Early research on the biological effects of microwave radiation: 1940–1960

Two overriding considerations shaped the development of early research on the biological effects of microwave radiation—possible medical application (diathermy) and uncertainty about the hazards of exposure to radar. Reports in the late 1940s and early 1950s of hazards resulting from microwave exposure led to the near abandonment of medical research related to microwave diathermy at the same time that military and industrial concern over hazards grew, culminating in the massive research effort known as ‘the Tri-Service program’ (1957–1960). Both the early focus on medical application and the later search for hazards played important roles in dictating how this field of research developed as a science.     

History of the Lenz–Ising model 1965–1971: the role of a simple model in understanding critical phenomena

This is the last in a series of three papers on the history of the Lenz–Ising model from 1920 to the early 1970s. In the first paper, I studied the invention of the model in the 1920s, while in the second paper, I documented a quite sudden change in the perception of the model in the early 1960s when it was realized that the Lenz–Ising model is actually relevant for the understanding of phase transitions. In this article, which is self-contained, I study how this realization affected attempts to understand critical phenomena, which can be understood as limiting cases of (first-order) phase transitions, in the epoch from circa 1965 to 1970, where these phenomena were recognized as a research field in its own right. I focus on two questions: What kinds of insight into critical phenomena was the employment of the Lenz–Ising model thought to give? And how could a crude model, which the Lenz–Ising model was thought to be, provide this understanding? I document that the model played several roles: At first, it played a role analogous to experimental data: hypotheses about real systems, in particular relations between critical exponents and what is now called the hypothesis of scaling, which was advanced by Benjamin Widom and others, were confronted with numerical results for the model, in particular the model’s so-called critical exponents. A positive result of a confrontation was seen as positive evidence for this hypothesis. The model was also used to gain insight into specific aspects of critical phenomena, for example that diverse physical systems exhibit similar behavior close to a critical point. Later, a more systematic program of understanding critical phenomena emerged that involved an explicit formulation of what it means to understand critical phenomena, namely, the elucidation of what features of the Hamiltonian of models lead to what kinds of behavior close to critical points. Attempts to accomplish this program culminated with the so-called hypothesis of universality, put forward independently by Robert B. Griffiths and Leo P. Kadanoff in 1970. They divided critical phenomena into classes with similar critical behavior. I also study the crucial role of the Lenz–Ising model in the development and justification of these ideas.     

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.     

The platypus in Edinburgh: Robert Jameson,Robert Knox and the place of the Ornithorhynchus in nature, 1821–24

The duck-billed platypus, or Ornithorhynchus, was the subject of an intense debate among natural historians in the late eighteenth and early nineteenth centuries. Its paradoxical mixture of mammalian, avian and reptilian characteristics made it something of a taxonomic conundrum. In the early 1820s Robert Jameson (1774–1854), the professor of natural history at the University of Edinburgh and the curator of the University's natural history museum, was able to acquire three valuable specimens of this species. He passed one of these on to the anatomist Robert Knox (1791–1862), who dissected the animal and presented his results in a series of papers to the Wernerian Natural History Society, which later published them in its Memoirs. This paper takes Jameson's platypus as a case study on how natural history specimens were used to create and contest knowledge of the natural world in the early nineteenth century, at a time when interpretations of the relationships between animal taxa were in a state of flux. It shows how Jameson used his possession of this interesting specimen to provide a valuable opportunity for his protégé Knox while also helping to consolidate his own position as a key figure in early nineteenth-century natural history.     

The chemical versatility of the β–α–β fold: Catalytic promiscuity and divergent evolution in the tautomerase superfamily

Tautomerase superfamily members have an amino-terminal proline and a β–α–β fold, and include 4-oxalocrotonate tautomerase (4-OT), 5-(carboxymethyl)-2-hydroxymuconate isomerase (CHMI), trans- and cis-3-chloroacrylic acid dehalogenase (CaaD and cis-CaaD, respectively), malonate semialdehyde decarboxylase (MSAD), and macrophage migration inhibitory factor (MIF), which exhibits a phenylpyruvate tautomerase (PPT) activity. Pro-1 is a base (4-OT, CHMI, the PPT activity of MIF) or an acid (CaaD, cis-CaaD, MSAD). Components of the catalytic machinery have been identified and mechanistic hypotheses formulated. Characterization of new homologues shows that these mechanisms are incomplete. 4-OT, CaaD, cis-CaaD, and MSAD also have promiscuous activities with a hydratase activity in CaaD, cis-CaaD, and MSAD, PPT activity in CaaD and cis-CaaD, and CaaD and cis-CaaD activities in 4-OT. The shared promiscuous activities provide evidence for divergent evolution from a common ancestor, give hints about mechanistic relationships, and implicate catalytic promiscuity in the emergence of new enzymes. Received 22 May 2008; received after revision 20 June 2008; accepted 02 July 2008     

On the Role of the Michelson–Morley Experiment: Einstein in Chicago

This article discusses new material, published in volume 12 of the Collected Papers of Albert Einstein, that addresses Einstein’s knowledge of the Michelson–Morley experiment prior to 1905: in a lecture in Chicago in 1921, Einstein referred to the experiment, mentioned when he came upon it and hinted at its influence. Arguments are presented to explain the contrast with Einstein’s later pronouncements on the role of the experiment.     

Implication of the VRK1 chromatin kinase in the signaling responses to DNA damage: a therapeutic target?

DNA damage causes a local distortion of chromatin that triggers the sequential processes that participate in specific DNA repair mechanisms. This initiation of the repair response requires the involvement of a protein whose activity can be regulated by histones. Kinases are candidates to regulate and coordinate the connection between a locally altered chromatin and the response initiating signals that lead to identification of the type of lesion and the sequential steps required in specific DNA damage responses (DDR). This initiating kinase must be located in chromatin, and be activated independently of the type of DNA damage. We review the contribution of the Ser-Thr vaccinia-related kinase 1 (VRK1) chromatin kinase as a new player in the signaling of DNA damage responses, at chromatin and cellular levels, and its potential as a new therapeutic target in oncology. VRK1 is involved in the regulation of histone modifications, such as histone phosphorylation and acetylation, and in the formation of γH2AX, NBS1 and 53BP1 foci induced in DDR. Induction of DNA damage by chemotherapy or radiation is a mainstay of cancer treatment. Therefore, novel treatments can be targeted to proteins implicated in the regulation of DDR, rather than by directly causing DNA damage.     

Can the binding of GABA, glycine and beta-alanine to synaptic receptors be determined in the presence of a physiological concentration of Na+?

Bicuculline- and strychnine-sensitive components of the binding of GABA, glycine and beta-alanine, which can be demonstrated in the presence of a physiological concentration of Na+, might be related to synaptic receptors.     

Animal experiments, vital forces and courtrooms: Mateu Orfila, François Magendie and the study of poisons in nineteenth-century France

The paper follows the lives of Mateu Orfila and Fran?ois Magendie in early nineteenth-century Paris, focusing on their common interest in poisons. The first part deals with the striking similarities of their early careers: their medical training, their popular private lectures, and their first publications. The next section explores their experimental work on poisons by analyzing their views on physical and vital forces in living organisms and their ideas about the significance of animal experiments in medicine. The last part describes their contrasting research on the absorption of poisons and the divergences in their approaches, methods, aims, standards of proof, and intended audiences. The analysis highlights the connections between nineteenth-century courtrooms and experimental laboratories, and shows how forensic practice not only prompted animal experimentation but also provided a substantial body of information and new research methods for dealing with major theoretical issues like the absorption of poisons.     

History of the Lenz–Ising Model 1950–1965: from irrelevance to relevance

This is the second in a series of three papers that charts the history of the Lenz–Ising model (commonly called just the Ising model in the physics literature) in considerable detail, from its invention in the early 1920s to its recognition as an important tool in the study of phase transitions by the late 1960s. By focusing on the development in physicists’ perception of the model’s ability to yield physical insight—in contrast to the more technical perspective in previous historical accounts, for example, Brush (Rev Modern Phys 39: 883–893, 1967) and Hoddeson et al. (Out of the Crystal Maze. Chapters from the History of Solid-State Physics. Oxford University Press, New York, pp. 489–616, 1992)—the series aims to cover and explain in depth why this model went from relative obscurity to a prominent position in modern physics, and to examine the consequences of this change. In the present paper, which is self-contained, I deal with the development from the early 1950s to the 1960s and document that this period witnessed a major change in the perception of the model: In the 1950s it was not in the cards that the model was to become a pivotal tool of theoretical physics in the following decade. In fact, I show, based upon recollections and research papers, that many of the physicists in the 1950s interested in understanding phase transitions saw the model as irrelevant for this endeavor because it oversimplifies the nature of the microscopic constituents of the physical systems exhibiting phase transitions. However, one group, Cyril Domb’s in London, held a more positive view during this decade. To bring out the basis for their view, I analyze in detail their motivation and work. In the last part of the paper I document that the model was seen as much more physically relevant in the early 1960s and examine the development that led to this change in perception. I argue that the main factor behind the change was the realization of the surprising and striking agreement between aspects of the model, notably its critical behavior, and empirical features of the physical phenomena.     

Alsatian chemists in Paris in the 19th century: a network, a school?

During the nineteenth century French chemistry was marked by an outstanding number of Alsatian chemists whose scientific contributions cannot be ignored. Especially following the Franco-Prussian War, their regional origin was given a particular importance as a means of affirming their singularity on the French scientific scene. However, some questions may be raised: can we distinguish the Alsatians from other French chemists before 1870? Were they a homogeneous group sharing a common origin? The aim of this article therefore, is, to show that by their theoretical options within chemistry, their personal and professional relationships, as well as by their participation in various common initiatives, they organized themselves both formally and informally within the Parisian scientific community. Amongst these forms of organization the research school of Charles Adolphe Wurtz (1817-84) emerges as the nucleus of what we may envisage as a network of Alsatian chemists working in Paris, in the second half of the nineteenth century.     

Can the binding of GABA,glycine and β-alanine to synaptic receptors be determined in the presence of a physiological concentration of Na+?

Summary Bicuculline- and strychnine-sensitive components of the binding of GABA, glycine and -alanine, which can be demonstrated in the presence of a physiological concentration of Na⁺, might be related to synaptic receptors.     

Mechanizing the astronomer's vision: On the role of photography in Swedish astronomy,c.1880–1914

The beginnings of photographic astronomy in Sweden are taken as a case study of the incorporation of a new scientific technology. The introduction of photography during the late nineteenth century profoundly changed the way astronomers worked. Observational material became more mobile; photographic plates could be examined at a later date or transported to another location. Photography was presented in a rhetorical language, making it a truly objective way of observing the sky. The new technology was developed at the leading observatories, and was imported into countries such as Sweden through a network of scientific communication.     

α-Endosulfine, a new entity in the control of insulin secretion

ATP-dependent potassium (K_ATP) channels occupy a key position in the control of insulin release from the pancreatic β cell since they couple cell polarity to metabolism. These channels close when more ATP is produced via glucose metabolism. They are also controlled by sulfonylureas, a class of drugs used in type 2 diabetic patients for triggering insulin secretion from β cells that have lost part of their sensitivity to glucose. We have demonstrated the existence of endogenous counterparts to sulfonylureas which we have called ‘endosulfines.’ In this review, we describe the discovery, isolation, cloning, and biological features of the high-molecular-mass form, α-endosulfine, and discuss its possible role in the physiology of the β cell as well as in pathology. Received 1 February 1999; received after revision 26 March 1999; accepted 26 March 1999     

Establishment of left–right asymmetry in vertebrate development: the node in mouse embryos

Establishment of vertebrate left–right asymmetry is a critical process for normal embryonic development. After the discovery of genes expressed asymmetrically along the left–right axis in chick embryos in the mid 1990s, the molecular mechanisms responsible for left–right patterning in vertebrate embryos have been studied extensively. In this review article, we discuss the mechanisms by which the initial symmetry along the left–right axis is broken in the mouse embryo. We focus on the role of primary cilia and molecular mechanisms of ciliogenesis at the node when symmetry is broken and left–right asymmetry is established. The node is considered a signaling center for early mouse embryonic development, and the results we review here have led to a better understanding of how the node functions and establishes left–right asymmetry.