Academic literature on the topic 'Degree Discipline: Cell and Molecular Bioscience'

Abstract Abstract 237 Von Willebrand Disease (VWD) is an inherited rare bleeding disorder caused by a deficiency of von Willebrand factor (VWF). VWF is the largest soluble multimeric plasma glycoprotein, which facilitates platelet aggregation and stabilizes FVIII in the circulation. Patients with type 3 disease display severe hemorrhagic symptoms, mainly in mucosal tissues, muscle and joints. Replacement of VWF stabilizes endogenous FVIII to hemostatic levels within hours. Commercially available VWF/FVIII concentrates are plasma-derived (pd) and subject to limitations such as donor dependency, risk of blood-borne pathogen transmission, lack of high molecular weight VWF multimers, and variation in multimer composition. A novel recombinant human VWF (rhVWF) has been developed using a plasma-free method, which represents the largest protein ever produced using recombinant technology. Safety, tolerability and pharmacokinetics of the rhVWF combined at a fixed ratio with rFVIII were investigated in a Phase 1 multicenter, international clinical study in 31 patients with type 3 VWD and severe type 1 VWD. Four concentrations of rhVWF (2, 7.5, 20 and 50 IU VWF:RCo/kg) were administered in a dose-escalating manner in separate cohorts. rhVWF was well tolerated, and no thrombotic events, VWF inhibitors or other serious adverse reactions were observed. Pharmacokinetics of rhVWF/rhFVIII (50 IU VWF:RCo/kg and 38.5 IU FVIII/kg) compared with pdVWF/pdFVIII (50 IU VWF:RCo/kg and 21 IU/kg FVIII/kg) were evaluated in a sub-group of 8/31 patients using a randomized, crossover design (8-day minimum washout period). Interim data in 8 subjects show a higher degree of secondary FVIII activity with rhVWF/rhFVIII compared to pdVWF/pdFVIII (see Figure 1) that is not solely due the difference in the rhVVF:FVIII infusion ratio (1.3:1 rhVWF/rhFVIII vs. approximately 2:1 pdVWF/pdFVIII). The pharmacokinetics of the rhVWF:RCo and pdVWF:RCo were comparable and were also reflected in the VWF:Ag and collagen binding activity. Evidence is also provided for the in vivo cleavage of the ultra-high molecular weight multimers of rhVWF by endogenous ADAMTS13. In summary, interim data from the ongoing Phase 1 study, demonstrate that rhVWF is safe and well tolerated, has VWF:RCo pharmacokinetics that are comparable to pdVWF and enhances stabilization of endogenous FVIII. Multiple doses of rhVWF/rhFVIII would be expected to have beneficial effects in major surgery and severe mucosal bleeding events. These data would also support the treatment concept to administer rhVWF alone once a therapeutic baseline level of endogenous FVIII is achieved (after 1–2 doses).Figure 1:Preliminary PK data from 8 subjects post-infusion of either rhVWF/rhFVIII or pdVWF/pdFVIII. Endogenous FVIII activity reached a plateau after 6 hours and remained stable for at least 30 hours. FVIII was still elevated well above baseline at 96 hoursFigure 1:. Preliminary PK data from 8 subjects post-infusion of either rhVWF/rhFVIII or pdVWF/pdFVIII. Endogenous FVIII activity reached a plateau after 6 hours and remained stable for at least 30 hours. FVIII was still elevated well above baseline at 96 hours Disclosures: Suiter: Baxter BioScience: Employment. Laffan:Baxter BioScience: Consultancy. Mannucci:Baxter BioScience: Consultancy. Kempton:Baxter BioScience: Consultancy. Romond:Baxter BioScience: Consultancy. Shapiro: Baxter BioSci- ence: Consultancy. Birschmann:Baxter BioScience: Consultancy. Gill:Baxter BioScience: Consultancy. Ragni:Baxter BioScience: Consultancy. Turecek:Baxter BioScience: Employment. Ewenstein:Baxter Bioscience: Employment. Baxter BioScience:Baxter BioScience: Employment.

Abstract Abstract 3328 Joint bleeding is the most frequent serious manifestation of hemophilia and results in significant morbidity, cost and decrement in quality of life. Although prophylaxis has significantly reduced both the frequency of joint bleeding and the development of arthropathy, hemarthrosis continues to be a problem, especially in patients with inhibitors. Understanding the pathobiology of blood-induced joint disease and developing measures to counter this problem remain as central issues in the field. The use of animal models to interrogate the earliest molecular and biochemical steps in this process is useful since such information is not available from humans. As the degree of induced joint bleeding in factor VIII deficient mice is heterogeneous, it is crucial to preclinical and basic research to assess and/or control bleeding severity in each comparable experimental group. Previously, we have created a mouse model of phenotypic variability based on injecting mice with varying concentrations of rFVIII. A chromogenic assay was used to assess the plasma levels of FVIII activity following treatment. [Hemophilia (2011), 17,565] Here we report on an objective system of four independent but inter-related measurements to document this phenotypic variability in a mouse model of hemophilia A: Visual Bleeding Score (VBS), joint diameter, Gross Bleeding Score (GBS) and Histological Bleeding Score (HBS). In order to achieve similar severities of hemarthrosis, groups of F8−/− mice were injected with rFVIII at specified time points prior to induction of bleeding. Each day following injury, the knee joints were examined for the presence of blood and the VBS was assigned. Three days after injury all mice were sacrificed, knee diameters were measured, GBS was assigned and the joints collected for histological examination to determine the HBS. At all-time points the data show a statistically significant correlation between gross (GBS) and histological (HBS) changes (0.87–0.99, P<0.0001) and the residual plasma factor VIII activity measured at the time of injury. The validation study of GBS included 256 samples and five raters blinded to the experimental conditions and showed high and statistically significant correlations between the actual joint scores and the scores of each rater (Spearman correlation, 0.93–0.97). There were no statistically significant differences among intra-observer scores (Friedman test, 0.1–0.8). In conclusion, this scoring system can be used to objectively document phenotypic variability in a mouse model of Hemophilia A. The next step is to use this model to probe the efficacy of novel agents to treat Hemophilia in pre-clinical and clinical development. Disclosures: Valentino: Baxter Bioscience, Bayer Healthcare, GTC Biotherapeutics, NovoNordisk, Pfizer, CSL Behring, Inspiration Bioscience, and Biogen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Abstract Introduction ALK-negative anaplastic large cell lymphoma (ALK- ALCL) is an uncommon type of T-cell non-Hodgkin lymphoma (T-NHL) with worse prognosis compared to ALK-positive (ALK+) ALCLs. Most published studies on the genomics of T-NHL have focused on peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), and previous studies of ALCL described rearrangements in DUSP22 and TP63 and mutations in genes comprising the JAK/STAT pathway as common genetic drivers in ALK- ALCL. The degree to which these drivers affect survival or other molecular features of ALK- ALCL remains unknown. Here, we describe novel subgroups of ALK- ALCL that exhibit distinct survival. One subgroup appears molecularly similar to ALK+ALCLs and is associated with favorable survival while the second subgroup is quite distinct from ALK- ALCLs and associated with poor outcomes. Methods and Results Eighty-two ALK- ALCL patients were recruited to the Atlas of Blood Cancer (ABC) genomes project, a worldwide consortium established to define the molecular origins of blood cancers. Tumor biopsies from these patients, as well as 10 ALK+ ALCL samples for comparison were obtained from participating institutions. Each case was subjected to centralized pathology review by an experienced panel of hematopathologists to ensure the accuracy of the diagnosis. All cases, along with paired normal tissues, were subjected to DNA and RNA (whole exome-level) sequencing on the Illumina platform to identify mutations and expression changes for each of these cases using methods well established in our group and described previously. We first examined the genetic alterations in ALK- ALCLs. In addition to frequently described genetic alterations such as TP63 and DUSP22 rearrangements, as well as mutations in JAK1, STAT3 and TP53, we also detected mutations in ERBB4, SETD2 and KMT2D, which may serve as potential novel drivers and have not been described previously to our knowledge. We next performed comparative gene expression analysis of the ALK- and ALK+ ALCLs. Surprisingly, a proportion of ALK- ALCL cases (38%) clustered together with ALK+ ALCLs and had a signature resembling ALK+ cases, which we designated as "ALK-like ALCL" here. Both the ALK-like ALCLs and the other ALK- ALCL cases showed decreased ALK expression compared to the ALK+ ALCLs by gene expression analysis. These results point to downstream pathways that are common among ALK+ALCLs and ALK-like ALCLs, but different from the other ALK- ALCLs. Gene set enrichment analysis revealed that the ALK-like ALCLs overexpressed genes in pathways related to monocyte and fibroblast activation, whereas the remaining ALK- ALCLs overexpressed genes in the T follicular helper cells, memory T cells and adaptive immune response-related pathways (P&lt;0.001 in all cases). Kaplan-Meier survival analysis revealed that patients with ALK-like ALCL had significantly better overall survival compared to the other cases (P=0.01, Wald test). Conclusion Our data indicate that ALK- ALCLs represent a heterogeneous group of diseases and comprise at least two distinct subgroups that can be identified based on their similarity to the ALK+ ALCLs. The ALK-like ALCLs demonstrated distinct molecular features and favorable outcomes. Our results provide a potentially new approach to patient risk-stratification and pathological classification of this disease. Disclosures Kwong: Celgene: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; BeiGene: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding. Jaye: Stemline Therapeutics: Honoraria. Behdad: Roche/Foundation Medicine: Speakers Bureau; Thermo Fisher: Speakers Bureau; Lilly: Speakers Bureau. Hsi: AbbVie Inc, Eli Lilly: Research Funding. Dave: Data Driven Bioscience: Current equity holder in publicly-traded company.

There are many ways of describing and explaining the properties of living systems; causal, functional, and reductive accounts are necessary but no one account has primacy. The history of biology as a discipline has given excessive authority to reductionism, which collapses higher level accounts, such as social or behavioural ones, into molecular ones. Such reductionism becomes crudely ideological when applied to the human condition, with its claims for genes “for” everything from sexual orientation to compulsive shopping. The current enthusiasm for genetics and ultra-Darwinist accounts, with their selfish-gene metaphors for living processes, misunderstand both the phenomena of development and the interactive role that DNA and the fluid genome play in the cellular orchestra. DNA is not a blueprint, and the four dimensions of life (three of space, one of time) cannot be read off from its one-dimensional strand. Both developmental and evolutionary processes are more than merely instructive or selective; the organism constructs itself, a process known as autopoiesis, through a lifeline trajectory. Because organisms are thermodynamically open systems, living processes are homeodynamic, not homeostatic. The self-organising membrane-bound and energy-utilising metabolic web of the cell must have evolved prior to so-called naked replicators. Evolution is constrained by physics, chemistry, and structure; not all change is powered by natural selection, and not all phenotypes are adaptive. Finally, therefore, living processes are radically indeterminate; like all other living organisms, but to an even greater degree, we make our own future, though in circumstances not of our own choosing.

Abstract Background The molecular pattern of severe burn-induced acute lung injury, characterized by cell structure damage and leukocyte infiltration, remains unknown. This study aimed to determine whether calpain, a protease involved in both processes, mediates severe burn-induced acute lung injury. Methods Rats received full-thickness scald burns covering 30% of the total body surface area, followed by instant fluid resuscitation. MDL28170 (Tocris Bioscience), an inhibitor of calpain, was given intravenously 1 h before or after the scald burn. The histological score, wet/dry weight ratio, and caspase-3 activity were examined to evaluate the degree of lung damage. Calpain activity and its source were detected by an assay kit and immunofluorescence staining. The proteolysis of membrane skeleton proteins α-fodrin and ankyrin-B, which are substrates of calpain, was measured by Western blot. Results Time-course studies showed that tissue damage reached a peak between 1 and 6 h post-scald burn and gradually diminished at 24 h. More importantly, calpain activity reached peak levels at 1 h and was maintained until 24 h, paralleled by lung damage to some extent. Western blot showed that the levels of the proteolyzed forms of α-fodrin and ankyrin-B correlated well with the degree of damage. MDL28170 at a dose of 3 mg/kg b. w. given 1 h before burn injury not only antagonized the increase in calpain activity but also ameliorated scald burn-induced lung injury, including the degradation of α-fodrin and ankyrin-B. Immunofluorescence images revealed calpain 1 and CD45 double-positive cells in the lung tissue of rats exposed to scald burn injury, suggesting that leukocytes were a dominant source of calpain. Furthermore, this change was blocked by MDL28170. Finally, MDL28170 given at 1 h post-scald burn injury significantly ameliorated the wet/dry weight ratio compared with burn injury alone. Conclusions Calpain, a product of infiltrating leukocytes, is a mediator of scald burn-induced acute lung injury that involves enhancement of inflammation and proteolysis of membrane skeleton proteins. Its late effects warrant further study.

Health Health is a production, a process, and not a goal. It is a means and not an end state, required “to liberate life wherever it is imprisoned by and within man, by and within organisms and genera” (Deleuze). We live our health as a network, within networks, within social, technological, political and biological networks, but how does the network concept understand health? And how does the network concept implicate health within other networks, for better or for worse? Biopolitical Relations In its diverse forms, network thinking institutes a relational ontology, an ontology of connection and of connectedness. Whether the connections being explored are those governing the proverbial ‘six degrees of separation’, the small world in which “no-one is more than a few handshakes from anyone else”, the rhizomatic imperative that not only is everything connected but it must be, or even the ordinality of the mathematical regimen of belonging (Alain Badiou), one gains the impression that network thinking is the expression of a common world-view, a zeitgeist. Yet to think in this way is not only to lose sight of the important qualitative differences evident in the manifold conceptions of ‘network’ but is also to overlook differences in descent in the genealogy of knowledges and hence the differential inscription of those knowledges in power relations (another network…). The case of immunology is analysed here as one line of descent in network thinking, selected here for its susceptibility to exemplify a series of biopolitical implications which may not be so evident in other scientific fields. What follows is an attempt to address some of these implications for our understanding of the materiality of communications. Self - Nonself Since the groundbreaking work of Sir Frank MacFarlane Burnett in the 1940s and 1950s, immunology has become known as the ‘science of self-nonself discrimination’. In the first half of the twentieth century, as Pauline Mazumdar has argued, immunology was caught up in a classificatory problematic of the nature of species and specificity. In the latter half of the twentieth century, it might be argued, this concern becomes a more general one of the nature of biological identity and the mechanisms of organic integrity. Yet it is licit to see in these innocently scientific concerns the play of another set of interests, another set of issues or, to put it slightly differently, another problematic. We can see in the autonymic definition of immunology as the ‘science of self-nonself discrimination’ a biopolitical concern with the nature, maintenance and protection of populations: a delegation of the health of the body to a set of autonomous biological mechanisms, an interiorisation of a social and political problematic parallel to the interiorisation of the social repression of desire traced out by Gilles Deleuze and Felix Guattari in their Anti-Oedipus. There are a number of points which are relevant here. The intellectual roots of immunology are to be found in Darwinian theory. Socially, however, immunology develops out of a set of public health practices, a set of public health reforms. Immunology locates the mechanisms for maintaining the integrity of the organism ‘under the skin’ and in a sense shifts the focal point of the problem of health to the internal workings of the organism. In this way, it reconfigures the field of social action. The enormous success of vaccination programmes and a concentration on the ‘serologic’ of immunisation focalises immunological research on outer-directed reactions. We can find a trace of the social field to which immunology is related in the name of the discipline itself. The term ‘immunology’ derives from the Latin term ‘immunitas’ which signified an exemption from public duty. The mechanisms of the immune system are routinely figured as weapons in a war against the enemy (Paul Ehrlich: “magic bullets”). And war, as Agamben has argued, exemplifies a state of exception. Given the way in which immunology shifts health inside the body, its enemies become ‘any enemies whatever’, microphysical forces with no apparent connection to the socius. The ability to combat any enemy whatever offers decisive evidence of the miraculous abilities of the self, the sovereignty of its powers. The self which the immune system protects is imagined to be defined anterior to that system, on a genetic basis, independent of the rules governing interactions in the system itself. The ability of the immune system to respond to and destroy any enemy whatever and thus maintain the organism’s sovereign identity demonstrates its ‘intolerance for foreign matter’ (Macfarlane Burnet). The molecular terrain on which its combat is waged is only apparently divorced from the socius. Idiotypy Network theory offers an interesting response to this set of ideas. Niels Jerne developed idiotypic network theory as a way of overcoming some of the difficulties in the accepted version of how the immune system works. The immune system possesses the remarkable ability to distinguish between everything which is a friend of the organism and everything which is an enemy. The key question which this poses is this: how and on what basis does the immune system not react to self, why does it posses what Paul Ehrlich called ‘horror autotoxicus’? The standard wisdom is to maintain that those elements which can react to self are firstly only very small in number and, secondly, eliminated by a process of learning (‘clonal deletion’). Yet this view is wrong on both counts – there is a far higher concentration of ‘auto-antibodies’ in the individual organism than the standard theory suggests, and an organism which develops in the absence of contact with ‘antigens’ originating in the environment can nevertheless develop a perfectly functional immune system. Jerne’s theory develops as a piece of self-organisational wisdom. Everything in the immune system is connected. The activities of all the elements in the system are regulated by the activities of every other. One type of cell specifically recognises and thus is stimulated into action (i.e. the production of clones) by another. However, this reaction is dampened down by another recognition event: the proliferation of clones of the first type of cell is regulated by the response of a third (also a production), and so on. This cascading chain of stimulus-response events is called an idiotypic network, by Jerne, a recurrent set of ‘eigen-behaviours’, and it reverses the conventional wisdom about the way in which the immune system operates: the destructive response to the other is no longer an exception but a limiting case in the auto-consistent behaviour of a self-organising network. An immune reaction is not a characteristic of the miraculous power of the immune system but a consequence of the network’s loss of plasticity. Autopoiesis Francisco Varela and the so-called ‘Paris School’ have managed to draw out the radical consequences of this way of looking at organic processes. The first point they make is that idiotypic network theory substitutes an autonomous conception of immunity for the predominantly heteronomous view of immunity as a set of defensive mechanisms. A variant on the more general autopoietic postulate of the circular causality inhering in living systems, the eigen-behaviour used to characterise immune networks attempts to move our understanding of biological processes away from the biopolitical problematic of defence and security. As Varela and Anspach put it, “to say that immunity is fundamentally defence is as distorted as saying that the brain is fundamentally concerned with defence and avoidance. We certainly defend ourselves and avoid attack, but this is hardly what cognition is about, that is flexibility in living”. An idiotypic network is thus conceptualised as a radically autonomous system, which effectively knows no outside. The idea that the immune network has defence as its prime function is argued by Varela to result from the epistemically relative nature of the claims made by the biologist: it is a claim which makes sense from the specific point of view of the observer but does not – cannot – explain what the immune network is doing in its own terms. The place of the observer in biology is fundamentally contingent. The assertion of the contingent nature of the observation in biology is not, however, accompanied by an analysis of the immanent implication of these observations in the socius. As Maturana himself has noted, “the fact that science as a cognitive domain is constituted and validated in the operational coherences of the praxis of living of the standard observers as they operate in their experiential domains without reference to an independent reality does not make scientific statements subjective”. Certainly not, if these statements can be demonstrated to belong to a specific set of discursive ‘regularities’. The argument that the immune network does not have defence as its primary function of course raises the question of what the immune network is actually for. The research carried out by Varela and his associates suggests, and this is the second point, that the immune network is responsible for the assertion of organic identity. Far from being a secondary mechanism for the protection of a sovereign identity defined elsewhere and otherwise, the organisation of the immune network as a recurrent set of mutually reinforcing chemical interactions (in which defence is instead the result of an excessive perturbation of the system), suggests that the network has a primary role in defining identity. To put it another way, the immune network is a means of individuation. The field of theoretical immunology more generally has explored the logic of the network constitution of individuality. Experimental evidence suggests that vertebrate organisms replace up to 20% of the chemical components constituting the immune network daily, thus demonstrating a highly productive processual character, but how does this activity cohere into the development of a consistent set? Theoretical immunologists use some of the arguments of complexity theory to show that even the continuous random production of notional molecular compounds (which would correspond to the elements of the immune network – B-cells, T-cells and so on) can yield an organised consistent set. They argue that this set or network of interactions forms a ‘cognitive field’ which determines the sensitivity of the network to any one of its elements at any moment in time. The sensitivity of the network – equally its degree of connectedness – determines the likelihood that any element will be integrated or rejected. The less connected the network to any element, the more likely that element will be rejected. Interestingly, the shape of the cognitive field of the network – what it is sensitive to – varies over time, and the network is more flexible, or plastic, at earlier stage in its history than later. The crucial point, however, is that there are no necessarily enduring components to this network. A useful term to describe this is metastability: immune networks provide evidence for an ongoing process of individuation, itself a more or less chaotic process. Such a view is far from gaining univocal adherence in the immunological community and yet it certainly offers an interesting and inventive way of looking at the anomalies of currently available experimental evidence, not least the difficulties standard theory has of grasping auto-immune diseases. But does the network conception of immunity displace the biopolitical problematic ? As mentioned above, for Varela this view of the immune network as an autonomous, cognitive system offers a way out of the predominantly militaristic characterisation of the organism’s maintenance mechanisms, and thus permits the conceptualisation of what he calls ‘flexibility in living’. Yet, if the claim sketched out above concerning the link between immunology and biopolitics is correct, one is entitled to ask about the extent to which network thought as a way of grasping biological processes can really constitute a locus of resistance to contemporary biopolitical imperatives. Pacification To finish, it is worth noting firstly that with biopolitics, in the genealogy sketched out by Foucault, mutations in power are accompanied by a shift in its phenomenal manifestation: the noisy destructiveness of sovereignty, with its power over life and death, is replaced by the anonymity of the grey procedures of knowledge. Cognition could perhaps be another form of power. And power is for Foucault, of course, a network. Or, to take another view, contemporary power may be characterised by the state of the exception becoming the rule (Agamben): the exceptional response of the sovereign has spread across the whole social fabric or by the generalised diffusion of the death drive across the whole of the socius (Deleuze and Guattari). The diffuse cognitive qualities of the network conception of immunity might in this sense correspond to contemporary shifts in the nature of power and its exercise. As Francois Ewald has put it in his discussion of Foucault’s Discipline and Punish, “[n]ormative knowledge appeals to nothing exterior to that which it works on, that which it makes visible. What precisely is the norm? It is the measure which simultaneously individualises, makes ceaseless individualisation possible and creates comparability”. Works Cited Giorgio Agamben Homo Sacer (Stanford University Press, Stanford CA, 1998) Albert-Làszló Barabàsi Linked: The New Science of Networks (Perseus, Cambridge MA,2002) Gilles Deleuze and Felix Guattari Anti-Oedipus (Minnesota University Press, Minneapolis, 1983) François Ewald ‘A power without an exterior’ in T.J. Armstrong (ed.) Michel Foucault Philosopher (Harvester Wheatsheaf, Hemel Hempstead, 1992) Pauline Mazumdar Species and Specificity (Cambridge University Press, Cambridge, 1995) Francisco Varela and Mark Anspach ‘The Body Thinks: The Immune System in the Process of Somatic Individuation’ in Hans Ulrich Gumbrecht and K.Ludwig Pfeiffer (eds.) Materialities of Communication (Stanford University Press, Stanford CA,1994) Cary Wolfe ‘In Search of Post-Humanist Theory: The Second-Order Cybernetics of Maturana and Varela’ in Cultural Critique (Spring 1995) 30:36 <http://www.santafe.edu/projects/immunology/> Links http://www.santafe.edu/projects/immunology/%20 Citation reference for this article Substitute your date of access for Dn Month Year etc... MLA Style Goffey, Andrew. "Idiotypic Networks, Normative Networks" M/C: A Journal of Media and Culture< http://www.media-culture.org.au/0308/07-idiotypic.php>. APA Style Goffey, A. (2003, Aug 26). Idiotypic Networks, Normative Networks. M/C: A Journal of Media and Culture, 6,< http://www.media-culture.org.au/0308/07-idiotypic.php>

IntroductionIf human beings have become a geophysical force, capable of impacting the very crust and atmosphere of the planet, and if geophysical forces become objects of study, presences able to be charted over millions of years—one of our many problems is a 'naming' problem. - Bethany NowviskieThe anthropocene "denotes the present time interval, in which many geologically significant conditions and processes are profoundly altered by human activities" (S.Q.S.). Although the narrative and terminology of the anthropocene has not been officially legitimized by the scientific community as a whole, it has been adopted worldwide by a plethora of social and cultural studies. The challenges of the anthropocene demand interdisciplinary efforts and actions. New contexts, situations and environments call for original naming propositions: new terminologies are always illegitimate at the moment of their first appearance in the world.Against the background of the naming challenges of the anthropocene, we will map the emergence and tell the story of a tiny world within the world of media studies: the world of the term 'nanomedia' and its hyphenated sister 'nano-media'. While we tell the story of the uses of this term, its various meanings and applications, we will provide yet another possible interpretation and application to the term, one that we believe might be helpful to interdisciplinary media studies in the context of the anthropocene. Contemporary media terminologies are usually born out of fortuitous exchanges between communication technologies and their various social appropriations: hypodermic media, interactive media, social media, and so on and so forth. These terminologies are either recognised as the offspring of legitimate scientific endeavours by the media theory community, or are widely discredited and therefore rendered illegitimate. Scientific legitimacy comes from the broad recognition and embrace of a certain term and its inclusion in the canon of an epistemology. Illegitimate processes of theoretical enquiry and the study of the kinds of deviations that might deem a theory unacceptable have been scarcely addressed (Delborne). Rejected terminologies and theories are marginalised and gain the status of bastard epistemologies of media, considered irrelevant and unworthy of mention and recognition. Within these margins, however, different streams of media theories which involve conceptual hybridizations can be found: creole encounters between high culture and low culture (James), McLuhan's hybrid that comes from the 'meeting of two media' (McLuhan 55), or even 'bastard spaces' of cultural production (Bourdieu). Once in a while a new media epistemology arises that is categorised as a bastard not because of plain rejection or criticism, but because of its alien origins, formations and shape. New theories are currently emerging out of interdisciplinary and transdisciplinary thinking which are, in many ways, bearers of strange features and characteristics that might render its meaning elusive and obscure to a monodisciplinary perspective. Radical transdisciplinary thinking is often alien and alienated. It results from unconventional excursions into uncharted territories of enquiry: bastard epistemologies arise from such exchanges. Being itself a product of a mestizo process of thinking, this article takes a look into the term nanomedia (or nano-media): a marginal terminology within media theory. This term is not to be confounded with the term biomedia, coined by Eugene Thacker (2004). (The theory of biomedia has acquired a great level of scientific legitimacy, however it refers to the moist realities of the human body, and is more concerned with cyborg and post-human epistemologies. The term nanomedia, on the contrary, is currently being used according to multiple interpretations which are mostly marginal, and we argue, in this paper, that such uses might be considered illegitimate). ’Nanomedia’ was coined outside the communications area. It was first used by scientific researchers in the field of optics and physics (Rand et al), in relation to flows of media via nanoparticles and optical properties of nanomaterials. This term would only be used in media studies a couple of years later, with a completely different meaning, without any acknowledgment of its scientific origins and context. The structure of this narrative is thus illegitimate, and as such does not fit into traditional modalities of written expression: there are bits and pieces of information and epistemologies glued together as a collage of nano fragments which combine philology, scientific literature, digital ethnography and technology reviews. Transgressions Illegitimate theories might be understood in terms of hybrid epistemologies that intertwine disciplines and perspectives, rendering its outcomes inter or transdisciplinary, and therefore prone to being considered marginal by disciplinary communities. Such theories might also be considered illegitimate due to social and political power struggles which aim to maintain territory by reproducing specific epistemologies within a certain field. Scientific legitimacy is a social and political process, which has been widely addressed. Pierre Bourdieu, in particular, has dedicated most of his work to deciphering the intricacies of academic wars around the legitimacy or illegitimacy of theories and terminologies. Legitimacy also plays a role in determining the degree to which a certain theory will be regarded as relevant or irrelevant:Researchers’ tendency to concentrate on those problems regarded as the most important ones (e.g. because they have been constituted as such by producers endowed with a high degree of legitimacy) is explained by the fact that a contribution or discovery relating to those questions will tend to yield greater symbolic profit (Bourdieu 22).Exploring areas of enquiry which are outside the boundaries of mainstream scientific discourses is a dangerous affair. Mixing different epistemologies in the search for transversal grounds of knowledge might result in unrecognisable theories, which are born out of a combination of various processes of hybridisation: social, technological, cultural and material.Material mutations are happening that call for new epistemologies, due to the implications of current technological possibilities which might redefine our understanding of mediation, and expand it to include molecular forms of communication. A new terminology that takes into account the scientific and epistemological implications of nanotechnology applied to communication [and that also go beyond cyborg metaphors of a marriage between biology and cibernetics] is necessary. Nanomedia and nanomediations are the terminologies proposed in this article as conceptual tools to allow these further explorations. Nanomedia is here understood as the combination of different nanotechnological mediums of communication that are able to create and disseminate meaning via molecular exchange and/ or assembly. Nanomediation is here defined as the process of active transmission and reception of signs and meaning using nanotechnologies. These terminologies might help us in conducting interdisciplinary research and observations that go deeper into matter itself and take into account its molecular spaces of mediation - moving from metaphor into pragmatics. Nanomedia(s)Within the humanities, the term 'nano-media' was first proposed by Mojca Pajnik and John Downing, referring to small media interventions that communicate social meaning in independent ways. Their use of term 'nano-media' proposes to be a revised alternative to the plethora of terms that categorise such media actions, such as alternative media, community media, tactical media, participatory media, etc. The metaphor of smallness implied in the term nano-media is used to categorise the many fragments and complexities of political appropriations of independent media. Historical examples of the kind of 'nano' social interferences listed by Downing (2),include the flyers (Flugblätter) of the Protestant Reformation in Germany; the jokes, songs and ribaldry of François Rabelais’ marketplace ... the internet links of the global social justice (otromundialista) movement; the worldwide community radio movement; the political documentary movement in country after country.John Downing applies the meaning of the prefix nano (coming from the Greek word nanos - dwarf), to independent media interventions. His concept is rooted in an analysis of the social actions performed by local movements scattered around the world, politically engaged and tactically positioned. A similar, but still unique, proposition to the use of the term 'nano-media' appeared 2 years later in the work of Graham St John (442):If ‘mass media’ consists of regional and national print and television news, ‘niche media’ includes scene specific publications, and ‘micro media’ includes event flyers and album cover art (that which Eshun [1998] called ‘conceptechnics’), and ‘social media’ refers to virtual social networks, then the sampling of popular culture (e.g. cinema and documentary sources) using the medium of the programmed music itself might be considered nano-media.Nano-media, according to Graham St John, "involves the remediation of samples from popular sources (principally film) as part of the repertoire of electronic musicians in their efforts to create a distinct liminalized socio-aesthetic" (St John 445). While Downing proposes to use the term nano-media as a way to "shake people free of their obsession with the power of macro-media, once they consider the enormous impact of nano-technologies on our contemporary world" (Downing 1), Graham St John uses the term to categorise media practices specific to a subculture (psytrance). Since the use of the term 'nano-media' in relation to culture seems to be characterised by the study of marginalised social movements, portraying a hybrid remix of conceptual references that, if not completely illegitimate, would be located in the border of legitimacy within media theories, I am hereby proposing yet another bastard version of the concept of nanomedia (without a hyphen). Given that neither of the previous uses of the term 'nano-media' within the discipline of media studies take into account the technological use of the prefix nano, it is time to redefine the term in direct relation to nanotechnologies and communication devices. Let us start by taking a look at nanoradios. Nanoradios are carbon nanotubes connected in such a way that when electrodes flow through the nanotubes, various electrical signals recover the audio signals encoded by the radio wave being received (Service). Nanoradios are examples of the many ways in which nanotechnologies are converging with and transforming our present information and communication technologies. From molecular manufacturing (Drexler) to quantum computing (Deutsch), we now have a wide spectrum of emerging and converging technologies that can act as nanomedia - molecular structures built specifically to act as communication devices.NanomediationsBeyond literal attempts to replicate traditional media artifacts using nanotechnologies, we find deep processes of mediation which are being called nanocommunication (Hara et al.) - mediation that takes place through the exchange of signals between molecules: Nanocommunication networks (nanonetworks) can be used to coordinate tasks and realize them in a distributed manner, covering a greater area and reaching unprecedented locations. Molecular communication is a novel and promising way to achieve communication between nanodevices by encoding messages inside molecules. (Abadal & Akyildiz) Nature is nanotechnological. Living systems are precise mechanisms of physical engineering: our molecules obey our DNA and fall into place according to biological codes that are mysteriously written in our every cell. Bodies are perfectly mediated - biological systems of molecular communication and exchange. Humans have always tried to emulate or to replace natural processes by artificial ones. Nanotechnology is not an exception. Many nanotechnological applications try to replicate natural systems, for example: replicas of nanostructures found in lotus flowers are now being used in waterproof fabrics, nanocrystals, responsible for resistance of cobwebs, are being artificially replicated for use in resistant materials, and various proteins are being artificially replicated as well (NNI 05). In recent decades, the methods of manipulation and engineering of nano particles have been perfected by scientists, and hundreds of nanotechnological products are now being marketed. Such nano material levels are now accessible because our digital technologies were advanced enough to allow scientific visualization and manipulation at the atomic level. The Scanning Tunneling Microscopes (STMs), by Gerd Binnig and Heinrich Rohrer (1986), might be considered as the first kind of nanomedia devices ever built. STMs use quantum-mechanical principles to capture information about the surface of atoms and molecules, allowed digital imaging and visualization of atomic surfaces. Digital visualization of atomic surfaces led to the discovery of buckyballs and nanotubes (buckytubes), structures that are celebrated today and received their names in honor of Buckminster Fuller. Nanotechnologies were developed as a direct consequence of the advancement of digital technologies in the fields of scientific visualisation and imaging. Nonetheless, a direct causal relationship between nano and digital technologies is not the only correlation between these two fields. Much in the same manner in which digital technologies allow infinite manipulation and replication of data, nanotechnologies would allow infinite manipulation and replication of molecules. Nanocommunication could be as revolutionary as digital communication in regards to its possible outcomes concerning new media. Full implementation of the new possibilities of nanomedia would be equivalent or even more revolutionary than digital networks are today. Nanotechnology operates at an intermediate scale at which the laws of classical physics are mixed to the laws of quantum physics (Holister). The relationship between digital technologies and nanotechnologies is not just instrumental, it is also conceptual. We might compare the possibilities of nanotechnology to hypertext: in the same way that a word processor allows the expression of any type of textual structure, so nanotechnology could allow, in principle, for a sort of "3-D printing" of any material structure.Nanotechnologies are essentially media technologies. Nanomedia is now a reality because digital technologies made possible the visualization and computational simulation of the behavior of atomic particles at the nano level. Nanomachines that can build any type of molecular structure by atomic manufacturing could also build perfect replicas of themselves. Obviously, such a powerful technology offers medical and ecological dangers inherent to atomic manipulation. Although this type of concern has been present in the global debate about the social implications of nanotechnology, its full implications are yet not entirely understood. A general scientific consensus seems to exist, however, around the idea that molecules could become a new type of material alphabet, which, theoretically, would make possible the reconfiguration of the physical structures of any type of matter using molecular manufacturing. Matter becomes digital through molecular communication.Although the uses given to the term nano-media in the context of cultural and social studies are merely metaphorical - the prefix nano is used by humanists as an allegorical reference of a combination between 'small' and 'contemporary' - once the technological and scientifical realities of nanomedia present themselves as a new realm of mediation, populated with its own kind of molecular devices, it will not be possible to ignore its full range of implications anymore. A complexifying media ecosystem calls for a more nuanced and interdisciplinary approach to media studies.ConclusionThis article narrates the different uses of the term nanomedia as an illustration of the way in which disciplinarity determines the level of legitimacy or illegitimacy of an emerging term. We then presented another possible use of the term in the field of media studies, one that is more closely aligned with its scientific origins. The importance and relevance of this narrative is connected to the present challenges we face in the anthropocene. The reality of the anthropocene makes painfully evident the full extent of the impact our technologies have had in the present condition of our planet's ecosystems. For as long as we refuse to engage directly with the technologies themselves, trying to speak the language of science and technology in order to fully understand its wider consequences and implications, our theories will be reduced to fancy metaphors and aesthetic explorations which circulate around the critical issues of our times without penetrating them. The level of interdisciplinarity required by the challenges of the anthropocene has to go beyond anthropocentrism. Traditional theories of media are anthropocentric: we seem to be willing to engage only with that which we are able to recognise and relate to. Going beyond anthropocentrism requires that we become familiar with interdisciplinary discussions and perspectives around common terminologies so we might reach a consensus about the use of a shared term. For scientists, nanomedia is an information and communication technology which is simultaneously a tool for material engineering. For media artists and theorists, nano-media is a cultural practice of active social interference and artistic exploration. However, none of the two approaches is able to fully grasp the magnitude of such an inter and transdisciplinary encounter: when communication becomes molecular engineering, what are the legitimate boundaries of media theory? If matter becomes not only a medium, but also a language, what would be the conceptual tools needed to rethink our very understanding of mediation? Would this new media epistemology be considered legitimate or illegitimate? Be it legitimate or illegitimate, a new media theory must arise that challenges and overcomes the walls which separate science and culture, physics and semiotics, on the grounds that it is a transdisciplinary change on the inner workings of media itself which now becomes our vector of epistemological and empirical transformation. 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