Drosophila responds to a septic injury by the rapid synthesis of antimicrobial peptides. These molecules are predominantly produced by the fat body, a functional equivalent of mammalian liver, and are secreted into the hemolymph where their concentrations can reach up to 100 μM. Six distinct antibacterial peptides (plus isoforms) and one antifungal peptide have been characterized in Drosophila and their genes cloned. The induction of the gene encoding the antifungal peptide relies on the spätzle/Toll/cactus gene cassette, which is (...) involved in the control of dorsoventral patterning in the embryo, and shows interesting structural and functional similarities with cytokine‐induced activation of NF‐ϰB in mammalian cells. An additional pathway, dependent on the as yet unidentified imd (for immune‐deficiency) gene, is required for the full induction of the antibacterial peptide genes. Mutants deficient for the Toll and imd pathways exhibit a severely reduced survival to fungal and bacterial infections, respectively. Recent data on the molecular mechanisms underlying recognition of non‐self are also discussed in this review. (shrink)

The human intestines are constantly under the influence of numerous pathological factors: enteropathogenic microorganisms, food antigens, physico‐chemical stress associated with digestion and bacterial metabolism, therefore it must be provided with a system of protection against adverse impact. Recent studies have shown that Paneth cells play a crucial role in maintaining homeostasis of the small intestines. Paneth cells perform many vital functions aimed at maintaining a homeostatic balance between normal microbiota, infectious pathogens and the human body, regulate the qualitative composition and (...) number of intestinal microorganisms, prevent the introduction of potentially pathogenic species, and protect stem cells from damage. Paneth cells take part in adaptive and protective‐inflammatory reactions. Paneth cells maintain dynamic balance between microbial populations, and the macroorganism, preventing the development of intestinal infections and cancer. They play a crucial role in gastrointestinal homeostasis and may be key factors in the etiopathological progression of intestinal diseases. (shrink)

The importance of seminal plasma in fertilization was appreciated as early as 1677 and would thus hardly seem a source for the search of antibacterial agents. The observation that seminal plasma had the ability to inhibit the growth of microorganisms in 1940 led to a systematic search for molecules possessing antimicrobial activity in addition to factors that might have a role in reproductive physiology. Extensive investigations led to the discovery in bovine seminal fluid of a 47‐residue peptide, possessing (...) potent antimicrobial activity as well as calcium transport modulatory properties in bovine sperm. We describe in this article the two, apparently unrelated, biological activities of this peptide. (shrink)

In Europe ≈15,000 patients receive larval therapy for wound treatment annually. Over the past few years, clinical studies have demonstrated the success of larvae of Lucilia sericata as debridement agents. This is based on a combination of physical and biochemical actions. Laboratory investigations have advanced our understanding of the biochemical mechanisms underlying the beneficial effects of larval secretions, including removal of dead tissue, reduction of the bacterial burden, and promotion of tissue regeneration. The present article summarizes our current understanding of (...) the microbiological, immunological, and wound healing actions of larval therapy, and the molecules involved in these beneficial effects. Future studies will focus on the isolation, identification, and (pre)clinical testing of the effective molecules of L. sericata larvae. These molecules may be candidates for the development of new agents for the treatment of several infectious and inflammatory diseases, including chronic wounds. (shrink)

This chapter explores the question of whether or not individual agents are under a moral obligation to reduce their ‘antimicrobial footprint’. An agent’s antimicrobial footprint measures the extent to which her actions are causally linked to the use of antibiotics. As such, it is not necessarily a measure of her contribution to antimicrobial resistance. Talking about people’s antimicrobial footprint in a way we talk about our carbon footprint may be helpful for drawing attention to the global (...) effects of individual behaviour and for highlighting that our choices can collectively make a real difference. But can we be morally obligated to make a contribution to resolving a collective action problem when our individual contributions by themselves make no discernible difference? I will focus on two lines of argument in favour of such obligations: whether a failure to reduce one’s antimicrobial footprint is unfair and whether it constitutes wrongdoing because it is harmful. I conclude by suggesting that the argument from collective harm is ultimately more successful. (shrink)

At the very beginning of L’Homme-Machine, La Mettrie claims that Leibnizians with their monads have “rather spiritualized matter than materialized the soul”; a few years later Pierre-Louis Moreau de Maupertuis, President of the Berlin Academy of Sciences and natural philosopher with a strong interest in the modes of transmission of ‘genetic’ information, conceived of living minima which he termed molecules, “endowed with desire, memory and intelligence,” in his Système de la nature ou Essai sur les corps organisés. This text (...) first appeared in Latin in 1751 under the title Dissertatio inauguralis metaphysica de universali naturae systemate, with the pseudonym Dr Baumann; it was translated by Maupertuis in 1754 as Essai sur la formation des corps organisés and was later included in his 1756 Œuvres under the title Système de la nature. Now, it is clear that Maupertuis was a kind of Leibnizian; and that his molecule possessed higher-level, ‘mental’ properties. In that sense he falls under the first category described by La Mettrie. But he was also involved in a debate on this issue with Diderot, who put forth a sustained critique of Maupertuis’ theory of the molecule in the additions to his 1753 Pensées sur l’interprétation de la nature. Where Maupertuis attributes higher-level properties to his living minima, Diderot argues that these properties are ‘organizational’, i.e., they can only be properties of the whole. At issue here is the degree of commitment to a form of materialism. (shrink)

To explore how molecules became signs I will ask: “What sort of process is necessary and sufficient to treat a molecule as a sign?” This requires focusing on the interpreting system and its interpretive competence. To avoid assuming any properties that need to be explained I develop what I consider to be a simplest possible molecular model system which only assumes known physics and chemistry but nevertheless exemplifies the interpretive properties of interest. Three progressively more complex variants of this (...) model of interpretive competence are developed that roughly parallel an icon-index-symbol hierarchic scaffolding logic. The implication of this analysis is a reversal of the current dogma of molecular and evolutionary biology which treats molecules like DNA and RNA as the original sources of biological information. Instead I argue that the structural characteristics of these molecules have provided semiotic affordances that the interpretive dynamics of viruses and cells have taken advantage of. These molecules are not the source of biological information but are instead semiotic artifacts onto which dynamical functional constraints have been progressively offloaded during the course of evolution. (shrink)

The problem of antimicrobial resistance is so dire that people are predicting that the era of antibiotics may be coming to an end, ushering in a ‘post-antibiotic’ era. A comprehensive policy response is therefore urgently needed. A part of this response will require framing the problem in such a way that adequately reflects its nature as well as encompassing an approach that has the best prospect of success. This paper considers framing the problem as a slowly emerging disaster, including (...) its potential benefits and difficulties, from a conceptual and policy perspective. (shrink)

What is morality? How many moral values are there? And what are they? According to the theory of morality-as-cooperation, morality is a collection of biological and cultural solutions to the problems of cooperation recurrent in human social life. This theory predicts that there will be as many different types of morality as there are different types of cooperation. Previous research, drawing on evolutionary game theory, has identified at least seven different types of cooperation, and used them to explain seven different (...) types of morality: family values, group loyalty, reciprocity, heroism, deference, fairness and property rights. Here we explore the conjecture that these simple moral ‘elements’ combine to form a much larger number of more complex moral ‘molecules’, and that as such morality is a combinatorial system. For each combination of two elements, we hypothesise a candidate moral molecule, and successfully locate an example of it in the professional and popular literature. These molecules include: fraternity, blood revenge, family pride, filial piety, gavelkind, primogeniture, friendship, patriotism, tribute, diplomacy, common ownership, honour, confession, turn taking, restitution, modesty, mercy, munificence, arbitration, mendicancy, and queuing. These findings indicate that morality – like many other physical, biological, psychological and cultural systems – is indeed a combinatorial system. Thus morality-as-cooperation provides a principled and powerful theory, that explains why there are many moral values, and successfully predicts what they will be; and it generates a systematic framework that has the potential to explain all moral ideas, possible and actual. Pursuing the many implications of this theory will help to place the study of morality on a more secure scientific footing. (shrink)

Governments can practically and efficiently address zoonoses and AMR –– within the text of the new pandemic instrument. We map the overlaps between the efforts needed to address both pandemic threats, including (a) equitable access to medical countermeasures, (b) globally integrated One Health surveillance and monitoring systems, (c) increased technical and laboratory capacity in low- and middle-income countries, and (d) a regulatory framework governing the stewardship of antimicrobials. By outlining potential dual-purpose provisions that could be included in a pandemic instrument, (...) we argue that addressing AMR in the pandemic instrument is practicable, the most effective use of limited time and resources, and provides the best opportunity for future global pandemic readiness. (shrink)

Antimicrobial therapy is a cornerstone of therapy in critically ill patients; however, the wide use of antibiotics has resulted in increased antimicrobial resistance and outbreaks of resistant disease. To counter this, many hospitals have instituted antimicrobial stewardship programmes as a way to reduce the inappropriate use of antibiotics. However, uptake of antimicrobial stewardship programmes has been variable, as many clinicians fear that they may put individual patients at risk of treatment failure. In this paper, I argue (...) that antimicrobial stewardship programmes are indeed a form of bedside rationing, and explore the risks and benefits of such programmes for individual patients in the intensive care unit, and the critically ill population in general. Using Norman Daniels’ Accountability for Reasonableness as a framework for evaluating resource allocation policies, I conclude that antimicrobial stewardship programmes are an ethically sound form of bedside rationing. (shrink)

Antimicrobial resistance (AMR) is increasingly recognised as a threat to human, animal and environmental health. In an effort to counter this threat, several intervention plans have been proposed and implemented by states and organisations such as the WHO. A One Health policy approach, which targets multiple domains (healthcare, animal husbandry and the environment), has been identified as useful for curbing AMR. Johnson and Matlock have recently argued that One Health policies in the AMR context require special ethical justification because (...) of the so-called least restrictive alternative principle. This article analyses and rejects two assumptions that this argument relies on. The first assumption is that One Health policies are generally more restrictive than their alternatives because they target more domains and impact more people. The second assumption is that the least restrictive alternative principle has a special normative importance in that it establishes a systematic presumption in favour of the least restrictive policy options. Once these assumptions are rejected, the use of One Health policies on AMR can be justified more easily than Johnson and Matlock argue. (shrink)

As we combat the COVID-19 pandemic, both the prescription of antimicrobials and the use of biocidal agents have increased in many countries. Although these measures can be expected to benefit existing people by, to some extent, mitigating the pandemic's effects, they may threaten long-term well-being of existing and future people, where they contribute to the problem of antimicrobial resistance (AMR). A trade-off dilemma thus presents itself: combat COVID-19 using these measures, or stop using them in order to protect against (...) AMR. Currently, I argue, we are choosing to continue with these measures, and thus to prioritize combatting COVID-19, without adequate ethical reflection on the AMR-associated costs of these measures. I discuss the magnitude of the possible costs and benefits involved in making the trade-off in favour of COVID-19, and their distribution. I highlight two salient aspects of distribution that can help determine whether combatting COVID-19 whilst exacerbating AMR produces justly distributed costs and benefits: distribution between current and future populations, and distribution between existing geographical populations. Adopting this account, I argue that based on the magnitude and distribution of costs and benefits of combatting COVID-19, we have good reason to rethink this trade-off, and instead consider prioritizing protecting current and future people against AMR, but jettisoning measures against COVID-19 that also exacerbate AMR. (shrink)

As we combat the COVID-19 pandemic, both the prescription of antimicrobials and the use of biocidal agents have increased in many countries. Although these measures can be expected to benefit existing people by, to some extent, mitigating the pandemic's effects, they may threaten long-term well-being of existing and future people, where they contribute to the problem of antimicrobial resistance (AMR). A trade-off dilemma thus presents itself: combat COVID-19 using these measures, or stop using them in order to protect against (...) AMR. Currently, I argue, we are choosing to continue with these measures, and thus to prioritize combatting COVID-19, without adequate ethical reflection on the AMR-associated costs of these measures. I discuss the magnitude of the possible costs and benefits involved in making the trade-off in favour of COVID-19, and their distribution. I highlight two salient aspects of distribution that can help determine whether combatting COVID-19 whilst exacerbating AMR produces justly distributed costs and benefits: distribution between current and future populations, and distribution between existing geographical populations. Adopting this account, I argue that based on the magnitude and distribution of costs and benefits of combatting COVID-19, we have good reason to rethink this trade-off, and instead consider prioritizing protecting current and future people against AMR, but jettisoning measures against COVID-19 that also exacerbate AMR. (shrink)

Antimicrobial resistance kills people. According to a recent estimate, ‘7 00 000 people die of resistant infections every year’, and ‘by 2050 10 million lives a year are at risk due to drug resistant infections, as are 100 trillion USD of economic output’.1 Today, ‘bacteria are resistant to nearly all antibiotics that were earlier active against them’.2 For all these reasons, antimicrobial resistance is considered a ‘slowly emerging disaster’3 and a ‘global health security issue’.4 The prospect we are (...) facing is that of a ‘post antibiotic era’,5 in which we risk losing the availability of effective antibiotics and, with them, of medical interventions that require effective antibiotics, such as chemotherapy, transplantation and major surgery. One of the causes of antimicrobial resistance is antimicrobial consumption. As put by the Centers for Disease Control and Prevention, ‘the use of antibiotics is the single most important factor leading to antibiotic resistance around the world: simply using antibiotics creates resistance’.6 According to the 2016 Review on Antimicrobial Resistance commissioned by the UK Government, ‘more consumption of antibiotics directly leads to more resistance’.1 This is because microbes that are not killed by antimicrobials are more likely to reproduce and proliferate and to pass their resistance genes on to other microbes. Thus, exactly like the consumption of many other finite resources, antibiotic and antimicrobial consumption gives rise to the collective action problem known as ‘tragedy of the commons’: consuming a certain resource, such as antimicrobials, is in an individual’s best short-term interest, but many instances of individual consumption erode the resource and therefore conflict with the collective interest in preserving the good. How to solve a tragedy of the commons? As is the case with the consumption of other finite resources, the answer is quite simple: by rationing the resource. Simon Oczkowski’s article …. (shrink)

Antimicrobial resistance (AMR) describes the evolution of treatment‐resistant pathogens, with potentially catastrophic consequences for human medicine. AMR is driven by the over‐prescription of antibiotics, and could be reduced through consideration of the ethical dimensions of the dilemma faced by doctors. This dilemma involves balancing apparently opposed interests of current and future patients, and unique contextual factors in different countries, which may modify the core dilemma. We describe three example countries with different economic backgrounds and cultures—South Africa, Sri Lanka and (...) the United Kingdom. Then we discuss how country‐specific factors impact on the prominence of various ethical dimensions of the dilemma (visibility and moral equality of future generations; Rule of Rescue; prescribing autonomy and conflicts of interest; consensus on collective action). We conclude that a nuanced understanding of national prescribing dilemmas is critical to inform the design of effective stewardship approaches. (shrink)

Antimicrobial resistance is a growing public health concern and is associated with the over- or inappropriate use of antimicrobials in both humans and agriculture. While there has been reco- gnition of this problem on the part of agricultural and public health authorities, there has none- theless been significant difficulty in translating policy recommendations into practical guidelines. In this paper, we examine the process of public health policy development in Quebec agriculture, with a focus on the case of pork production (...) and the role of food animal veterinarians in policy making. We argue that a tendency to employ strictly techno-scientific risk analyses of antimicro- bial use ignores the fundamental social, economic and political realities of key stakeholders and so limits the applicability of policy recommendations developed by government advisory groups. In particular, we suggest that veterinarians’ personal and professional interests, and their ethi- cal norms of practice, are key factors to both the problem of and the solution to the current over-reliance on antimicrobials in food production. (shrink)

Antimicrobial resistance is a growing public health concern and is associated with the over - or inappropriate use of antimicrobials in both humans and agriculture. While there has been recognition of this problem on the part of agricultural and public health authorities, there has nonetheless been significant difficulty in translating policy recommendations into practical guidelines. In this paper, we examine the process of public health policy development in Quebec agriculture, with a focus on the case of pork production and (...) the role of food animal veterinarians in policy making. We argue that a tendency to employ strictly techno- scientific risk analyses of antimicro- bial use ignores the fundamental social, economic and political realities of key stakeholders and so limits the applicability of policy recommendations developed by government advisory groups. In particular, we suggest that veterinarians’ personal and professional interests, and their ethical norms of practice, are key factors to both the problem of and the solution to the current over -reliance on antimicrobials in food production. (shrink)

A theory that treats language not as an abstract symbol system but as a function of our brains and experience, integrating recent findings from biology, ...

Antimicrobial resistance (AMR) has become one of the defining challenges of the twenty-first century. Food production and farming are a key if troubling component of that challenge. Livestock production accounts for well over half of annual global consumption of antimicrobials, though the contribution of the sector to drug resistance is less clear. As a result, there is an injunction to act in advance of incontrovertible evidence for change. In this paper we engage with the role of market actors in (...) the precautionary regulation of farming practices and AMR threats. The paper takes the UK poultry sector as exemplary of an audit-led process that has, in recent years, achieved impressive reductions in antimicrobial use. Using qualitative interview data with farmers and veterinarians we chart the changing practices that have accompanied this reduction in treatments. We use this analysis to raise some cautions around audit-led systems of regulation. Audits can lock farms and animals into particular versions of farming and animal health; they can elevate harmful compensatory practices (including disinfectant uses); and they can reproduce an actuarial approach to an issue that does not fit the conventions of risk management. The paper presents the considerable successes that have been achieved over a short period of time in a livestock sector, while generating notes of caution concerning the audit-led management of livestock-related AMR threats. (shrink)

Antimicrobial resistance (AMR) in bacterial infections is a growing threat to humanity and a challenge to healthcare systems worldwide. Healthcare professionals have an important role in preventing AMR and the spreading of infections. This article focuses on trade union financed journals for nurses in Scandinavia studying how the journals articulate AMR to its readership. A systematic literature search over an eleven‐year period was conducted, using web‐based national trade union financed journals, searching for ‘bacteria’ and ‘resistance’. A thematic analysis, inspired (...) by Foucault's concepts of power and governmentality, was made of 131 texts to understand, which kind of practices, strategies and policies the journals frame regarding AMR. The time period studied resulted in the recognition of four separate themes: the horror scenario, the ‘dangerous’ other, healthcare professionals as a source of resistance development and AMR as a field of research and producer of research qualifications. The study concludes that the journals tend: to present AMR in apocalyptic terms with more research and pharmaceutical industries needed for avoidance; to point out problems in other countries, populations, and sometimes nurses’ working conditions, but primarily with other professionals’ behaviour; and lastly, to present the nurse as a good fairy and disciplinator of doctors. (shrink)

In this paper, we provide a state-of-the-art overview of the ethical challenges that arise in the context of antimicrobial resistance, which includes an introduction to the contributions to the symposium in this issue. We begin by discussing why AMR is a distinct ethical issue, and should not be viewed purely as a technical or medical problem. In the second section, we expand on some of these arguments and argue that AMR presents us with a broad range of ethical problems (...) that must be addressed as part of a successful policy response to emerging drug resistance. In the third section, we discuss how some of these ethical challenges should be addressed, and we argue that this requires contributions from citizens, ethicists, policy makers, practitioners and industry. We conclude with an overview of steps that should be taken in moving forward and addressing the ethical problems of AMR. (shrink)

ArgumentThis article examines how antimicrobial resistance (AMR) came to be constituted as a matter of public concern in Sweden in conjunction with the development of an inter-professional organization called Strama, founded to promote rational prescription of antibiotics. An outbreak of penicillin-resistant pneumococci in the mid-1990s was crucial for this development, because it brought attention to AMR as an urgent public threat. This outbreak fuelled the constitution of AMR as caused by consumption of antibiotics and as a matter of disease (...) control. As a consequence, Strama was able to mobilize the Swedish health officers responsible for disease control. The outbreak is conceptualized as a “transformative event” – an event that makes an issue and its associated risks concrete and urgent. Transformative events play the crucial role of expediting the transformation of issues into matters of public concern. (shrink)

"In his third lecture Crick anticipates events and trends that have in fact come to pass in the past four decades, including the increasing use of computer technology and robotics in mind-brain research, explorations into right-side versus left-side uses of the brain, and controversies surrounding the existence of the soul."--BOOK JACKET.

Because most chemical reactions, by definition, cannot avoid breaking of bonds, weakly bonded species exist fleetingly in almost every chemical change. Historically, chemical quantum mechanics was aimed at explaining the nature of strong bonds. The theory involved a number of approximations to the full solution of the Schrödinger equation. The study of non‐Kekulé molecules provides an opportunity to test whether modern quantum chemical computations are competent to deal with the nature of molecules with very weak bonds. †To contact (...) the author, please write to: Department of Chemistry, Yale University, New Haven, CT: 06520‐8107; e‐mail: [email protected]. (shrink)

Almost all computational models of the mind and brain ignore details about neurotransmitters, hormones, and other molecules. The neglect of neurochemistry in cognitive science would be appropriate if the computational properties of brains relevant to explaining mental functioning were in fact electrical rather than chemical. But there is considerable evidence that chemical complexity really does matter to brain computation, including the role of proteins in intracellular computation, the operations of synapses and neurotransmitters, and the effects of neuromodulators such as (...) hormones. Neurochemical computation has implications for understanding emotions, cognition, and artificial intelligence. (shrink)

The issue of regularly feeding low levels of antibiotics to farm animals in order to increase productivity is often portrayed as a dilemma. On the one hand, such antibiotic use is depicted as a necessary condition for producing cheap and plentiful food, such that were such use to stop, food prices would rise significantly and our ability to feed people in developing nations would decrease. On the other hand, such antibiotic use seems to breed antibiotic resistance into pathogens affecting human (...) health. Resolving this dilemma, it is alleged, will require great amounts of research into risk/benefit assessment. Contrary to this claim, we will argue that society has all the data it needs to make a reasonable ethical decision, which would be curtailing such use. Such curtailment will not harm consumers significantly, will not harm developing nations'' evolving agriculture, and could produce hitherto unnoticed benefits, namely restoring the possibility of a more husbandry-based, sustainable agriculture to replace the high-tech agriculture that has hurt animals, the environment, small farms, and sustainability. (shrink)

Macromolecular interactions play a central role in many biological processes. Protein‐protein interactions have mostly been studied by co‐immunoprecipitation, which cannot provide quantitative information on all possible molecular connections present in the complex. We will review a new approach that allows cellular proteins and biomolecular complexes to be studied in real‐time at the single‐molecule level. This technique is called single‐molecule pull‐down (SiMPull), because it integrates principles of conventional immunoprecipitation with the powerful single‐molecule fluorescence microscopy. SiMPull is used to count how many (...) of each protein is present in the physiological complexes found in cytosol and membranes. Concurrently, it serves as a single‐molecule biochemical tool to perform functional studies on the pulled‐down proteins. In this review, we will focus on the detailed methodology of SiMPull, its salient features and a wide range of biological applications in comparison with other biosensing tools. (shrink)

Chronobiology, especially the study of circadian rhythms, provides a model scientific field in which philosophers can study how investigators from a variety of disciplines working at different levels of organization are each contributing to a multi-level account of the responsible mechanism. I focus on how the framework of mechanistic explanation integrates research designed to decompose the mechanism with efforts directed at recomposition that relies especially on computation models. I also examine how recently the integration has extended beyond basic research to (...) the processes through which the disruption of circadian rhythms contributes to disease, including various forms of cancer. Understanding these linkages has been facilitated by discoveries about how circadian mechanisms interact with mechanisms involved in other physiological processes, including the cell cycle and the immune system. (shrink)

Microbial ecology is flourishing, and in the process, is making contributions to how the ecology and biology of large organisms is understood. Ongoing advances in sequencing technology and computational methods have enabled the collection and analysis of vast amounts of molecular data from diverse biological communities. While early studies focused on cataloguing microbial biodiversity in environments ranging from simple marine ecosystems to complex soil ecologies, more recent research is concerned with community functions and their dynamics over time. Models and concepts (...) from traditional ecology have been used to generate new insight into microbial communities, and novel system-level models developed to explain and predict microbial interactions. The process of moving from molecular inventories to functional understanding is complex and challenging, and never more so than when many thousands of dynamic interactions are the phenomena of interest. We outline the process of how epistemic transitions are made from producing catalogues of molecules to achieving functional and predictive insight, and show how those insights not only revolutionize what is known about biological systems but also about how to do biology itself. Examples will be drawn primarily from analyses of different human microbiota, which are the microbial consortia found in and on areas of the human body, and their associated microbiomes (the genes of those communities). Molecular knowledge of these microbiomes is transforming microbiological knowledge, as well as broader aspects of human biology, health and disease. (shrink)

What does it take for a scientific model to represent? Scientific models have received a great deal of attention in recent philosophical literature. Following Morgan and Morrison’s account of “Models as Mediators”, analysis of how models represent has changed from questioning what properties of models can be said to correlate with the world to asking how models are used to relate to an intended target-system. This turn to a practice-oriented approach of understanding models was a response to a general philosophical (...) problem that attends the empirical application of scientific representations such as models. This problem is twofold. Models, on the one hand, are often said to make false claims about the world.. (shrink)

This paper widens the scope of our previous paper (Harré and Llored in Found Chem 13:63–76, 2011) by scrutinizing how whole/parts relations are involved in the study of molecules. In doing so, we point out two mereological fallacies which endanger both philosophical and chemical inferences. We also further explore how the concept of affordance is related to our mereological investigation. We then refer to quantum chemistry in order to pave the way for a new mereological approach for chemistry.

Chronobiology, especially the study of circadian rhythms, provides a model scientific field in which philosophers can study how investigators from a variety of disciplines working at different levels of organization are each contributing to a multi-level account of the responsible mechanism. I focus on how the framework of mechanistic explanation integrates research designed to decompose the mechanism with efforts directed at recomposition that relies especially on computation models. I also examine how recently the integration has extended beyond basic research to (...) the processes through which the disruption of circadian rhythms contributes to disease, including various forms of cancer. Understanding these linkages has been facilitated by discoveries about how circadian mechanisms interact with mechanisms involved in other physiological processes, including the cell cycle and the immune system. (shrink)

I argue that molecules may not have structure in isolation. I support this by investigating how quantum models identify structure for isolated molecules. Specifically, I distinguish between two sets of models: those that identify structure in isolation and those that do not. The former identify structure because they presuppose structural information about the target system via the Born- Oppenheimer approximation. However, it is an idealisation to assume structure in isolation because there is no empirical evidence of this. In (...) fact, whenever structure is empirically examined it is always partially determined by factors that are absent in isolation. Together with the growing empirical evidence that isolated molecules behave in non-classical ways, this shows that the quantum models that do not identify structure are more faithful representations of isolated molecules. (shrink)

Antimicrobial resistance is one of the greatest public health crises of our time. The natural biological process that causes microbes to become resistant to antimicrobial drugs presents a complex social challenge requiring more effective and sustainable management of the global antimicrobial commons—the common pool of effective antimicrobials. This special issue of Health Care Analysis explores the potential of two legal approaches—one long-term and one short-term—for managing the antimicrobial commons. The first article explores the lessons for (...) class='Hi'>antimicrobial resistance that can be learned from recent climate change agreements, and the second article explores how existing international laws can be adapted to better support global action in the short-term. (shrink)

Theories of perception have traditionally dismissed the sense of smell as a notoriously variable and highly subjective sense, mainly because it does not easily fit into accounts of perception based on visual experience. So far, philosophical questions about the objects of olfactory perception have started by considering the nature of olfactory experience. However, there is no philosophically neutral or agreed conception of olfactory experience: it all depends on what one thinks odors are. We examine the existing philosophical methodology for addressing (...) our sense of smell: on the one hand appeals to phenomenology that focus on the experiential dimensions of odor perception and on the other approaches that look at odor sources and their material dimensions. We show that neither strategy provides enough information to account for the human sense of smell and argue that the inclusion of the missing dimension of biology, with its concern for the function (or functions) of olfaction, provides the means to develop a satisfactory and empirically informed philosophy of smell. (shrink)

Although molecular biology has meant different things at different times, the term is often associated with a tendency to view cellular causation as conforming to simple linear schemas in which macro-scale effects are specified by micro-scale structures. The early achievements of molecular biologists were important for the formation of such an outlook, one to which the discovery of recombinant DNA techniques, and a number of other findings, gave new life even after the complexity of genotype–phenotype
relations had become apparent. Against this (...) background we outline how a range of scientific developments and conceptual considerations can be regarded as enabling and perhaps necessitating contemporary systems approaches. We suggest that philosophical ideas have a valuable part to play in making sense of complex scientific and disciplinary issues. (shrink)

In his Système de la nature ou Essai sur les corps organisés, Pierre-Louis Moreau de Maupertuis, President of the Berlin Academy of Sciences and a natural philosopher with a strong interest in the modes of transmission of 'genetic' information, described living minima which he termed molecules, “endowed with desire, memory and intelligence.” Now, Maupertuis was a Leibnizian of sorts; his molecules possessed higher-level, 'mental' properties, recalling La Mettrie's statement in L'Homme-Machine, that Leibnizians have “rather spiritualized matter than materialized (...) the soul.” But Maupertuis also debated this issue with Diderot, who critiqued this theory in the additions to his 1753 Pensées sur l'interprétation de la nature. Where Maupertuis attributes higher-level properties to his living minima, Diderot argues that these can only be 'organizational', i.e., properties of the whole. At issue here is the degree of commitment to a form of materialism. (shrink)

Existing ethical frameworks for public health provide insufficient guidance on how to evaluate the risks of public health programs that compromise the best clinical interests of present patients for the benefit of others. Given the relevant similarity of such programs to clinical research, we suggest that insights from the long‐standing debate about acceptable risk in clinical research can helpfully inform and guide the evaluation of risks posed by public health programs that compromise patients’ best clinical interests. We discuss how lessons (...) learned regarding the ethics of risk in one context can be fruitfully transferred to the other, using the example of a so‐called ‘rational antibiotic use’ guideline that limits antimicrobial prescribing in order to curb antimicrobial resistance. (shrink)

Of Minds and Molecules is the first anthology devoted exclusively to work in the philosophy of chemistry. The essays, written by both chemists and philosophers, adopt distinctive philosophical perspectives on chemistry and collectively offer both a conceptualization of and a justification for this emerging field.

Fractal time fluctuations of the spectral “1/f” form are universal in natural self-organizing systems. Neurobiology is uniquely infused with fractal fluctuations in the form of statistically self-similar clusters or bursts on all levels of description from molecular events such as protein chain fluctuations, ion channel currents and synaptic processes to the behaviors of neural ensembles or the collective behavior of Internet users. It is the thesis of this essay that the brain self-organizes via a vertical collation of these spontaneous events (...) in order to perceive the world and generate adaptive behaviors. REM sleep, which coalesces from self-similar clusters of burst-within-burst behavior during ontogeny, is essential to cognitive-emotional function, and has recurrent fractal organization. Empirical fMRI observations further support the association of fractal fluctuations in the temporal lobes, brainstem and cerebellum during the expression of emotional memory, spontaneous fluctuations of thought and meditative practice. Cognitive-emotional integration arises as amygdaloid-brainstem-cerebellar systems harmonize the vertical “1/f” symphony of coupled isochronous cortical oscillations in the pursuit of mindfulness. (shrink)

From its genesis in the 1960s, the focus of inquiry in neuroscience has been on the cellular and molecular processes underlying neural activity. In this pursuit neuroscience has been enormously successful. Like any successful scientific inquiry, initial successes have raised new questions that inspire ongoing research. While there is still much that is not known about the molecular processes in brains, a great deal of very important knowledge has been secured, especially in the last 50 years. It has also attracted (...) the attention of a number of philosophers, some of whom have viewed it as evidence for a ruthlessly reductionistic program that will eventually explain how mental processes are performed in the brain in purely molecular terms. As neuroscience developed, however, there emerged a smaller group of researchers who focused on systems, behavioral, and cognitive neuroscience. These investigators have also made impressive advances in the last 50 years and they have been the focus of an even larger group of philosophers, who have appealed to systems level understanding of the brain as providing the appropriate point of connection to the information processing accounts advanced in psychology. (shrink)

Outer membrane proteins (OMPs) maintain the viability of Gram‐negative bacteria by functioning as receptors, transporters, ion channels, lipases, and porins. Folding and assembly of OMPs involves synchronized action of chaperones and multi‐protein machineries which escort the highly hydrophobic polypeptides to their target outer membrane in a folding competent state. Previous studies have identified proteins and their involvement along the OMP biogenesis pathway. Yet, the mechanisms of action and the intriguing ability of all these molecular machines to work without the typical (...) cellular energy source of ATP, but solely based on thermodynamic principles, are still not well understood. Here, we highlight how different single‐molecule studies can shed additional light on the mechanisms and kinetics of OMP biogenesis. (shrink)