Reflections on the ambivalent helix

The helix is nature's favourite shape. Because of its elementary geometry and distinctive appearance it is also the clearest instance of an enantiomorphic object--a helix and its mirror image are identical in all respects except their screw sense. This is a distinction that can be ignored from the points of view of pure geometry and pure group theory but any helical structure is actually available as either or both hands. Whether in nature helices do occur as just one hand, or both, is one of the best--perhaps the best--puzzles of the science of form. In this short review I look at a few examples of naturally occurring helices, some where only one hand is found, some where both are commonly found, and perhaps the most interesting examples in biological terms--those where both are found but one hand is very much rarer than the other. I review what mechanisms--physico-chemical, genetic, evolutionary--underlie the different manifestations of left- and right-handedness.     

Ionic currents in morphogenesis

Summary Morphogenetic fields must be generated by mechanisms based on known physical forces which include gravitational forces, mechanical forces, electrical forces, or some combination of these. While it is unrealistic to expect a single force, such as a voltage gradient, to be the sole cause of a morphogenetic event, spatial and temporal information about the electrical fields and ion concentration gradients in and around a cell or embryo undergoing morphogenesis can take us one step further toward understanding the entire morphogenetic mechanism. This is especially true because one of the handful of identified morphogens is Ca²⁺, an ion that will not only generate a current as it moves, but which is known to directly influence the plasma membrane's permeability to other ions, leading to other transcellular currents. It would be expected that movements of this morphogen across the plasma membrane might generate ionic currents and gradients of both electrical potential and intracellular concentration. Such ionic currents have been found to be integral components of the morphogenetic mechanism in some cases and only secondary components in other cases. My goal in this review is to discuss examples of both of these levels of involvement that have resulted from investigations conducted during the past several years, and to point to areas that are ripe for future investigation. This will include the history and theory of ionic current measurements, and a discussion of examples in both plant and animal systems in which ionic currents and intracellular concentration gradients are integral components of morphogenesis as well as cases in which they play only a secondary role. By far the strongest cases for a direct role of ionic currents in morphogenesis is the polarizing fucoid egg where the current is carried in part by Ca²⁺ and generates an intracellular concentration gradient of this ion that orients the outgrowth, and the insect follicle in which an intracellular voltage gradient is responsible for the polarized transport from nurse cell to oocyte. However, in most of the systems studied, the experiments to determine if the observed ionic currents are directly involved in the morphogenetic mechanism are yet to be done. Our experience with the fucoid egg and the fungal hypha ofAchlya suggest that it is the change in the intracellular ion concentration resulting from the ionic current that is critical for morphogenesis.     

Cross-presentation of IgG-containing immune complexes

IgG is a molecule that functionally combines facets of both innate and adaptive immunity and therefore bridges both arms of the immune system. On the one hand, IgG is created by adaptive immune cells, but can be generated by B cells independently of T cell help. On the other hand, once secreted, IgG can rapidly deliver antigens into intracellular processing pathways, which enable efficient priming of T cell responses towards epitopes from the cognate antigen initially bound by the IgG. While this process has long been known to participate in CD4⁺ T cell activation, IgG-mediated delivery of exogenous antigens into a major histocompatibility complex (MHC) class I processing pathway has received less attention. The coordinated engagement of IgG with IgG receptors expressed on the cell-surface (FcγR) and within the endolysosomal system (FcRn) is a highly potent means to deliver antigen into processing pathways that promote cross-presentation of MHC class I and presentation of MHC class II-restricted epitopes within the same dendritic cell. This review focuses on the mechanisms by which IgG-containing immune complexes mediate such cross-presentation and the implications that this understanding has for manipulation of immune-mediated diseases that depend upon or are due to the activities of CD8⁺ T cells.     

The potassium channel KcsA and its interaction with the lipid bilayer

The crystal structure of the K⁺ channel KcsA explains many features of ion channel function. The selectivity filter corresponds to a narrow region about 12 Å long and 3 Å wide, lined by carbonyl groups of the peptide backbone, through which a K⁺ ion can only move in a dehydrated form. The selectivity filter opens into a central, water-filled cavity leading to a gating site on the intracellular side of the channel. The channel is tetrameric, each monomer containing two transmembrane a helices, M1 and M2. Helix M1 faces the lipid bilayer and helix M2 faces the central channel pore; the M2 helices participate in subunit-subunit interactions. Helices M1 and M2 in each subunit pack as a pair of antiparallel coils with a heptad repeat, but the M2 helices of neighbouring subunits show fewer interactions, crossing at an angle of about –40°. Trp residues at the ends of the transmembrane helices form clear girdles on the two faces of the membrane, which, together with girdles of charged residues, define a hydrophobic thickness of about 37 Å for the channel. Binding constants for phosphatidylcholines to KcsA vary with fatty acyl chain length, the optimum chain length being C22. A phosphatidylcholine with this chain length gives a bilayer of thickness about 34 Å in the liquid crystalline phase, matching the hydrophobic thickness of the protein. However, a typical biological membrane has a hydrophobic thickness of about 27 Å. Thus either the transmembrane a helices of KcsA are more tilted in the native membrane than they are in the crystal structure, or the channel is under stress in the native membrane. The efficiency of hydrophobic matching between KcsA and the surrounding lipid bilayer is high over the chain length range C10–C24. The channel requires the presence of some anionic lipids for function, and fluorescence quenching studies show the presence of two classes of lipid binding site on KcsA; at one class of site (nonannular sites) anionic phospholipids bind more strongly than phosphatidylcholine, whereas at the other class of site (annular sites) phosphatidylcholines and anionic phospholipids bind with equal affinity.     

Interactions between mechanics and differential geometry in the 19th century

Conclusion 79. This study of the interaction between mechanics and differential geometry does not pretend to be exhaustive. In particular, there is probably more to be said about the mathematical side of the history from Darboux to Ricci and Levi Civita and beyond. Statistical mechanics may also be of interest and there is definitely more to be said about Hertz (I plan to continue in this direction) and about Poincaré's geometric and topological reasonings for example about the three body problem [Poincaré 1890] (cf. also [Poincaré 1993], [Andersson 1994] and [Barrow-Green 1994]). Moreover, it would be interesting to find out how the 19^th century ideas discussed here influenced the developments in the 20^th century. Einstein himself is a hotly debated case.Yet, despite these shortcommings, I hope that this paper has shown that the interactions between mechanics and differential geometry is not a 20^th century invention. Klein's view (see my Introduction) that Riemannian geometry grew out of mechanics, more specifically the principle of least action, cannot be maintained. On the other hand, when Riemannian geometry became known around 1870 it was immediately used in mechanics by Lipschitz. He began a continued tradition in this field, which had several elements in common with the new view of mechanics conceived by the physicists and explicitly carried out by Hertz.Before 1870 we found only scattered interactions between differential geometry and mechanics and only direct ones for systems of two or three degrees of freedom. For more degrees of freedom the geometrical ideas were in some interesting cases taken over by analogy, but these analogies did not lead to formal introduction of geometries of more than three dimensions.     

Structure,biosynthesis and functions of glycoprotein glycans

Since the pioneering work on structure and function of heteroglycans compiled in the classical books edited by A. Gottschalk in 1972¹, there have been several promising developments in glycoconjugate research, as reviewed in this article.In Part 1, contributed by A. Kobata, current knowledge on heteroglycan structures is presented and representative examples taken from higher organisms are given. Part 2, written by J. F. G. Vliegenthart and J. P. Kamerling, covers the most important achievements in methodology: procedures to obtain pure glycans and to analyze their structures. Part 3, contributed by J. Paulson, is devoted to biosynthesis of glycans now describable as pathways since several of the glycosyltransferases have been isolated and analyzed for specificity. In Part 4, contributed by E. Buddecke, current knowledge on functional roles of glycans is presented. It will become apparent that the prerequisite for valid work either in biosynthetic or functional context depends on solid structural information. This is particularly true whenever glycosyltransferase reaction products are being analyzed, or glycans involved in biological functions are investigated. Although in past years, a great deal of important knowledge has been gathered by use of crude glycosidase or glycosyltransferase activities (a notable example is found in reference 2), one may now postulate that glycans implicated in biological reactions should be thoroughly analyzed.This review may familiarize newcomers with the field of glycoconjugate research with special emphasis on glycoprotein glycans. Glycolipids are not included in this article as they have recently been reviewed by S. I. Hakomori³. The reader is also referred to several excellent monographs^4,5 and the Proceedings of the Glycoconjugate Symposia held biannually^6–8.     

Bias and values in scientific research

When interests and preferences of researchers or their sponsors cause bias in experimental design, data interpretation or dissemination of research results, we normally think of it as an epistemic shortcoming. But as a result of the debate on science and values, the idea that all ‘extra-scientific’ influences on research could be singled out and separated from pure science is now widely believed to be an illusion. I argue that nonetheless, there are cases in which research is rightfully regarded as epistemologically deficient due to the influence of preferences on its outcomes. I present examples from biomedical research and offer an analysis in terms of social epistemology.     

Ionic currents in morphogenesis

Morphogenetic fields must be generated by mechanisms based on known physical forces which include gravitational forces, mechanical forces, electrical forces, or some combination of these. While it is unrealistic to expect a single force, such as a voltage gradient, to be the sole cause of a morphogenetic event, spatial and temporal information about the electrical fields and ion concentration gradients in and around a cell or embryo undergoing morphogenesis can take us one step further toward understanding the entire morphogenetic mechanism. This is especially true because one of the handful of identified morphogens is Ca2+, an ion that will not only generate a current as it moves, but which is known to directly influence the plasma membrane's permeability to other ions, leading to other transcellular currents. It would be expected that movements of this morphogen across the plasma membrane might generate ionic currents and gradients of both electrical potential and intracellular concentration. Such ionic currents have been found to be integral components of the morphogenetic mechanism in some cases and only secondary components in other cases. My goal in this review is to discuss examples of both of these levels of involvement that have resulted from investigations conducted during the past several years, and to point to areas that are ripe for future investigation. This will include the history and theory of ionic current measurements, and a discussion of examples in both plant and animal systems in which ionic currents and intracellular concentration gradients are integral components of morphogenesis as well as cases in which they play only a secondary role. By far the strongest cases for a direct role of ionic currents in morphogenesis is the polarizing fucoid egg where the current is carried in part by Ca2+ and generates an intracellular concentration gradient of this ion that orients the outgrowth, and the insect follicle in which an intracellular voltage gradient is responsible for the polarized transport from nurse cell to oocyte. However, in most of the systems studied, the experiments to determine if the observed ionic currents are directly involved in the morphogenetic mechanism are yet to be done. Our experience with the fucoid egg and the fungal hypha of Achlya suggest that it is the change in the intracellular ion concentration resulting from the ionic current that is critical for morphogenesis.     

One phenomenon, many models: Inconsistency and complementarity

The paper examines philosophical issues that arise in contexts where one has many different models for treating the same system. I show why in some cases this appears relatively unproblematic (models of turbulence) while others represent genuine difficulties when attempting to interpret the information that models provide (nuclear models). What the examples show is that while complementary models needn’t be a hindrance to knowledge acquisition, the kind of inconsistency present in nuclear cases is, since it is indicative of a lack of genuine theoretical understanding. It is important to note that the differences in modeling do not result directly from the status of our knowledge of turbulent flows as opposed to nuclear dynamics—both face fundamental theoretical problems in the construction and application of models. However, as we shall, the ‘problem context(s)’ in which the modeling takes plays a decisive role in evaluating the epistemic merit of the models themselves. Moreover, the theoretical difficulties that give rise to inconsistent as opposed to complementary models (in the cases I discuss) impose epistemic and methodological burdens that cannot be overcome by invoking philosophical strategies like perspectivism, paraconsistency or partial structures.     

Principle or constructive relativity

Appealing to Albert Einstein's distinction between principle and constructive theories, Harvey Brown has argued for an interpretation of the theory of relativity as a dynamic and constructive theory. Brown's view has been challenged by Michel Janssen and in this paper I investigate their dispute. I argue that their disagreement appears larger than it actually is due to the two frameworks used by Brown and Janssen to express their respective views: Brown's appeal to Einstein's principle–constructive distinction and Janssen's framing of the disagreement as one over the question whether relativity provides a kinematic or a dynamic constraint. I appeal to a distinction between types of theories drawn by H. A. Lorentz two decades before Einstein's distinction to argue that Einstein's distinction represents a false dichotomy. I argue further that the disagreement concerning the kinematics–dynamics distinction is a disagreement about labels but not about substance. There remains a genuine disagreement over the explanatory role of spacetime geometry and here I agree with Brown arguing that Janssen sees a pressing need for an explanation of Lorentz invariance where no further explanation is needed.     

Conformational change of the extracellular parts of the CFTR protein during channel gating

Cystic fibrosis can be treated by potentiators, drugs that interact directly with the cystic fibrosis transmembrane conductance regulator (CFTR) Cl^? channel to increase its open probability. These substances likely target key conformational changes occurring during channel opening and closing, however, the molecular bases of these conformational changes, and their susceptibility to manipulation are poorly understood. We have used patch clamp recording to identify changes in the three-dimensional organization of the extracellularly accessible parts of the CFTR protein during channel opening and closing. State-dependent formation of both disulfide bonds and Cd²⁺ bridges occurred for pairs of cysteine side-chains introduced into the extreme extracellular ends of transmembrane helices (TMs) 1, 6, and 12. Between each of these three TMs, we found that both disulfide bonds and metal bridges formed preferentially or exclusively in the closed state and that these inter-TM cross-links stabilized the closed state. These results indicate that the extracellular ends of these TMs are close together when the channel is closed and that they separate from each other when the channel opens. These findings identify for the first time key conformational changes in the extracellular parts of the CFTR protein that can potentially be manipulated to control channel activity.     

Reading Gauss in the Computer Age: On the U.S. Reception of Gauss’s Number Theoretical Work (1938–1989)

C.F Gauss’s computational work in number theory attracted renewed interest in the twentieth century due to, on the one hand, the edition of Gauss’s Werke, and, on the other hand, the birth of the digital electronic computer. The involvement of the U.S. American mathematicians Derrick Henry Lehmer and Daniel Shanks with Gauss’s work is analysed, especially their continuation of work on topics as arccotangents, factors of n ² + a ², composition of binary quadratic forms. In general, this strand in Gauss’s reception is part of a more general phenomenon, i.e. the influence of the computer on mathematics and one of its effects, the reappraisal of mathematical exploration. I would like to thank the Alexander-von-Humboldt-Stiftung for funding this research. For their comments I would like to thank Catherine Goldstein, Norbert Schappacher and especially John Brillhart.     

Sterol carrier protein-2: structure reveals function

The multiple actions of sterol carrier protein-2 (SCP-2) in intracellular lipid circulation and metabolism originate from its gene and protein structure. The SCP-x/pro-SCP-2 gene is a fusion gene with separate initiation sites coding for 15-kDa pro-SCP-2 (no enzyme activity) and 58-kDa SCP-x (a 3-ketoacyl CoA thiolase). Both proteins share identical cDNA and amino acid sequences for 13-kDa SCP-2 at their C-termini. Cellular 13-kDa SCP-2 derives from complete, posttranslational cleavage of the 15-kDa pro-SCP-2 and from partial posttranslational cleavage of 58-kDa SCP-x. Putative physiological functions of SCP-2 have been proposed on the basis of enhancement of intermembrane lipid transfer (e.g., cholesterol, phospholipid) and activation of enzymes involved in fatty acyl CoA transacylation (cholesterol esters, phosphatidic acid) in vitro, in transfected cells, and in genetically manipulated animals. At least four important SCP-2 structural domains have been identified and related to specific functions. First, the 46-kDa N-terminal presequence present in 58-kDa SCP-x is a 3-ketoacyl-CoA thiolase specific for branched-chain acyl CoAs. Second, the N-terminal 20 amino acid presequence in 15-kDa pro-SCP-2 dramatically modulates the secondary and tertiary structure of SCP-2 as well as potentiating its intracellular targeting coded by the C-terminal peroxisomal targeting sequence. Third, the N-terminal 32 amino acids form an amphipathic a-helical region, one face of which represents a membrane-binding domain. Positively charged amino acid residues in one face of the amphipathic helices allow SCP-2 to bind to membrane surfaces containing anionic phospholipids. Fourth, the hydrophobic faces of the N-terminal amphipathic a helices along with beta strands 4, 5, and helix D form a ligand-binding cavity able to accommodate multiple types of lipids (e. g., fatty acids, fatty acyl CoAs, cholesterol, phospholipids, isoprenoids). Two-dimensional 1H-15N heteronuclear single quantum coherence spectra of both apo-SCP-2 and of the 1:1 oleate-SCP-2 complex, obtained at pH 6.7, demonstrated the homogenous formation of holo-SCP-2. While comparison of the apo- and holoprotein amide fingerprints revealed about 60% of the resonances remaining essentially unchanged, 12 assigned amide residues underwent significant chemical-shift changes upon oleic acid binding. These residues were localized in three regions: the juncture of helices A and B, the mid-section of the beta sheet, and the interface formed by the region of beta strands 4, 5, and helix D. Circular dichroism also showed that these chemical-shift changes, upon oleic acid binding, did not alter the secondary structure of SCP-2. The nuclear magnetic resonance chemical shift difference data, along with mapping of the nearby hydrophobic residues, showed the oleic acid-binding site to be comprised of a pocket created by the face of the beta sheet, helices A and B on one end, and residues associated with beta strands 4, 5, and helix D at the other end of the binding cavity. Furthermore, the hydrophobic nature of the previously ill-defined C-terminus suggested that these 20 amino acids may form a 'hydrophobic cap' which closes around the oleic acid upon binding. Thus, understanding the structural domains of the SCP-x/pro-SCP-2 gene and its respective posttranslationally processed proteins has provided new insights into their functions in intracellular targeting and metabolism of lipids.     

On the notion of free will in the Free Will Theorem

The (Strong) Free Will Theorem (fwt) of Conway and Kochen (2009) on the one hand follows from uncontroversial parts of modern physics and elementary mathematical and logical reasoning, but on the other hand seems predicated on an undefined notion of free will (allowing physicists to “freely choose” the settings of their experiments). This makes the theorem philosophically vulnerable, especially if it is construed as a proof of indeterminism or even of libertarian free will (as Conway & Kochen suggest).However, Cator and Landsman (Foundations of Physics 44, 781–791, 2014) previously gave a reformulation of the fwt that does not presuppose indeterminism, but rather assumes a mathematically specific form of such “free choices” even in a deterministic world (based on a non-probabilistic independence assumption). In the present paper, which is a philosophical sequel to the one just mentioned, I argue that the concept of free will used in the latter version of the fwt is essentially the one proposed by Lewis (1981), also known as ‘local miracle compatibilism’ (of which I give a mathematical interpretation that might be of some independent interest also beyond its application to the fwt). As such, the (reformulated) fwt in my view challenges compatibilist free will à la Lewis (albeit in a contrived way via bipartite epr-type experiments), falling short of supporting libertarian free will.     

Potentiation by crude kallikrein of the myotropic effect of angiotensin I in the isolated rabbit aortic strip

Summary Crude kallikrein (Padutin^®), but not pure kallikrein, when preincubated with angiotensin I caused a potentiation of the myotropic effect of decapeptide on the isolated continuously superfused rabbit aortic strip. Addition of converting enzyme inhibitor, SQ 20881, to the medium inhibited this potentiation. The potentiation by crude kallikrein of the myotropic effect of angiotensin I is probably due to the conversion of decapeptide to octapeptide angiotensin II. This study indicates that Padutin is not a pure kallikrein preparation and probably contains a kininase fraction which causes the conversion of angiotensin I.The authors are greatful to Prof. G. L. Haberland, Bayer AG, Elberfeld (BRD), for his generous gift of pure Kallikrein^® KZC 1/75; to Bayer, Leverkusen (BRD), for Padutin^® and to Squibb, New Jersey, USA, for SQ 20881. This work is supported in part by Eczacibai Research Foundation, Levent, Istanbul, Turkey. The technical assistance of Mr. M. Kabaçam is greatly appreciated.     

Determination of the kinetic parameters of enzyme inhibition of the K-type mechanism: application to the control of alpha-glucosidase activity of honeybee hemolymph by glucose]

The alpha-glucosidasic activity of emerging honeybees haemolymph is submitted to a feed-back inhibition by glucose, according to a mechanism of the "K" type (competitive). The "resulting affinity-constant" (measured in the presence of the enzyme both with substrate and inhibitor) is linear function of the inhibitor concentration. The affinity constants between enzyme and pure substrate on one hand, and between enzyme and pure inhibitor on the other hand, were determined by means of this relation, which led to respectively equivalent values after determinations under in vitro or in vivo inhibitions.     

Helix H1 of the prion protein is rather stable against environmental perturbations: molecular dynamics of mutation and deletion variants of PrP(90–231)

We need to understand the underlying factors that promote or reverse the amyloid-type structure of the prion protein (PrP). In an earlier study, we showed that mutations within the first strand can extend the short sheet in the normal protein into a larger sheet at neutral pH. To determine the impact of the point mutation P102L and the deletion of either the first or the second strand on PrP, we performed further long molecular explicit water dynamics simulations. The trajectories show that all mutations do not exert a uniform effect on the dynamics of the N-terminal tail. The results of the deletion of the two strands confirm the idea that partially unfolded conformations are involved in the structural transition. In the deletion variants, the helices H2 and H3 are disordered, while helix H1 is either fully stable or partially disordered. This finding, consistent with recent spectroscopic analyses on peptides spanning helix H1 and flanking sequences, demonstrates that unfolding of the full domain containing helix H1 is not an early step in PrP interconversion. This result also raises questions regarding a current view of PrP^Sc structure that transforms helix H1 into a sheet conformation.Received 16 December 2003; received after revision 16 January 2004; accepted 21 January 2004     

Conventionalism in Reid’s ‘geometry of visibles’

The subject of this investigation is the role of conventions in the formulation of Thomas Reid’s theory of the geometry of vision, which he calls the ‘geometry of visibles’. In particular, we will examine the work of N. Daniels and R. Angell who have alleged that, respectively, Reid’s ‘geometry of visibles’ and the geometry of the visual field are non-Euclidean. As will be demonstrated, however, the construction of any geometry of vision is subject to a choice of conventions regarding the construction and assignment of its various properties, especially metric properties, and this fact undermines the claim for a unique non-Euclidean status for the geometry of vision. Finally, a suggestion is offered for trying to reconcile Reid’s direct realist theory of perception with his geometry of visibles.While Thomas Reid is well-known as the leading exponent of the Scottish ‘common-sense’ school of philosophy, his role in the history of geometry has only recently been drawing the attention of the scholarly community. In particular, several influential works, by N. Daniels and R. B. Angell, have claimed Reid as the discoverer of non-Euclidean geometry; an achievement, moreover, that pre-dates the geometries of Lobachevsky, Bolyai, and Gauss by over a half century. Reid’s alleged discovery appears within the context of his analysis of the geometry of the visual field, which he dubs the ‘geometry of visibles’. In summarizing the importance of Reid’s philosophy in this area, Daniels is led to conclude that ‘there can remain little doubt that Reid intends the geometry of visibles to be an alternative to Euclidean geometry’;¹ while Angell, similarly inspired by Reid, draws a much stronger inference: ‘The geometry which precisely and naturally fits the actual configurations of the visual field is a non-Euclidean, two-dimensional, elliptical geometry. In substance, this thesis was advanced by Thomas Reid in 1764 ...’² The significance of these findings has not gone unnoticed in mathematical and scientific circles, moreover, for Reid’s name is beginning to appear more frequently in historical surveys of the development of geometry and the theories of space.³Implicit in the recent work on Reid’s ‘geometry of visibles’, or GOV, one can discern two closely related but distinct arguments: first, that Reid did in fact formulate a non-Euclidean geometry, and second, that the GOV is non-Euclidean. This essay will investigate mainly the latter claim, although a lengthy discussion will be accorded to the first. Overall, in contrast to the optimistic reports of a non-Euclidean GOV, it will be argued that there is a great deal of conceptual freedom in the construction of any geometry pertaining to the visual field. Rather than single out a non-Euclidean structure as the only geometry consistent with visual phenomena, an examination of Reid, Daniels, and Angell will reveal the crucial role of geometric ‘conventions’, especially of the metric sort, in the formulation of the GOV (where a ‘metric’ can be simply defined as a system for determining distances, the measures of angles, etc.). Consequently, while a non-Euclidean geometry is consistent with Reid’s GOV, it is only one of many different geometrical structures that a GOV can possess. Angell’s theory that the GOV can only be construed as non-Euclidean, is thus incorrect. After an exploration of Reid’s theory and the alleged non-Euclidean nature of the GOV, in 1 and 2 respectively, the focus will turn to the tacit role of conventionalism in Daniels’ reconstruction of Reid’s GOV argument, and in the contemporary treatment of a non-Euclidean visual geometry offered by Angell ( 3 and 4). Finally, in the conclusion, a suggestion will be offered for a possible reconstruction of Reid’s GOV that does not violate his avowed ‘direct realist’ theory of perception, since this epistemological thesis largely prompted his formulation of the GOV.     

Pure science and the problem of progress

How should we understand scientific progress? Kuhn famously discussed science as its own internally driven venture, structured by paradigms. He also famously had a problem describing progress in science, as problem-solving ability failed to provide a clear rubric across paradigm change—paradigm changes tossed out problems as well as solving them. I argue here that much of Kuhn’s inability to articulate a clear view of scientific progress stems from his focus on pure science and a neglect of applied science. I trace the history of the distinction between pure and applied science, showing how the distinction came about, the rhetorical uses to which the distinction has been put, and how pure science came to be both more valued by scientists and philosophers. I argue that the distinction between pure and applied science does not stand up to philosophical scrutiny, and that once we relinquish it, we can provide Kuhn with a clear sense of scientific progress. It is not one, though, that will ultimately prove acceptable. For that, societal evaluations of scientific work are needed.