Online research in philosophy

This paper follows the circuitous path of theories concerning the origins of viruses from the early years of the twentieth century until the present, considering RNA viruses in particular. I focus on three periods during which new understandings of the nature of viruses guided the construction and reconstruction of origin hypotheses. During the first part of the twentieth century, viruses were mostly viewed from within the framework of bacteriology and the discussion of origin centered on the (...) “degenerative” or the “retrograde evolution theory.” However, concomitantly, in the context of origin-of-life theorizing, the notion that viruses are vestiges of a prebiotic world was also being contemplated. In the 1960s the idea that viruses were genetic elements that “escaped” from cells became prevalent. These traditional hypotheses are being revisited nowadays by evolutionary virologists, who have placed them within a new conceptual framework that is supported by cutting-edge genomic and proteomic data. Two current, opposing scenarios of virus origin are presented. The philosophical dimensions of “revisiting” the original hypotheses are briefly discussed. (shrink)

In a previous issue of Zygon (Carvalho 2007), I explored the role of scientists—especially those engaging the science-religion dialogue—within the arena of global equity health, world poverty, and human rights. I contended that experimental biologists, who might have reduced agency because of their professional workload or lack of individual resources, can still unite into collective forces with other scientists as well as human rights organizations, medical doctors, and political and civic leaders to foster progressive change in our world. In this (...) article, I present some recent findings from research on three emerging viruses—HIV, dengue, and rotavirus—to explore the factors that lead to the geographical expansion of these viruses and the increase in frequency of the infectious diseases they cause. I show how these viruses are generating problems for geopolitical stability, human rights, and equity health care for developing nations that are already experiencing a growing poverty crisis. I suggest some avenues of future research for the scientific community for the movement toward resolution of these problems and indicate where the science-religion field can be of additional aid. (shrink)

The genetic code has evolved from its initial non-degenerate wobble version until reaching its present state of degeneracy. By using the stereochemical hypothesis, we revisit the problem of codon assignations to the synonymy classes of amino-acids. We obtain these classes with a simple classifier based on physico-chemical properties of nucleic bases, like hydrophobicity and molecular weight. Then we propose simple RNA (or more generally XNA, with X for D, P or R) ring structures that present, overlap included, one and only (...) one codon by synonymy class as solutions of a combinatory variational problem. We compare these solutions to sequences of present RNAs considered as relics, with a high interspecific invariance, like invariant parts of tRNAs and micro-RNAs. We conclude by emphasizing some optimal properties of the genetic code. (shrink)

We study the appearance of genetic information starting from a system where self-reproductive and enzymatic functions are supported by the same sort of molecules. In a first phase, the information must have arisen in the form of rate independent sequences as records of enzymatic functions. Although this stage must have played an important role in evolution, it will be shown how its evolutive capacities were blocked by the impossibility of appearance of geno/phenotype duality. Finally, a logical scheme is proposed for (...) a transition process toward a system with a code offering a simplification of the conditions required from the assumption of a maximum use of the double RNA capacity, both reproductive and enzymatic. (shrink)

It is becoming increasingly evident that the driving forces of evolutionary novelty are not randomly derived chance mutations of the genetic text, but a precise genome editing by omnipresent viral agents. These competences integrate the whole toolbox of natural genetic engineering, replication, transcription, translation, genomic imprinting, genomic creativity, enzymatic inventions and all types of genetic repair patterns. Even the non-coding, repetitive DNA sequences which were interpreted as being ancient remnants of former evolutionary stages are now recognized as being of viral (...) descent and crucial for higher-order regulatory and constitutional functions of protein structural vocabulary. In this article I argue that non-randomly derived natural genome editing can be envisioned as (a) combinatorial (syntactic), (b) context-specific (pragmatic) and (c) content-sensitive (semantic) competences of viral agents. These three-leveled biosemiotic competences could explain the emergence of complex new phenotypes in single evolutionary events. After short descriptions of the non-coding regulatory networks, major viral life strategies and pre-cellular viral life three of the major steps in evolution serve as examples: There is growing evidence that natural genome-editing competences of viruses are essential (1) for the evolution of the eukaryotic nucleus, (2) the adaptive immune system and (3) the placental mammals. (shrink)

Two aspects of the chromatin repeat length (r t) are discussed: (i) Why is r t, longer for slowly dividing cells than in rapidly dividing cells?, and (ii) Why is the temporal evolution of r ta decreasing function of time (t) in mammalian cortical neurons, whereas it is an increasing function of t for granule cells around the time of birth? These questions are discussed in terms of a hypothesis which assumes a correlation between deoxyribonucleic acid (DNA) packaging, transcription, and (...) replication. (shrink)

Still the Heart of Darkness analyzes Richard Preston's best-selling account of an Ebola virus outbreak in Reston, Virginia in 1989. Through a textual examination of The Hot Zone, this essay demonstrates how Preston grounds his narrative about the threat of rare emerging viruses from the third world in terms of the colonialist discourse about Africa as the white man's grave, most notably Joseph Conrad's Heart of Darkness. By foregrounding previous outbreaks in Africa, Preston simultaneously darkens its landscape and inscribes (...) the Ebola filovirus as an external biological threat to Americans in a post-Cold War world with porous borders. (shrink)

Viruses are major drivers of global biogeochemistry and the etiological agents of many diseases. They are also the winners in the game of life: there are more viruses on the planet than cellular organisms and they encode most of the genetic diversity on the planet. In fact, it is reasonable to view life as a viral incubator. Nevertheless, most ecological and evolutionary theories were developed, and continue to be developed, without considering the virosphere. This means these theories need (...) to be to reinterpreted in light of viral knowledge or we need to develop new theory from the viral point-of-view. Here we briefly introduce our viral planet and then address a major outstanding question in biology: why is most of life viral? A key insight is that during an infection cycle the original virus is completely broken down and only the associated information is passed on to the next generation. This is different for cellular organisms, which must pass on some physical part of themselves from generation to generation. Based on this premise, it is proposed that the thermodynamic consequences of physical information (e.g., Landauer’s principle) are observed in natural viral populations. This link between physical and genetic information is then used to develop the Viral Information Hypothesis, which states that genetic information replicates itself to the detriment of system energy efficiency (i.e., is viral in nature). Finally, we show how viral information can be tested, and illustrate how this novel view can explain existing ecological and evolutionary theories from more fundamental principles. (shrink)

At the beginning of "The Law of Mind," Charles S. Peirce makes this striking admission (W8:135):I may mention, for the benefit of those who are curious in studying mental biographies, that I was born and reared in the neighborhood of Concord—I mean in Cambridge—at the time when Emerson, Hedge, and their friends were disseminating the ideas that they had caught from Schelling, and Schelling from Plotinus, from Boehm, or from God knows what minds struck with the monstrous mysticism of the (...) East. But the atmosphere of Cambridge held many an antiseptic against Concord transcendentalism; and I am not conscious of having contracted any of that virus. Nevertheless, it is probable that some cultured bacilli, some benignant .. (shrink)

Qualitative validation consists in showing that a model is able to mimic available observed data. In population level biological models, the available data frequently represent a group status, such as pool testing, rather than the individual statuses. They are aggregated. Our objective was to explore an approach for qualitative validation of a model with aggregated data and to apply it to validate a stochastic model simulating the bovine viral-diarrhoea virus (BVDV) spread within a dairy cattle herd. Repeated measures of the (...) level of BVDV-specific antibodies in the bulk-tank milk (total milk production of a herd) were used to summarise the BVDV herd status. First, a domain of validation was defined to ensure a comparison restricted to dynamics of pathogen spread well identified among observed aggregated data (new herd infection with a wide BVDV spread). For simulations, scenarios were defined and simulation outputs at the individual animal level were aggregated at the herd level using an aggregation function. Comparison was done only for observed data and simulated aggregated outputs that were in the domain of validation. The validity of our BVDV model was not rejected. Drawbacks and ways of improvement of the approach are discussed. (shrink)

Background The potential for transmission of blood-borne pathogens such as hepatitis B virus from infected healthcare workers to patients is an important and difficult issue facing healthcare policymakers internationally. Law and policy on the subject is still in its infancy, and subject to a great degree of uncertainty and controversy. Policymakers have made few recommendations regarding the specifics of practice restriction for health care workers who are hepatitis B seropositive. Generally, they have deferred this work to vaguely defined "expert panels" (...) which will have the power to dictate the conditions under which infected health care workers may continue to practice. Discussion In this paper we use recent Canadian policy statements as a critical departure point to propose more specific recommendations regarding disclosure of transmission risks in a way that minimizes practice restriction of hepatitis B seropositive health care workers without compromising patient safety. The range of arguments proposed in the literature are critically examined from the perspective of ethical analysis. Summary A process for considering the ethical implications of the disclosure of the sero-status of health care workers is advanced that considers the varied perspectives of different stakeholders. (shrink)

In this paper, we deal with the theoretical framework for a single-walled carbon nanotube serving as a virus or bacterium sensor, with the complicating influences of non-locality and surface effects taken into account. It is demonstrated that these effects are not negligible as is often assumed in the literature; they may greatly influence both the vibration behaviour as well as the identification process of the virus or bacterium.

A simplified model using kinetic logic is proposed to approach the problem after Hepatitis B viral (HBV) infection. It accounts for several stable regimes or attractors corresponding to the essential dynamic behaviour of the replication of the Hepatitis B virus. Infection with the virus can result in viral clearance, fulminant hepatic failure and death, or chronic transmissible infection, that is multistationarity corresponding to the existence of the positive feedback circuit in our modelling. Another implication of this model is the existence (...) of oscillations or homeostatic mechanisms, sometimes observed in the viral cycle, consistent with the existence of the negative feedback circuit. Thus, this report shows how a simple model of kinetic logic may be used to account for the variety of manifestations of HBV infection. This model implies the presence of the Hepatitis B e antigen, whose conservation suggests that it plays an important role in the life cycle of hepadnaviruses. Its function in the viral cycle is still unknown, but our model suggests that this antigen could explain the passage from one state of the viral infection (acute or latent) to another, as well as the oscillatory behavior which may account for the intermittent symptoms of hepatitis observed in some patients. Furthermore, this model shows a virgin state. This state is also reached after recovery. The model proposed demonstrates that starting from a viral acute infection, the host's immune response, depending on the immunological status of the patient, can lead to viral clearance, or to periodic spontaneous reactivation. (shrink)

Health care workers with needlestick exposures to patients' blood often request a test of the patient for evidence of infection with human immunodeficiency virus. If the patient refuses the test, a conflict develops between the interests of the health care worker and those of the patient. Traditional approaches to this dilemma attempt to balance the rights or utilities of abstract patients and health care workers. While these approaches have the advantage of offering clear guidelines in advance of conflict, the interests (...) of the actual participants may differ from those used to create the guidelines. In nonmedical settings, conflicts are often resolved efficiently through negotiation and monetary exchanges. Although negotiated monetary settlements between health care workers and patients may be an impractical way to resolve medical conflicts, models developed from these perspectives provide insights into the individual interests of physicians and patients. Changing existing rules about medical record documentation, or increasing the penalties for the misuse of medical information, may satisfy the interests on both sides of the conflict and so represent integrative bargaining solutions. Even so, as the relationship between health care workers and their patients evolves, more explicit strategies for negotiation may become a reasonable solution to the problem of conflict. Keywords: acquired immunodeficiency syndrome, confidentiality, ethics, game theory, health policy, human immunodeficiency virus, privacy, professional-patient relations CiteULike Connotea Del.icio.us What's this? (shrink)

Social justice has strong historical roots in public health. This does not mean that we always understand what it entails when conducting an ethical analysis of a particular public health program. This article shows that Powers and Faden’s theory of social justice can provide important insights and nuance to such an analysis. The Ontario human papilloma virus vaccination program that is underway in Canada provides an important and timely case where we can surface ethical issues pertaining to social justice that (...) may otherwise remain unarticulated in the context of this program. This analysis focuses on the normative issues raised by the prioritization of a school-based program for girls only. It also examines the relevant domains of well-being identified in Powers and Faden’s theory to see whether the program is likely to enhance the well-being of those for whom it is most important. Finally, the role of vaccines in general in promoting well-being is discussed. (shrink)

Are there really beliefs? Or are we learning (from neuroscience and psychology, presumably) that, strictly speaking, beliefs are figments of our imagination, items in a superceded ontology? Philosophers generally regard such ontological questions as admitting just two possible answers: either beliefs exist or they don't. There is no such state as quasi-existence; there are no stable doctrines of semi-realism. Beliefs must either be vindicated along with the viruses or banished along with the banshees. A bracing conviction prevails, then, to (...) the effect that when it comes to beliefs (and other mental items) one must be either a realist or an eliminative materialist. (shrink)

I will defend what Peter van Inwagen (1990) calls nihilism: the view that nothing is a (proper) part of anything. This formulation needs refining, but it will do for now.1 Nihilism may seem absurd. The world of common sense and science seems, after all, to consist primarily of entities with parts: persons, animals, plants, planets, stars, galaxies, molecules, viruses, rocks, mountains, rivers, tables, chairs, telephones, skyscrapers, cities… But the denial of such entities is not absurd when it is coupled (...) with the acceptance of their simple subatomic particles.2 Consider three subatomic particles, a, b , and c, arranged in a triangular pattern. According to me, there exist only three things here: a, b , and c. According to others, there exists a fourth thing: a triangle, T , which contains a, b , and c as parts. (Forgive my calling T a triangle even though it consists solely of the vertices.) Picture our disagreement thus. (shrink)

In this paper, I argue against John Beatty’s position in his paper “The Evolutionary Contingency Thesis” by counterexample. Beatty argues that there are no distinctly biological laws because the outcomes of the evolutionary processes are contingent. I argue that the heart of the Caspar–Klug theory of virus structure—that spherical virus capsids consist of 60T subunits (where T = k 2 + hk + h 2 and h and k are integers)—is a distinctly biological law even if the existence of spherical (...) viruses is evolutionarily contingent. (shrink)

From the very first milk you suckle, your food is genetically engineered. The natural world is completely made over, invaded and distorted beyond recognition by genetically engineered trees, plants, animals, insects, bacteria, and viruses, both planned and run amok. Illnesses are very different too. Most of the old ones are gone or mutated into new forms, yet most people are suffering from genetically engineered pathogens, either used in biowarfare, or mistakenly released into the environment, or recombined in toxic form (...) from originally harmless but rapidly mutating engineered organisms. Genetic engineering is so commonplace, you start your own simple experiments with it in elementary school. (shrink)

Of all contemporary social theorists, Luhmann has best understood the centrality of the concept of meaning to social theory and has most extensively worked out the notion's implications. However, despite the power of his theory, the theory suffers from difficulties impeding its reception. This article attempts to remedy this situation with some critical arguments and proposals for revision. First, the theory Luhmann adopted from biology as the basis of his own theory was a poor choice since that theory has no (...) explanatory power, being purely descriptive; furthermore, that theory is fundamentally flawed since it implies that viruses are impossible. Second, Luhmann's theory of meaning cannot coherently make the social domain autonomous as he desires since Luhmann does not take into account the distinction between syntax and semantics. By introducing this distinction, making clear that social systems consist of rules, not just communications, and raising the rule concept to the same prominence in social theory as those of actor and system, autonomy can be maintained while avoiding the counterintuitive aspects of Luhmann's theory. (shrink)

In a now classic paper published in 1991, Alberch introduced the concept of genotype–phenotype (G!P) mapping to provide a framework for a more sophisticated discussion of the integration between genetics and developmental biology that was then available. The advent of evo-devo first and of the genomic era later would seem to have superseded talk of transitions in phenotypic space and the like, central to Alberch’s approach. On the contrary, this paper shows that recent empirical and theoretical advances have only sharpened (...) the need for a different conceptual treat- ment of how phenotypes are produced. Old-fashioned metaphors like genetic blueprint and genetic programme are not only woefully inadequate but positively misleading about the nature of G!P, and are being replaced by an algorithmic approach emerging from the study of a variety of actual G!P maps. These include RNA folding, protein function and the study of evolvable soft- ware. Some generalities are emerging from these disparate fields of analysis, and I suggest that the concept of ‘developmental encoding’ (as opposed to the classical one of genetic encoding) provides a promising computational–theoretical underpinning to coherently integrate ideas on evolvability, modularity and robustness and foster a fruitful framing of the G!P mapping problem. (shrink)

Traditional approaches to theory structure and theory change in science do not fare well when confronted with the practice of certain fields of science. We offer an account of contemporary practice in molecular biology designed to address two questions: Is theory change in this area of science gradual or saltatory? What is the relation between molecular biology and the fields of traditional biology? Our main focus is a recent episode in molecular biology, the discovery of enzymatic RNA. We argue that (...) our reconstruction of this episode shows that traditional approaches to theory structure and theory change need considerable refinement if they are to be defended as generally applicable. 1This paper emerged from discussions between us, and we are both equally responsible for its errors. We would like to thank Yvonne Paterson for helpful comments. (shrink)

In this paper, I offer one example of conceptual change. Specifically, I contend that the discovery that viruses could cause cancer represents an excellent example of branch jumping, one of Thagard’s nine forms of conceptual change. Prior to about 1960, cancer was generally regarded as a degenerative, chronic, non-infectious disease. Cancer causation was therefore usually held to be a gradual process of accumulating cellular damage, caused by relatively non-specific component causes, acting over long periods of time. Viral infections, on (...) the other hand, were generally understood to be acute processes, whereby single, specific and necessary causal agents acted alone to produce disease. However, during the 1960s and 1970s, a number of cancers were discovered to have an infectious aetiology. Of particular note were two—Burkitt’s lymphoma and cervical cancer—which I will discuss in detail later in this piece. Together, these discoveries led, in the short term, to a tentative aetiological reclassification of some types of cancer as infectious diseases and, in the longer term, to a full-blown reclassification of cancer as an aetiological disease branch in its own right. This process of reclassification forms the empirical basis for my concluding remarks on the influence of classification upon causation in medicine. Through this, I aim to demonstrate that conceptual change, far from being a purely abstract concern of the philosopher of science, is of substantial import to scientific practitioners. (shrink)

The concept of information has acquired a strikingly prominent role in contemporary biology. This trend is especially marked within genetics, but it has also become important in other areas, such as evolutionary theory and developmental biology, particularly where these fields border on genetics. The most distinctive biological role for informational concepts, and the one that has generated the most discussion, is in the description of the relations between genes and the various structures and processes that genes play a role in (...) causing. For many biologists, the causal role of genes should be understood in terms of their carrying information about their various products. That information might require the cooperation of various environmental factors before it can be "expressed," but the same can be said of other kinds of message. An initial response might be to think that this mode of description is entirely anchored in a set of well-established facts about the role of DNA and RNA within protein synthesis, summarized in the familiar chart representing the "genetic code," mapping DNA base triplets to amino acids. However, informational enthusiasm in biology predates even a rudimentary understanding of these mechanisms (Schrodinger 1944). And more importantly, current applications of informational concepts extend far beyond anything that can receive an obvious justification in terms of the familiar facts about the specification of protein molecules by DNA. This includes: 1 (i) The description of whole-organism phenotypic traits (including complex behavioral traits) as specified or coded for by information contained in the genes, (ii) The treatment of many causal processes within cells, and perhaps of the wholeorganism developmental sequence, in terms of the execution of a program stored in the genes, (iii) The idea that genes themselves, for the purpose of evolutionary theorizing, should be seen as, in some sense, "made" of information.. (shrink)

Although much has been learned about hereditary mechanisms since Gregor Mendel’s famous experiments, gene concepts have always remained vague, notwithstanding their central role in biology. During over hundred years of genetic research, gene concepts have often and dynamically changed to accommodate novel experimental findings, without ever providing a generally accepted definition of the ‘gene.’ Yet, the distinction between ‘regulatory genes’ and ‘structural genes’ has remained a common theme in modern gene concepts since the definition of the operon-model. This distinction is (...) now challenged by recent findings which suggest that, at least in eukaryotes, structural genes may in many situations have a regulatory function that is independent of the function of the gene product (protein or non-coding RNA molecule). This brief paper discusses these new findings and some possible implications for the notion of the ‘regulatory gene.’. (shrink)

Aristotelian, or non-Platonist, realism holds that mathematics is a science of the real world, just as much as biology or sociology are. Where biology studies living things and sociology studies human social relations, mathematics studies the quantitative or structural aspects of things, such as ratios, or patterns, or complexity, or numerosity, or symmetry. Let us start with an example, as Aristotelians always prefer, an example that introduces the essential themes of the Aristotelian view of mathematics. A typical mathematical truth is (...) that there are six different pairs in four objects: Figure 1. There are 6 different pairs in 4 objects The objects may be of any kind, physical, mental or abstract. The mathematical statement does not refer to any properties of the objects, but only to patterning of the parts in the complex of the four objects. If that seems to us less a solid truth about the real world than the causation of flu by viruses, that may be simply due to our blindness about relations, or tendency to regard them as somehow less real than things and properties. But relations (for example, relations of equality between parts of a structure) are as real as colours or causes. (shrink)

Life appears to be a natural property of matter, but the problem of its origin only arose after early scientists refuted continuous spontaneous generation. There is no chance of life arising ‘all at once’, we need the standard scientific incremental explanation with large numbers of small steps, an approach used in both physical and evolutionary sciences. The necessity for considering both theoretical and experimental approaches is emphasized. After describing basic principles that are available (including the Darwin-Eigen cycle), the search for (...) origins is considered under four main themes. These are the RNA-world hypothesis; potential intermediates between an RNA-world and a modern world via the evolution of protein synthesis and then of DNA; possible alternatives to an RNA-world; and finally the earliest stages from the simple prebiotic systems to RNA. The triplicase/proto-ribosome theory for the origin of the ribosome is discussed where triples of nucleotides are added to a replicating RNA, with the origin of a triplet code well-before protein synthesis begins. The length of the code is suggested to arise from the early development of a ratchet mechanism that overcomes the problem of continued processivity of an RNA-based RNA-polymerase. It is probable that there were precursor stages to RNA with simpler sugars, or just two nucleotides, but we do not yet know of any better alternatives to RNA that were likely to arise naturally. For prebiotic stages (before RNA) a flow-reactor model is suggested to solve metabolism, energy gradients, and compartmentation simultaneously – thus the intense interest in some form of flow reactor. If an autocatalytic cycle could arise in such a system we would be major steps ahead. The most likely physical conditions for the origin of life require further clarification and it is still unclear whether the origin of life is more of an entropy (information) problem (and therefore high temperatures would be detrimental), rather than a kinetic problem (where high temperatures may be advantageous). (shrink)

Recently improved understanding of evolutionary processes suggests that tree-based phylogenetic analyses of evolutionary change cannot adequately explain the divergent evolutionary histories of a great many genes and gene complexes. In particular, genetic diversity in the genomes of prokaryotes, phages, and plasmids cannot be fit into classic tree-like models of evolution. These findings entail the need for fundamental reform of our understanding of molecular evolution and the need to devise alternative apparatus for integrated analysis of these genomes. We advocate the development (...) of integrative phylogenomics for analyzing these genomes and their histories, with tools suited to analyzing the importance of lateral gene transfer (LGT) and of DNA evolution in extra-cellular mobile genetic elements (e.g., viruses, plasmids). These phenomena greatly increase the complexity of relationships among interacting genetic partners, as they exchange functional genetic units. We examine the ontology of functional genetic units, interacting genetic partners, and emergent genetic associations, argue that these three categories of entities are required for a successful integrated phylogenomics. We conclude with arguments to suggest that the proposed new perspective and associated tools are suitable, and perhaps required, as a replacement for the bifurcating trees that have dominated evolutionary thinking for the last 150 years. (shrink)

This essay will not attempt to provide a definition that answers Schrödinger’s question. We shall instead address it by describing a spectrum of biological entities that illustrates why no sharp dividing line between living and non-living things is likely to be useful. The more positive goal of these reflections will be to offer a flexible view of life that does in fact make good sense of why particular organizations of matter can be described as living. By identifying the different capacities (...) exhibited by the various entities constituting our spectrum, especially problem cases such as viruses, we hope to address at least some of the issues that lie behind Schrödinger’s question and its many earlier precursors and subsequent echoes. Such concerns have been raised in a striking way by recent attempts under the rubric of ‘synthetic biology’ to synthesize life from basic chemical building blocks. (shrink)

This paper is devoted to an examination of the discovery, characterization, and analysis of the functions of microRNAs, which also serves as a vehicle for demonstrating the importance of exploratory experimentation in current (post-genomic) molecular biology. The material on microRNAs is important in its own right: it provides important insight into the extreme complexity of regulatory networks involving components made of DNA, RNA, and protein. These networks play a central role in regulating development of multicellular organisms and illustrate the importance (...) of epigenetic as well as genetic systems in evolution and development. The examination of these matters yields principled arguments for the historicity of the functions of key biological molecules and for the indispensability of exploratory experimentation in contemporary molecular biology as well as some insight into the complex interplay between exploratory experimentation and hypothesis-driven science. This latter result is not only of importance for philosophy of science, but also of practical importance for the evaluation of grant proposals, although the elaboration of this latter claim must be left for another occasion. (shrink)

Our aim in this article is to attempt to discuss propagating organization of process, a poorly articulated union of matter, energy, work, constraints and that vexed concept, “information”, which unite in far from equilibrium living physical systems. Our hope is to stimulate discussions by philosophers of biology and biologists to further clarify the concepts we discuss here. We place our discussion in the broad context of a “general biology”, properties that might well be found in life anywhere in the cosmos, (...) freed from the specific examples of terrestrial life after 3.8 billion years of evolution. By placing the discussion in this wider, if still hypothetical, context, we also try to place in context some of the extant discussion of information as intimately related to DNA, RNA and protein transcription and translation processes. While characteristic of current terrestrial life, there are no compelling grounds to suppose the same mechanisms would be involved in any life form able to evolve by heritable variation and natural selection. In turn, this allows us to discuss at least briefly, the focus of much of the philosophy of biology on population genetics, which, of course, assumes DNA, RNA, proteins, and other features of terrestrial life. Presumably, evolution by natural selection—and perhaps self-organization—could occur on many worlds via different causal mechanisms. Here we seek a non-reductionist explanation for the synthesis, accumulation, and propagation of information, work, and constraint, which we hope will provide some insight into both the biotic and abiotic universe, in terms of both molecular self reproduction and the basic work energy cycle where work is the constrained release of energy into a few degrees of freedom. The typical requirement for work itself is to construct those very constraints on the release of energy that then constitute further work. Information creation, we argue, arises in two ways: first information as natural selection assembling the very constraints on the release of energy that then constitutes work and the propagation of organization. Second, information in a more extended sense is “semiotic”, that is about the world or internal state of the organism and requires appropriate response. The idea is to combine ideas from biology, physics, and computer science, to formulate explanatory hypotheses on how information can be captured and rendered in the expected physical manifestation, which can then participate in the propagation of the organization of process in the expected biological work cycles to create the diversity in our observable biosphere. Our conclusions, to date, of this enquiry suggest a foundation which views information as the construction of constraints, which, in their physical manifestation, partially underlie the processes of evolution to dynamically determine the fitness of organisms within the context of a biotic universe. (shrink)

We present a uni!ed diagnosis of three well"known puzzles about proper names, based on a new view of the metaphysics of words and proper names in particular adumbrated by David Kaplan in #Words$. Exploring the analogy of words and viruses, we sketch an account of words as entia suc! cessiva, highlighting the crucial phenomenon of linguistic coordination. Understanding the famous puzzles as coordination failures, we think, brings to the fore important issues in the metaphysical foundations of direct reference. Words, (...) it turns out, can themselves play some of the roles modes of presentation have been called up for. (shrink)

College of Medicine, University of South Alabama Mobile, AL 36688-0002, USA wbp501{at}jaguar1.usouthal.edu ' + u + '@' + d + ' '//--> Abstract Recent work in viral genomics has shown that bacteriophages exhibit a high degree of mosaicism, which is most likely due to a long history of prolific horizontal gene transfer (HGT). Given these findings, we argue that each of the most plausible attempts to properly classify bacteriophages into distinct species fail. Mayr's biological species concept fails because there is (...) no useful viral analog to sexual reproduction. Phenetic species concepts fail because they obscure the mosaicism and the rich reticulated viral histories. Phylogenetic species concepts, even when extended to take into account reticulation, fail because there is no non-arbitrary distinction between recombination events that create a new viral species and those that do not. There is good reason to think that bacteriophages, arguably the Earth's most abundant biological agent, evolve without forming species. Introduction The Biology of Viruses 2.1 Bacteriophage life cycles 2.2 Mechanisms of HGT The Species Problem and Species Concepts 3.1 Phenetic species concepts 3.2 The biological species concept 3.3 Phylogenetic species concepts 3.4 The ecological species concept 3.5 Homeostatic property cluster species Viruses and Species Taxonomy Reticular Phylogenies Conclusion CiteULike Connotea Del.icio.us What's this? (shrink)

The primary impediment to formulating a general theory for adaptive evolution has been the unknown distribution of fitness effects for new beneficial mutations. By applying extreme value theory, Gillespie circumvented this issue in his mutational landscape model for the adaptation of DNA sequences, and Orr recently extended Gillespie's model, generating testable predictions regarding the course of adaptive evolution. Here we provide the first empirical examination of this model, using a single-stranded DNA bacteriophage related to phiX174, and find that our data (...) are consistent with Orr's predictions, provided that the model is adjusted to incorporate mutation bias. Orr's work suggests that there may be generalities in adaptive molecular evolution that transcend the biological details of a system, but we show that for the model to be useful as a predictive or inferential tool, some adjustments for the biology of the system will be necessary. (shrink)

The problem of how a mixture of chemicals can spontaneously transform themselves into even a simple living organism remains one of the great outstanding challenges to science. Various primordial soup theories have been proposed in which chemical self- organization brings about the required level of complexity. Major conceptual obstacles remain, however, such as the emergence of the genetic code, and the “chicken-and-egg” problem concerning which came first: nucleic acids or proteins. Currently fashionable is the so-called RNA world theory, which casts (...) RNA in the role of both chicken and egg. Other theories assume that protein chemistry and even clay crystal life came before nucleic acids. To be fully successful, a theory of biogenesis has to explain not merely the emergence of molecular replication and chemical complexity, but the crucial information content and information processing capabilities of the living cell. (shrink)

Whereas telomeres protect terminal ends of linear chromosomes, telomerases identify natural chromosome ends, which differ from broken DNA and replicate telomeres. Although telomeres play a crucial role in the linear chromosome organization of eukaryotic cells, their molecular syntax most probably descended from an ancient retroviral competence. This indicates an early retroviral colonization of large double-stranded DNA viruses, which are putative ancestors of the eukaryotic nucleus. This contribution demonstrates an advantage of the biosemiotic approach towards our evolutionary understanding of telomeres, (...) telomerases, other reverse transcriptases and mobile elements. Their role in genetic/ genomic content organization and maintenance is no longer viewed as an object of randomly derived alterations (mutations) but as a highly sophisticated hierarchy of regulatory networks organized and coordinated by natural genome-editing competences of viruses. (shrink)

Abstract Many apparently complex mechanisms in biology, especially in embryology and molecular biology, can be explained easily by reasoning at the level of the “efficient cause” of the observed phenomenology: the mechanism can then be explained by a simple geometrical argument or a variational principle, leading to the solution of an optimization problem, for example, via the co-existence of a minimization and a maximization problem (a min–max principle). Passing from a microscopic (or cellular) level (optimal min–max solution of the simple (...) mechanistic system) to the macroscopic level often involves an averaging effect (linked to the repetition of a large number of such microscopic systems with possible random choice of the parameters of each of them) that gives birth to a global functional feature (e.g. at the tissue level). We will illustrate these general principles by building in four different domains of application “a minima” models and showing the main properties of their solutions: (1) extraction of a minimal RNA structure functioning as the first “peptidic machine,” a kind of ancestral ribosome; (2) study of a genetic regulatory network of Drosophila centred on Engrailed gene and expressing successively two genes inside a limit cycle; (3) study of a genetic network regulating neural activity and proliferation in mammals; and (4) study of a simple geometric model of epiboly in zebrafish. Content Type Journal Article Category Regular Article Pages 1-17 DOI 10.1007/s10441-012-9146-4 Authors L. Almeida, AGIM, FRE CNRS 3405, Faculty of Medicine of Grenoble, University J. Fourier, 38 700 La Tronche, France J. Demongeot, AGIM, FRE CNRS 3405, Faculty of Medicine of Grenoble, University J. Fourier, 38 700 La Tronche, France Journal Acta Biotheoretica Online ISSN 1572-8358 Print ISSN 0001-5342. (shrink)

New concepts may prove necessary to profit from the avalanche of sequence data on the genome, transcriptome, proteome and interactome and to relate this information to cell physiology. Here, we focus on the concept of large activity-based structures, or hyperstructures, in which a variety of types of molecules are brought together to perform a function. We review the evidence for the existence of hyperstructures responsible for the initiation of DNA replication, the sequestration of newly replicated origins of replication, cell division (...) and for metabolism. The processes responsible for hyperstructure formation include changes in enzyme affinities due to metabolite-induction, lipid-protein affinities, elevated local concentrations of proteins and their binding sites on DNA and RNA, and transertion. Experimental techniques exist that can be used to study hyperstructures and we review some of the ones less familiar to biologists. Finally, we speculate on how a variety of in silico approaches involving cellular automata and multi-agent systems could be combined to develop new concepts in the form of an Integrated cell (I-cell) which would undergo selection for growth and survival in a world of artificial microbiology. (shrink)

The question which is never entirely resolved is: what is life? Biology, claims to stand for the study of life and living things, yet we would say that it cannot make a thoroughly clear distinction between living and non living, except in some very obvious cases. There are textbook definitions, of course, based on certain notable properties such as the ability to metabolize or reproduce, but these are arbitrary. If we are familiar with the characteristics of a particular animal or (...) plant, we know enough to be able to pronounce that it is dead when certain internal and external behaviours are no longer evident. Even this has difficulties - such as revealed in the arguments about whether to switch off a human life support system or not. When you find a squishy object on the seashore, can you be sure if it is alive or dead - or never living? The same dilemma confronts medical scientists and microbiologists trying to decide, for example, whether viruses are living, or quasi living, or intermittently living, or what. (shrink)

The rationale of patents on transgenic organisms leads to the startling notion of the human qua infringement. The moral reasons by which we may tenably reject such notion are not conclusive as to human life forms outside the body. A close look at recombinant DNA experimentation reveals ingenious processes, but not entities that the body lacks. Except for artificial genes, the genes of biotechnology are found on chromosomes, albeit nonconsecutively, and their uninterrupted transcripts appear in messenger RNA. An enhanced form (...) of protection for ingenious processes, the human methods patent, is proposed and defended as a replacement for product patents. The proposed patent would pertain to biotechnology manufacturing and genetic intervention in somatic and germ cells. A counterpart could govern nonhuman life forms. It is argued that compulsory licensing protections should be a condition of such patent. Contrary to the conservative assumption that statutory sobriquets suffice, the reckoning of what qualifies as a patentable ingenious process will continue to require systematic scientific guidance. (shrink)

In this paper I use a case study—the discovery of the chaperon function exerted by proteins in the various steps of the hereditary process—to re-discuss the question whether the nucleic acids are the sole repositories of relevant information as assumed in the information theory of heredity. The evidence I here present of a crucial role for molecular chaperones in the folding of nascent proteins, as well as in DNA duplication, RNA folding and gene control, suggests that the family of proteins (...) acting as molecular chaperones provides information that is complementary to that stored in the nucleic acids, and equally important. A re-evaluation of the role of proteins in the hereditary process is in order away from the gene-centric approach of the information theory of heredity, to which neo-Darwinian evolutionists adhere. (shrink)

Agricultural biotechnology is a social pursuit, undertaken by social agents within social institutions.1 Any attempt to explore the social dimensions of a profound and complex technological development such as biotechnology is bound to be controversial, and any attempt to formulate an ethical assessment of such a development is bound to be yet more complex and controversial. This surely explains why many choose to ignore these inquiries. But the social dimensions of biotechnology are just as real as viruses, bacteria, enzymes, (...) and cells. To refuse to investigate them with the same seriousness that viruses, bacteria, enzymes and cells are investigated is to place an arbitrary restriction on the scope of rational inquiry. (shrink)

It is remarkable how similar today's mind-body debates are to the philosophical critiques of biological science, such as Henri Bergson's Vitalism at the turn of the last century. Philosophers like Bergson became famous arguing that science could never account for life. One reason was that living creatures could not be decomposed into fundamental units, in spite of the empirical finding that all animate things consist of basic cells with remarkably general properties in a bewildering profusion of variation. Today we know (...) that each of those cells has nearly identical DNA-RNA mechanisms, and that, to give one example, humans have about 50% of DNA in common with such creatures as yeast and C. elegans, the tiny worms that is now almost completely defined in genotype and phenotype. The cell and its genetic machinery can plausibly be called the atom of life. So Bergson's anti-atomism was wrong in large part. Indeed, had we followed his advice about 1900, we would still be living in the first great industrial age. (shrink)

Scientific anomalies are observations and facts that contradict current scientific theories and they are instrumental in scientific theory change. Philosophers of science have approached scientific theory change from different perspectives as Darden (Theory change in science: Strategies from Mendelian genetics, 1991) observes: Lakatos (In: Lakatos, Musgrave (eds) Criticism and the growth of knowledge, 1970) approaches it as a progressive “research programmes” consisting of incremental improvements (“monster barring” in Lakatos, Proofs and refutations: The logic of mathematical discovery, 1976), Kuhn (The structure (...) of scientific revolutions, 1996) observes that changes in “paradigms” are instigated by a crisis from some anomaly, and Hanson (In: Feigl, Maxwell (eds) Current issues in the philosophy of science, 1961) proposes that discovery does not begin with hypothesis but with some “problematic phenomena requiring explanation”. Even though anomalies are important in all of these approaches to scientific theory change, there have been only few investigations into the specific role anomalies play in scientific theory change. Furthermore, much of these approaches focus on the theories themselves and not on how the scientists and their experiments bring about scientific change (Gooding, Experiment and the making of meaning: Human agency in scientific observation and experiment, 1990). To address these issues, this paper approaches scientific anomaly resolution from a meaning construction point of view. Conceptual integration theory (Fauconnier and Turner, Cogn Sci 22:133–187, 1996; The way we think: Conceptual blending and mind’s hidden complexities, 2002) from cognitive linguistics describes how one constructs meaning from various stimuli, such as text and diagrams, through conceptual integration or blending. The conceptual integration networks that describe the conceptual integration process characterize cognition that occurs unconsciously during meaning construction. These same networks are used to describe some of the cognition while resolving an anomaly in molecular genetics called RNA interference (RNAi) in a case study. The RNAi case study is a cognitive-historical reconstruction (Nersessian, In: Giere (ed) Cognitive models of science, 1992) that reconstructs how the RNAi anomaly was resolved. This reconstruction traces four relevant molecular genetics publications in describing the cognition necessary in accounting for how RNAi was resolved through strategies (Darden 1991), abductive reasoning (Peirce, In: Hartshorne, Weiss (eds) Collected papers, 1958), and experimental reasoning (Gooding 1990). The results of the case study show that experiments play a crucial role in formulating an explanation of the RNAi anomaly and the integration networks describe the experiments’ role. Furthermore, these results suggest that RNAi anomaly resolution is embodied. It is embodied in a sense that cognition described in the cognitive-historical reconstruction is experientially based. (shrink)

Science is now studying biodiversity on a massive scale. These studies are occurring not just at the scale of larger plants and animals, but also at the scale of minute entities such as bacteria and viruses. This expansion has led to the development of a specific sub-field of “microbial diversity”. In this paper, I investigate how microbial diversity faces two of the classical issues encountered by the concept of “biodiversity”: the issues of defining the units of biodiversity and of (...) choosing a mathematical measure of diversity. I also show that the extension of the scope of biodiversity to microbial entities such as viruses and many other not-clearly-alive entities raises yet another foundational issue: that of defining a “lower-limit” of biodiversity. (shrink)

The paper describes the change from molecular genetics to postgenomic biology. It focuses on phenomena in the regulation of gene expression that provide a break with the central dogma, according to which sequence specificity for a gene product must be template derived. In its place we find what is called here ‘constitutive molecular epigenesis’. Its three classes of phenomena, which I call sequence ‘activation’, ‘selection’ and ‘creation’, are exemplified by processes such as transcriptional activation, alternative cis- and trans-splicing, and RNA (...) editing. These phenomena support the following main theses of the paper: 1. Other molecular resources share the causal role of ‘genes’: the ‘causal specificity’ for the linear sequence of any gene product is distributed between the coding sequence, cis-acting sequences, trans-acting factors, environmental signals, and the contingent history of the cell (the cellular code) (thesis of distributed causal specificity). 2. These multiple and overlapping processing and targeting mechanisms amplify the repertoire of RNA and protein products specified through the eukaryotic genome, expanding the possibilities specified by the literal code of DNA (thesis of genetic underdeterminism). 3. These mechanisms of gene expression change the focus of postgenomic research from single molecules and their molecular, biochemical and intrinsic function to their cellular, constituent, component or contextual function due to their recruitment and organization in complex cellular networks. In other words, all agents involved in the regulation of gene expression, including DNA, must interact with other agents to achieve full specificity, which is imposed by regulated recruitment and combinatorial control (theses of regulated recruitment and of system analysis). I conclude from these three main theses that the complexity of higher organisms lies not in its number of genes but in the flexibility, versatility and reactivity of its whole genome. (shrink)

How to interpret the “molecular gene” concept is discussed in this paper. I argue that the architecture of biological systems is hierarchical and multi-layered, exhibiting striking similarities to that of modern computers. Multiple layers exist between the genotype and system level property, the phenotype. This architectural complexity gives rise to the intrinsic complexity of the genotype-phenotype relationships. The notion of a gene being for a phenotypic trait or traits lacks adequate consideration of this complexity and has limitations in explaining the (...) genotype-phenotype relationships. I explore ways toward an integrative interpretation of the gene in the context of multi-layered biological systems. A gene, I argue, should be interpreted as a functional unit that is responsible for the trans-generation passage of the capacity to dynamically produce a biochemical activity or biochemical activities. At the molecular level, a gene is a genetic unit, a stretch of DNA sequence, which dictates the behavior and the dynamic production of the encoded cellular component(s). Embedded in a gene’s quadruple DNA code are the regulatory signals, such as those for RNA splicing and/or editing, as well as for transcription factor binding. A regulatory signal can be recognized by the gene expression machinery in one state, but not in another. The confusion caused by RNA splicing, editing, and a gene’s selective tissue distribution pattern is addressed. Instead of a context-dependent definition of the gene, I argue for the view that it is the same gene displaying multiple meanings, subject to differential interpretation by the cellular machinery in different states. In other words, the same gene gives rise to different products and expression levels under different conditions. (shrink)

“DNA-RNA-Protein-everything else” (Arthur Kornberg) on its detail, satisfactory answers to central questions – What is life? head and who try to understand protein bodies as context- How did it originate and how do we view ourselves as living dependent interpreters of the genetic text, (3.) a philosophy that beings? – have been lost in a universe of analytical units.

Our aim in this article is to attempt to discuss propagating organization of process, a poorly articulated union of matter, energy, work, constraints and that vexed concept, “information”, which unite in far from equilibrium living physical systems. Our hope is to stimulate discussions by philosophers of biology and biologists to further clarify the concepts we discuss here. We place our discussion in the broad context of a “general biology”, properties that might well be found in life anywhere in the cosmos, (...) freed from the specific examples of terrestrial life after 3.8 billion years of evolution. By placing the discussion in this wider, if still hypothetical, context, we also try to place in context some of the extant discussion of information as intimately related to DNA, RNA and protein transcription and translation processes. While characteristic of current terrestrial life, there are no compelling grounds to suppose the same mechanisms would be involved in any life form able to evolve by heritable variation and natural selection. In turn, this allows us to discuss at least briefly, the focus of much of the philosophy of biology on population genetics, which, of course, assumes DNA, RNA, proteins, and other features of terrestrial life. Presumably, evolution by natural selection—and perhaps self-organization—could occur on many worlds via different causal mechanisms. Here we seek a non-reductionist explanation for the synthesis, accumulation, and propagation of information, work, and constraint, which we hope will provide some insight into both the biotic and abiotic universe, in terms of both molecular self reproduction and the basic work energy cycle where work is the constrained release of energy into a few degrees of freedom. The typical requirement for work itself is to construct those very constraints on the release of energy that then constitute further work. Information creation, we argue, arises in two ways: first information as natural selection assembling the very constraints on the release of energy that then constitutes work and the propagation of organization. Second, information in a more extended sense is “semiotic”, that is about the world or internal state of the organism and requires appropriate response. The idea is to combine ideas from biology, physics, and computer science, to formulate explanatory hypotheses on how information can be captured and rendered in the expected physical manifestation, which can then participate in the propagation of the organization of process in the expected biological work cycles to create the diversity in our observable biosphere. Our conclusions, to date, of this enquiry suggest a foundation which views information as the construction of constraints, which, in their physical manifestation, partially underlie the processes of evolution to dynamically determine the fitness of organisms within the context of a biotic universe. (shrink)

The three processes needed to create life, compartmentalization, metabolism, and information transfer (memory stored in nucleic acids and manipulation operated by proteins) are embedded in organized genome features. The core of life puts together growth and maintenance (which drives survival), while life in context explores and exploits specific niches. Analysis of gene persistence in a large number of genomes shows that the former constitutes the paleome, which recapitulates the three phases of the origin of life: metabolism of small molecules on (...) surfaces, substitution of surfaces by an RNA-world where transfer RNA played a central role, and invention of template mediated information transfer. Colonization of each niche is performed using an almost unlimited set of genes, forming the cenome. The agreement of the paleome structure with a consistent scenario for the origin of life is such that we may consider extant genomes as providing us with an archive of the origin rather than as a palimpsest where most of our past would be irremediably hidden. (shrink)

There is probably only one information system in living nature — the macromolecular system including DNA, RNA and protein. Its unity for the genetic and nervous activity can be followed in the storage of information (heredity, memory) and in its processing (recombination and selection of both genetic and mental information). According to the hypothesis of the code of nerve impulses, nucleotide triplets of the nucleus, or more likely amino acids of the surface protein of the impulse generating area of a (...) neuron, generate a limited variety of interspike intervals so that each amino acid corresponds to a certain interspike interval and this particular interval initiates by means of a specific neurotransmitter, the synthesis of the same amino acid (or nucleotide triplet) in the postsynaptic neuron. Thus, a series of impulses produces in the postsynaptic neuron a sequence of amino acids in a form of a polypeptide identical to the polypeptide of the presynaptic neuron. (shrink)

It is often said that the only reason why so many mischief-makers or criminals develop viruses/worms/trojan-horses that attack PCs running Windows is that there are far more PCs running Windows accessible via the internet than any other operating system.

Agent-based modeling is starting to crack problems that have resisted treatment by analytical methods. Many of these are in the physical and biological sciences, such as the growth of viruses in organisms, flocking and migration patterns, and models of neural interaction. In the social sciences, agent-based models have had success in such areas as modeling epidemics, traffic patterns, and the dynamics of battlefields. And in recent years, the methodology has begun to be applied to economics, simulating such phenomena as (...) energy markets and the design of auctions. (shrink)

Many historical studies have been devoted to the French school of molecular biology, in particular to the work of Jacques Monod on adaptive enzymes. By focusing on Francois Jacob's studies on lysogeny between 1950 and 1960, we intend to redress the imbalance of historiography, as well as proposing a more fruitful point of view for understanding the relative importance of international contacts and local traditions in the genesis of the operon model.Elie Wollman and Jacob's work on temperate bacteriophages rendered respectable (...) a system that had been considered an artefact for more than two decades. They did this firstly by modelling their studies on those of the US phage group and secondly by basing these studies on a complex vision of the relations between bacteria and bacteriophages. The interaction between bacteria and temperate bacteriophages was considered ab initio as a biochemical process, the mechanisms of which would eventually be characterized. It was also considered as a ''normal'' phenomenon that could be used as a model to understand the process of differentiation, as well as the role of viruses in diseases and cancer. The temperate bacteriophage was a model system that was far more epistemologically open and, for this reason, in a sense more productive than the virulent phage studied by the US phage group. (shrink)

I attempt to define the concept of ‘living organism’. Intuitively, a living organism is a substantial entity with a capacity for certain relevant activities. But biology has discovered that living organisms have a particular compositional or microstructural nature. This nature includes carbon-based macromolecules and water molecules. I argue that such living organisms belong to a natural kind of compound physical object, viz., carbon-based living organism. My definition of a living organism encompasses both the intuitively relevant activities and the empirically discovered (...) compositional nature. The definition is designed to deal with a variety of problem cases, e.g., viruses, proteinoid microspheres, sterile organisms, suspended animation cases, and living parts of organisms. (shrink)

During the course of its short history the discipline concerned with the origin of life has given birth to several scientific programmes in the Lakatosian sense, two of the most prominent and widespread being those initiated by Oparin (life began from protein entities) and Muller-Haldane (life began from genetic entities). The present paper sets down the bases for the rational reconstruction of both views by identifying their hard core and some of their successive developments. An assessment is made of the (...) various stages in the evolution of these programmes with respect to the crucial Lakatosian notions of progressivity and regressivity and of how their arguments stand up against one another. This epistemological analysis also establishes the internal reasons why the RNA version of the genotype programme (developed in particular by L. Orgel and S. Spiegelman) has today taken on a progressive character and enjoys recognition by the international scientific community. (shrink)

Firstly we consider the new results about enzymatic capabilities in the RNA. In this framework we analyse the sequence-folding duality as a precursor of the genotype/phenotype duality. We discuss then which are the evolutive potentialities and limitations for a system with the absence and the presence of a nucleic acid to proteins translator code. We study the arise of the code in the living systems as a form of deep interlooking between the logic of the machinery and its hardware, discussing (...) some problems that abstract modelization of this process implies. Finaly we propose to redefine the informational vocabulary usually employed in Molecular Biology. (shrink)

The molecular biology of viruses can be effectively described by kinetic logic as several feedback loops are implicated in all viral cycles and as viral proteins generally display several functions. We applied this method to the study of the rhabdovirus cycle.Formally, the dynamics of the model are explored on the basis of a discrete caricature (kinetic logic), with special emphasis on the role of the constitutive feedback loops to determine the essential dynamical behaviour of the viral cycle. From a (...) biological point of view, our model accounts for several stable regimes or attractors: healthy cells, acute infection and different kinds of persistent infections, a multistationarity in good agreement with the existence of several positive feedback loops in our system. (shrink)

Moates, Anne The prospect of a virulent human influenza pandemic causing large scale mortality and morbidity is a cause for global concern. The most likely candidate is the avian or 'bird' flu which is a strain of influenza virus named because it is found in birds. There are three groups of flu viruses, influenza A, B and C. Type A viruses are able to infect a wide variety of warm-blooded animals. B and C types are mostly confined to (...) humans. Avian influenza is caused by a Type A virus and typically affects birds' respiratory, digestive and nervous systems.[1]. (shrink)

Firstly we consider the new results about enzymatic capabilities in the RNA. In this framework we analyse the sequence-folding duality as a precursor of the genotype/phenotype duality. We discuss then which are the evolutive potentialities and limitations for a system with the absence and the presence of a nucleic acid to proteins translator code. We study the arise of the code in the living systems as a form of deep interlooking between the logic of the machinery and its hardware, discussing (...) some problems that abstract modelization of this process implies. Finaly we propose to redefine the informational vocabulary usually employed in Molecular Biology. (shrink)

In this paper, we present an argument showing why the general properties of a self-organizing system (e.g. being far from equilibrium) may be too weak to characterize biological and proto-biological systems. The special character of biological systems, tell us that its distinctive capacities could have been developed in pre-biotic times. In other words, the basic properties of life would be better comprehended if we think that they were much more likely early in time. We developed a conceptual proposal on the (...) origins of pre-biotic world, a kind of protocellular system which is made up of simple molecular compounds interconnecting three different types of processes. The interrelation of these processes characterizes the “Informational Dynamical System” (our conceptualprotocell proposal) as an autonomous dynamical system that can maintain by itself in far from equilibrium state, as opposed to those that depend on external causes. Consequently it follows that, in the dawn of pre-biotic world, there was no DNA or RNA or proteins to begin with. As well, our proposal implies the separation of biological evolution from the kind of open-ended evolution that gave rise to first breed of animate matter. (shrink)

Love-alpha -- Language and life -- Premises -- Respect -- On conscious co-creation -- Interrelationship -- A map of the worlds -- Balance -- Trust : viruses -- Messengers -- Cooperation/community -- Truth -- The spirits of things -- Harmony -- The deva of fleas -- Communication -- Love : omega.

Love-alpha -- Language and life -- Premises -- Respect -- On conscious co-creation -- Interrelationship -- A map of the worlds -- Balance -- Trust : viruses -- Messengers -- Cooperation/community -- Truth -- The spirits of things -- Harmony -- The deva of fleas -- Communication -- Love : omega.

Love-alpha -- Language and life -- Premises -- Respect -- On conscious co-creation -- Interrelationship -- A map of the worlds -- Balance -- Trust : viruses -- Messengers -- Cooperation/community -- Truth -- The spirits of things -- Harmony -- The deva of fleas -- Communication -- Love : omega.

. The sequencing of the human genome and the initiation of the structural genomics projects have ushered in a new age of biology that involves multi-lab, high-cost projects with broad task-oriented goals rather than the more conventional hypothesis-driven approach of the past. The new biology has led to the development of new sets of tools for the scientist to use in the quest to solve mysteries of human disease, biomolecular structure-function relationships, and other burning biological questions. Nevertheless, the impact of (...) the new biology on the field of AIDS investigation has been minimal, predominantly because many of the tools in the HIV field of study were developed before the full advance of the new biology was felt in the biomedical community. Many of the high-cost megaprojects that involve large technological advances and are marketed as projects of promise to the biomedical community are not likely to significantly impact the field of HIV/AIDS research and cannot serve as a substitute for direct funding to the HIV/AIDS scientists working for vaccine development, an understanding of mechanisms of disease causation, and new tools for therapeutic intervention. (shrink)

Ducks lay eggs' is a true sentence, and `ducks are female' is a false one. Similarly, `mosquitoes carry the West Nile virus' is obviously true, whereas `mosquitoes don't carry the West Nile virus' is patently false. This is so despite the egg-laying ducks' being a subset of the female ones and despite the number of mosquitoes that don't carry the virus being ninety-nine times the number that do. Puzzling facts such as these have made generic sentences defy adequate semantic treatment. (...) However complex the truth conditions of generics appear to be, though, young children grasp generics more quickly and readily than seemingly simpler quantifiers such as `all' and `some'. I present an account of generics that not only illuminates the strange truth conditions of generics, but also explains how young children find them so comparatively easy to acquire. I then argue that generics give voice to our most cognitively primitive generalizations and that this hypothesis accounts for a variety of facts ranging from acquisition patterns to cross-linguistic data concerning the phonological articulation of operators. I go on to develop an account of the nature of these cognitively fundamental generalizations and argue that this account explains the strange truth-conditional behavior of generics. (shrink)

Intelligent design—the idea that a designing intelligence plays a substantive and empirically significant role in the natural world—no longer sits easily in our intellectual environment. Science rejects it for invoking an unnecessary teleology. Philosophy rejects it for committing an argument from ignorance. And theology rejects it for, as Edward Oakes contends, making the task of theodicy impossible.1 I want in this lecture to address all these concerns but especially the last. For many thinkers, particularly religious believers, intelligent design exacerbates the (...) problem of natural evil—intelligent design makes natural evil not an accident of natural history or a price exacted by evolution or a necessary consequence of creation’s freedom but an outcome fully intended by a sadistic designer. Or, as Robert Russell put it to me on the PBS program Uncommon Knowledge, “The notion of intelligent design is incoherent because it’s either a natural cause, in which case you don’t go anywhere, or it’s a divine cause, in which case you don’t have the biblical God.”2 The biblical God, presumably, would not design the rabies virus, the bubonic plague bacterium, or the mosquito. (shrink)

Let me begin with what may seem a very minor point, but one which I think reveals something about how many philosophers today conceive of their subject. During the past few decades, there has been an increasing tendency for references in philosophy books and articles to be formatted in the ‘author and date’ style (‘see Fodor (1996)’, ‘see Smith (2001)’.) A neat and economical reference system, you may think; and it certainly saves space, albeit inconveniencing readers by forcing them to (...) flip back to the end of the chapter or book to find the title of the work being referred to. But what has made this system so popular among philosophers? A factor which I suspect exerts a strong subconscious attraction for many people is that it makes a philosophy article look very like a piece of scientific research. For if one asks where the ‘author-date’ system originated, the answer is clear: it comes from the science journals.[1] And in that context, the choice of referencing system has a very definite rationale. In the progress-driven world of science, priority is everything, and it’s vitally important for a career that a researcher is able to proclaim his work as breaking new ground. Bloggs (2005) developed a technique for cloning a certain virus; Coggs (2006) showed how certain bits of viral DNA could be spliced; and now Dobbs (2007) draws on both techniques to develop the building blocks of a new vaccine. The idea is that our knowledge-base is enhanced, month by month and year by year, in small incremental steps (perhaps with occasional major breakthroughs); and in the catalogue of advances, the date tagged to each name signals when progress was made, and by whom. (shrink)

The term pseudoscience refers to a highly heterogeneous set of practices, beliefs, and claims sharing the property of appearing to be scientific when in fact they contradict either scientific findings or the methods by which science proceeds. Classic examples of pseudoscience include astrology, parapsychology, and ufology; more recent entries are the denial of a causal link between the HIV virus and AIDS or the claim that vaccines cause autism. To distinguish between science and pseudoscience is part of what the philosopher (...) Karl Popper referred to as the demarcation problem, a project that has been dismissed by another philosopher, Larry Laudan, but that keeps gathering much interest in philosophers, scientists, educators, and policymakers. This entry provides the basics of the debate about demarcation, as well as a brief discussion of why it is of vital importance not just intellectually but for society at large. (shrink)

In this thesis, I give a metascientific account of causality in medicine. I begin with two historical cases of causal discovery. These are the discovery of the causation of Burkitt’s lymphoma by the Epstein-Barr virus, and of the various viral causes suggested for cervical cancer. These historical cases then support a philosophical discussion of causality in medicine. This begins with an introduction to the Russo- Williamson thesis (RWT), and discussion of a range of counter-arguments against it. Despite these, I argue (...) that the RWT is historically workable, given a small number of modifications. I then expand Russo and Williamson’s account. I first develop their suggestion that causal relationships in medicine require some kind of evidence of mechanism. I begin with a number of accounts of mechanisms and produce a range of consensus features of them. I then develop this consensus position by reference to the two historical case studies with an eye to their operational competence. In particular, I suggest that it is mechanistic models and their representations which we are concerned with in medicine, rather than the mechanism as it exists in the world. -/- I then employ these mechanistic models to give an account of the sorts of evidence used in formulating and evaluating causal claims. Again, I use the two human viral oncogenesis cases to give this account. I characterise and distinguish evidence of mechanism from evidence of difference-making, and relate this to mechanistic models. I then suggest the relationship between types of evidence presents us with a means of tackling the reference-class problem. This sets the scene for the final chapter. Here, I suggest the manner in which these two different classes of evidence become integrated is also reflected in the way that developing research programmes change as their associated causal claims develop. (shrink)

Since the 1930s, scientists studying the neurological disease scrapie had assumed that the infectious agent was a virus. By the mid 1960s, however, several unconventional properties had arisen that were difficult to reconcile with the standard viral model. Evidence for nucleic acid within the pathogen was lacking, and some researchers considered the possibility that the infectious agent consisted solely of protein. In 1982, Stanley Prusiner coined the term `prion' to emphasize the agent's proteinaceous nature. This infectious protein hypothesis was denounced (...) by many scientists as `heretical'.This essay asks why the concept of an infectious protein was considered controversial. Some biologists justified their evaluation of this hypothesis on the grounds that an infectious protein contradicted the `central dogma of molecular biology'. Others referred to vague theoretical constraints such as molecular biology's `theoretical structure' or `framework'. Examination of the objections raised by researchers reveals exactly what generalizations were being challenged by a protein model of infection.This two-part survey of scrapie and prion research reaches several conclusions: (1) A theoretical framework is present in molecular biology, exerting its influence in hypothesis formation and evaluation; (2) This framework consists of several related, yet separable, generalizations or `elements', including Francis Crick's Central Dogma and Sequence Hypothesis, plus notions concerning infection, replication, protein synthesis, and protein folding; (3) The term `central dogma' has stretched beyond Crick's original 1958 definition to encompass at least two other `framework elements': replication and protein synthesis; and (4) From the study of scrapie and related diseases, biological information has been delineated into at least two classes: sequential and what I call `conformational'.In Part I of this essay, a brief review of the central dogma, as outlined by both Francis Crick and James Watson, will be given. The developments in scrapie research from 1965 to 1972 will then be traced. This section will summarize many of the puzzling, non-viral-like properties of the scrapie agent. Alternative hypotheses to the viral explanation will also be presented, including early versions of a protein-only hypothesis. Part II of this essay will follow the developments in scrapie and prion research from the mid 1970s through 1991. The growing prominence of a protein-only model of infection will be balanced by continued objections from many researchers to a pathogen devoid of nucleic acid. These objections will help illuminate those generalizations in molecular biology that were indeed challenged by a protein-only model of infection. (shrink)

Ice Cube "What's a brother gotta do to get a message through to the Red, White, and Blue?" Ice-T Rap music has emerged as one of the most distinctive and controversial music genres of the past decade. A significant part of hip hop culture, [1] rap articulates the experiences and conditions of African-Americans living in a spectrum of marginalized situations ranging from racial stereotyping and stigmatizing to struggle for survival in violent ghetto conditions. In this cultural context, rap provides a (...) voice to the voiceless, a form of protest to the oppressed, and a mode of alternative cultural style and identity to the marginalized. Rap is thus not only music to dance and party to, but a potent form of cultural identity. It has become a powerful vehicle for cultural political expression, serving as the "CNN of black people" (Chuck D), or upping the high-tech ante, as their "satellite communication system" (Heavy D). It is an informational medium to tune into, one that describes the rage of African-Americans facing growing oppression, declining opportunities for advancement, changing moods on the streets, and everyday life as a matter of sheer survival. In turn, it has become a cultural virus, circulating its images, sounds, and attitude throughout the culture and body politic. (shrink)

The marketing of infant formula in third-world countries in the 1970s by Nestlé S.A. gave rise to a consumer boycott that came to be a widely taught case study in the field of Business Ethics. This article extends that case study by identifying three specific individuals who were associated with managing Nestlé’s response to that boycott. It reveals their subsequent direct involvement in a number of additional “classic” 1980s business scandals (some of which ended with major criminal trials and the (...) imprisonment of eminent business figures)—and describes tangential linkages to other business scandals of the time. The article discloses a behind-the-scenes pattern of business villainy, adding both depth and breadth to previous accounts of these scandals. The article offers a conceptual framework that goes beyond personal greed as an explanatory factor for such unethical behavior in the business world, suggesting the presence of personal and organizational networks of intrigue and opportunity. The linkages between the scandals suggest an epidemiological process with the plotters acting as “virus” carriers contaminating various corporate cultures. (shrink)

Debates over vaccine mandates raise intense emotions, as reflected in the current controversy over whether to mandate the vaccine against human papilloma virus (HPV), the virus that can cause cervical cancer. Public health ethics so far has failed to facilitate meaningful dialogue between the opposing sides. When stripped of its emotional charge, the debate can be framed as a contest between competing ethical values. This framework can be conceptualized graphically as a conflict between autonomy on the one hand, which militates (...) against government intrusion, and beneficence, utilitarianism, justice, and nonmaleficence on the other, which may lend support to intervention. When applied to the HPV vaccine, this framework would support a mandate based on utilitarianism, if certain conditions are met and if herd immunity is a realistic objective. (shrink)

Despite decades of prevention efforts, millions of persons worldwide continue to become infected by the human immunodeficiency virus (HIV) every year. This urgent problem of global epidemic control has recently lead to significant changes in HIV testing policies. Provider-initiated approaches to HIV testing have been embraced by the Centers for Disease Control and Prevention and the World Health Organization, such as those that routinely inform persons that they will be tested for HIV unless they explicitly refuse ('opt out'). While these (...) policies appear to increase uptake of testing, they raise a number of ethical concerns that have been debated in journals and at international AIDS conferences. However, one special form of 'provider-initiated' testing is being practiced and promoted in various parts of the world, and has advocates within international health agencies, but has received little attention in the bioethical literature: mandatory premarital HIV testing. This article analyses some of the key ethical issues related to mandatory premarital HIV testing in resource-poor settings with generalized HIV epidemics. We will first briefly mention some mandatory HIV premarital testing proposals, policies and practices worldwide, and offer a number of conceptual and factual distinctions to help distinguish different types of mandatory testing policies. Using premarital testing in Goma (Democratic Republic of Congo) as a point of departure, we will use influential public health ethics principles to evaluate different forms of mandatory testing. We conclude by making concrete recommendations concerning the place of mandatory premarital testing in the struggle against HIV/AIDS. (shrink)

In early 1984, the AIDS epidemic was less than four years old. Chemists at the pharmaceutical company Syntex, situated in the rolling green hills near Stanford University in Palo Alto, California, had recently synthesized a new antiviral drug (Martin et al. 1983). The drug, at first given the awkward chemical abbreviation DHPG, later came to be known by the generic name ganciclovir. Ganciclovir was a potent drug for the treatment of herpes virus infection (such as genital herpes or chickenpox), but (...) the unique characteristic of ganciclovir was that it worked against cytomegalovirus (CMV), a heretofore untreatable virus infection. Although relatively harmless in healthy individuals, CMV caused .. (shrink)