Why was M. S. Tswett’s chromatographic adsorption analysis rejected?

The present paper claims that M. S. Tswett’s chromatographic adsorption analysis, which today is a ubiquitous and instrumentally sophisticated chemical technique, was either ignored or outright rejected by chemists and botanists in the first three decades of the twentieth century because it did not make sense in terms of accepted chemical theory or practice. Evidence for this claim is culled from consideration of the botanical and chemical context of Tswett’s technique as well as an analysis of the protracted debate over Tswett’s chromatographic analysis of chlorophyll between him and Leon Marchlewski, a noted chlorophyll chemist of the period. In this way, the paper expands and amends what it calls the ‘textbook story’ of the early history of chromatography, examples of which may be found in historical notes in many textbooks of chemical instrumental analysis and numerous short articles in chemistry journals. The paper also provides an accessible introduction to the early history of chromatography for historians of science likely to know little or nothing about it.     

Scientific pluralism and the Chemical Revolution

In a number of papers and in his recent book, Is Water H₂O? Evidence, Realism, Pluralism (2012), Hasok Chang has argued that the correct interpretation of the Chemical Revolution provides a strong case for the view that progress in science is served by maintaining several incommensurable “systems of practice” in the same discipline, and concerning the same region of nature. This paper is a critical discussion of Chang's reading of the Chemical Revolution. It seeks to establish, first, that Chang's assessment of Lavoisier's and Priestley's work and character follows the phlogistonists' “actors' sociology”; second, that Chang simplifies late-eighteenth-century chemical debates by reducing them to an alleged conflict between two systems of practice; third, that Chang's evidence for a slow transition from phlogistonist theory to oxygen theory is not strong; and fourth, that he is wrong to assume that chemists at the time did not have overwhelming good reasons to favour Lavoisier's over the phlogistonists' views.     

Hypothesis and experiment in the early development of Kekulé's Benzene theory

This article attempts a contextual study of the origin and early development of August Kekulé's theory of aromatic compounds. The terminus a quo is essentially August Hofmann's coining of the modern chemical denotation of ‘aromatic’ in 1855; the terminus ad quem is the first full codification of Kekulé's theory in the sixth fascicle of his Lehrbuch der organischen Chemie, published in the summer of 1866. Kekulé's theory is viewed in context with the earlier and concurrent experimental work of such chemists as Hermann Kolbe, Friedrich Beilstein, Rudolph Fittig, and Hugo Müller. The reception of the theory is briefly examined. Attention is paid to the role of Kekulé's molecular models and of his celebrated dream anecdote of the snake that seizes its own tail. The episode is used as a case study for the continuity of scientific progress, and to illustrate the close reciprocal interactions of hypothesis and experiment in the evolution of a scientific theory.     

Molecular superdelocalizability. A correlation with diamagnetic susceptibility

Summary Diamagnetic susceptibilities of 44 divers aromatic molecules were successfully predicted from molecular superdelocalizabilities calculated from Hückel molecular orbital theory.     

John Dalton’s puzzles: from meteorology to chemistry

Historical research on John Dalton has been dominated by an attempt to reconstruct the origins of his so-called “chemical atomic theory”. I show that Dalton’s theory is difficult to define in any concise manner, and that there has been no consensus as to its unique content among his contemporaries, later chemists, and modern historians. I propose an approach which, instead of attempting to work backward from Dalton’s theory, works forward, by identifying the research questions that Dalton posed to himself and attempting to understand how his hypotheses served as answers to these questions. I describe Dalton’s scientific work as an evolving set of puzzles about natural phenomena. I show how an early interest in meteorology led Dalton to see the constitution of the atmosphere as a puzzle. In working on this great puzzle, he gradually turned his interest to specifically chemical questions. In the end, the web of puzzles that he worked on required him to create his own novel philosophy of chemistry for which he is known today.     

Atomism and ‘subtlety’ in Francis Bacon's philosophy

Francis Bacon's reflections on atomism have generally been misunderstood because they have never been systematically studied in relation to the speculative chemical philosophy which he developed in the interval between about 1592 and his death in 1626. This philosophy, in many respects unknown to historians until quite recently, was the only body of positive science which Bacon ever accepted. The speculative philosophy was, on the whole, chemical and non-mechanical, and consequently not consistent with atomist doctrines. In fact, Bacon never at any time accepted the principal atomist tenets. It is therefore necessary to explain why he was interested in atomism at all. Of the several reasons for his interest one (hitherto unrecognised) is especially important—namely, his belief that the speculative and atomic philosophies had affinities. In particular, he believed that of all the ancient philosophies atomism alone approached the ideals associated with the key notion of ‘subtlety’—ideals represented in their highest form (as he imagined) in the speculative philosophy.     

Chemical chaperone therapy for GM1-gangliosidosis

We have proposed a chemical chaperone therapy for lysosomal diseases, based on a paradoxical phenomenon that an exogenous competitive inhibitor of low molecular weight stabilizes the target mutant molecule and restores its catalytic activity as a molecular chaperone intracellularly. After Fabry disease experiments, we investigated a new synthetic chaperone compound N-octyl-4-epi-β-valienamine (NOEV) in a G_M1-gangliosidosis model mice. Orally administered NOEV entered the brain through the blood-brain barrier, enhanced β-galactosidase activity, reduced the substrate storage, and clinically improved neurological deterioration. We hope that chemical chaperone therapy will prove useful for some patients with G_M1-gangliosidosis and potentially other lysosomal storage diseases with central nervous system involvement. Received 10 October 2007; received after revision 31 October 2007; accepted 6 November 2007     

The autonomy of models and explanation: anomalous molecular rearrangements in early twentieth-century physical organic chemistry

During the 1930s and 1940s, American physical organic chemists employed electronic theories of reaction mechanisms to construct models offering explanations of organic reactions. But two molecular rearrangements presented enormous challenges to model construction. The Claisen and Cope rearrangements were predominantly inaccessible to experimental investigation and they confounded explanation in theoretical terms. Drawing on the idea that models can be autonomous agents in the production of scientific knowledge, I argue that one group of models in particular were functionally autonomous from the Hughes–Ingold theory. Cope and Hardy’s models of the Claisen and Cope rearrangements were resources for the exploration of the Hughes–Ingold theory that otherwise lacked explanatory power. By generating ‘how-possibly’ explanations, these models explained how these rearrangements could happen rather than why they did happen. Furthermore, although these models were apparently closely connected to theory in terms of their construction, I argue that partial autonomy issued in extra-logical factors concerning the attitudes of American chemists to the Hughes–Ingold theory. And in the absence of a complete theoretical hegemony, a degree of consensus was reached concerning modelling the Claisen rearrangement mechanism.     

Initiation of cancer and other diseases by catechol ortho-quinones: a unifying mechanism

Exposure to estrogens is a risk factor for breast and other human cancers. Initiation of breast, prostate and other cancers has been hypothesized to result from reaction of specific estrogen metabolites, catechol estrogen-3,4-quinones, with DNA to form depurinating adducts at the N-7 of guanine and N-3 of adenine by 1,4-Michael addition. The catechol of the carcinogenic synthetic estrogen hexestrol, a hydrogenated derivative of diethylstilbestrol, is metabolized to its quinone, which reacts with DNA to form depurinating adducts at the N-7 of guanine and N-3 of adenine. The catecholamine dopamine and the metabolite catechol (1,2-dihydroxybenzene) of the leukemogen benzene can also be oxidized to their quinones, which react with DNA to form predominantly analogous depurinating adducts. Apurinic sites formed by depurinating adducts are converted into tumor-initiating mutations by error-prone repair. These mutations could initiate cancer by estrogens and benzene, and Parkinson's disease by the neurotransmitter dopamine. These data suggest a unifying molecular mechanism of initiation for many cancers and neurodegenerative diseases and lay the groundwork for designing strategies to assess risk and prevent these diseases. Received 4 September 2001; received after revision 28 November 2001; accepted 2 December 2001     

The chemists go to war: The mobilization of civilian chemists and the british war effort, 1914–1918

The outbreak of war in 1914 found Britain unprepared for a lengthy conflict. British science and industry were particularly ill-prepared to meet the demands of static warfare. Within two years, however, mobilization had made appreciable strides, and, as Britain's munitions industries moved from crisis to confidence, Britain's chemical industry was transformed by an arsenal of ‘garrison chemists’, with skills either born of necessity or borrowed from overseas. At the same time, Britain's chemical leadership traced a path that led them from voluntarist to corporate methods, from private to public initiatives, and from individual to collective behaviours. This paper suggests four key stages in this mobilization, and hints at the significance of the war for the emergence of new sub-disciplines, for the careers of chemists, for academic-government relations in research, and for the image, status, and international position of British chemistry on the threshold of the postwar world.     

Paper tools in experimental cultures

The paper studies various functions of Berzelian formulas in European organic chemistry prior to the mid-nineteenth century from a semiotic, historical and epistemological perspective. I argue that chemists applied Berzelian formulas as productive ‘paper tools’ for creating a chemical order in the ‘jungle’ of organic chemistry. Beginning in the late 1820s, chemists applied chemical formulas to build models of the binary constitution of organic compounds in analogy to inorganic compounds. Based on these formula models, they constructed new classifications of organic substances. They further applied Berzelian formulas in a twofold way to experimentally investigate organic chemical reactions: as tools which supplemented laboratory tools and as tools for constructing interpretive models of organic reactions. The scrutiny of chemists' performances with chemical formulas on paper also reveals a dialectic which contributed considerably to the formation of the new experimental culture of synthetic carbon chemistry that emerged between the late 1820s and the early 1840s. In an unintended and unforeseen way, the tools reacted back on the goals of their users and contributed to conceptual development and a shift of scientific objects and practices (‘substitution’) which transcended the originally intended chemical order.     

Chemists Employed in the Manchester Area, 1902–1936

Contrary to previous views of an acute shortage of chemists at the beginning of the twentieth century, this study found that the number of chemists identifiable by name in the Manchester area was substantial, even in 1902. Moreover, the majority were qualified to some extent. The total number of chemists and their degree of formal qualification increased rapidly during the period 1902-36. Employment data demonstrate that they worked not only in the chemical industry, but in a wide range of manufacturing industry and commerce. Only a relatively small proportion was employed in education. Research chemists were active in the area in the late nineteenth century: by 1936, 28% of Manchester chemists recorded their job title as research chemist or research manager. If Manchester were typical of Britain as a whole the number of chemists employed in 1902 would greatly exceed previous estimates. More speculatively, the number of chemists in Britain in 1902 may even have been comparable to that in Germany.     

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.     

The selective BH4-domain biology of Bcl-2-family members: IP3Rs and beyond

Anti-apoptotic Bcl-2-family members not only neutralize pro-apoptotic proteins but also directly regulate intracellular Ca²⁺ signaling from the endoplasmic reticulum (ER), critically controlling cellular health, survival, and death initiation. Furthermore, distinct Bcl-2-family members may selectively regulate inositol 1,4,5-trisphosphate receptor (IP₃R): Bcl-2 likely acts as an endogenous inhibitor of the IP₃R, preventing pro-apoptotic Ca²⁺ transients, while Bcl-X_L likely acts as an endogenous IP₃R-sensitizing protein promoting pro-survival Ca²⁺ oscillations. Furthermore, distinct functional domains in Bcl-2 and Bcl-X_L may underlie the divergence in IP₃R regulation. The Bcl-2 homology (BH) 4 domain, which targets the central modulatory domain of the IP₃R, is likely to be Bcl-2’s determining factor. In contrast, the hydrophobic cleft targets the C-terminal Ca²⁺-channel tail and might be more crucial for Bcl-X_L’s function. Furthermore, one amino acid critically different in the sequence of Bcl-2’s and Bcl-X_L’s BH4 domains underpins their selective effect on Ca²⁺ signaling and distinct biological properties of Bcl-2 versus Bcl-X_L. This difference is evolutionary conserved across five classes of vertebrates and may represent a fundamental divergence in their biological function. Moreover, these insights open novel avenues to selectively suppress malignant Bcl-2 function in cancer cells by targeting its BH4 domain, while maintaining essential Bcl-X_L functions in normal cells. Thus, IP₃R-derived molecules that mimic the BH4 domain’s binding site on the IP₃R may function synergistically with BH3-mimetic molecules selectivity suppressing Bcl-2’s proto-oncogenic activity. Finally, a more general role for the BH4 domain on IP₃Rs, rather than solely anti-apoptotic, may not be excluded as part of a complex network of molecular interactions.     

Reception and discovery: the nature of Johann Wilhelm Ritter’s invisible rays

Ultraviolet radiation is generally considered to have been discovered by Johann Wilhelm Ritter in 1801. In this article, we study the reception of Ritter’s experiment during the first decade after the event—Ritter’s remaining lifetime. Drawing on the attributional model of discovery, we are interested in whether the German physicists and chemists granted Ritter’s observation the status of a discovery and, if so, of what. Two things are remarkable concerning the early reception, and both have to do more with neglect than with (positive) reception. Firstly, Ritter’s observation was sometimes accepted as a fact but, with the exception of C. J. B. Karsten’s theory of invisible light, it played almost no role in the lively debate about the nature of heat and light. We argue that it was the prevalent discourse based on the metaphysics of Stoffe that prevented a broader reception of Ritter’s invisible rays, not the fact that Ritter himself made his findings a part of his Naturphilosophie. Secondly, with the exception of C. E. Wünsch’s experiments on the visual spectrum, there was no experimental examination of the experiment. We argue that theorizing about ontological systems was more common than experimenting, because, given its social and institutional situation, this was the appropriate way of contributing to physics. Consequently, it was less clear in 1810 than in 1801 what, if anything, had been discovered by Ritter.     

Biology-inspired synthesis of compound libraries

Biologically active small molecules represent the basis for chemical biology applications in which small molecules are used as chemical tools to probe biological processes. In this report, we review two approaches to design and synthesize compound libraries for biological screenings, i.e., diversity-oriented synthesis (DOS) and biology-oriented synthesis (BIOS). Received 23 October 2007; received after revision 26 November 2007; accepted 28 November 2007     

Instruments and rules: R. B. Woodward and the tools of twentieth-century organic chemistry

The paper illustrates how organic chemists dramatically altered their practices in the middle part of the twentieth century through the adoption of analytical instrumentation — such as ultraviolet and infrared absorption spectroscopy and nuclear magnetic resonance spectroscopy — through which the difficult process of structure determination for small molecules became routine. Changes in practice were manifested in two ways: in the use of these instruments in the development of ‘rule-based’ theories; and in an increased focus on synthesis, at the expense of chemical analysis. These rule-based theories took the form of generalizations relating structure to chemical and physical properties, as measured by instrumentation. This ‘Instrumental Revolution’ in organic chemistry was two-fold: encompassing an embrace of new tools that provided unprecedented access to structures, and a new way of thinking about molecules and their reactivity in terms of shape and structure. These practices suggest the possibility of a change in the ontological status of chemical structures, brought about by the regular use of instruments. The career of Robert Burns Woodward (1917–1979) provides the central historical examples for the paper. Woodward was an organic chemist at Harvard from 1937 until the time of his death. In 1965, he won the Nobel Prize in Chemistry.     

Synthesis of dinucleoside tetraphosphates in transfected cells by a firefly luciferase reporter gene

The firefly luciferase gene is widely used as a reporter gene and its expression is generally considered to be non-toxic. In addition to its light-producing reaction, luciferase can synthesise dinucleoside polyphosphates, intracellular signalling molecules, in vitro. Here we show that COS-7 cells transfected with a luciferase expression vector accumulate up to 0.5 mM adenine-containing dinucleoside tetraphosphates (Ap₄N) during the 24 h following luciferin addition. The optimal external concentration of luciferin was 0.4–0.6 mM. In agreement with its poor ability to synthesise adenine-containing dinucleoside triphosphates in vitro, the level of these compounds did not increase after transfection. Consequently, the results of experiments involving luciferase-mediated light production by live cells should now be viewed in the light of the possible effects of an increased intracellular Ap₄N concentration on the properties of the system under investigation. This observation also points to a useful non-invasive procedure for the specific enhancement of intracellular Ap₄N for studies directed at understanding the functions of these compounds.Received 12 November 2003; received after revision 10 December 2003; accepted 12 December 2003     

Arte rates reguntur: Nautical handbooks in antiquity?

Given the huge number of technical handbooks on multifarious subjects, ranging from astronomy and music to rhetoric, horticulture, and cooking, the absence of ancient nautical handbooks comes as a surprise. Such handbooks did exist in antiquity in some form, likely having been written in the period of the Hellenistic boom of technical texts, but disappearing at some later point, perhaps around the third or fourth century AD. This disappearance could be due to a number of reasons, suggesting that the tastes and needs of the audience(s) for nautical technai were changing. These nautical handbooks may have been superseded by more specialized works, such as treatises on astronomy and mathematics, geography and periploi, and naval tactics, which may have been regarded as being of greater use than an interdisciplinary book on sailing. From a purely aesthetic perspective, many readers will probably not feel inclined to bemoan the loss of all ancient handbooks on navigation, as they will have looked similar to the periploi, containing many imperatives, short main clauses in hypotaxis, and many numerals.