However, a special type of chemotaxis in response to a chemical gradient is found in cells gliding very slowly in semisolid media. In contrast to classical chemotaxis by leukocytes, which is solely positive towards chemo‐attractants, the oriented chemokinesis by gliding Tetrahymena involves both positive and negative elements. The major chemo‐attractants are peptides and/or proteins, and they may be compounds which signal the presence of (...) food in the natural environment of this freshwater phagotroph. (shrink)

Atherosclerosis is the major cause of death in the industrialised world. Though much work on the pathogenesis of atherosclerosis points to 'oxidised' low density lipoprotein (LDL) as a key aetiological feature in the generation of the atherosclerotic plaque, the nature of this 'oxidised' LDL in vivo remains an enigma. We argue here that glycated LDL shows many of the characteristics attributed to 'oxidised LDL' and may be the source of the latter in vivo. These include the increased uptake and impaired (...) degradation of glycated LDL by macrophages and the stimulation of transendothelial chemotaxis of monocytes, cytokine secretion and platelet aggregation. We hypothesise that the covalent binding of glycated LDL to the endothelial cell wall may result in the formation of the early atherosclerotic lesion of the fatty streak and that apolipoprotein E may mediate the physiological clearance of glycated moieties. The proposed role of glycation in the pathogenesis of atherosclerosis would explain its high incidence among diabetics and the contentious epidemiological and experimental correlations between dietary sugar and atherosclerosis. (shrink)

A considerable challenge confronts, any developing neuron. Before it can establish a functional and specific connection, it must extend an axon over tens and sometimes hundreds of microns through a complex and mutable environment to reach one out of many possible destinations. The field of axonal guidance concerns the control of this navigation process. To satisfactorily identify the cell interactions and molecular mechanisms that mediate axonal guidance, it is essential to first identify the pertinent cell populations. Embryonic surgeries have provided (...) solid information on which tissues are critical and which are irrelevant to the navigation of motor axons within the chick embryo. The gross anatomical nerve pattern is established as axons respond to both positive (path) and negative (barrier) tissue environments. Analysis of the interactions of motoneurons with these tissues reveals that several cellular interactions – chemotaxis, substratum preference, and perhaps contact paralysis – are important to the common patterns of motor axon advance. Axons simultaneously interact with population‐specific cues that have begun to be identified on the tissue level. (shrink)

Heterotrimeric G proteins, consisting of α, β, and γ subunits, couple ligand-bound seven transmembrane domain receptors to the regulation of effector proteins and production of intracellular second messengers. G protein signaling mediates the perception of environmental cues in all higher eukaryotic organisms, including yeast, Dictyostelium, plants, and animals. The nematode Caenorhabditis elegans is the first animal to have complete descriptions of its cellular anatomy, cell lineage, neuronal wiring diagram, and genomic sequence. In a recent paper, Jansen et al.(1) used sequence (...) searches of the C. elegans genome database to identify all heterotrimeric G protein genes (20 Gα, 2 Gβ, 2 Gγ). C. elegans encodes one ortholog of each of the four Gα classes found in metazoans and 16 new Gα genes. The orthologous genes are widely expressed, whereas 14 of the divergent Gα genes are almost exclusively expressed in sensory neurons where they may regulate perception and chemotaxis.BioEssays 21:713–717, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

Interferon (IFN) induced during a virus infection mediates antiviral effects both by direct inhibition of virus replication and by influencing the proliferation, differentiation, and chemotaxis of cyto‐toxic lymphocytes which control the infection. Cells from tissue taken from virus‐infected mice are conditioned by IFN to resist lysis by natural killer (NK) cells, while they become increasingly susceptible to lysis by cytotoxic Tlymphocytes (CTL). This is due to marked IFN‐induced biochemical changes, including an up‐regulation of major histocompatibility antigens, which are targets (...) for CTL. Cytopathic viruses, which inhibit cellular RNA and protein synthesis, render target cells refractory to IFN‐mediated protection against NK cells, thereby providing a mechanism for NK cells to mediate antiviral effect by preferentially lysing virus‐infected but not uninfected cells. (shrink)

Heterotrimeric G proteins, consisting of α, β, and γ subunits, couple ligand-bound seven transmembrane domain receptors to the regulation of effector proteins and production of intracellular second messengers. G protein signaling mediates the perception of environmental cues in all higher eukaryotic organisms, including yeast, Dictyostelium, plants, and animals. The nematode Caenorhabditis elegans is the first animal to have complete descriptions of its cellular anatomy, cell lineage, neuronal wiring diagram, and genomic sequence. In a recent paper, Jansen et al.(1) used sequence (...) searches of the C. elegans genome database to identify all heterotrimeric G protein genes (20 Gα, 2 Gβ, 2 Gγ). C. elegans encodes one ortholog of each of the four Gα classes found in metazoans and 16 new Gα genes. The orthologous genes are widely expressed, whereas 14 of the divergent Gα genes are almost exclusively expressed in sensory neurons where they may regulate perception and chemotaxis.BioEssays 21:713–717, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

It has long been unclear as to why particular cancers preferentially metastasize to certain sites. The possibilities usually discussed involve differential survival and proliferation at these sites, or selective trapping with or without preferential homing. A recent report by Muller et al.(1) provides evidence for preferential homing of breast cancer to metastatic sites. The findings indicate that the chemokine receptors CXCR4 and CCR7 are found on breast cancer cells and their ligands are highly expressed at sites associated with breast cancer (...) metastases. This results in chemotaxis, or directed migration of tumor cells from their primary site via the circulation to the preferential sites of metastases. The evidence for this model and its significance are reviewed here. BioEssays 23:674–676, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Cell signalling mediators derived from membrane phospholipids are frequent participants in biological processes. The family of phosphoinositide 3-kinases (PI3Ks) phosphorylate the membrane lipid phosphatidylinositol, generating second messengers that direct diverse responses. These PI3K products are fundamental for leukocyte migration or chemotaxis, a pivotal event during the immune response. This system is therefore of significant biomedical interest. This review focuses on the biochemistry and signalling pathways of PI3K, with particular emphasis on chemokine (chemotactic cytokine)-directed responses. The key objectives of (...) class='Hi'>chemotaxis are motility and direction. The latter—direction—requires distinct events at the front and back of a cell. In light of this, the coordinated localisation of signalling factors, an event choreographed by a sharp intracellular gradient of PI3K-derived products, is a common theme. BioEssays 27:153–163, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

ZusammenfassungNach zwölf Jahren intensiver Forschung etablierte der Ophthalmologe Theodor Leber (1840–1917) am Ende des 19. Jahrhunderts in der Entzündungsforschung die Chemotaxis der Leukozyten. Obwohl sich seine Theorie damals reibungslos in die immunologische Forschung einschrieb, wird sein Name jedoch bis heute nur in der englischsprachigen Fachliteratur mit der Chemotaxis verknüpft. In seinem Experimentalsystem hatte Leber zwar schon Anfang der 1880er Jahre eine Theorie der chemischen Attraktion der Leukozyten beim Entzündungsprozess entwickeln können. Aber seine unkonventionelle Methodik—die Einführung von chemisch indifferentem (...) Fremdmaterial zur Auslösung einer Entzündung am Kaninchenauge—widersprach schon vom Ansatz her dem zu diesem Zeitpunkt dominant bakteriologischen Denkstil der Entzündungsforschung. In diesem Forschungsfeld hielt Leber an einer Forschungspraxis fest, die aus einer engen Verzahnung von experimenteller und theoretischer Arbeit bestand. Erst als eine Öffnung des bakteriologischen Denkstils eingetreten war, gelang es Leber seine auf losen Protokollseiten festgehaltenen Versuchsbeobachtungen in überzeugende Belege seiner Entzündungstheorie zu transformieren. Die mikrohistorische Rekonstruktion von Lebers experimenteller und schriftlicher Arbeit anhand seiner Laborprotokolle erschließt die Forschungspraxis eines Wissenschaftlers, der in der damals etablierten mikrobiologischen Entzündungsforschung kaum Anerkennung fand. Durch Verbindung der mikrohistorischen Rekonstruktion mit einer makrohistorischen Analyse lassen sich außerdem Beharrungsfaktoren im Prozess der Wissensentstehung offenlegen. Leber entwickelte eine spezifische Papiertechnik, durch die er seine experimentellen Erkenntnisse zwar mobilisierte und stabilisierte, aber nicht mit dem Fortschreiten der Wissenschaft mithalten konnte. (shrink)

ZusammenfassungNach zwölf Jahren intensiver Forschung etablierte der Ophthalmologe Theodor Leber (1840–1917) am Ende des 19. Jahrhunderts in der Entzündungsforschung die Chemotaxis der Leukozyten. Obwohl sich seine Theorie damals reibungslos in die immunologische Forschung einschrieb, wird sein Name jedoch bis heute nur in der englischsprachigen Fachliteratur mit der Chemotaxis verknüpft. In seinem Experimentalsystem hatte Leber zwar schon Anfang der 1880er Jahre eine Theorie der chemischen Attraktion der Leukozyten beim Entzündungsprozess entwickeln können. Aber seine unkonventionelle Methodik—die Einführung von chemisch indifferentem (...) Fremdmaterial zur Auslösung einer Entzündung am Kaninchenauge—widersprach schon vom Ansatz her dem zu diesem Zeitpunkt dominant bakteriologischen Denkstil der Entzündungsforschung. In diesem Forschungsfeld hielt Leber an einer Forschungspraxis fest, die aus einer engen Verzahnung von experimenteller und theoretischer Arbeit bestand. Erst als eine Öffnung des bakteriologischen Denkstils eingetreten war, gelang es Leber seine auf losen Protokollseiten festgehaltenen Versuchsbeobachtungen in überzeugende Belege seiner Entzündungstheorie zu transformieren. Die mikrohistorische Rekonstruktion von Lebers experimenteller und schriftlicher Arbeit anhand seiner Laborprotokolle erschließt die Forschungspraxis eines Wissenschaftlers, der in der damals etablierten mikrobiologischen Entzündungsforschung kaum Anerkennung fand. Durch Verbindung der mikrohistorischen Rekonstruktion mit einer makrohistorischen Analyse lassen sich außerdem Beharrungsfaktoren im Prozess der Wissensentstehung offenlegen. Leber entwickelte eine spezifische Papiertechnik, durch die er seine experimentellen Erkenntnisse zwar mobilisierte und stabilisierte, aber nicht mit dem Fortschreiten der Wissenschaft mithalten konnte. (shrink)