Beyond Mendelism and Biometry

Historiographical analyses of the development of genetics in the first decade of the 20th century have been to a great extent framed in the context of the Mendelian-Biometrician controversy. Much has been discussed on the nature, origin, development, and legacy of the controversy. However, such a framework is becoming less useful and fruitful. This paper challenges the traditional historiography framed by the Mendelian-Biometrician distinction. It argues that the Mendelian-Biometrician distinction fails to reflect the theoretical and methodological diversity in the controversy. It also argues that the Mendelian-Biometrician distinction is not helpful to make a full understanding of the development of genetics in the first decade of the twentieth century.     

Problems and promises: How to tell the story of a Genome Wide Association Study?

The promise of treatments for common complex diseases (CCDs) is understood as an important force driving large scale genetics research over the last few decades. This paper considers the phenomenon of the Genome Wide Association Study (GWAS) via one high profile example, the Wellcome Trust Case Control Consortium (WTCCC). The WTCCC despite not fulfilling promises of new health interventions is still understood as an important step towards tackling CCDs clinically. The ‘sociology of expectations’ has considered many examples of failure to fulfil promises and the subsequent negative consequences including disillusionment, disappointment and disinvestment. In order to explore why some domains remain resilient in the face of apparent failure, I employ the concept of the ‘problematic’ found in the work of Giles Deleuze. This alternative theoretical framework challenges the idea that the failure to reach promised goals results in largely negative outcomes for a given field. I will argue that collective scientific action is motivated not only by hopes for the future but also by the drive to create solutions to the actual setbacks and successes which scientists encounter in their day-to-day work. I draw on eighteen interviews.     

Essay Review: Looking for the Rhetoric of Science

The characteristics of inductivist historiography of science, as practised by earlier scientist/historians, and Whig historiography, as practised by earlier political historians, are described, according to the accounts of Agassi and Butterfield. It is suggested that the writings of Geikie on the history of geology allow us to characterize him as a Whig/inductivist historian of science who formulated anachronistic judgements. It is further suggested that his writings have had a considerable long-term effect on interpretations of the history of geology. The character of Geikie's historiography is related to his social, political and religious views, his historicism, and his romantic enthusiasm for Nature. His methodological pronouncements are examined: he believed that the present is the key to the past, and also that the past is the key to the present. He was an empiricist and inductivist. These epistemological and methodological views impinged on his historiography of science. If one attempts to criticize Geikie's historiography, though one may try to judge his work according to the norms of his own day and age, historical anachronism cannot be avoided entirely and one may oneself be charged with acting ‘Whiggishly’. Historians of science, in the process of professionalization, have accepted the historiographical norms of general historians (perhaps for socio-economic reasons), but in so doing have inherited a problem that arises whenever they contemplate earlier historical writings. It is suggested that there may be more room for Whiggish historiography of science than is presently deemed acceptable. Alternatively, one may wish to draw a careful distinction between science and its meta-discipline, the historiography of science. Whig historiography conflates the two, and the work of Geikie (a scientist/historian par excellence) provides a good illustration of this.     

Geographical expansion and the reconfiguration of medical authority: Garcia de Orta's Colloquies on the simples and drugs of India (1563)

The Colloquies on the simples and drugs of India (1563) were conceived and published at a sensitive moment, both in terms of the history of print culture and of European geographical expansion. They represented the culmination of a life-time project for their author Garcia de Orta who had lived for almost thirty years in Portuguese Goa. Although the importance of the work in sixteenth-century natural history and medicine has been generally acknowledged in Portuguese and international historiography, there are very few recent, detailed studies of the book informed by new approaches. This paper presents an integrated analysis of Orta's Colloquies as a literary, medical and cultural text. It aims to reveal not only the rich and subtle dynamics of the work but also to contribute to a better understanding of Orta's legitimation strategies as an author in a sixteenth-century world reconfigured by the new opportunities of the printing press, geographical expansion and increased material and cultural mobility.     

Quantitative genetics of zooplankton life histories

Quantitative genetic techniques are powerful tools for use in understanding the microevolutionary process. Because of their size, lifespan, and ease of culture, many zooplankton species are ideal for quantitative genetic approaches. As model systems, studies of zooplankton life histories are becoming increasingly used for examination of the central paradigms of evolutionary theory. Two of the fundamental empirical questions that zooplankton quantitative genetics studies can answer are: 1) How much genetic variance exists in natural populations for life history traits? 2) What is the empirical evidence for trade-offs that permeate life history theory based on optimality approaches? A review of existing data onDaphnia indicates substantial genetic variance for body size, clutch size, and age at first reproduction. Average broad-sense heritabilities for these three characters across 19 populations of 6 species are 0.31, 0.31, and 0.34, respectively. Although there is some discrepancy between the two pertinent studies that were designed to decompose the total genetic variance into its additive and non-additive components, a crude average seems to suggest that approximately 60% of the total genetic variance has an additive basis. The existing data are somewhat inconsistent with respect to presence/absence of trade-offs (negative genetic correlations) among life history traits. A composite of the existing data seems to argue against the existence of strong trade-offs between offspring size and offspring number, between present and future reproduction, and between developmental rate and fecundity. However, there is some evidence for a shift toward more negative (less positive) covariances in more stressful environments (e.g., low food). Zooplankton will prove to be very useful in future study in several important areas of research, including the genetics and physiology of aging, the importance of genotype-environment interaction for life history traits, and the evolution of phenotypic plasticity.     

From ‘Beastly Philosophy’ to Medical Genetics: Eugenics in Russia and the Soviet Union

This essay offers an overview of the three distinct periods in the development of Russian eugenics: Imperial (1900–1917), Bolshevik (1917–1929), and Stalinist (1930–1939). Began during the Imperial era as a particular discourse on the issues of human heredity, diversity, and evolution, in the early years of the Bolshevik rule eugenics was quickly institutionalized as a scientific discipline—complete with societies, research establishments, and periodicals—that aspired an extensive grassroots following, generated lively public debates, and exerted considerable influence on a range of medical, public health, and social policies. In the late 1920s, in the wake of Joseph Stalin's ‘Great Break’, eugenics came under intense critique as a ‘bourgeois’ science and its proponents quickly reconstituted their enterprise as ‘medical genetics’. Yet, after a brief period of rapid growth during the early 1930s, medical genetics was dismantled as a ‘fascist science’ towards the end of the decade. Based on published and original research, this essay examines the factors that account for such an unusual—as compared to the development of eugenics in other locales during the same period—historical trajectory of Russian eugenics.     

What is a text?

This paper argues that textuality—the property of being a text—is assigned by the reader, rather than constituting an inherent property, and that the being of texts was both captured and mystified by the figure of ‘the text’ as this developed from the 1970s onwards. Textuality consists in the abstraction of verbal content from its origins, entailing the apprehension of that content as copresent with the reader; and it is given a material embodiment in the process of publication, especially in the production of canonical works, which together comprise the locus classicus of the textual apprehension. Whole disciplines—here termed the hermeneutico-canonical disciplines—are based upon that apprehension, and the discipline or approach known as hermeneutics consists of its theoretical elaboration. In contrast, the discipline of history rests upon the apprehension of the verbal under the sign of the document or its cognates, and this difference renders intelligible the longstanding relationship of mutual suspicion between hermeneutics and history. The historiography of science, remarkably enough, manages to combine these approaches; the paper concludes by suggesting that these can be brought into a more fruitful synthesis by investigating historically the construction of scientific canons.     

What was classical genetics?

I present an account of classical genetics to challenge theory-biased approaches in the philosophy of science. Philosophers typically assume that scientific knowledge is ultimately structured by explanatory reasoning and that research programs in well-established sciences are organized around efforts to fill out a central theory and extend its explanatory range. In the case of classical genetics, philosophers assume that the knowledge was structured by T. H. Morgan’s theory of transmission and that research throughout the later 1920s, 30s, and 40s was organized around efforts to further validate, develop, and extend this theory. I show that classical genetics was structured by an integration of explanatory reasoning (associated with the transmission theory) and investigative strategies (such as the ‘genetic approach’). The investigative strategies, which have been overlooked in historical and philosophical accounts, were as important as the so-called laws of Mendelian genetics. By the later 1920s, geneticists of the Morgan school were no longer organizing research around the goal of explaining inheritance patterns; rather, they were using genetics to investigate a range of biological phenomena that extended well beyond the explanatory domain of transmission theories. Theory-biased approaches in history and philosophy of science fail to reveal the overall structure of scientific knowledge and obscure the way it functions.     

Heritability of locomotor performance and its correlates in a natural population

Summary Locomotor capacities and their physiological bases are thought to be of considerable selective importance in natural populations. Within this functional complex, organismal performance traits (e.g., speed, stamina) are expected to be of more direct selective importance than their suborganismal determinants (e.g., heart size). Quantitative genetics theory predicts that traits of greater selective importance should generally have lower heritabilities at equilibrium. Contrary to these expectations, we report that organismal performance traits had the highest heritabilities in a natural population of garter snakes.     

Sydney Chapman on the Layering of the Atmosphere: Conceptual Unity and the Modelling of the Ionosphere

Sydney Chapman is unanimously considered to have played a founding role in modern geomagnetism and to have opened up new lines of research in geophysics generally. Nevertheless, Chapman's conviction regarding the synthesis of the explanatory mechanisms of the atmosphere has gone practically unnoticed in the historiography of geophysics. This paper examines Chapman's contribution to ionospheric physics. It aims to understand Chapman's theory of ionospheric layer formation, and particularly its link to his theory of ozone formation. It deals first with the traits which characterized Chapman's personality, as a way of explaining—and even perhaps justifying— his quest for the integration and synthesis of geophysical knowledge. It then analyses Chapman's model of ionospheric layers and his suggestions regarding its use as an operational tool (without ontological connotations), before continuing with his account of the formation of the ozone layer, which seemed to constitute the missing link for understanding ionosphere layer formation. The paper concludes with Chapman's attempt to reconcile geomagnetic and radio evidence.     

Stress and the nonsense-mediated RNA decay pathway

Cells respond to internal and external cellular stressors by activating stress-response pathways that re-establish homeostasis. If homeostasis is not achieved in a timely manner, stress pathways trigger programmed cell death (apoptosis) to preserve organism integrity. A highly conserved stress pathway is the unfolded protein response (UPR), which senses excessive amounts of unfolded proteins in the ER. While a physiologically beneficial pathway, the UPR requires tight regulation to provide a beneficial outcome and avoid deleterious consequences. Recent work has demonstrated that a conserved and highly selective RNA degradation pathway—nonsense-mediated RNA decay (NMD)—serves as a major regulator of the UPR pathway. NMD degrades mRNAs encoding UPR components to prevent UPR activation in response to innocuous ER stress. In response to strong ER stress, NMD is inhibited by the UPR to allow for a full-magnitude UPR response. Recent studies have indicated that NMD also has other stress-related functions, including promoting the timely termination of the UPR to avoid apoptosis; NMD also regulates responses to non-ER stressors, including hypoxia, amino-acid deprivation, and pathogen infection. NMD regulates stress responses in species across the phylogenetic scale, suggesting that it has conserved roles in shaping stress responses. Stress pathways are frequently constitutively activated or dysregulated in human disease, raising the possibility that “NMD therapy” may provide clinical benefit by downmodulating stress responses.     

Insights into the genetic basis of congenital heart disease

Cardiovascular malformations are the most common type of birth defect and result in significant mortality worldwide. The etiology for the majority of these anomalies remains unknown. Advances in the characterization of the molecular pathways critical for normal cardiac development have led to the identification of numerous genes necessary for this complex morphogenetic process. This work has aided the discovery of an increasing number of single genes being implicated as the cause of human cardiovascular malformations. This review summarizes normal cardiac development and outlines the recent discoveries of the genetic causes of congenital heart disease. Received 4 November 2005; received after revision 14 January 2006; accepted 1 February 2006     

“The soul of the fact”—Poincaré and proof

Henri Poincaré acquired a reputation in his lifetime for being difficult to read. It was said that he missed out important steps in his arguments, assumed the truth of claims that would be difficult if not impossible to prove, and in short that he lacked rigour. In the years after his death this view coalesced into an exaggerated claim that his work was simply too vague, and has become a cliché. This paper argues that Poincaré was far from indifferent to rigour, and that what characterises his work is an attempt to convey a particular sense of what it is to understand a topic. Throughout his working life Poincaré was concerned to promote the understanding of many domains of mathematics and physics. This is as apparent in his views about geometry, his conventionalism, and his theory of knowledge, as it is in his work on electricity and optics, on number theory, and function theory. It is one of the ways Poincaré discharged his responsibilities as a scientist, and that it accounts not only for a surprising degree of unity in his work but also gives it its distinctive character—at once profound and elusive.     

Science, truth and history, part II. Metaphysical bolt-holes for the Sociology of Scientific Knowledge?

Historians of science have frequently sought to exclude modern scientific knowledge from their narratives. Part I of this paper, published in the previous issue, cautioned against seeing more than a literary preference at work here. In particular, it was argued—contra advocates of the Sociology of Scientific Knowledge (SSK)—that a commitment to epistemological relativism should not be seen as having straightforward historiographical consequences. Part II considers further SSK-inspired attempts to entangle the currently fashionable historiography with particular positions in the philosophy of science. None, I argue, is promising. David Bloor’s proposed alliance with scientific realism relies upon a mistaken view of contrastive explanation; Andrew Pickering’s appeal to instrumentalism is persuasive for particle physics but much less so for science as a whole; and Bruno Latour’s home-grown metaphysics is so bizarre that its compatibility with SSK is, if anything, a further blow to the latter’s plausibility.     

Whole genome sequencing as a means to assess pathogenic mutations in medical genetics and cancer

The past decade has seen the emergence of next-generation sequencing (NGS) technologies, which have revolutionized the field of human molecular genetics. With NGS, significant portions of the human genome can now be assessed by direct sequence analysis, highlighting normal and pathological variants of our DNA. Recent advances have also allowed the sequencing of complete genomes, by a method referred to as whole genome sequencing (WGS). In this work, we review the use of WGS in medical genetics, with specific emphasis on the benefits and the disadvantages of this technique for detecting genomic alterations leading to Mendelian human diseases and to cancer.     

Can patents prohibit research? On the social epistemology of patenting and licensing in science

A topic of growing importance within philosophy of science is the epistemic implications of the organization of research. This paper identifies a promising approach to social epistemology—nonideal systems design—and uses it to examine one important aspect of the organization of research, namely the system of patenting and licensing and its role in structuring the production and dissemination of knowledge. The primary justification of patenting in science and technology is consequentialist in nature. Patenting should incentivize research and thereby promote the development of knowledge, which in turn facilitates social progress. Some have disputed this argument, maintaining that patenting actually inhibits knowledge production. In this paper, I make a stronger argument; in some areas of research in the US—in particular, research on GM seeds—patents and patent licenses can be, and are in fact being, used to prohibit some research. I discuss three potential solutions to this problem: voluntary agreements, eliminating patents, and a research exemption. I argue against eliminating patents, and I show that while voluntary agreements and a research exemption could be helpful, they do not sufficiently address the problems of access that are discussed here. More extensive changes in the organization of research are necessary.     

The goal of explanation

I defend the claim that understanding is the goal of explanation against various persistent criticisms, especially the criticism that understanding is not truth-connected in the appropriate way, and hence is a merely psychological (rather than epistemic) state. Part of the reason why understanding has been dismissed as the goal of explanation, I suggest, is because the psychological dimension of the goal of explanation has itself been almost entirely neglected. In turn, the psychological dimension of understanding—the Aha! experience, the sense that a certain explanation “feels right”, and so on—has been conspicuously overemphasized. I try to correct for both of these exaggerations. Just as the goal of explanation includes a richer psychological—including phenomenological—dimension than is generally acknowledged, so too understanding has a stronger truth connection than is generally acknowledged.     

Gender and philosophy of science: The case of Mary Hesse

This article is composed of two intertwining narratives. The first is a discussion of the concept of gender in relation to philosopher of science Mary Hesse's theoretical contributions and academic experiences. The second narrative takes issue with the gender concept at a more general level and particularly to discuss its strengths and limits. The article alternates between a discussion of different claims from gender theorists and a presentation of Mary Hesse's academic experiences. I conclude that although the gender concept has, until now, only been used in an asymmetrical sense, i.e., negatively linked to women's careers and positively to men's, it will not necessarily be identically used in the future. Both empirical findings and conceptual changes may make room for a more differentiated understanding of gender.     

Feyerabend,truth, and relativisms: Footnotes to the Italian debate

There is a substantial literature on Feyerabend's relativism—including a few papers in this collection—but fewer specific studies of the ways that his writings and ideas have been taken up among the non-academic public. This is odd, given his obvious interest in the lives and concerns of persons who were not ‘intellectuals’—a term that, for him, had a pejorative ring to it. It is also odd, given the abundance of evidence of how Feyerabend's relativism played a role in a specific national and cultural context—namely, contemporary Italian debates about relativism. This paper offers a study of how Feyerabend's ideas have been deployed by Italian intellectuals and cultural commentators—including the current Pope—and critically assesses them.