The history of biochemistry and molecular biology is replete with examples of erroneous theories that persisted for considerable lengths of time before they were rejected. This paper examines patterns of dissolution of three such erroneous hypotheses: The idea that nucleic acids are tetrads of the four nucleobases (‘the tetranucleotide hypothesis’); the notion that proteins are collinear with their encoding genes in all branches of life; and the hypothesis that proteins are synthesized by reverse action of proteolytic enzymes. Analysis of these (...) cases indicates that amassed contradictory empirical findings did not prompt critical experimental testing of the prevailing theories nor did they elicit alternative hypotheses. Rather, the incorrect models collapsed when experiments that were not purposely designed to test their validity exposed new facts. (shrink)

Research ethics education in the biosciences has not historically been a priority for research universities despite the fact that funding agencies, government regulators, and the parties involved in the research enterprise agree that it ought to be. The confluence of a number of factors, including scrutiny and regulation due to increased public awareness of the impact of basic research on society, increased public and private funding, increased diversity and collaboration among researchers, the impressive success and speed of research advances, and (...) high-profile cases of misconduct, have made it necessary to reexamine how the bioscience research community at all levels provides ethics education to its own. We discuss the need to and reasons for making ethics integral to the education of bioscientists, approaches to achieving this goal, challenges this goal presents, and responses to those challenges. (shrink)

The concept of mechanism is analyzed in terms of entities and activities, organized such that they are productive of regular changes. Examples show how mechanisms work in neurobiology and molecular biology. Thinking in terms of mechanisms provides a new framework for addressing many traditional philosophical issues: causality, laws, explanation, reduction, and scientific change.

Scientific research is constrained by limited resources, so it is imperative that it be conducted efficiently. This paper introduces the notion of epistemic expression, a kind of representation that expedites the solution of research problems. Epistemic expressions are representations that (i) contain information in a way that enables more reliable information to place the most stringent constraints on possible solutions and (ii) make new information readily extractible by biasing the search through that space. I illustrate these conditions using historical and (...) contemporary examples of biomolecular structure determination. Then, I argue that the notion of epistemic expression parts ways with pragmatic accounts of scientific representation and an understanding of models as artifacts, neither of which require models to accurately represent. Explicating epistemic expression thus fills a gap in our understanding of scientific practice, extending Morrison and Morgan's (1999) conception of models as investigative instruments. (shrink)

Historically, hypotheses failed in most cases to correctly forecast the workings of complex biological systems. Francis Crick’s adaptor hypothesis, however, stands out as an exceptional case of a confirmed abstract prediction. This hypothesis presciently anticipated the existence of RNA adaptors that function as bridges between amino acids and the chemically different nucleic acid template for proteins. Crick conjectured that the adaptors are enzymatically charged with cognate amino acids, they bind to complementary protein-coding nucleic acid, and their liberated amino acids are (...) incorporated into growing protein chains. Independently from and concomitantly with Crick’s hypothesis, Mahlon Hoagland and Paul Zamecnik conducted experiments with no guiding theory that culminated in discoveries of the actual adaptors, transfer RNA (tRNA) molecules, and their amino acids charging enzymes. This paper traces the parallel histories of Crick’s adaptor hypothesis and of the experimental discovery of tRNA and compares their relative impacts on the scientific community. Remarkably, despite the brilliance of Crick’s confirmed prognostication, it had marginal impact on practicing scientists. Conversely, Hoagland and Zamecnik’s experimental discoveries and their evidence-based model of protein synthesis had immediate and enduring impact. I discuss possible explanations for the different impacts of the theoretical prediction and experimental identifications of the same entities. (shrink)

In this paper I shall defend the idea that there is an abstract and general core meaning of objectivity, and what is seen as a variety of concepts or conceptions of objectivity are in fact criteria of, or means to achieve, objectivity. I shall then discuss the ideal of value-free science and its relation to the objectivity of science; its status can be at best a criterion of, or means for, objectivity. Given this analysis, we can then turn to the (...) problem of inductive risk. Do the value judgements regarding inductive risk really pose a threat to the objectivity of science? I claim that this is not the case because they do not lower the thresholds scientifically postulated for objectivity. I shall conclude the paper with a discussion of under-appreciated influences of values on science, which indeed pose a serious threat to the objectivity of some scientific disciplines. (shrink)

Genes and messages have a long association in biology, dating back at least to Weismann. But, through most of this history, even with the dramatic concreteness that molecular biology lent to this association, the image dominating most thinking about messages was drawn from the nineteenth-century technology of the telegraph. In the mid-twentieth century, a new technology, the computer, arrived to displace the telegraph. With that displacement, the meanings of many terms—of “message,” “information,” “organization,” indeed, “organism” —have, over the past few (...) decades, all been transformed. In this article, I explore the computer’s impact on biological representation of the organism in two disciplines: molecular biology and developmental biology. (shrink)

What kinds of norms constrain mechanistic discovery and explanation? In the mechanistic literature, the norms for good explanations are directly derived from answers to the metaphysical question of what explanations are. Prominent mechanistic accounts thus emphasize either ontic or epistemic norms. Still, mechanistic philosophers on both sides agree that there is no sharp distinction between the processes of discovery and explanation. Thus, it seems reasonable to expect that ontic and epistemic accounts of explanation will be accompanied by ontic and epistemic (...) accounts of discovery, respectively. As we will show here, however, recent discovery accounts implicitly rely on both ontic and epistemic norms to characterize the discovery process. In this paper, we develop an account that makes explicit that, and how, ontic and epistemic norms work together throughout the discovery process. By describing mechanism discovery as a process of pattern recognition we demonstrate that scientists have to develop epistemic activities to distinguish a pattern from its background. Furthermore, they have to determine which epistemic activities successfully describe how the pattern is implemented by identifying the pattern’s components. Our approach reveals that ontic and epistemic norms are equally important in mechanism discovery. (shrink)

Diauxie is at the origin of research that led Jacques Monod, François Jacob, and André Lwoff to win the Nobel Prize in Physiology or Medicine in 1965 for their description of the first genetic regulatory model. Diauxie is a term coined by Jacques Monod in 1941 in his doctoral dissertation that refers to microbial growth in two phases. In this article, we first examine Monod’s thesis to demonstrate how and why Monod interpreted diauxie as a phenomenon of enzyme inhibition or (...) suppression of adaptive enzymes. We also briefly investigate prior enzyme suppression studies, before Monod’s work, which indicate that he is the first person to observe diauxic growth. Second, we analyse Monod’s post-thesis publications throughout his scientific career, revealing that diauxic inhibition was a significant part of Monod’s scientific activities and greatly fascinated Monod until the end of his life. Paradoxically, Monod’s work and interest on diauxic inhibition are still neglected in historical recounts, focused mostly on Monod’s enzymatic adaptation studies. Indeed, we uncovered a statement by Monod’s colleague, Lwoff, who transformed a quotation from Monod by replacing the word phenomenon with enzymatic adaptation, which we believe has influenced historians. Finally, we offer hypotheses to explain why Lwoff altered Monod’s statement. (shrink)

In this review, we describe some of the central philosophical issues facing origins-of-life research and provide a targeted history of the developments that have led to the multidisciplinary field of origins-of-life studies. We outline these issues and developments to guide researchers and students from all fields. With respect to philosophy, we provide brief summaries of debates with respect to (1) definitions (or theories) of life, what life is and how research should be conducted in the absence of an accepted theory (...) of life, (2) the distinctions between synthetic, historical, and universal projects in origins-of-life studies, issues with strategies for inferring the origins of life, such as (3) the nature of the first living entities (the “bottom up” approach) and (4) how to infer the nature of the last universal common ancestor (the “top down” approach), and (5) the status of origins of life as a science. Each of these debates influences the others. Although there are clusters of researchers that agree on some answers to these issues, each of these debates is still open. With respect to history, we outline several independent paths that have led to some of the approaches now prevalent in origins-of-life studies. These include one path from early views of life through the scientific revolutions brought about by Linnaeus (von Linn.), Wöhler, Miller, and others. In this approach, new theories, tools, and evidence guide new thoughts about the nature of life and its origin.We also describe another family of paths motivated by a” circularity” approach to life, which is guided by such thinkers as Maturana & Varela, Gánti, Rosen, and others. These views echo ideas developed by Kant and Aristotle, though they do so using modern science in ways that produce exciting avenues of investigation. By exploring the history of these ideas, we can see how many of the issues that currently interest us have been guided by the contexts in which the ideas were developed. The disciplinary backgrounds of each of these scholars has influenced the questions they sought to answer, the experiments they envisioned, and the kinds of data they collected. We conclude by encouraging scientists and scholars in the humanities and social sciences to explore ways in which they can interact to provide a deeper understanding of the conceptual assumptions, structure, and history of origins-of-life research. This may be useful to help frame future research agendas and bring awareness to the multifaceted issues facing this challenging scientific question. (shrink)

This article analyzes a number of recently published autobiographies by leading participants in the Human Genome Project (HGP), in order to determine to what extent they may further our understanding of the history, scientific significance and societal impact of this major research endeavor. Notably, I will focus on three publications that fall under this heading, namely The common thread by John Sulston (2002/2003), The language of God (2006) by Francis Collins and A life decoded by Craig Venter (2007).1 What may (...) we learn from these autobiographical sources about the dynamics of scientific change? What is their added value in understanding science in general and the HGP in particular? These questions will be elaborated in three directions: on the level of knowledge (epistemology), power (politics) and the Self (ethics). On the epistemological level, genomics is often presented as a paradigm shift in the life sciences, a tremendous up-scaling of research, an “informatization” of life. Autobiographies may reveal how this shift – usually discussed in more general terms from a philosophy of science or science studies perspective – manifests itself on an individual scale, on a micro- epistemological level. On the political level, autobiographies may inform us about the micro-politics of scientific change. Finally, on the level of Self, autobiographies may allow us to analyze how researchers, through practices of Self, are actively engaged in constituting themselves as responsible subjects in the face of unpredictable dynamics and unforeseen dilemmas. (shrink)

Historians tend to speak of the problem of the origin of species or the species question, as if it were a monolithic problem. In reality, the phrase refers to a, historically, surprisingly fluid and pluriform scientific issue. It has, in the course of the past five centuries, been used in no less than ten different ways or contexts. A clear taxonomy of these separate problems is useful or relevant in two ways. It certainly helps to disentangle confusions that have inevitably (...) emerged in the literature in its absence. It may, secondly, also help us to gain a more thorough understanding, or sharper view, of the history of evolutionary thought. A consequent problem-centric look at that history through the lens of various origin of species problems certainly yields intriguing results, including and particularly for our understanding of the genesis of the Wallace–Darwin theory of evolution through natural selection. (shrink)

This paper explores multiple experimental interventions in molecular biology. By “multiple,” we mean that molecular biologists often use different modes of experimental interventions in a series of experiments for one and the same subject. In performing such a series of experiment, scientists may use different modes of interventions to realize plural goals such as testing given hypotheses and exploring novel phenomena. In order to illustrate this claim, we develop a framework of multiple modes of experimental interventions to analyze a series (...) of experiments for a single subject. Our argument begins with a brief characterization of Craver and Darden’s taxonomy of experiments, because the taxonomy they have made implies various modes of interventions. We propose to extract two interventional directions and two interventional effects from their taxonomy as the basis of classification. The vertical or inter-level direction means that an intervention is performed between different levels of organization and the horizontal or inter-stage direction means that an intervention is performed between different stages of a mechanism. Interventions may produce an excitatory or an inhibitory effect. As a consequence, we can classify modes of interventions according to different directions and effects. We illustrate our claims by doing a case study of the PaJaMo experiment, which is a series of experiments for a single subject. The final goal in this paper is to provide a taxonomy of characteristics of experimentation in which the PaJaMo experiment is adequately located. (shrink)

Scientific hypotheses may either predict particular unknown facts or accommodate previously-known data. Although affirmed predictions are intuitively more rewarding than accommodations of established facts, opinions divide whether predictive hypotheses are also epistemically superior to accommodation hypotheses. This paper examines the contribution of predictive hypotheses to discoveries of several bio-molecular systems. Having all the necessary elements of the system known beforehand, an abstract predictive hypothesis of semiconservative mode of DNA replication was successfully affirmed. However, in defining the genetic code whose biochemical (...) basis was unclear, hypotheses were only partially effective and supplementary experimentation was required for its conclusive definition. Markedly, hypotheses were entirely inept in predicting workings of complex systems that included unknown elements. Thus, hypotheses did not predict the existence and function of mRNA, the multiple unidentified components of the protein biosynthesis machinery, or the manifold unknown constituents of the ubiquitin–proteasome system of protein breakdown. Consequently, because of their inability to envision unknown entities, predictive hypotheses did not contribute to the elucidation of cation theories remained the sole instrument to explain complex bio-molecular systems, the philosophical question of alleged advantage of predictive over accommodative hypotheses became inconsequential. (shrink)

In 2003, biophysicist and Nobel Laureate Maurice Wilkins published his autobiography entitled The Third Man. In the preface, he diffidently points out that the title was chosen by his publisher, as a reference to the famous 1949 movie no doubt, featuring Orson Welles in his classical role as penicillin racketeer Harry Lime. In this paper I intend to show that there is much more to this title than merely its familiar ring. If subjected to a comparative analysis, multiple correspondences between (...) movie and memoirs can be brought to the fore. Taken together, these documents shed an intriguing light on the vicissitudes of budding life sciences research during the post-war era. I will focus my comparative analysis on issues still relevant today, such as dual use, the handling of sensitive scientific information and, finally, on the interwovenness of science and warfare. Thus, I will explain how science autobiographies on the one hand and genres of the imagination on the other may deepen our comprehension of tensions and dilemmas of life sciences research then and now. For that reason, science autobiographies can provide valuable input for teaching philosophy and history of science to science students. (shrink)

Since the 1930s, scientists studying the neurological disease scrapie had assumed that the infectious agent was a virus. By the mid 1960s, however, several unconventional properties had arisen that were difficult to reconcile with the standard viral model. Evidence for nucleic acid within the pathogen was lacking, and some researchers considered the possibility that the infectious agent consisted solely of protein. In 1982, Stanley Prusiner coined the term `prion' to emphasize the agent's proteinaceous nature. This infectious protein hypothesis was denounced (...) by many scientists as `heretical'.This two-part essay asks why the concept of an infectious protein was considered controversial. Some biologists justified their evaluation of this hypothesis on the grounds that an infectious protein contradicted the `central dogma of molecular biology'. Others referred to vague theoretical constraints such as molecular biology's `theoretical structure' or `framework'. Examination of the objections raised by researchers reveals exactly what generalizations were being challenged by a protein model of infection.This two-part survey of scrapie and prion research reaches several conclusions: A theoretical framework is present in molecular biology, exerting its influence in hypothesis formation and evaluation; This framework consists of several related, yet separable, generalizations or `elements', including Francis Crick's Central Dogma and Sequence Hypothesis, plus notions concerning infection, replication, protein synthesis, and protein folding; The term `central dogma' has stretched beyond Crick's original 1958 definition to encompass at least two other `framework elements': replication and protein synthesis; and From the study of scrapie and related diseases, biological information has been delineated into at least two classes: sequential and what I call `conformational'.In Part I of this essay, a brief review of the central dogma was given, and the developments in scrapie research from 1965 to 1972 were traced. This section summarized many of the puzzling, non-virus-like properties of the scrapie agent. Alternative hypotheses to the viral explanation were presented, including early versions of a protein-only hypothesis. Part II of this essay will follow the developments in scrapie and prion research from the mid-1970s through 1991. The growing prominence of a protein-only model of infection will be countered by continued objections from many researchers to a pathogen devoid of nucleic acid. These objections will help illuminate those generalizations in molecular biology that were indeed challenged by a protein-only model of infection. (shrink)

Unlike in physics, the category of thought experiment is not very common in biology. At least there are no classic examples that are as important and as well-known as the most famous thought experiments in physics, such as Galileo’s, Maxwell’s or Einstein’s. The reasons for this are far from obvious; maybe it has to do with the fact that modern biology for the most part sees itself as a thoroughly empirical discipline that engages either in real natural history or in (...) experimenting on real organisms rather than fictive ones. While theoretical biology does exist and is recognized as part of biology, its role within biology appears to be more marginal than the role of theoretical physics within physics. It could be that this marginality of theory also affects thought experiments as sources of theoretical knowledge. Of course, none of this provides a sufficient reason for thinking that thought experiments are really unimportant in biology. It is quite possible that the common perception of this matter is wrong and that there are important theoretical considerations in biology, past or present, that deserve the title of thought experiment just as much as the standard examples from physics. Some such considerations may even be widely known and considered to be important, but were not recognized as thought experiments. In fact, as we shall see, there are reasons for thinking that what is arguably the single most important biological work ever, Charles Darwin’s On the Origin of Species, contains a number of thought experiments. There are also more recent examples both in evolutionary and non-evolutionary biology, as we will show. Part of the problem in identifying positive examples in the history of biology is the lack of agreement as to what exactly a thought experiment is. Even worse, there may not be more than a family resemblance that unifies this epistemic category. We take it that classical thought experiments show the following characteristics: They serve directly or indirectly in the non-empirical epistemic evaluation of theoretical propositions, explanations or hypotheses. Thought experiments somehow appeal to the imagination. They involve hypothetical scenarios, which may or may not be fictive. In other words, thought experiments suppose that certain states of affairs hold and then try to intuit what would happen in a world where these suppositions are true. We want to examine in the following sections if there are episodes in the history of biology that satisfy these criteria. As we will show, there are a few episodes that might satisfy all three of these criteria, and many more if the imagination criterion is dropped or understood in a lose sense. In any case, this criterion is somewhat vague in the first place, unless a specific account of the imagination is presupposed. There will also be issues as to what exactly “non-empirical” means. In general, for the sake of discussion we propose to understand the term “thought experiment” here in a broad rather than a narrow sense here. We would rather be guilty of having too wide a conception of thought experiment than of missing a whole range of really interesting examples. (shrink)

Since the 1930s, scientists studying the neurological disease scrapie had assumed that the infectious agent was a virus. By the mid 1960s, however, several unconventional properties had arisen that were difficult to reconcile with the standard viral model. Evidence for nucleic acid within the pathogen was lacking, and some researchers considered the possibility that the infectious agent consisted solely of protein. In 1982, Stanley Prusiner coined the term `prion' to emphasize the agent's proteinaceous nature. This infectious protein hypothesis was denounced (...) by many scientists as `heretical'.This two-part essay asks why the concept of an infectious protein was considered controversial. Some biologists justified their evaluation of this hypothesis on the grounds that an infectious protein contradicted the `central dogma of molecular biology'. Others referred to vague theoretical constraints such as molecular biology's `theoretical structure' or `framework'. Examination of the objections raised by researchers reveals exactly what generalizations were being challenged by a protein model of infection.This two-part survey of scrapie and prion research reaches several conclusions: A theoretical framework is present in molecular biology, exerting its influence in hypothesis formation and evaluation; This framework consists of several related, yet separable, generalizations or `elements', including Francis Crick's Central Dogma and Sequence Hypothesis, plus notions concerning infection, replication, protein synthesis, and protein folding; The term `central dogma' has stretched beyond Crick's original 1958 definition to encompass at least two other `framework elements': replication and protein synthesis; and From the study of scrapie and related diseases, biological information has been delineated into at least two classes: sequential and what I call `conformational'.In Part I of this essay, a brief review of the central dogma was given, and the developments in scrapie research from 1965 to 1972 were traced. This section summarized many of the puzzling, non-virus-like properties of the scrapie agent. Alternative hypotheses to the viral explanation were presented, including early versions of a protein-only hypothesis. Part II of this essay will follow the developments in scrapie and prion research from the mid-1970s through 1991. The growing prominence of a protein-only model of infection will be countered by continued objections from many researchers to a pathogen devoid of nucleic acid. These objections will help illuminate those generalizations in molecular biology that were indeed challenged by a protein-only model of infection. (shrink)

In the 1950s and 1960s, an interfield interaction between molecular biologists and biochemists integrated important discoveries about the mechanism of protein synthesis. This extended discovery episode reveals two general reasoning strategies for eliminating gaps in descriptions of the productive continuity of mechanisms: schema instantiation and forward chaining/backtracking. Schema instantiation involves filling roles in an overall framework for the mechanism. Forward chaining and backtracking eliminate gaps using knowledge about types of entities and their activities. Attention to mechanisms highlights salient features of (...) this historical episode while providing general reasoning strategies for mechanism discovery. (shrink)

Philosophers of science turned to historical case studies in part in response to Thomas Kuhn's insistence that such studies can transform the philosophy of science. In this issue Joseph Pitt argues that the power of case studies to instruct us about scientific methodology and epistemology depends on prior philosophical commitments, without which case studies are not philosophically useful. Here I reply to Pitt, demonstrating that case studies, properly deployed, illustrate styles of scientific work and modes of argumentation that are not (...) well handled by currently standard philosophical analyses. I illustrate these claims with exemplary findings from case studies dealing with exploratory experimentation and with interdisciplinary cooperation across sciences to yield multiple independent means of access to theoretical entities. The latter cases provide examples of ways that scientists support claims about theoretical entities that are not available in work performed within a single discipline. They also illustrate means of correcting systematic biases that stem from the commitments of each discipline taken separately. These findings illustrate the transformative power of case study methods, allow us to escape from the horns of Pitt's "dilemma of case studies," and vindicate some of the post-Kuhn uses to which case studies have been put. (shrink)

The ArgumentThis paper focuses on the opening of a discursive space: the emergence of informational and scriptural representations of life and their self-negating consequences for the construction of biological meaning. It probes the notion of writing and the book of life and shows how molecular biology's claims to a status of language and texuality undermines its own objective of control. These textual significations were historically contingent. The informational representations of heredity and life were not an outcome of the internal cognitive (...) momentum of molecular biology; they were not a logical necessity of the unravelling of the base-pairing of the DNA double-helix. They were transported into molecular biology still within the protein paradigm of the gene in the 1940s and permeated nearly every discipline in the life and social sciences. These information-based models, metaphors, linguistic, and semiotic tools which were central to the formulation of the genetic code were transported into molecular biology from cybernetics, information theory, electronic computing, and control and communication systems — technosciences that were deeply embedded with the military experiences of world war II and the Cold War. The information discourse thus became fixed in molecular biology not because it worked in the narrow epistemic sense (it did not), but because it positioned molecular biology within postwar discourse and culture, perhaps within the transition to a post-modern information-based society. (shrink)

The Pajama (Pardee, Jacob, Monod) experiment provided a breakthrough in our understanding of the molecular mechanisms by which gene expression is regulated. Today, twenty‐five years later it provides a paradigm for thinking about problems of gene expression, such as growth regulation and differentiation. From this experiment emerged entities such as repressors, regulatory genes, the operon as a group of jointly controlled genes, and messenger RNA.

The thesis of theory-ladenness of observations, in its various guises, is widely considered as either ill-conceived or harmless to the rationality of science. The latter view rests partly on the work of the proponents of New Experimentalism who have argued, among other things, that experimental practices are efficient in guarding against any epistemological threat posed by theory-ladenness. In this paper I show that one can generate a thesis of theory-ladenness for experimental practices from an influential New Experimentalist account. The notion (...) I introduce for this purpose is the concept of ‘theory-driven data reliability judgments’, according to which theories which are sought to be tested with a particular set of data guide reliability judgments about those very same data. I provide various prominent historical examples to show that TDRs are used by scientists to resolve data conflicts. I argue that the rationality of the practices which employ TDRs can be saved if the independent support of the theories driving TDRs is construed in a particular way. (shrink)

A central idea of developmental systems theory is ‘parity’ or ‘symmetry’ between genes and non-genetic factors of development. The precise content of this idea remains controversial, with different authors stressing different aspects and little explicit comparisons among the various interpretations. Here I characterise and assess several influential versions of parity.

The chemical characterization of the substance responsible for the phenomenon of “transformation” of pneumococci was presented in the now famous 1944 paper by Avery, MacLeod, and McCarty. Reception of this work was mixed. Although interpreting their results as evidence that deoxyribonucleic acid (DNA) is the molecule responsible for genetic changes was, at the time, controversial, this paper has been retrospectively celebrated as providing such evidence. The mixed and changing assessment of the evidence presented in the paper was due to the (...) work’s interpretive flexibility – the evidence was interpreted in various ways, and such interpretations were justified given the neophytic state of molecular biology and methodological limitations of Avery’s transformation studies. I argue that the changing context in which the evidence presented by Avery’s group was interpreted partly explains the vicissitudes of the assessments of the evidence. Two less compelling explanations of the reception are a myth-making account and an appeal to the wartime historical context of its publication. (shrink)

Cells are cognitive entities possessing great computational power. DNA serves as a multivalent information storage medium for these computations at various time scales. Information is stored in sequences, epigenetic modifications, and rapidly changing nucleoprotein complexes. Because DNA must operate through complexes formed with other molecules in the cell, genome functions are inherently interactive and involve two-way communication with various cellular compartments. Both coding sequences and repetitive sequences contribute to the hierarchical systemic organization of the genome. By virtue of nucleoprotein complexes, (...) epigenetic modifications, and natural genetic engineering activities, the genome can serve as a read-write storage system. An interactive informatic conceptualization of the genome allows us to understand the functional importance of DNA that does not code for protein or RNA structure, clarifies the essential multidirectional and systemic nature of genomic information transfer, and emphasizes the need to investigate how cellular computation operates in reproduction and evolution. (shrink)

An interdisciplinary fusion between the philosophy of science and the teaching of science can help to eradicate the disciplinary rigidity entrenched in both. In this paper I approach the history of sciencethematically, identifying general themes which transcend the boundaries of individual disciplines. Such conceptual themes can be used as a basis for an interdisciplinary introduction to university science, encouraging certain important cognitive skills not exercised during the disciplinary training emphasised in traditional approaches. Courses which teach themes such as conservation, randomness, (...) and holism/reductionism have already proved successful, and these innovations should encourage philosophers and historians to explore the exciting new possibilities which arise from stepping outside the confines of a single discipline. (shrink)

A major theme in biological research is the quest for mechanism, embodied in explanatory reductionism: the interpretation of phenomena through links to the entities and laws of more fundamental sciences. For example, the form of Starling's Law of the Heart, relating contractile force to heart volume, follows from the sliding-filament hypothesis of muscle contraction, a molecular concept. Although alternative mechanisms for muscle contraction and cardiac regulation could be deduced from biochemical principles, the formulation provides clear correspondence with the phenomena and (...) a deeper understanding of cardiac function. Moreover, even if the reduction provides no better formulation of the phenomenon, of the macro-regularity, it is still prized as a nearer approach to physical reality, as a step toward realizing fundamental unities and codifying general principles, and as a door to new experimental opportunities. (shrink)

Barbara McClintock (1902–1992), the renowned American maize geneticist, received the 1983 Nobel Prize “for her discovery of mobile genetic elements,” becoming the seventh woman scientist to receive a Nobel Prize. However, Nathaniel Comfort points out that McClintock viewed her primary contribution as the elucidation of control systems, rather than the discovery of mobile elements. McClintock’s interest in control systems dates back to the 1940s, and this paper investigates her 1961 conversation with François Jacob and Jacques Monod, where she sought to (...) shape the interpretation of her work by drawing parallels between maize control systems and a bacterial system they had recently discovered. Despite McClintock’s efforts, Jacob and Monod rejected her parallels and suggested that her contribution was limited to mobile elements. Through an examination of their published papers, I argue that Jacob and Monod’s rejection stemmed from their failure to fully comprehend maize control systems. Disciplinary discrepancy helps explain Jacob and Monod’s lack of comprehension: they were molecular geneticists working on bacteria, while McClintock was a classical geneticist studying maize. I further argue that gender played a role, as McClintock experienced the Matilda effect—the under-recognition of her contribution, reinforced by the reactions of two male geneticists, and ironically, by the award of the Nobel Prize. Control systems, stemming from McClintock’s reverence for organisms, embodied what Evelyn Fox Keller defines as “gender-neutral science.” This divergent view of science provides insight into why Jacob and Monod failed to grasp McClintock’s work in 1961. (shrink)

A longstanding philosophical premise perceives simplicity as a desirable attribute of scientific theories. One of several raised justifications for this notion is that simple theories are more likely to indicate the true makeup of natural systems. Qualitatively parsimonious hypotheses and theories keep to a minimum the number of different postulated entities within a system. Formulation of such ontologically simple working hypotheses proved to be useful in the experimental probing of narrowly defined bio systems. It is less certain, however, whether qualitatively (...) parsimonious theories are effective indicators of the true nature of complex biological systems. This paper assesses the success of ontologically simple theories in envisaging the makeup of three complex systems in bacteriology, immunology, and molecular biology. Evidence shows that parsimonious theories completely misconstrued the actual ontologically complex constitutions of the three examined systems. Since evolution and selective pressures typically produce ontologically intricate rather than simple bio systems, qualitatively parsimonious theories are mostly inapt indicators of the true nature of complex biological systems. (shrink)

The structures of protein and DNA were discovered primarily by means of synthesizing component-level information about bond types, lengths, and angles, rather than analyzing X-ray diffraction photographs of these molecules. In this paper, I consider the synthetic and analytic approaches to exemplify alternative heuristics for approaching mid-twentieth-century macromolecular structure determination. I argue that the former was, all else being equal, likeliest to generate the correct structure in the shortest period of time. I begin by characterizing problem solving in these cases (...) as proceeding via the elimination of candidate structures through the successive application of component-level information and interpretations of X-ray diffraction photographs, each of which serves as a kind of constraint on structure. Then, I argue that although each kind of constraint enables the elimination of a considerable proportion of candidate structures, component-level constraints are significantly more likely to do so correctly. Thus, considering them before X-ray diffraction photographs is a better heuristic than one that reverses this order. Because the synthetic approach that resulted in the determination of the protein and DNA structures exemplifies such a heuristic, its use can help account for these discoveries. (shrink)

This Ph.D. thesis provides a pilosophical account of the structure of the evolutionary synthesis of the 1930s and 40s. The first, more historical part analyses how classical genetics came to be integrated into evolutionary thinking, highlighting in particular the importance of chromosomal mapping of Drosophila strains collected in the wild by Dobzansky, but also the work of Goldschmidt, Sumners, Timofeeff-Ressovsky and others. The second, more philosophical part attempts to answer the question wherein the unity of the synthesis consisted. I argue (...) that it exemplifies a weak of form of explanatory unification. (shrink)

The traditional practice of establishing morphological types and investigating morphological organization has found new support from evolutionary developmental biology (evo-devo), especially with respect to the notion of body plans. Despite recurring claims that typology is at odds with evolutionary thinking, evo-devo offers mechanistic explanations of the evolutionary origin, transformation, and evolvability of morphological organization. In parallel, philosophers have developed non-essentialist conceptions of natural kinds that permit kinds to exhibit variation and undergo change. This not only facilitates a construal of species (...) and higher taxa as natural kinds, but also broadens our perspective on the diversity of kinds found in biology. There are many different natural kinds relevant to the investigative and explanatory aims of evo-devo, including homologues and developmental modules. (shrink)

In this paper I present a model of rational belief change, and I show how to use it to obtain a better insight into the debate about the nature of pneumococcal transformation, genes and DNA that took place in the forties, as a result of Oswald T. Avery’s work. The model offers a particular elaboration of the concept of inference to the best explanation, along decision theoretic lines. Within this framework, I distinguish different senses in which Avery’s team can be (...) said to have proceeded with caution, thus throwing some light upon a persistent source of disagreement among researchers in the history of genetics. In addition, I explain why we are entitled to say that rival parties such as physicist Maclyn McCarty and biochemist Alfred Mirsky were epistemically rational, in spite of the fact that they reached different conclusions on the basis of the same evidence. (shrink)

Philosophers have proposed various kinds of relations between Mendelian genetics and molecular biology: reduction, replacement, explanatory extension. This paper argues that the two fields are best characterized as investigating different, serially integrated, hereditary mechanisms. The mechanisms operate at different times and contain different working entities. The working entities of the mechanisms of Mendelian heredity are chromosomes, whose movements serve to segregate alleles and independently assort genes in different linkage groups. The working entities of numerous mechanisms of molecular biology are larger (...) and smaller segments of DNA plus related molecules. Discovery of molecular DNA mechanisms filled black boxes that were noted, but unilluminated, by Mendelian genetics. (shrink)

In this study we have examined the reception of Mendelism in France from 1900 to 1940, and the place of some of the extra-Mendelian traditions of research that contributed to the development of genetics in France after World War II.

This essay recognizes that the interactions that define medical care are problematic and that narrative is invoked to overcome these strains. Being grounded in science, medicine, too, might be influenced by a particular world-view that arose in the natural philosophy of the Scientific Revolution. If narrative responds to this sort of medicine, it may retain traces of this mindset. A feminist approach responds to this viewpoint and may used beneficially to analyze both the story of medicine and the stories within (...) medicine. Tensions discussed from this perspective are those between sickness and health and those between patient and provider; also questioned are suitable form(s) of narrative and whose narratives are valued. Suggestions for broadening narrative to address these issues include letting the body speak for itself, overcoming the power differential in the patient/provider interaction and using standpoints to foster a more equal and just medical system. (shrink)

The central dogma of biology holds that genetic information normally flows from DNA to RNA to protein. As a consequence it has been generally assumed that genes generally code for proteins, and that proteins fulfil not only most structural and catalytic but also most regulatory functions, in all cells, from microbes to mammals. However, the latter may not be the case in complex organisms. A number of startling observations about the extent of non-protein-coding RNA (ncRNA) transcription in the higher eukaryotes (...) and the range of genetic and epigenetic phenomena that are RNA-directed suggests that the traditional view of the structure of genetic regulatory systems in animals and plants may be incorrect. ncRNA dominates the genomic output of the higher organisms and has been shown to control chromosome architecture, mRNA turnover and the developmental timing of protein expression, and may also regulate transcription and alternative splicing. This paper re-examines the available evidence and suggests a new framework for considering and understanding the genomic programming of biological complexity, autopoletic development and phenotypic variation. BioEssays 25:930-939,2003. (C) 2003 Wiley Periodicals, Inc. (shrink)

We argue that the physics of complex materials and self-organizing processes should be made central to the biology of form. Rather than being encoded in genes, form emerges when cells and certain of their molecules mobilize physical forces, effects, and processes in a multicellular context. What is inherited from one generation to the next are not genetic programs for constructing organisms, but generative mechanisms of morphogenesis and pattern formation and the initial and boundary conditions for reproducing the specific traits of (...) a taxon. There is no inherent antagonism between this “physicalist” perspective and genetics, since physics acts on matter, and gene products are essential material components of living systems whose variability affects the systems’ parameters. We make this notion concrete by summarizing the concept of “dynamical patterning modules” (DPMs; Newman and Bhat, Phys Biol 5:1–14, 2008; Int J Dev Biol 53:693–705, 2009), an explicit physico-genetic framework for the origin and evolution of multicellular form in animals, as well as (when differences in interaction toolkit genes and applicable physical processes are taken into account) in multicellular plants (Hernández-Hernández et al., Int J Dev Biol 56:661–674, 2012). DPMs provide the missing link between development and evolution by revealing how genes acting in concert with physics can generate and transform morphology in a heritable fashion. (shrink)