The 'experimental stable' of the BCG vaccine: safety, efficacy, proof, and standards, 1921-1933

The anti-tuberculosis BCG (Bacille Calmette-Guérin) vaccine was conceived and developed between 1905 and 1921 at Pasteur Institutes in France. Between 1921 and A. Calmette's death in 1933, the vaccine went through a first period of national and international production and distribution for its use in humans. In France these activities were exclusively carried out by Calmette and his collaborators at the Pasteur Institute in Paris. Initially improvised production in a small room in the cellar gave way in 1931 to the construction of the spacious and magnificent 'New laboratories for research on tuberculosis and the preparation of the BCG' within the premises of the Pasteur Institute. Presentation and image-building of the vaccine in France insisted on the fact that the BCG was not a commercial specialty but distributed free of charge. The technical monopoly of its production nevertheless lay with the Paris Pasteur Institute and standardization of scientific proof of safety, efficacy and stability was dominated by that Institute in France. In contrast, the international production and distribution of the vaccine was entrusted and transferred, free of charge, to trustworthy laboratories outside France. Multiplication of producers and users led to an increased need for standardization. For this process the analysis distinguishes between the standardization of scientific proof concerning safety, efficacy and stability of the vaccine and standardization of its medical uses. Whereas standardization was rather successful in the inter-war period in France, the international efforts remained rather unsuccessful. Only after world war II under Scandinavian leadership and in the context of mass vaccination programs supported by the WHO and UNICEF was the international standardization effectively implemented and succeeded at least to some extend.     

Contribution of L-alanine dehydrogenase to in vivo persistence and protective efficacy of the BCG vaccine

The tuberculosis (TB) vaccine strain Mycobacterium bovis BCG is unable to utilise alanine and this deficiency is thought to inhibit the growth of the vaccine in vivo and limit vaccine efficacy. In this report we demonstrate that L-alanine catabolism can be conferred on BCG by introduction of the gene encoding L-alanine dehydrogenase (Ald) of Mycobacterium tuberculosis. Restoration of Ald activity did not change the in vivo growth of BCG in macrophages or mice, and protection against aerosol M. tuberculosis infection was not altered by addition of ald to the BCG vaccine. These results demonstrate that the inability to utilise L-alanine is not a contributing factor to the attenuated phenotype of BCG and does not influence the protective efficacy of the vaccine against TB.     

The ‘making of’ the Mulligans Flat – Goorooyarroo experimental restoration project

What happens when park managers and ecological researchers join forces to build an evidence‐based approach to restoring a nature reserve? This project shows how a spirit of cooperation and inventiveness overcome a range of challenges at one of the National Capital region’s most valuable examples of critically endangered box‐gum grassy woodland.     

The ‘philosophical grasp of the appearances’ and experimental microscopy: Johannes Müller’s microscopical research, 1824–1832

Romantic Naturphilosophie has been at the centre of almost every account of early nineteenth-century sciences, be it as an obstacle or as an aid for scientific advancement. The following paper suggests a change of perspective. I seek to read Naturphilosophie as one manifestation among others of a more general concern with the question of how experience enables the subject to acquire knowledge about objects. To illustrate such an approach, I focus on Johannes Müller’s early work. Here one finds two contrasting images of microscopical observation, its set-up, and the observer: the embryological study of 1830 demands a ‘philosophical grasp’ of the appearances. In contrast, the investigations of blood of 1832 are presented as a series of controlled experiments. I argue that an interpretation of this contrast in terms of an appropriation and casting aside of Naturphilosophie is not altogether convincing. Instead, both images of microscopy are manifestations of a more general problem, namely, the problem of exactly how subject and object came together in experience. I show how this concern not only shaped the methodological sensibilities particular to Müller’s embryology and the investigation of bodily liquids but also provided the epistemological principles and the target for his sense-physiological experiments. It bound Müller’s work together with Naturphilosophie and linked Naturphilosophie with other contemporaneous projects in philosophy. All of these enterprises sought to contribute to ongoing debates about how experience allowed the subject to acquire knowledge about the world.     

‘Not anymore,not yet’: Australian–Hungarians rediscover the ‘old‐new’ Hungary

This article examines the return visits of Australian‐Hungarians to their homeland after 1989 and the different types of homecoming experiences after an extended period of separation. The focus of the paper is returnees’ perceptions of changes to Hungary or lack thereof. I analyse the distinction between the ‘desired/nostalgic past’, which Hungarian returnees nurtured during the decades of separation and expected to rediscover upon return, and the ‘disdained past’ of the Communist dictatorship, which they had fled and hoped never to encounter again. The findings demonstrate that people interpret both past and present in relation to hopes, expectations and disappointments situated within particular nationalist imaginaries, political projects and ideological prisms. This allows us to analyse the nexus between local, national and diasporic belonging through post‐socialist identities, orientations toward democracy and understandings of ‘nation’.     

A plea for ‘genealogical thinking’ in comparative biology – a rebuttal to the reply of Szucsich,Wirkner, and Pass to my article ‘Deconstructing Morphology’

Scholtz G. in press. A plea for ‘genealogical thinking’ in comparative biology – a rebuttal to the reply of Szucsich, Wirkner, and Pass to my article ‘Deconstructing Morphology’. —Acta Zoologica (Stockholm) 00 : 1–4. Szucsich et al. (in press) claim that – in contrast to my statement – morphological thinking has to be ‘cladistic.’ Based on this premise, they stress the difference between the relationships among states of characters versus those among structures assigned to the same character state as implemented in numerical cladistic reasoning. SEA claim that my approach to the homology concept only deals with the problem of the integration of various character states into the same character, whereas the necessary relationships among structures assigned to the same state are not covered. Based on this distinction, SEA also criticise the application of similarity in my definition of homology. Furthermore, they address the issue of evolutionarily independent units.     

The ‘sparkle’ in fake eyes – the protective effect of mimic eyespots in lepidoptera

Many species of lepidoptera bear conspicuous circular patterns on their wings, known as eyespots, that are hypothesised to protect their bearers against predatory birds. In this study, we focus on a small but ubiquitous feature occurring naturally in lepidopteran eyespots, namely the so‐called ‘sparkle’. The ‘pupil’ in an eyespot is often highlighted by a ‘sparkle’, which is hypothesised to mimic a natural corneal total light reflection evident as a highlight, twinkle, or sparkle in the vertebrate eye. In a study exploring the presence of such sparkles, we found that 53% of lepidopteran eyespots exceeding 1 mm in diameter have a central, pinpoint‐like ‘sparkle’, 12% have a marginal, crescent‐shaped ‘sparkle’, 13% have a semi‐circular ‘sparkle’, and 22% have an intermediate semi‐circular to crescent‐shaped ‘sparkle’. In the lepidopterans’ natural resting position, the marginal ‘sparkles’ are positioned in the upper part of the eyespots’‘pupil’ and thus may create the illusion of a spherical eyeball. The ‘sparkles’ in lepidopteran eyespots do not only appear white to humans, but also reflect ultraviolet light. White and UV‐reflecting ‘sparkles’ also appear ‘white’ for UV‐sensitive viewers such as birds, and thus may effectively mimic the natural highlight in vertebrate eyes as an area of total light reflection. In field experiments using lepidopteran dummies baited with a mealworm, we show that the ‘sparkle’ is one of several components of eyespots eliciting a deterrent effect and that eyespots with a ‘sparkle’ in a natural position have a stronger deterrent effect than those with a ‘sparkle’ in an unnatural position. These findings support the eye mimicry hypothesis that better vertebrate eye mimicry improves the deterrent effect of eyespots.     

The AAT1 locus is critical for the biosynthesis of esters contributing to ‘ripe apple’ flavour in ‘Royal Gala’ and ‘Granny Smith’ apples

The ‘fruity’ attributes of ripe apples (Malus × domestica) arise from our perception of a combination of volatile ester compounds. Phenotypic variability in ester production was investigated using a segregating population from a ‘Royal Gala’ (RG; high ester production) × ‘Granny Smith’ (GS; low ester production) cross, as well as in transgenic RG plants in which expression of the alcohol acyl transferase 1 (AAT1) gene was reduced. In the RG × GS population, 46 quantitative trait loci (QTLs) for the production of esters and alcohols were identified on 15 linkage groups (LGs). The major QTL for 35 individual compounds was positioned on LG2 and co‐located with AAT1. Multiple AAT1 gene variants were identified in RG and GS, but only two (AAT1‐RGa and AAT1‐GSa) were functional. AAT1‐RGa and AAT1‐GSa were both highly expressed in the cortex and skin of ripe fruit, but AAT1 protein was observed mainly in the skin. Transgenic RG specifically reduced in AAT1 expression showed reduced levels of most key esters in ripe fruit. Differences in the ripe fruit aroma could be perceived by sensory analysis. The transgenic lines also showed altered ratios of biosynthetic precursor alcohols and aldehydes, and expression of a number of ester biosynthetic genes increased, presumably in response to the increased substrate pool. These results indicate that the AAT1 locus is critical for the biosynthesis of esters contributing to a ‘ripe apple’ flavour.     

From clear lakes to murky waters – tracing the functional response of high‐latitude lake communities to concurrent ‘greening’ and ‘browning’

Climate change and the intensification of land use practices are causing widespread eutrophication of subarctic lakes. The implications of this rapid change for lake ecosystem function remain poorly understood. To assess how freshwater communities respond to such profound changes in their habitat and resource availability, we conducted a space‐for‐time analysis of food‐web structure in 30 lakes situated across a temperature‐productivity gradient equivalent to the predicted future climate of subarctic Europe (temperature +3°C, precipitation +30% and nutrient +45 μg L^?1 total phosphorus). Along this gradient, we observed an increase in the assimilation of pelagic‐derived carbon from 25 to 75% throughout primary, secondary and tertiary consumers. This shift was overwhelmingly driven by the consumption of pelagic detritus by benthic primary consumers and was not accompanied by increased pelagic foraging by higher trophic level consumers. Our data also revealed a convergence of the carbon isotope ratios of pelagic and benthic food web endmembers in the warmest, most productive lakes indicating that the incorporation of terrestrial derived carbon into aquatic food webs increases as land use intensifies. These results, reflecting changes along a gradient characteristic of the predicted future environment throughout the subarctic, indicate that climate and land use driven eutrophication and browning are radically altering the function and fuelling of aquatic food webs in this biome.     

The ‘successful’ return: Caribbean narratives of migration,family, and gender

Research on female migrant caregivers has tended to focus upon the emotional and social problems they encounter working abroad, given women's traditional role as caregivers for their own families. This article analyses how Caribbean women who have returned after a period abroad as domestic workers inscribe their migration experiences within the gendered narrative of the good relative who migrates to help the family left behind and therefore deserves social recognition in the community of origin. It argues that this narrative allows the women to both affirm and reinterpret local family and gender roles within the context of migration. This analysis points to the close connection between narrative structures, accounts of migration experiences, and self‐presentations and suggests that narratives about family and gender roles not only reflect people's lives, but are also a malleable resource that can be (re)shaped to validate a variety of life‐courses.     

‘The Miserablest People in the World’: Race,Humanism and the Australian Aborigine

This paper considers how an idea of the Australian Aborigine impacted upon the development of racial thinking throughout the nineteenth century. We distinguish three phases of this development. Against the background of what was considered to be a distinctly human capacity to rise above nature, our central argument however is that the extreme and irremediable savagery attributed to the Aborigine led to the mid‐nineteenth shift to a polygenist, or an innatist, idea of race. The first part of our discussion, covering the early 1800s, elicits a specifically humanist puzzlement at the unimproved condition of the Aborigines. But, as we will show in the central part of our discussion, it was not only the Aborigines' inclination but their capacity for ‘improvement’ that came to be doubted. Challenging the very basis upon which ‘the human’ had been defined, and the unity of humankind assumed, the Aborigine could not be accommodated within a prevailing conception of racial difference as a mere variety of the human. The elaboration of polygenism may therefore be understood as arising out of this humanist incomprehension: as an attempt to account for the ontologically inexplicable difference of the Australian Aborigine. In the final part of our discussion, we trace the legacy of the Aborigine's place within polygenism through the evolutionary thought of the late nineteenth century. Despite an explicit return to monogenism, here the Aborigine is invoked to support the claim that race constitutes a more or less permanent difference and, for certain races, a more or less permanent deficiency. And as, in these terms, the anomalous Aborigine became an anachronism, so Australia's indigenous peoples came to embody the most devastating conclusion of evolutionary thought: that in the human struggle for existence certain races were destined not even to survive.     

‘The muck of the past’: revolution,social transformation,and the Maoists in India

This article analyses revolutionary social change by exploring how people attempt to create a radically different future by taking action in the present, and the challenges that beset this transformation. Examining the relationship between the future, the present, and the past, the article takes the case of the spread of armed underground Maoist guerrillas in India to ask two questions: First, why does India hang on to this form of utopianism when the rest of the world appears to have abandoned it? Second, how and why does the ‘muck of the past’ influence the production of a radically different future? In answering these questions, this article suggests that for both processes of radical social change and our theories of them, we need to reinsert our analyses of politico‐economic conditions into our ideologies of social change.     

The ‘biomineralization toolkit’ and the origin of animal skeletons

Biomineralized skeletons are widespread in animals, and their origins can be traced to the latest Ediacaran or early Cambrian fossil record, in virtually all animal groups. The origin of animal skeletons is inextricably linked with the diversification of animal body plans and the dramatic changes in ecology and geosphere–biosphere interactions across the Ediacaran–Cambrian transition. This apparent independent acquisition of skeletons across diverse animal clades has been proposed to have been driven by co‐option of a conserved ancestral genetic toolkit in different lineages at the same time. This ‘biomineralization toolkit’ hypothesis makes predictions of the early evolution of the skeleton, predictions tested herein through a critical review of the evidence from both the fossil record and development of skeletons in extant organisms. Furthermore, the distribution of skeletons is here plotted against a time‐calibrated animal phylogeny, and the nature of the deep ancestors of biomineralizing animals interpolated using ancestral state reconstruction. All these lines of evidence point towards multiple instances of the evolution of biomineralization through the co‐option of an inherited organic skeleton and genetic toolkit followed by the stepwise acquisition of more complex skeletal tissues under tighter biological control. This not only supports the ‘biomineralization toolkit’ hypothesis but also provides a model for describing the evolution of complex biological systems across the Ediacaran–Cambrian transition.     

Air‐filled postcranial bones in theropod dinosaurs: physiological implications and the ‘reptile’–bird transition

Pneumatic (air‐filled) postcranial bones are unique to birds among extant tetrapods. Unambiguous skeletal correlates of postcranial pneumaticity first appeared in the Late Triassic (approximately 210 million years ago), when they evolved independently in several groups of bird‐line archosaurs (ornithodirans). These include the theropod dinosaurs (of which birds are extant representatives), the pterosaurs, and sauropodomorph dinosaurs. Postulated functions of skeletal pneumatisation include weight reduction in large‐bodied or flying taxa, and density reduction resulting in energetic savings during foraging and locomotion. However, the influence of these hypotheses on the early evolution of pneumaticity has not been studied in detail previously. We review recent work on the significance of pneumaticity for understanding the biology of extinct ornithodirans, and present detailed new data on the proportion of the skeleton that was pneumatised in 131 non‐avian theropods and Archaeopteryx. This includes all taxa known from significant postcranial remains. Pneumaticity of the cervical and anterior dorsal vertebrae occurred early in theropod evolution. This ‘common pattern’ was conserved on the line leading to birds, and is likely present in Archaeopteryx. Increases in skeletal pneumaticity occurred independently in as many as 12 lineages, highlighting a remarkably high number of parallel acquisitions of a bird‐like feature among non‐avian theropods. Using a quantitative comparative framework, we show that evolutionary increases in skeletal pneumaticity are significantly concentrated in lineages with large body size, suggesting that mass reduction in response to gravitational constraints at large body sizes influenced the early evolution of pneumaticity. However, the body size threshold for extensive pneumatisation is lower in theropod lineages more closely related to birds (maniraptorans). Thus, relaxation of the relationship between body size and pneumatisation preceded the origin of birds and cannot be explained as an adaptation for flight. We hypothesise that skeletal density modulation in small, non‐volant, maniraptorans resulted in energetic savings as part of a multi‐system response to increased metabolic demands. Acquisition of extensive postcranial pneumaticity in small‐bodied maniraptorans may indicate avian‐like high‐performance endothermy.     

Ideologies of discrimination: personhood and the ‘genetic group’

‘Ideologies of Discrimination’ considers the implications of the new genetics for understandings of personhood and for understandings of the relationship between people in groups. In particular, the essay delineates and examines the emerging notion of a ‘genetic group’ and considers the social implications of redefining families, racial groups and ethnic groups through express, and often exclusive, reference to a shared genome. One consequence of such redefinition has been the justification and elaboration of stigmatizing images of and discrimination against such groups—especially those, such as Jews and African-Americans, that have long been identified with specific somatic characteristics. A few worrisome trends begin to emerge in the response of the American legal system to the notion of genetic groups. Among these is a shift in the locus of privacy and identity from the autonomous individual to the genetic group. This shift challenges (and threatens) long-standing Western values (including equality and liberty) that depend upon the ideological centrality of autonomous individuality.     

Hypofolins A – L,ent‐Labdane Diterpenoids from the Roots of Hypoestes phyllostachya ‘Pink Splash’

Twelve new ent‐labdane diterpenoids, hypofolins A – F ( 1 – 6 ) and hypofolins G – L ( 7a / 7b , 8a / 8b , and 9a / 9b ), were isolated from the roots of Hypoestes phyllostachya ‘Pink Splash’. Their structures were elucidated by extensive 1D‐ and 2D‐NMR spectroscopic and HR‐MS data. The absolute configurations of 1 , 2 , 5 , and 7a / 7b were determined by single crystal X‐ray diffraction and ECD analysis, as well as chemical transformations. Compounds 7a / 7b , 8a / 8b , and 9a / 9b were isolated as three pairs of interconverting mixture of two isomers between ketone and hemiketal types. Compound 1 showed weak cytotoxicity against SMMC‐7721 cell line with IC₅₀ value of 31.40 μm .     

The ‘wet–dry’ in the wet–dry tropics drives river ecosystem structure and processes in northern Australia

1. Northern Australia is characterised by a tropical wet–dry climate that regulates the distinctive character of river flow regimes across the region. There is marked hydrological seasonality, with most flow occurring over only a few months of the year during the wet season. Flow is also characterised by high variability between years, and in the degree of flow cessation, or intermittency, over the dry season. 2. At present, the relatively low human population density and demand for water in the region means that most rivers have largely unmodified flow regimes. These rivers therefore provide a good opportunity to understand the role of natural flow variability in river ecosystem structure and processes. 3. This review describes the major flow regime classes characterising northern Australian rivers, from perennial to seasonally intermittent to extremely intermittent, and how these regimes give rise to marked differences in the ecological character of these tropical rivers, particularly their floodplains. 4. We describe the key features of these flow regimes, namely the wet and dry seasons and the transitions between these seasons, and how they regulate the biophysical heterogeneity, primary productivity and movement of biota in Australia’s wet–dry tropical rivers. 5. We develop a conceptual model that predicts the likely hydrological and ecological consequences of future increases in water abstraction (e.g. for agriculture), and suggest how such impacts can be managed so that the distinctive ecological character of these rivers is maintained.