Koch's postulates and the etiology of AIDS: an historical perspective.

This paper examines the debate over the human immunodeficiency virus (HIV) as the cause of acquired immunodeficiency syndrome (AIDS) from an historical perspective. The changing criteria for proving the link between putative pathological agents and diseases are discussed, beginning with Robert Koch's research on anthrax in the late nineteenth century. Various versions of 'Koch's postulates' are analyzed in relation to the necessity and sufficiency arguments of logical reasoning. In addition, alterations to Koch's postulates are delineated, specifically those required by the discovery of rickettsiae and viruses in the early twentieth century and by the immunological testing developed after mid-century to demonstrate the links between elusive viral agents and two diseases, hepatitis B and infectious mononucleosis. From this perspective, an examination of the AIDS debate is constructed. Molecular biologist Peter Duesberg's argument that HIV is not the cause of AIDS is analyzed in light of his contention that a version of Koch's postulates has not been satisfied. Additional research findings through 1990 relating to the etiology of AIDS are also noted.     

The contribution of plant biology to the concept of virus (1886-1917).

Between 1860 and 1880 the so-called "theory of the infective germ", which stated in final way that every infectious disease was produced by a living pathogen agent, achieved great consent. The criteria of determining the presence of infectious pathogens (fungi, bacteria, protozoa) were established by "Koch's postulate", a set of experimental procedures conceived for isolating and determining single pathogens. In the last quarter of the 19th century became however evident that the agents of severe infectious diseases could not be identified through the "postulates". These agents could not be seen in light microscopy nor cultured in vitro but could pass through the thin pores of filters which hold back cellular micro-organisms. This last characteristic became a selective method to recognise these peculiar agents, from then named "filterable viruses". Most microbiologists considered the filterable viruses as living micro-organisms because of their extraordinary capacity of in vivo proliferation, and the impossibility of pointing out their structures was due to limits of the experimental techniques. Between the end of the 19th century and 1917, four plant biologists suggested that the filterable viruses were complex chemical substances rather than cellular microorganisms. Their contribution, not appreciated by the contemporary colleagues, laid the foundation of the modern concept of virus.     

An Euler contribution to stable theory from Süssmilch's göttliche Ordnung

In a paper published in 1760, the great Swiss mathematician Leonard Euler developed relationships between age structure and vital rates that would hold for stable populations, but without attention to the process by which stabilization comes about. He had not overlooked the latter problem. We introduce in this paper an earlier brief communication of his to Johann Peter Süssmilch in which he postulates that stability must ultimately result if fertility and mortality regimes are fixed. The mathematical treatment of this concept had not been thought to predate Alfred Lotka's work in the early part of the present century.     

HOW DO SPERM WHALES CATCH SQUIDS?

Vision may play a central role in sperm whale predation. Two complementary hypotheses regarding the detection and capture of prey items are presented, based on a review of mesopelagic ecology. The first hypothesis postulates that sperm whales locate their prey visually, either silhouetted against the midwater "sky," or by searching for bioluminescence produced by the movements of their prey. The second hypothesis postulates that sperm whales create a zone of stimulated bioluminescence around the mouth, which attracts squids and other visual predators. Studies of midwater fishes and invertebrates document the importance of vision in mesopelagic communities. If sperm whales search for silhouetted prey, they should be oriented upside-down to improve visual coverage and to facilitate the transition from search to prey capture. Prey capture events should be marked by excursions toward the surface. If they lure their prey, they should swim at a steady pace, with little rapid acceleration, and spend most of their time foraging at depths with the greatest potential for stimulated bioluminescence.     

Quantitative tests of general models for the evolution of development

Comparative developmental biologists have proposed models to describe patterns of conserved features in vertebrate ontogeny. The hourglass model suggests evolutionary change is most difficult at an intermediate "phylotypic" stage, the adaptive penetrance model suggests change is easiest at an intermediate stage, and the early conservation model suggests change is easier later in ontogeny. Although versions of some of these models have been discussed since the nineteenth century, quantitative approaches have been proposed only recently. Here we present quantitative phylogenetic approaches to evaluating trends in the evolution of ontogeny. We apply these approaches to the proposed models and demonstrate that an existing approach to assessing these models is biased. We show that the hourglass, adaptive penetrance, and early conservation models are unnecessarily complex explanations of the patterns observed in developmental event data for 14 species of vertebrates. Rather, a simpler model that postulates that evolutionary change is easier between ontogenetically adjacent events is adequate.     

The apoptosome activates caspase-9 by dimerization

The apical protease of the human intrinsic apoptotic pathway, caspase-9, is activated in a polymeric activation platform known as the apoptosome. The mechanism has been debated, and two contrasting hypotheses have been suggested. One of these postulates an allosteric activation of monomeric caspase-9; the other postulates a dimer-driven assembly at the surface of the apoptosome--the "induced proximity" model. We show that both Hofmeister salts and a reconstituted mini-apoptosome activate caspase-9 by a second-order process, compatible with a conserved dimer-driven process. Significantly, replacement of the recruitment domain of the apical caspase of the extrinsic apoptotic pathway, caspase-8, by that of caspase-9 allows activation of this hybrid caspase by the apoptosome. Consequently, apical caspases can be activated simply by directing their zymogens to the apoptosome, ruling out the requirement for allosteric activation and supporting an induced proximity dimerization model for apical caspase activation in vivo.     

Alpheus Spring Packard and cave fauna in the evolution debate

Conclusion Packard attempted to incorporate cave fauna into a general theory of evolution that would be consistent with the principle of recapitulation, and would have as the primary mechanism the inheritance of the effects of the environment. Beyond this, he also attempted to demonstrate that the evolution of cave fauna was consistent with progressive evolution. The use he made of comparative anatomy and embryology places him within the tradition of classical morphology that was dominant through much of the last half of the nineteenth century, but of waning importance by the time of Packard's death in 1905. The importance Packard gave to cave fauna as evidence for Lamarckian evolution stimulated interest in the phenomenon; this interest, and references to cave fauna in the scientific literature, declined after his death. Since then, the importance of cave fauna in evolutionary theory has declined from their status as the star evidence in Packard's theory to their present status as a difficult anomaly within the modern synthetic theory.     

Predictions and tests of climate-based hypotheses of broad-scale variation in taxonomic richness

Broad‐scale variation in taxonomic richness is strongly correlated with climate. Many mechanisms have been hypothesized to explain these patterns; however, testable predictions that would distinguish among them have rarely been derived. Here, we examine several prominent hypotheses for climate–richness relationships, deriving and testing predictions based on their hypothesized mechanisms. The ‘energy–richness hypothesis’ (also called the ‘more individuals hypothesis’) postulates that more productive areas have more individuals and therefore more species. More productive areas do often have more species, but extant data are not consistent with the expected causal relationship from energy to numbers of individuals to numbers of species. We reject the energy–richness hypothesis in its standard form and consider some proposed modifications. The ‘physiological tolerance hypothesis’ postulates that richness varies according to the tolerances of individual species for different sets of climatic conditions. This hypothesis predicts that more combinations of physiological parameters can survive under warm and wet than cold or dry conditions. Data are qualitatively consistent with this prediction, but are inconsistent with the prediction that species should fill climatically suitable areas. Finally, the ‘speciation rate hypothesis’ postulates that speciation rates should vary with climate, due either to faster evolutionary rates or stronger biotic interactions increasing the opportunity for evolutionary diversification in some regions. The biotic interactions mechanism also has the potential to amplify shallower, underlying gradients in richness. Tests of speciation rate hypotheses are few (to date), and their results are mixed.     

A message emerging from development: the repression of mitochondrial β-F1-ATPase expression in cancer

Mitochondrial research has experienced a considerable boost during the last decade because organelle malfunctioning is in the genesis and/or progression of a vast array of human pathologies including cancer. The renaissance of mitochondria in the cancer field has been promoted by two main facts: (1) the molecular and functional integration of mitochondrial bioenergetics with the execution of cell death and (2) the implementation of ¹⁸FDG-PET for imaging and staging of tumors in clinical practice. The latter, represents the bed-side translational development of the metabolic hallmark that describes the bioenergetic phenotype of most cancer cells as originally predicted at the beginning of previous century by Otto Warburg. In this minireview we will briefly summarize how the study of energy metabolism during liver development forced our encounter with Warburg’s postulates and prompted us to study the mechanisms that regulate the biogenesis of mitochondria in the cancer cell.     

A mechanism for the observed recovery from ineffectiveness of synapses in the central nervous system

Three recent experiments have shown that synaptic connections in the central nervous system that are structurally present but functionally ineffective can be made to recover their effectiveness for exciting neurons. The common features of these experiments are briefly reviewed. A mechanism is proposed requiring three postulates that are each consistent with orthodox physiology. There is an opportunity for a quantitative treatment to test against future experimental results.     

On the History of Vegetable Gardens in North-west Europe

Summary

The early history of vegetable gardens is little documented. Only a few references to and depictions of mediaeval vegetable gardens are available. The possible reason is that they were too common, too vulgar, to record and to write about, and to paint or to draw. From the 16th century onwards much information is available on the history of gardens, but information on vegetable gardens is still quite limited. Many of the Flemish and Dutch paintings of the 16th to 18th centuries show vegetable stalls on markets. These paintings show us the vegetables and their variation at the time the paintings were made. More data on the history of vegetable gardens will become available as a result of archaeobotanical research.     

Uexküll, Peirce, and Other Affinities Between Biosemiotics and Biolinguistics

The purpose of this paper is to describe some parallels and theoretical affinities between biosemiotics and biolinguistics. In particular, this paper examines the importance of Uexküll's Umwelt and Peircean abduction as foundational concepts for Sebeok's biosemiotics and Chomsky's biolinguistic program. Other affinities touched upon in this paper include references to concepts articulated by Immanuel Kant, Konrad Lorenz, Marcel Florkin, François Jacob, C.H. Waddington, D'Arcy Thomson and Ernst Haeckel. While both programs share theoretical influences and historiographical parallels in their mid-century origins continuing throughout the late twentieth century, recent articulations of biosemiotics and biolinguistics privilege different intellectual styles and methods of inquiry that define their future objectives as intellectual movements. The goal of this paper is to show that, in spite of the different scholarly agendas of biosemiotics and biolinguistics, both movements share a theoretical and philosophical core in Peirce and Uexküll.     

A Genomic Safe Haven for Mutant Complementation in Cryptococcus neoformans

Just as Koch’s postulates formed the foundation of early infectious disease study, Stanley Falkow’s molecular Koch’s postulates define best practice in determining whether a specific gene contributes to virulence of a pathogen. Fundamentally, these molecular postulates state that if a gene is involved in virulence, its removal will compromise virulence. Likewise, its reintroduction should restore virulence to the mutant. These approaches are widely employed in Cryptococcus neoformans, where gene deletion via biolistic transformation is a well-established technique. However, the complementation of these mutants is less straightforward. Currently, one of three approaches will be taken: the gene is reintroduced at the original locus, the gene is reintroduced into a random site in the genome, or the mutant is not complemented at all. Depending on which approach is utilized, the mutant may be complemented but other genes are potentially disrupted in the process. To counter the drawbacks of the current approaches to complementation we have created a new tool to assist in this key step in the study of a gene’s role in virulence. We have identified and characterized a small gene-free region in the C. neoformans genome dubbed the “safe haven”, and constructed a plasmid vector that targets DNA constructs to this preselected site. The plasmid vector integrates with high frequency, effectively complementing a mutant strain without disrupting adjacent genes. qRT-PCR of the flanking genes on either side of the safe haven site following integration of the targeting vector revealed no changes in their expression, and no secondary phenotypes were observed in a range of phenotypic assays including an intranasal murine infection model. Combined, these data confirm that we have successfully created a much-needed molecular resource for the Cryptococcus community, enabling the reliable fulfillment of the molecular Koch’s postulates.     

Carl Düsing (1884) on the regulation of the sex-ratio

In three publications in 1883 and 1884 Carl Düsing of Jena gave a mathematical account of the influence of natural selection on the sex ratio based on the same argument that Darwin had advanced in The Descent of Man (1871). The argument thus became quite well known, being included in the principal books on the subject around the turn of the century, as well as in the Encyclopaedia Britannica, references to Düsing being given. By 1930, when Fisher gave a verbal account of the argument in The Genetical Theory of Natural Selection, he saw no need to give references, and no other book of the period treated the subject, as a result of which Düsing's contribution became lost to view. We here give the important paragraphs of Düsing's mathematical account, translated into English.     

Concepts for describing the interaction of two agents

This paper reviews general concepts for understanding the effects of two or more agents. Models describing exposures to mixed fields of radiation are developed on the basis of very general postulates, and some of their consequences are examined against a set of experimental data.     

On the Number of Rays in Starfish

Multiradiate starfish evolved independently in fourteen livingfamilies. Twenty living families are strictly 5-rayed. The FIVE-PLUShypothesis is that supernumerary rays develop separately fromthe five primary rays. The ontogeny of the primary rays is proposedto be highly integrated ("en bloc" hypothesis), closely timed(synchronic hypothesis) and a developmental constraint ("tamper-proof"hypothesis). The "en bloc" hypothesis postulates that the fiveprimary rays develop as a unit. The deep structure of this unitis believed to be a 2-1-2, BA-A-BA, organization. The synchronichypothesis postulates that there is only a brief time at metamorphosisduring which the "en bloc" pathway operates. There is a pausebefore the development of supernumerary rays. The "tamper-proof"hypothesis postulates that the "en bloc" pathway has no heritablevariation and cannot be co-opted for the production of supernumeraryrays. There is diversity of timing and pattern in the developmentof supernumerary rays. Postgeneration of rays in the rudimentand intercalary regeneration of rays in the imago are independentray-producing pathways that may have been co-opted variouslyand recurrently in the multiple origins of multiradiate starfish.     

Generation of immune specificity: A working hypothesis

A speculative model for epigenetic generation of immune specificity is presented. It is based on the idea that combinatorial splicing within the same pre-mRNA molecule could generate a variety of mRNAs leading to a diversity of immunoglobulins. The model postulates a special role for the nuclear envelope where translation of intron sequences into messenger maturation proteins would take place. The postulates are justified and experimental implications of the model are discussed.     

The evolution of Brazilian studies on helminths and the Escola tropicalista bahiana (Bahia Tropical School) (1866-1892)

In the mid nineteenth century, laboratory research in embryology, development, ecology and pathogeny of helminths unexpectedly resulted in a change in the explication of the etiology of some human pathology that was traditionally attributed to environmental factors. The new postulates of the parasitology of helminths put in question the traditional explications as well as the recognized authorities in the fields of clinical medicine, hygiene, and of medical geography, affecting not only the traditional circles where the innovations were discussed, but also the institutions that controlled and validated medical knowledge. From the beginning of the decade of the 1860s, a group of Brazilian medical doctors, initially led by Otto Wucherer, took part in this scientific movement that had an important impact on the area of the domestic and international academic medicine. The causality of known diseases, such as intertropical hypoemia, hematochyluria and elephantiasis, became the focus of intense debate between 1866 and 1892. By the end of this period, the field of helminthic parasitology had available well-established methodological and conceptual criteria and the role of Ankylostomum duodenale and of Wuchereria bancrofti in the production of those diseases was fully accepted.     

A theoretical basis for understanding and managing biological populations with particular reference to the spruce bark beetle

The applicability of qualitative analysis and modelling is discussed with reference to the population dynamics of the spruce bark beetle Ips typographus . On the basis of a set of assumptions and postulates, the structure of the population dynamical interactions is discussed. Dynamic analysis suggest that the Scandinavian spruce bark beetle population is a stable system which may be triggered into "boom and bust" dynamics. We suggest that qualitative analysis should proceed, explicitly, through four steps: (1) An explicit statement of the biological assumptions and postulates. (2) A structural analysis, wherein the critical interaction network of the system is defined. (3) An equilibrium analysis, wherein the potential equilibrium points of the key organism (e.g., the pest species) are deduced. (4) A dynamic analysis, wherein the multispecies equilibrium points are found and their sensitivity to pertuberation analyzed. This formal approach should expose many and varied population systems to the interpretive and explanatory powers of qualitative analysis.