Early in the 20th century Bateson, Doncaster and Punnett formed a cooperative collective to share research findings on the chromosome theory of heredity (CTH). They cross-bred plants and animals to correlate behaviour of chromosomes and heredity of individual traits. Doncaster was the most enthusiastic proponent of the new theory and worked for years to convince Bateson and Punnett on its relevance to their own research. The two younger biologists collaborated with Bateson, the preeminent geneticist in England. As (...) their own reputations developed, their research findings allied with the consensus on the importance of the CTH by the broader scientific community. After Doncaster’s tragic death in 1920, major objections to the theory had been resolved; Bateson and Punnett then utilized the CTH to construct chromosome maps detailing locations of specific genes on particular chromosomes in several different species. The marriage of heredity and cytology enhanced confidence that the theory was an accurate mechanism to explain inheritance in both plants and animals. (shrink)

This paper examines the process that led to the identification of chromosomes as carriers of genes. It focuses on the role played by explanations in theory construction and analyzes the status given to the entities and processes introduced through such explanations. I argue that the theory of the gene was a functional explanation that, as such, could not offer decisive support for the existence of genes. However, I maintain that functional explanations set the conditions of identification needed to (...) discover the physical structure that has a certain function in a given system. In this case, the theory of the gene helped to select the chromosomes as the physical structure responsible for the Mendelian segregation of genes. In its turn, the theory of chromosome inheritance helped to reduce the permissive character of the theory of the gene, regulating its further development. (shrink)

Cytogenetics was born of the confluence of two so-far independent fields: cytological studies and breeding studies, which merged through the identification of genes with chromosomes. In this paper I argue that genes were introduced as functional entities. Functional explanations are presented here as a subclass of inferences to the best explanation and I argue that abductive arguments do not offer conclusive proof for the existence of the entities postulated through them. However, functional explanations usually follow a scheme laid out by (...) Fodor (1968): there is a first phase where hypothetical entities are postulated and individuated through their effects; there is a second phase where the physical structures responsible for these effects are sought. I analyze the development of both phases in the construction of the chromosome theory of Mendelian inheritance. I will argue that first-phase theories are important to set conditions of identification for the functions played by a certain structure in a given containing system. (shrink)

We may now ask the question: In what historical perspective should we place the work of Richard Goldschmidt? There is no doubt that in the period 1910–1950 Goldschmidt was an important and prolific figure in the history of biology in general, and of genetics in particular. His textbook on physiological genetics, published in 1938, was an amazing compendium of ideas put forward in the previous half-century about how genes influence physiology and development. His earlier studies on the genetic and geographic (...) distribution of the various species and races of Lymantria contributed soundly to an understanding of the inheritance and development of sex, as well as the genetics of speciation. He was a curious mixture of the experimentalist, empiricist, and theorizer, who could grasp both the large and the small at once and wrap them into the same integrated and coherent package.In insisting on trying to relate genetics to development, Goldschmidt was continually forced to speculate and to forsake experimental fact for generalized theory. In refusing to reconcile a physiological and developmental conception with a corpuscular theory of the gene, he forced himself to substitute for a large body of experimentally verified evidence, vague and general speculations which did not lead in any precise direction. L. C. Dunn summarizes succinctly the effect of Goldschmidt's thinking on the development of genetic theory: Although Goldschmidt's ideas had a considerable influence in directing attention to the developmental processes intervening between genes and characters, they did not lead to the establishment of a general theory of development in genetical terms. In fact, at the end of the period, as signalized by Goldschmidt's book of 1938 [Physiological Gentics] doubt remained whether there was a field with a defined problem which could be identified as developmental genetics.Yet the frequency with which Goldschmidt is cited by later writers suggests that there is a more positive side to his contribution than this. The early Mendelians had recognized the genic constitution of organisms and the Drosophila workers had uncovered in detail the chromosomal mechanism of heredity. These great discoveries were of classical character, solidly based on a multitude of well established facts. By themselves, however, they would not have been sufficient to place genetics in the central position within biology which it was to assume. Beyond the “static” analysis of gene transmission an insight was needed into the dynamic role of genes in cellular physiology, biochemistry, and development. Goldschmidt recognized this aspect and outlined in brilliant generalizations a physiological theory of genetics. Necessarily the prophetic nature of this achievement — romantic in the sense of Ostwald's classification of great scientists and their discoveries — transcended its factual basis. It was the audacity of the theoretician unimpeded by the still scanty data which gave a new focus to biological thought.Some have called Goldschmidt an “obstructionist” in the history of genetics—one whose efforts were largely directed toward useless and continual criticism — challenge for the sake of challenge. As this line of argument goes, time wasted answering Goldschmidt's poorly conceived criticisms could have been better used to pursue new lines of thought within the classical gene theory. Sometimes historians are upbraided for studying the work of such “obstructionists,” or even the work of those whose ideas have later proved to be inadequate. This argument misses the point of history and the lessons which it can teach. Perhaps Goldschmidt did take the time of a number of the classical geneticists who tried to answer his objections to the gene theory; and perhaps many of his own ideas about genes were, by today's view, “wrong.” These are always easier judgments to make by hindsight than at the moment. But that is not the point. Goldschmidt had a considerable influence on his contemporaries, and to dismiss him as an obstructionist because his opponents later proved to be more nearly right, distorts history and obscures significant questions which we might well be asking. It might be valuable to know why Goldschmidt felt compelled to be an iconoclast —and how that impulse, psychological in orgin, led him to overlook critical items of evidence which his opponents considered more carefully. It might also be valuable to try and understand how a contemporary of Goldschmidt or. Morgan really viewed the gene theory — what were its strong and weak point? Such questions are not readily answered by studying the work of only those men who were correct by later standards.Answers to some of the above questions can be gleaned from this study of Goldschmidt — though the first, and most psychologically oriented, question is largely untouched here.On the one hand, Goldschmidt forced classical geneticists to reexamine the foundation of their ideas about the nature, inviolability, and even physical dimensions of genes. He also kept alive the very real problems of gene physiology and its relations to development — a relationship that was given less attention by the Drosophila school in their pursuit of the transmission process. On a broader level he emphasized to the biological community a principle that was in danger of being lost in the enthusiasm surrounding the expansion of the Mendelian-chromosome theory. The point was that all theories in science are transient, logical constructs which should not be held as sacred. Time and again, as the history of science has shown, theories become rigid structures which retard new modes of thought. From Goldschmidt's perspective, the gene theory was in danger of performing just that function, for it was preventing workers from viewing the gene in a functional as well as a structural light.On the other hand, examining the work of critics (or even of outright “obstructionists”) gives the historian an opportunity to observe how the more established community of scholars at some point in time reacts to challenges of its cherished ideas. The fact that many workers in his own day (such as Beadle, Luria, Delbruck, Sturtevant, Bridges, and others), as well as most geneticists today, saw Goldschmidt as having been largely “obstructionist” is useful historical (and/or sociological) data. Clearly, as this paper has tried to show, Goldschmidt's ideas were not all obstructionist, and his viewpoint that genes must be considered functionally was one which was clearly valid, premature as it may have been from an experimental and technique point of view. Perhaps Goldschmidt's major fault was that he developed alternative theories which were not easily testable. Nonetheless, his challenge to a fundamental and established idea brought forth a reaction from many members of the genetic community which indicates how unwilling they were to reconsider the formalized theory on which their work was based. While many of Goldschmidt's criticisms — and particularly his way of making them — arose out of his own idiosyncrasies, they were also a product of his times. His view of the nature of theory-construction, and his rejection of old-style reductionism and mechanism, were part of a growing awareness within the world scientific community that explanations based on reducing complex phenomena to ultimate particles or units were clearly inadequate. The success of the Mendelian-chromosome theory had obscured that fact for many geneticists, but to Goldschmidt it was a point that could not be allowed to pass unnoticed. (shrink)

T. H. Morgan, A. H. Sturtevant, H. J. Muller and C. B. Bridges published their comprehensive treatise "The Mechanism of Mendelian Heredity" in 1915. By 1920 Morgan 's "Chromosome Theory of Heredity" was generally accepted by geneticists in the United States, and by British geneticists by 1925. By 1930 it had been incorporated into most general biology, botany, and zoology textbooks as established knowledge. In this paper, I examine the reasons why it was accepted as part of a (...) series of comparative studies of theory-acceptance in the sciences. In this context it is of interest to look at the persuasiveness of confirmed novel predictions, a factor often regarded by philosophers of science as the most important way to justify a theory. Here it turns out to play a role in the decision of some geneticists to accept the theory, but is generally less important than the CTH's ability to explain Mendelian inheritance, sex-linked inheritance, non-disjunction, and the connection between linkage groups and the number of chromosome pairs; in other words, to establish a firm connection between genetics and cytology. It is remarkable that geneticists were willing to accept the CTH as applicable to all organisms at a time when it had been confirmed only for Drosophila. The construction of maps showing the location on the chromosomes of genes for specific characters was especially convincing for non-geneticists. (shrink)

Bateson's belated acceptance of the chromosome theory came in two main stages, and was permanent, although he retained to the end reservations about some implications and extensions of the theory. Coleman's attempt to explain Bateson's resistance in terms of his conservative mode of thought is critically examined, and rejected: the attributes Coleman assigns to Bateson are all either inappropriate, or irrelevant to chromosome theory, or both. Instead, the diverse factors which contributed to Bateson's resistance are (...) enumerated and discussed. These include deficiencies in the evidence then available to support the theory; embryological difficulties; Bateson's aversion to microscopy combined with the lack of a close colleague skilled in cytology; his iconoclastic temperament, and the fact that he found T. H. Morgan, the leader of the Drosophila school, an uncongenial personality. Taken together, these factors suffice to account for his resistance. Bateson's position is contrasted with that of the other most eminent opponent, W. Johannsen, whose organismic outlook was the main obstacle to acceptance. (shrink)

Laudan's thesis that conceptual problem solving is at least as important as empirical problem solving in scientific research is given support by a study of the relation between the chromosome theory and the Mendelian research program. It will be shown that there existed a conceptual tension between the chromosome theory and the Mendelian program. This tension was to be resolved by changing the constraints of the Mendelian program. The relation between the chromosome theory and (...) the Mendelian program is shown to be a good illustration of the influence of science itself on the rational standards governing scientific development. (shrink)

Throughout the history of genetics, the concept of the gene has been a hot topic. Theories of the gene as a coherent structured particle, a large molecule, or part of such molecule, were prominent from the 1920s until well after the discovery of DNA structure and its function in the production of proteins in the 1950s and 1960s. As knowledge of the material basis of heredity advanced, new and more sophisticated definitions were proposed (see, for example, Gerstein et al. 2007; (...) Müller-Wille and Rheinberger 2012). But rapid growth of knowledge about the molecular basis of biological heredity and individual development during the last half-century has made the idea of a particulate “gene” more and more elusive. Or .. (shrink)

Laudan's thesis that conceptual problem solving is at least as important as empirical problem solving in scientific research is given support by a study of the relation between the chromosome theory and the Mendelian research program. It will be shown that there existed a conceptual tension between the chromosome theory and the Mendelian program. This tension was to be resolved by changing the constraints of the Mendelian program. The relation between the chromosome theory and (...) the Mendelian program is shown to be a good illustration of the influence of science itself on the rational standards governing scientific development. (shrink)

With the assumption of inactivation of small traits in bacteriophages “chromosomes” by ultraviolet irradiation the probability of multiplicity reactivation of irradiated phages is calculated. The result appears to be in agreement with the experimental results ofDulbecco.In the mathematical treatment of the problem a distinction is made between ordinary genes, with probability of inactivation negligible relative to the probability of inactivation of the whole phage, and a few vulnerable centers or genes whose probability of inactivation is not negligible. The hypothesis of (...) the existence of vulnerable centers appears necessary in order to explainDulbecco's experimental results.Postulant que de petites sections des „chromosomes” du bactériophage sont inactivés par l'irradiation ultraviolette, on a calculé la probabilité de réactivation par infection multiple des bactériophages traités par les rayons ultraviolets. Les résultats obtenus s'accordent avec les résultats expérimentaux de M.Dulbecco.Dans la tractation mathématique des problèmes une distinction a été faite entre les gènes ordinaires — dont la probabilité d'inactivation prise individuellement peut Être négligée relativement à la probabilité d'inactivation du phage entier — et quelques centres vulnérables ou gènes dont la probabilité d'inactivation ne pourrait Être négligée.L'hypothèse de l'existance des centres vulnérables s'est démontrée nécessaire à l'explication des résultats expérimentaux de M.Dulbecco.Die Wahrscheinlichkeit der Reaktivation durch multiplen Infektionen ist unter Voraussetzung, dass die Ultraviolett-Bestrahlung kleine Teile der Bakteriophagenchromosomen inaktiviert, berechnet. Das Ergebnis entspricht den experimentellen ResultatenDulbecco's.In der mathematischen Behandlung des Problems ist ein Unterschied gemacht worden zwischen gewöhnlichen Genen — wovon jeder eine geringe Wahrscheinlichkeit der Inaktivierung hat, in Bezug auf die Wahrscheinlichkeit der Inaktivierung der ganzen Bakteriophage — und einige verletzbare Stellen oder Genen, wovon die Wahrscheinlichkeit der Inaktivierung grössenordnungsmÄssig höher liegt. Die Hypothese über die verletzbaren Stellen war notwendig um die experimentellen ResultateDulbecco's zu erklÄren. (shrink)

One claim found in the received historiography of the biometrical school (comprised primarily of Francis Galton, Karl Pearson, and W. F. R. Weldon) is that one of the biometricians' great flaws was their inability to look past their population-focused, statistical, gradualist understanding of evolutionary change – which led, in part, to their ignoring developments in cellular biology around 1900. I will argue, on the contrary, that the work of the biometricians was, from its earliest days, fundamentally concerned with connections between (...) statistical patterns of inheritance and the underlying cellular features that gave rise to them. Such work remained current with contemporary knowledge of chromosomes, cytology, and development; in this article, I explore the first case. The biometricians were thus well positioned to understand the relationship between the patterns of Mendelian inheritance and the statistical distributions with which they primarily occupied themselves. Ignorance of this connection, then, is not the reason why they rejected Mendelism. Further, both Galton and Weldon – though each in their own unique way – decided to turn to biological detail as a way to better justify the generality of their statistical approaches to heredity. Perhaps paradoxically, then, for these biometricians, detail offered an approach to theoretical generality. (shrink)

The view that the initiation of branching into two sympatric species may not require natural selection emerged in Victorian times. In the 1980s paleontologist Stephen Jay Gould gave a theoretical underpinning of this nongenic “chromosomal” view, thus reinstating Richard Goldschmidt’s “heresy” of the 1930s. From modeling studies with computer-generated “biomorphs,” zoologist Richard Dawkins also affirmed Goldschmidt, proclaiming the “evolution of evolvability.” However, in the 1990s, while Gould and Dawkins were recanting, bioinformatic, biochemical, and cytological studies were providing a deeper underpinning. (...) In 2001 this came under attack from leaders in the field who favored Dawkins’ genic emphasis. Now, with growing evidence for the uncoupling of speciation from adaptation, we can reinstate again Goldschmidt’s view and clarify its 19th-century roots. (shrink)

Recent studies have revealed an astonishing diversity of sex chromosomes in many vertebrate lineages, prompting questions about the mechanisms of sex chromosome turnover. While there is considerable population genetic theory about the evolutionary forces promoting sex chromosome replacement, this theory has not yet been integrated with our understanding of the molecular and developmental genetics of sex determination. Here, we review recent data to examine four questions about how the structure of gene networks influences the evolution of (...) sex determination. We argue that patterns of epistasis, arising from the structure of genetic networks, may play an important role in regulating the rates and patterns of sex chromosome replacement. (shrink)

It has become increasingly evident that gene content of the sex chromosomes is markedly different from that of the autosomes. Both sex chromosomes appear enriched for genes related to sexual differentiation and reproduction; but curiously, the human X chromosome also seems to bear a preponderance of genes linked to brain and muscle functions. In this review, we will synthesize several evolutionary theories that may account for this nonrandom assortment of genes on the sex chromosomes, including 1) asexual degeneration, 2) (...) sexual antagonism, 3) constant selection, and 4) hemizygous exposure. Additionally, we will speculate on how the evolution of sex‐chromosome gene content might have impacted on the phenotypic evolution of mammals and particularly humans. Our discussion will focus on the mammalian sex chromosomes, but will cross reference other species where appropriate. BioEssays 26:159–169, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Gradual degradation seems inevitable for non‐recombining sex chromosomes. This has been supported by the observation of degenerated non‐recombining sex chromosomes in a variety of species. The human Y chromosome has also degenerated significantly during its evolution, and theories have been advanced that the Y chromosome could disappear within the next ∼5 million years, if the degeneration rate it has experienced continues. However, recent studies suggest that this is unlikely. Conservative evolutionary forces such as strong purifying selection and intrachromosomal (...) repair through gene conversion balance the degeneration tendency of the Y chromosome and maintain its integrity after an initial period of faster degeneration. We discuss the evidence both for and against the extinction of the Y chromosome. We also discuss potential insights gained on the evolution of sex‐determining chromosomes by studying simpler sex‐determining chromosomal regions of unicellular and multicellular microorganisms. (shrink)

Graphical AbstractOn the Black Swans of conventional sex determination theory: There aren't many, but when an exception to the standard model of sex determination (evolutionary turnover of genes playing the role of “master sex determiner”) arises, it certainly screams out for an explanation. In this issue, a novel one is put forward. It now awaits testing, particularly at the population level.

The human Y chromosome contains very low levels of nucleotide variation. It has been variously hypothesized that this invariance reflects historic reductions in the human male population, a very recent common ancestry, a slow rate of molecular evolution, an inability to evolve adaptively, or frequent selective sweeps acting on genes borne on the Y chromosome. We propose an alternative theory in which human Y chromosome evolution is driven by mutations in the maternally inherited mitochondrial genome, which (...) impair male fertility and ultimately lead to a reduction in the effective population size (Ne) and consequently the variability of the Y chromosome. BioEssays 24:275–279, 2002. © 2002 Wiley Periodicals, Inc.; DOI 10.1002/bies.10062. (shrink)

The chromosome theory of inheritance was established during the three first decades of the 20th century. During the early stage of its substantiating, there were lots of puzzles and little evidence that could validate it. The cytological processes were obscure and several scientists maintained serious doubts concerning the existence of a connection between Mendel’s principles and the behaviour of chromosomes during cell division. It was vital to associate an external, observable characteristic of the organism to a specific (...) class='Hi'>chromosome, and this was achieved when sex was connected to special chromosomes. At that time, however, some important scholars refused to accept or delayed acceptance of the conception that the hereditary factors (later called genes) were physical entities located along the chromosomes. Such was the case of Thomas Morgan (1866-1945) and William Bateson (1861-1926). Their attitudes could be explained by considering the doubtful ground of the hypothesis at that time. It is more difficult, however, to understand the attitude of Edmund Beecher Wilson (1856-1939). Being an expert in cytology he was acquainted with all the difficulties concerning the chromosome hypothesis. Nonetheless, from 1905 onward, he attributed little weight to the problems and dedicated a notable effort to obtaining evidence that could have grounded it. This paper analyses Wilson’s attitude focusing on his studies from 1900 to 1915 and the scientific context of this period. This study led to the conclusion that Wilson’s attitude could be explained in methodological terms by the adoption of an instrumentalist attitude, while Bateson and Morgan adopted a realistic perspective. (shrink)

In the 1990s, the key term used for the most recent discourses on sexuality is queer. Queer theory seeks to disempower its heterosexual opponents by appropriating one of their most insulting terms, just as abstract painters earlier this century reacted to ridicule of their work by calling themselves cubists. This theory challenges the belief that a stable relationship exists between chromosomal sex, social gender and sexual desire.

Historically, the scientific method has been said to require proposing a theory, making a prediction of something not already known, testing the prediction, and giving up the theory (or substantially changing it) if it fails the test. A theory that leads to several successful predictions is more likely to be accepted than one that only explains what is already known but not understood. This process is widely treated as the conventional method of achieving scientific progress, and was (...) used throughout the twentieth century as the standard route to discovery and experimentation. But does science really work this way? In Making 20th Century Science, Stephen G. Brush discusses this question, as it relates to the development of science throughout the last century. Answering this question requires both a philosophically and historically scientific approach, and Brush blends the two in order to take a close look at how scientific methodology has developed. Several cases from the history of modern physical and biological science are examined, including Mendeleev's Periodic Law, Kekule's structure for benzene, the light-quantum hypothesis, quantum mechanics, chromosome theory, and natural selection. In general it is found that theories are accepted for a combination of successful predictions and better explanations of old facts. Making 20th Century Science is a large-scale historical look at the implementation of the scientific method, and how scientific theories come to be accepted. (shrink)

The interrelationships among recent theories on the regulation of gene activity and differentiation in higher organisms are reviewed. Interpretations within these theories of the various components of chromosomes are re-evaluated and a unified conceptual framework of hierarchical genetic control mechanisms in eukaryotes is presented.

La parution récente en français du livre de M. Denton : “Evolution. Une théorie en crise” , qui traite des theories explicatives actuelles de l'évolution, nous amine à rappeler les caracteres généraux des grandes theories biologiques et à présenter une critique sommaire du livre en question.La science West pas une simple accumulation de connaissances. Le scientifique ne doit pas se contenter de decrire et de mesurer des faits. Son but eat d'essayer de les relier et de construire des théories qui (...) tentent de nous faire comprendre le “reel”, objet de ses recherches.Cependant, la nature du matériel biologique — c'est-à-dire les espèces vivantes et les catégories qu'on y a reconnues, classe ou ordre par exemple — est si complexe qua la biologie actuelle est fort loin encore Wavoir réalisé une synthèse qui ressemble, méme très approximativement, à la classification de Mendéleiev pour les éléments chimiques.Malgré cette complexité, les biologques ont réussi à construire la th6orie du fait de l'evolution et ils proposent aujourd'hui une théorie explicative de cette évolution qui, bien qua critiquée, est incontestablement bien étayee. Nous allons essayer de définir la structure des grandes théories biologiques; ensuite nous analyserons sommairement quelques-unes des critiques qui sont adressees aux theories de l'évolution.Considering the publication in French version of Michael Denton's book, Evolution : A Theory in crisis , in which he critizes the synthetical theory of the biological evolution, we thought it useful to point out the main errors of argumentation contained in that book by first referring to the characteristics of general biological theories.In biology, there exist elementary theories - such as that dealing with the extinction of giant Reptiles - and general theories - such as the chromosomic theory of heredity and the explanatory theory of evolution. The latter generally consist of a group of elementary theories imbricated so that they form a whole like a jig-saw puzzle. An example is provided by the synthetic theory of evolution that can be defined in 20 propositions divided into two categories : the propositions relating to the naturalists' observations - which correspond to descriptive concepts - and those relating to the data of the population genetics - which correspond to explanatory concepts . The general scheme of the theory is formed by a network of relations between the descriptive concepts and the explanatory concepts. There also exist other theories in general biology supported by thousands of minor facts which only together can be of proof of validity. These theories are quite reliable and cannot be questioned by facts still to be explained. Questioning can only happen if they are confronted to well-established data in nearly equal numbers.In his work, Denton does not deny the phenomenon of biological evolution, but he criticizes the syntheticians' ideas by emphasizing that no great evolutive changes can be accounted for by the complex mechanism of random mutations and selection. He goes back to a typological concept of the zoological classification in some way similar to that of Vialleton's. However, Denton agrees with the phenomenon of the biological evolution and accepts the existence of "saltations" among the great zoological groups. The arguments used by Denton merely show that he is not conversant with the complexity of sciences particularly in comparative anatomy and zoology, the teaching of which is being somehow neglected today.By giving as an example the structure of the aortic arches in Amphibians and by a summary of the variations of those structures and the evolution of the blood-circulation in Vertebrates, we proved that the typological argument is of no value. As a matter of fact, a study of the now living beings clearly shows the gradual transition - e.g. a transition by a very large number of feasible stages - from the Lower Vertebrates to the Higher Vertebrates. In particular, there have been several attempts at double circulation and there still exist many species in which the blood of the double circulation is mixed. It seems therefore obvious that the double circulation has been achieved, stage by stage, with many intermediate schemes; we are inclined, therefore, to conclude that this succession of small transformations was produced by a huge mechanism of selected small mutations.Our present-day biological knowledge includes a number of examples large enough to consider the “argument of the impossible” used by Denton is due to inadequate fossil data and not to any mysterious mechanism such as macromutations. Let us say again that the typological structures seem to occur only when the data of comparative anatomy and zoology are over-simplified. (shrink)

At the turn of the twentieth century, biologists such as Oscar Riddle, Thomas Hunt Morgan, Frank Lillie, and Richard Goldschmidt all puzzled over the question of sexual difference, the distinction between male and female. They all offered competing explanations for the biological cause of this difference, and engaged in a fierce debate over the primacy of their respective theories. Riddle propounded a metabolic theory of sex dating from the late-nineteenth century suggesting that metabolism lay at the heart of sexual (...) difference. Thomas Hunt Morgan insisted on the priority of chromosomes, Frank Lillie emphasized the importance of hormones, while Richard Goldschmidt supported a mixed model involving both chromosomes and hormones. In this paper, I will illustrate how the older metabolic theory of sex was displaced when those who argued for the relatively newer theories of chromosomes and hormones gradually formed an alliance that accommodated each other and excluded the metabolic theory of sex. By doing so, proponents of chromosomes and hormones established their authority over the question of sexual difference as they laid the foundations for the new disciplines of genetics and endocrinology. Their debate raised urgent questions about what constituted sexual difference, and how scientists envisioned the plasticity and controllability of this difference. These theories also had immediate political and cultural consequences at the turn of the twentieth century, especially for the eugenic and feminist movements, both of which were heavily invested in knowledge of sex and its determination, ascertainment, and command. (shrink)

According to the somatic mutation theory (SMT), cancer begins with a genetic change in a single cell that passes it on to its progeny, thereby generating a clone of malignant cells. It is strongly supported by observations of leukemias that bear specific chromosome translocations, such as Burkitt's lymphoma, in which a translocation activates the c‐myc gene, and chronic myeloid leukemia (CML), in which the Philadelphia chromosome causes production of the BCR‐ABL oncoprotein. Although the SMT has been modified (...) and extended to encompass tumor suppressor genes, epigenetic inheritance, and tumor progression through accumulation of further mutations, perhaps the strongest validation comes from the successful treatment of certain malignancies with drugs that directly target the product of the mutant gene.magnified imageDavid Vaux is at the Walter and Eliza Hall Institute and La Trobe Institute for Molecular Science, Melbourne, Australia. (shrink)

The extreme length of chromosomal DNA requires organizing mechanisms to both promote functional genetic interactions and ensure faithful chromosome segregation when cells divide. Microscopy and genome‐wide contact frequency analyses indicate that intra‐chromosomal looping of DNA is a primary pathway of chromosomal organization during all stages of the cell cycle. DNA loop extrusion has emerged as a unifying model for how chromosome loops are formed in cis in different genomic contexts and cell cycle stages. The highly conserved family of (...) SMC complexes have been found to be required for DNA cis‐looping and have been suggested to be the enzymatic core of loop extruding machines. Here, the current body of evidence available for the in vivo and in vitro action of SMC complexes is discussed and compared to the predictions made by the loop extrusion model. How SMC complexes may differentially act on chromatin to generate DNA loops and how they could work to generate the dynamic and functionally appropriate organization of DNA in cells is explored. -/- . (shrink)

A generalization of Ehrenfest''s urn model is suggested. This will allow usto treat a wide class of stochastic processes describing the changes ofmicroscopic objects. These processes are homogeneous Markov chains. Thegeneralization proposed is presented as an abstract conditional (relative)probability theory. The probability axioms of such a theory and some simpleadditional conditions, yield both transition probabilities and equilibriumdistributions. The resulting theory interpreted in terms of particles andsingle-particle states, leads to the usual formulae of quantum and classicalstatistical mechanics; in (...) terms of chromosomes and allelic types, it allowsthe deduction of many genetical models including the Ewens sampling formula;in terms of agents'' strategies, it gives a justification of the ``herdbehaviour'''' typical of a population of heterogeneous economic agents. (shrink)

This chapter highlights Carl Woese’s message about cellular complexity. It addresses the phenotypic distance between a putative, hypothetical ur-replicator or ur-chromosome and anything that can function as a cell that can effectively respond to its environment in ways that maintain its metabolic and physiological integrity. It describes what self-preserving and self-extending behavior in a chemical system minimally involves. This chapter shows that The Major Transitions in Evolution assumes that the emergence of a replicating molecular complex coincides with the emergence (...) of structures with self-preserving characteristics. It then speculates a reason why the “missing transition” has not been missed. (shrink)

Genetics was established on a strict particulate conception of heredity. Genetic linkage, the deviation from independent segregation of Mendelian factors, was conceived as a function of the material allocation of the factors to the chromosomes, rather than to the multiple effects (pleiotropy) of discrete factors. Although linkage maps were abstractions they provided strong support for the chromosomal theory of inheritance. Direct Cytogenetic evidence was scarce until X-ray induced major chromosomal rearrangements allowed direct correlation of genetic and cytological rearrangements. Only (...) with the discovery of the polytenic giant chromosomes in Drosophila larvae in the 1930s were the virtual maps backed up by physical maps of the genetic loci. Genetic linkage became a pivotal experimental tool for the examination of the integration of genetic functions in development and in evolution. Genetic mapping has remained a hallmark of genetic analysis. The location of genes in DNA is a modern extension of the notion of genetic linkage. (shrink)

"An important contribution to contemporary jurisprudential debate and to legal thought more generally, Just Interpretations is far ahead of currently available work."--Peter Goodrich, author of Oedipus Lex "I was struck repeatedly by the clarity of expression throughout the book. Rosenfeld's description and criticism of the recent work of leading thinkers distinguishes his work within the legal theory genre. Furthermore, his own theory is quite original and provocative."--Aviam Soifer, author of Law and the Company We Keep.

ABSTRACT A rereading of the American scientific literature on sex determination from 1902 to 1926 leads to a different understanding of the construction of the Mendelian‐chromosome theory after 1910. There was significant intellectual continuity, which has not been properly appreciated, underlying this scientific “revolution.” After reexamining the relationship between the ideas of key scientists, in particular Edmund B. Wilson and Thomas Hunt Morgan, I argue that, contrary to the historical literature, Wilson and Morgan did not adopt opposing views (...) on Mendelism and sex determination. Rather, each preferred a non‐Mendelian explanation of the determination of sex. Around 1910, both integrated the Mendelian and non‐Mendelian theories to create a synthetic theory. One problem was the need to avoid an overly deterministic view of sex while also accepting the validity of Mendelism. Morgan’s discovery of mutations on the X chromosome takes on different significance when set in the context of the debate about sex determination, and Calvin Bridges’s work on sex determination is better seen as a development of Morgan’s ideas, rather than a departure from them. Conclusions point to the role of synthesis within fields as a way to advance scientific theories and reflect on the relationship between synthesis and explanatory “pluralism” in biology. (shrink)