On the Virtues and Disadvantage of Quantification for Democratic Life

In this paper, a response to Ed Levy's discussion of medical quantification, I reflect on the ambitions of my book Trust in Numbers. I explore the idealized method of randomized clinical trials, revealed in his case study, as a social technology, one endowed with a persuasive scientific rationale but shaped also by political and social demands. The scholarly study of quantification requires not a choice between blind admiration and sweeping rejection, but a nuanced understanding. This should take into account not only the cognitive aspects of science, but also its role in relation to institutions and customs, examined with some specificity. While history is narrowed and distorted when it is written to support a position on some present issue, historical and social studies of science should at least provide tools of criticism. For this, the historian of science must look beyond narrow communities of specialists, and seek a wider perspective on science as an administrative tool and a bearer of cultural and political values.     

Craft,money and mercy: an apothecary's self-portrait in sixteenth-century Bologna1

The apothecary occupied a liminal position in early modern society between profit and healing. Finding ways to distance their public image from trade was a common problem for apothecaries across Europe. This article uses the case of a Bolognese apothecary, Filippo Pastarino, to address the question of how early modern apothecaries chose to represent themselves to political authorities and to the wider public. ‘Mercy’, alongside ‘craft’, was a pillar of apothecaries’ social identity. By contrast, no matter how central financial transactions (‘money’) were to their activity, apothecaries did not want to be perceived as merchants. Thus, the assistance and advice apothecaries provided to patients and customers resulted as central aspects of their social role. In this context, Bolognese apothecaries aimed to defend their current status, which had been challenged by naturalist Ulysses Aldrovandi, city authorities and local monasteries. However, Pastarino's claims can also be seen as antecedents to the self-legitimizing strategy that seventeenth-century artisans deployed when faced with the need to enhance their new status as natural philosophers. The present study attributes a name, a date of birth and a shop to Filippo Pastarino, revising previous interpretations. More broadly, by focusing on how these artisans defended their position in the city it enriches our understanding of the self-representation of apothecaries.     

Nova Geminorum 1912 and the origin of the idea of gravitational lensing

Einstein’s early calculations of gravitational lensing, contained in a scratch notebook and dated to the spring of 1912, are reexamined. A hitherto unknown letter by Einstein suggests that he entertained the idea of explaining the phenomenon of new stars by gravitational lensing in the fall of 1915 much more seriously than was previously assumed. A reexamination of the relevant calculations by Einstein shows that, indeed, at least some of them most likely date from early October 1915. But in support of earlier historical interpretation of Einstein’s notes, it is argued that the appearance of Nova Geminorum 1912 (DN Gem) in March 1912 may, in fact, provide a relevant context and motivation for Einstein’s lensing calculations on the occasion of his first meeting with Erwin Freundlich during a visit in Berlin in April 1912. We also comment on the significance of Einstein’s consideration of gravitational lensing in the fall of 1915 for the reconstruction of Einstein’s final steps in his path towards general relativity.     

Einstein Equations and Hilbert Action: What is missing on page 8 of the proofs for Hilbert's First Communication on the Foundations of Physics?

The history of the publication of the gravitational field equations of general relativity in November 1915 by Einstein and Hilbert is briefly reviewed. An analysis of the internal structure and logic of Hilbert's theory as expounded in extant proofs and in the published version of his relevant paper is given with respect to the specific question what information would have been found on a missing piece of Hilbert's proofs. The existing texts suggest that the missing piece contained the explicit form of the Riemann curvature scalar in terms of the Ricci tensor as a specification of the axiomatically underdetermined Lagrangian in Hilbert's action integral. An alternative reading that the missing piece of the proofs already may have contained the Einstein tensor, i.e. an explicit calculation of the gravitational part of Hilbert's Lagrangian is argued to be highly implausible.     

Science and the Mechanics' Institutes, 1820–1850: The case of Sheffield

This paper points out that the provincial mechanics' institutes of England in their early years were as much the product of a general and pervasive scientific culture as they were of a particular educational movement. To this extent the institutes can be interpreted within the context of wider social and economic changes. The bulk of the paper relates to the Mechanics' Institute at Sheffield in the period 1832–50, but through this and other material it is argued that this case study deserves general consideration.     

The Quantification and Differentiation of the Drug Receptor Theory,c. 1910–1960

While historians have dealt with the origins of the concept of drug receptors in the work of Paul Ehrlich (1854–1915) and John N. Langley (1852–1925) as well as with some of its applications in modern pharmaceutical research, the history of the receptor theory as such has been neglected. Discussing major developments and conceptual changes in receptor theory between about 1910 and 1960 (including relevant contributions by A. V. Hill, A. J. Clark, J. H. Gaddum, E. J. Ariëns and others), this paper attempts to fill this gap in historiography. It provides a case study of the unfolding of research under a new paradigm, but it considers also contemporary criticism and scepticism. By the early 1960s, quantitative investigations of drug action and interpretations of the experimental findings in terms of the receptor concept had become constitutive of the emerging field of ‘molecular pharmacology’. Even then, however, receptors were still hypothetical entities.     

Einstein's struggle for a Machian gravitation theory

The story of Einstein's struggle to create a general theory of relativity, and his early discontentment with the final form of the theory (1915), is well known in broad outline. Thanks to the work of John Norton and others, much of the fine detail of the story is also now known. One aspect of Einstein's work in this period has, however, been relatively neglected: Einstein's commitment to Mach's ideas on inertia, and the influence this commitment had on Einstein's work on general relativity from 1907 to 1918. In this paper published writings and archival material are examined, to try to reconstruct the details of Einstein's thinking about inertia and gravitation, and the role that Mach's ideas played in Einstein's crucial work on the general theory. By the end, a clear picture of Einstein's conceptions of Mach's ideas on inertia, and their philosophical motivations, will emerge. Several surprising conclusions also emerge: Einstein's desire for a Machian gravitation theory was the central force driving his work from 1912 to 1915, keeping him going despite numerous frustrating setbacks; Einstein's continued commitment to Mach's ideas in 1916–1917 kept him at work trying various strategies of modification of the field equations, in order to exclude anti-Machian solutions (including the addition of the cosmological constant in 1917); and as late as early 1918, Einstein was ready to call the whole General Theory a failure if no way of squaring it with Mach's ideas on inertia could be found. But by 1920 Einstein advocated a view that granted spacetime (under the name ‘ether’) independent existence with physical qualities of its own, a complete break with his earlier Machian views.     

The quantification and differentiation of the drug receptor theory, c. 1910-1960

While historians have dealt with the origins of the concept of drug receptors in the work of Paul Ehrlich (1854-1915) and John N. Langley (1852-1925) as well as with some of its applications in modern pharmaceutical research, the history of the receptor theory as such has been neglected. Discussing major developments and conceptual changes in receptor theory between about 1910 and 1960 (including relevant contributions by A. V. Hill, A. J. Clark, J. H. Gaddum, E. J. Ari?ns and others), this paper attempts to fill this gap in historiography. It provides a case study of the unfolding of research under a new paradigm, but it considers also contemporary criticism and scepticism. By the early 1960s, quantitative investigations of drug action and interpretations of the experimental findings in terms of the receptor concept had become constitutive of the emerging field of 'molecular pharmacology'. Even then, however, receptors were still hypothetical entities.     

The Newton letters (Vols. I and II)

The metaphysical commitment to the circle as the essential element in the analysis of celestial motion has long been recognized as the hallmark of classical astronomy. What has not always been clear, however, is that the circle continued to serve Kepler as a central element in his astronomy after the discovery of the elliptical orbit of Mars. Moreover, the circle also functioned for Kepler in geometry to select the basic polygons, in music to select the basic harmonies, and in astrology to select the basic aspects. His basic set of polygons consisted of those figures that could be constructed using only a compass and a rule; the set of fundamental harmonies consisted of the consonances of the just intonation; and the traditional set of astrological aspects were enlarged by Kepler to include three new aspects in order to make the astrological set consistent with geometry and music. And as the circle served to unify these three areas, so also did it serve to supply the fundamental answers to astronomical problems well after the discovery of his new astronomy—a topic to be discussed in Part II of this paper.     

Decision trees for forecasting

Recent years have seen an increasing cross-fertilization between the fields of decision analysis and forecasting. Decision-analytic models often require forecasts as inputs, and aspects of the Bayesian decision-theoretic framework underlying decision analysis have proved useful to forecasting, particularly in contexts where subjective judgemental inputs are required. This paper describes the use of decision tree analysis for forecasting and illustrates its use for corporate divisional forecasting and planning. A specialized decision-analytic technique, acts as events, is also described and illustrated to forecast a new product's earnings. Conclusions are drawn about the applicability of decision analysis for forecasting.     

For whom the bell tolls? DING proteins in health and disease

DING proteins, identified mainly by their eponymous N-terminal sequences, are ubiquitous in living organisms. Amongst bacteria, they are common in pseudomonads, and have been characterised with respect to genetics and structure. They form part of a wider family of phosphate-binding proteins, with emerging roles in phosphate acquisition and pathogenicity. Many DING proteins have been isolated in eukaryotes, in which they have been associated with very diverse biological activities, often in the context of possible signalling roles. Disease states in which DING proteins have been implicated include rheumatoid arthritis, lithiasis, atherosclerosis, some tumours and tumour-associated cachexia, and bacterial and viral adherence. Complete genetic and structural characterisation of eukaryotic DING genes and proteins is still lacking, though the phosphate-binding site seems to be conserved. Whether as bacterial proteins related to bacterial pathogenicity, or as eukaryotic components of biochemical signalling systems, DING proteins require further study. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Experiencing deep and global currents at a ‘Prototypical Strait’, 1870s and 1980s

Deep ocean currents are not accessible to direct human perception. Their insertion into global structures of circulation is even more profoundly removed from individual sensorial experience. But oceanographers tend to use wider concepts of experience to include instruments, traditions of observation and theoretical models. Historians and philosophers of science, as well as STS scholars, have also redefined scientific experience as operational and collective transformations of parts of the world around us into fragments of larger bodies of knowledge. This paper pursues this definition to follow the instrumental and epistemological resources available to those “observing” deep-water circulation at the Strait of Gibraltar in two very distinct moments, ca. 1870 and ca. 1985, respectively through the works of scientists like William B. Carpenter and the transnational team involved in the Gibraltar Experiment. Detecting and mapping the Gibraltar undercurrent necessitated taking data of temperature and salinity as proxies for masses of water. Making it relevant to world ocean currents required the use of models and moving across scales. In both contexts, empires of global reach provided the globalizing motivations and infrastructures.     

Mathematical understanding and the physical sciences

The author claims to have developed interactional expertise in gravitational wave physics without engaging with the mathematical or quantitative aspects of the subject. Is this possible? In other words, is it possible to understand the physical world at a high enough level to argue and make judgments about it without the corresponding mathematics? This question is empirically approached in three ways: (i) anecdotes about non-mathematical physicists are presented; (ii) the author undertakes a reflective reading of a passage of physics, first without going through the maths and then after engaging with it and discusses the difference between the experiences; (iii) the aforementioned exercise gives rise to a table of Levels of Understanding of mathematics, and physicists are asked about the level mathematical understanding they applied when they last read a paper. Each phase of empirical research suggests that mathematics is not as central to gaining an understanding of physics as it is often said to be. This does not mean that mathematics is not central to physics, merely that it is not essential for every physicist to be an accomplished mathematician, and that a division of labour model is adequate. This, in turn, suggests that a stream of undergraduate physics education with fewer mathematical hurdles should be developed, making it easier to train wider groups of people in physical science comprehension.     

The source of chemical bonding

Developments in the application of quantum mechanics to the understanding of the chemical bond are traced with a view to examining the evolving conception of the covalent bond. Beginning with the first quantum mechanical resolution of the apparent paradox in Lewis’s conception of a shared electron pair bond by Heitler and London, the ensuing account takes up the challenge molecular orbital theory seemed to pose to the classical conception of the bond. We will see that the threat of delocalisation can be overstated, although it is questionable whether this should be seen as reinstating the issue of the existence of the chemical bond. More salient are some recent developments in a longstanding discussion of how to understand the causal aspects of the bonding interaction—the nature of the force involved in the covalent link—which are taken up in the latter part of the paper.     

Human heart disease: lessons from human pluripotent stem cell-derived cardiomyocytes

Technical advances in generating and phenotyping cardiomyocytes from human pluripotent stem cells (hPSC-CMs) are now driving their wider acceptance as in vitro models to understand human heart disease and discover therapeutic targets that may lead to new compounds for clinical use. Current literature clearly shows that hPSC-CMs recapitulate many molecular, cellular, and functional aspects of human heart pathophysiology and their responses to cardioactive drugs. Here, we provide a comprehensive overview of hPSC-CMs models that have been described to date and highlight their most recent and remarkable contributions to research on cardiovascular diseases and disorders with cardiac traits. We conclude discussing immediate challenges, limitations, and emerging solutions.     

Mental processes and disorders: a neurobehavioral perspective in human biometeorology

Research concerning the complex relation between weather and psychological processes has emphasized three important issues: methodological problems, the determination of the major behavioral factors, and the isolation of neurobiological mechanisms. This paper reviews the current status of each issue. Weather changes are most frequently associated with behaviors that are the endpoints of inferred psychological processes that include mood, subclinical pain, anxiety, and the correlates of schedule shifts. Learning and conditioning appear to mediate a powerful influence over weather-related responses. This may explain the large individual variability in these behaviors. The most well-known group effects associated with weather changes involve psychiatric populations. Clinical subpopulations may respond in different ways to different aspects of the same weather system as well as to different types of air masses. Likely neurobiological mechanisms through which meteorogenic stimuli may mediate whole organismic effects include the locus coeruleal and limbic systems. Expected psychobiological consequences are examined in detail. The magnitude and temporal-spatial characteristics of weather effects indicate they are the subject matter of behavioral epidemiology.     

Mental processes and disorders: A neurobehavioral perspective in human biometeorology

Summary Research concerning the complex relation between weather and psychological processes has emphasized three important issues: methodological problems, the determination of the major behavioral factors, and the isolation of neurobiological mechanisms. This paper reviews the current status of each issue. Weather changes are most frequently associated with behaviors that are the endpoints of inferred psychological processes that include mood, subclinical pain, anxiety, and the correlates of schedule shifts. Learning and conditioning appear to mediate a powerful influence over weather-related responses. This may explain the large individual variability in these behaviors. The most well-known group effects associated with weather changes involve psychiatric populations. Clinical subpopulations may respond in different ways to different aspects of the same weather system as well as to different types of air masses. Likely neurobiological mechanisms through which meteorogenic stimuli may mediate whole organismic effects include the locus coeruleal and limbic systems. Expected psychobiological consequences are examined in detail. The magnitude and temporal-spatial characteristics of weather effects indicate they are the subject matter of behavioral epidemiology.     

Comparative myogenesis in teleosts and mammals

Skeletal myogenesis has been and is currently under extensive study in both mammals and teleosts, with the latter providing a good model for skeletal myogenesis because of their flexible and conserved genome. Parallel investigations of muscle studies using both these models have strongly accelerated the advances in the field. However, when transferring the knowledge from one model to the other, it is important to take into account both their similarities and differences. The main difficulties in comparing mammals and teleosts arise from their different temporal development. Conserved aspects can be seen for muscle developmental origin and segmentation, and for the presence of multiple myogenic waves. Among the divergences, many fish have an indeterminate growth capacity throughout their entire life span, which is absent in mammals, thus implying different post-natal growth mechanisms. This review covers the current state of the art on myogenesis, with a focus on the most conserved and divergent aspects between mammals and teleosts.     

Role of p21-activated kinases in cardiovascular development and function

p21-activated kinases (Paks) are a group of six serine/threonine kinases (Pak1-6) that are involved in a variety of biological processes. Recently, Paks, more specifically Pak1, -2, and -4, have been shown to play important roles in cardiovascular development and function in a range of model organisms including zebrafish and mice. These functions include proper morphogenesis and conductance of the heart, cardiac contractility, and development and integrity of the vasculature. The mechanisms underlying these effects are not fully known, but they likely differ among the various Pak isoforms and include both kinase-dependent and -independent functions. In this review, we discuss aspects of Pak function relevant to cardiovascular biology as well as potential therapeutic implications of small-molecule Pak inhibitors in cardiovascular disease.