Post-translational histone modifications and their biological effects have been described as a ‘histone code’. Independently, Barbieri used the term ‘organic code’ to describe biological codes in addition to the genetic code. He also provided the defining criteria for an organic code, but to date the histone code has not been tested against these criteria. This paper therefore investigates whether the histone code is a bona fide organic code. After introducing (...) the use of the term ‘code’ in biology, the criteria a putative organic code such as the histone code must conform to in order to be recognised as an organic code are described. Our current knowledge of histones and their major post-translational modifications, and the specific protein binding domains that recognise and translate these into specific biological effects, is then reviewed in detail. The histone modification system is then placed in the context of an organic code and it is concluded that it fulfils all the requirements of an organic code. The marks produced on histones by processes such as acetylation and methylation act as organic signs that are translated into unique biological effects, their biological meanings. These translations are accomplished by effector proteins that consist of a binding domain that recognises a specific histone mark and a regulatory domain that mediates the biological effect. Crucially, these domains can be experimentally interchanged between different effector proteins, thus altering the rules that specify the relationships between sign and meaning. The effector proteins therefore fulfil the role of adaptor molecules. (shrink)

Several metabolites serve as substrates for histone modifications and communicate changes in the metabolic environment to the epigenome. Technologies such as metabolomics and proteomics have allowed us to reconstruct the interactions between metabolic pathways and histones. These technologies have shed light on how nutrient availability can have a dramatic effect on various histone modifications. This metabolism–epigenome cross talk plays a fundamental role in development, immune function, and diseases like cancer. Yet, major challenges remain in understanding the interactions between (...) cellular metabolism and the epigenome. How the levels and fluxes of various metabolites impact epigenetic marks is still unclear. Discussed herein are recent applications and the potential of systems biology methods such as flux tracing and metabolic modeling to address these challenges and to uncover new metabolic–epigenetic interactions. These systems approaches can ultimately help elucidate how nutrients shape the epigenome of microbes and mammalian cells. (shrink)

The genetic code appeared on Earth at the origin of life, and the codes of culture arrived almost four billion years later. For a long time it has been assumed that these are the only codes that exist in Nature, and if that were true we would have to conclude that codes are extraordinary exceptions that appeared only at the beginning and at the end of the history of life. In reality, various other organic codes have been discovered in (...) the past few decades and it is likely that more will come to light in the future. The existence of many organic codes in Nature is therefore an experimental fact, but also more than that. It is one of those facts that have extraordinary implications. In this book it is shown that the genetic code was a precondition for the origin of the first cells, the signal transduction codes divided the first cells into three primary kingdoms (Archaea, Bacteria and Eukarya), the splicing codes were instrumental to the origin of the eukaryotic nucleus, the histone code provided a new regulation system in eukaryotic genomes, and the cytoskeleton codes allowed the Eukarya to perform internal movements, including those of mitosis and meiosis. It is shown, furthermore, that organic codes had a key role in multicellular life, in particular in the origin of animals, the origin of mind and the origin of language. The great events of macroevolution, in other words, were associated with the appearance of new organic codes, and we can easily understand why. The reason is that a new code brings into existence something that has never existed before because it creates arbitrary associations, relationships that are not determined by physical necessity. Another outstanding implication is the fact that codes involve meaning and we need therefore to introduce in biology, with the standard methods of science, not only the concept of biological information but also that of biological meaning. The research on biological codes, in conclusion, is bringing to light new mechanisms in evolution and new fundamental concepts in science. This research is the field of Code Biology, the study of all codes of life, from the genetic code to the codes of culture, from the origin of life to the origin of man. (shrink)

Histone post-translational modifications play important roles in transcriptional regulation. It is known that multiple histone modifications can act in a combinatorial manner. In this study, we investigated the effects of multiple histone modifications on expression levels of five gene categories in coding regions. The combinatorial patterns of modifications for the five gene categories were also studied in the regions. Our results indicated that the differences in the expression levels between any two gene categories were significant. There were (...) some corresponding differences in multiple histone modification levels among the five gene categories. Multiple histone modifications jointly impacted expression levels of every gene category. Four mutual combinations of histone modifications were found and analyzed. (shrink)

Coding characteristics have been discovered not only in protein synthesis, but also in various other natural processes, thus showing that the genetic code is not an isolated case in the organic world. Other examples are the sequence codes, the adhesion code, the signal transduction codes, the splicing codes, the sugar code, the histone code, and probably more. These discoveries however have not had a significant impact because of the widespread belief that organic codes are not (...) real but metaphorical entities. They are supposed to lack arbitrariness and codemakers, the two qualifying features of real codes. Here it is shown that the arbitrariness issue can be solved on an experimental basis, while the codemaker issue is dependent on our theoretical description of the cell and can only be solved by a new concept. In order to appreciate the reality of the organic codes, in short, it is necessary to have not only a more critical evaluation of the experimental data but also a new theory of the living system. (shrink)

The chromatin‐regulatory principles of histone post‐translational modifications (PTMs) are discussed with a focus on the potential alterations in chromatin functional state due to steric and mechanical constraints imposed by bulky histone modifications such as ubiquitin and SUMO. In the classical view, PTMs operate as recruitment platforms for histone “readers,” and as determinants of chromatin array compaction. Alterations of histone charges by “small” chemical modifications (e.g., acetylation, phosphorylation) could regulate nucleosome spontaneous dynamics without globally affecting nucleosome structure. (...) These fluctuations in nucleosome wrapping can be exploited by chromatin‐processing machinery. In contrast, ubiquitin and SUMO are comparable in size to histones, and it seems logical that these PTMs could conflict with canonical nucleosome organization. An experimentally testable hypothesis that by adding sterical bulk these PTMs can robustly alter nucleosome primary structure is proposed. The model presented here stresses the diversity of mechanisms by which histone PTMs regulate chromatin dynamics, primary structure and, hence, functionality. (shrink)

This article presents an update on known and unknown biological codes. While the genetic code has been recognized as a code for decades, most other codes were hidden in the shadow of this hallmark discovery. It was the dawn of the new millennium when the histone language and code were proclaimed in the years 2000 and 2001, respectively, marking the start of an explosion in the number of published codes across all biological disciplines since then. Actually, (...) there are hundreds to thousands of biological codes, but only a fraction—although still a substantial number—have been explicitly described as such. A first assessment of those codes allows for a simple categorization into structural and regulatory codes, at the same time maintaining Marcello Barbieri´s initial differentiation of organic versus neural codes. The article reviews prominent codes and showcases restriction-modification and toxin-antitoxin systems as code systems that have gone unrecognized until today. This article should read as a motivation for all those who want to discover ever more new codes—from literature or in the field. (shrink)

RNA polymerase II (RNAP II) non‐coding transcription is now known to cover almost the entire eukaryotic genome, a phenomenon referred to as pervasive transcription. As a consequence, regions previously thought to be non‐transcribed are subject to the passage of RNAP II and its associated proteins for histone modification. This is the case for the nucleosome‐depleted regions (NDRs), which provide key sites of entry into the chromatin for proteins required for the initiation of coding gene transcription and DNA replication. In (...) this review, recent data on the effects of pervasive transcription through NDRs are summarized and a model is proposed to explain how RNAP II‐driven transcription is able to modify the nucleosomes flanking the NDRs, leading to nucleosome repositioning and NDR closure. Even though much of the mechanistic detail underlying these events remains to be elucidated, such a model provides a basis to explain how non‐coding transcription through NDRs can regulate the initiation of coding gene expression and DNA replication. (shrink)

The “histone code” conjecture of gene regulation is our point of departure for analyzing the interplay between the (quasi)digital script in nucleic acids and proteins on the one hand and the body on the other, between the recorded and organic memory. We argue that the cell’s ability to encode its states into strings of “characters” dramatically enhances the capacity of encoding its experience (organic memory). Finally, we present our concept of interaction between the natural (bodily) world, and the (...) transcendental realm of the digital codes. (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)

Genomic function is dictated by a combination of DNA sequence and the molecular mechanisms controlling access to genetic information. Access to DNA can be determined by the interpretation of covalent modifications that influence the packaging of DNA into chromatin, including DNA methylation and histone modifications. These modifications are believed to be forms of “epigenetic codes” that exist in discernable combinations that reflect cellular phenotype. Although DNA methylation is known to play important roles in gene regulation and genomic function, its (...) contribution to the encoding of epigenetic information is just beginning to emerge. Here we discuss paradigms associated with the various components of DNA methylation/demethylation and recent advances in the understanding of its dynamic regulation in the genome, integrating these mechanisms into a framework to explain how DNA methylation could contribute to epigenetic codes. (shrink)

Here, the emerging data on DNA G‐quadruplexes (G4s) as epigenetic modulators are reviewed and integrated. This concept has appeared and evolved substantially in recent years. First, persistent G4s (e.g., those stabilized by exogenous ligands) were linked to the loss of the histone code. More recently, transient G4s (i.e., those formed upon replication or transcription and unfolded rapidly by helicases) were implicated in CpG island methylation maintenance and de novo CpG methylation control. The most recent data indicate that there (...) are direct interactions between G4s and chromatin remodeling factors. Finally, multiple findings support the indirect participation of G4s in chromatin reshaping via interactions with remodeling‐related transcription factors (TFs) or damage responders. Here, the links between the above processes are analyzed; also, how further elucidation of these processes may stimulate the progress of epigenetic therapy is discussed, and the remaining open questions are highlighted. (shrink)

The interactions between genetic and environmental risk factors contribute to the aetiology of complex human diseases. Genome‐wide association studies (GWAS) have revealed that most of the genetic variants associated with complex diseases are located in the non‐coding part of the genome, preferentially within enhancers. Enhancers are distal cis‐regulatory elements composed of clusters of transcription factors binding sites that positively regulate the expression of their target genes. The generation of genome‐wide maps for histone marks (e.g., H3K27ac), chromatin accessibility and transcription (...) factor and coactivator (e.g., p300) binding profiles have enabled the identification of enhancers across many human cell types and tissues. Nonetheless, the functional and pathological consequences of the majority of disease‐associated genetic variants located within enhancers seem to be rather minor under normal conditions, thus questioning their medical relevance. Here we propose that, due to the prevalence of enhancer redundancy, the pathological effects of many disease‐associated non‐coding genetic variants might be preferentially (or even only) manifested under environmental stress. (shrink)

Literature on maternal exposures and the risk of epigenetic changes or diseases in the offspring is growing. Paternal contributions are often not considered. However, some animal and epidemiologic studies on various contaminants, nutrition, and lifestyle‐related conditions suggest a paternal influence on the offspring's future health. The phenotypic outcomes may have been attributed to DNA damage or mutations, but increasing evidence shows that the inheritance of environmentally induced functional changes of the genome, and related disorders, are (also) driven by epigenetic components. (...) In this essay we suggest the existence of epigenetic windows of susceptibility to environmental insults during sperm development. Changes in DNA methylation, histone modification, and non‐coding RNAs are viable mechanistic candidates for a non‐genetic transfer of paternal environmental information, from maturing germ cell to zygote. Inclusion of paternal factors in future research will ultimately improve the understanding of transgenerational epigenetic plasticity and health‐related effects in future generations. (shrink)

The human and mouse genomes are complex from a genomic standpoint. Each cell has the same genomic sequence, yet a wide array of cell types exists due to the presence of a plethora of regulatory elements in the non‐coding genome. Recent advances in epigenomic profiling have uncovered non‐coding gene proximal promoters and distal enhancers of transcription genome‐wide. Extension of promoter‐associated H3K4me3 histone mark across the gene body, known as a broad H3K4me3 domain (H3K4me3‐BD), is a signature of constitutive expression (...) of cell‐type‐specific regulation and of tumour suppressor genes in healthy cells. Recently, it has been discovered that the presence of H3K4me3‐BDs over oncogenes is a cancer‐specific feature associated with their dysregulated gene expression and tumourigenesis. Moreover, it has been shown that the hijacking of clusters of enhancers, known as super‐enhancers (SE), by proto‐oncogenes results in the presence of H3K4me3‐BDs over the gene body. Therefore, H3K4me3‐BDs and SE crosstalk in healthy and cancer cells therefore represents an important mechanism to identify future treatments for patients with SE driven cancers. (shrink)

Protein post‐translational modifications (PTMs) play a crucial role in all cellular functions by regulating protein activity, interactions and half‐life. Despite the enormous diversity of modifications, various PTM systems show parallels in their chemical and catalytic underpinnings. Here, focussing on modifications that involve the addition of new elements to amino‐acid sidechains, I describe historical milestones and fundamental concepts that support the current understanding of PTMs. The historical survey covers selected key research programmes, including the study of protein phosphorylation as a regulatory (...) switch, protein ubiquitylation as a degradation signal and histone modifications as a functional code. The contribution of crucial techniques for studying PTMs is also discussed. The central part of the essay explores shared chemical principles and catalytic strategies observed across diverse PTM systems, together with mechanisms of substrate selection, the reversibility of PTMs by erasers and the recognition of PTMs by reader domains. Similarities in the basic chemical mechanism are highlighted and their implications are discussed. The final part is dedicated to the evolutionary trajectories of PTM systems, beginning with their possible emergence in the context of rivalry in the prokaryotic world. Together, the essay provides a unified perspective on the diverse world of major protein modifications. (shrink)

While heredity is predominantly controlled by what deoxyribonucleic acid (DNA) sequences are passed from parents to their offspring, a small but growing number of traits have been shown to be regulated in part by the non‐genetic inheritance of information. Transgenerational epigenetic inheritance is defined as heritable information passed from parents to their offspring without changing the DNA sequence. Work of the past seven decades has transitioned what was previously viewed as rare phenomenology, into well‐established paradigms by which numerous traits can (...) be modulated. For the most part, studies in model organisms have correlated transgenerational epigenetic inheritance phenotypes with changes in epigenetic modifications. The next steps for this field will entail transitioning from correlative studies to causal ones. Here, we delineate the major molecules that have been implicated in transgenerational epigenetic inheritance in both mammalian and non‐mammalian models, speculate on additional molecules that could be involved, and highlight some of the tools which might help transition this field from correlation to causation. (shrink)

There is increasing evidence that dynamic changes to chromatin, chromosomes and nuclear architecture are regulated by RNA signalling. Although the precise molecular mechanisms are not well understood, they appear to involve the differential recruitment of a hierarchy of generic chromatin modifying complexes and DNA methyltransferases to specific loci by RNAs during differentiation and development. A significant fraction of the genome-wide transcription of non-protein coding RNAs may be involved in this process, comprising a previously hidden layer of intermediary genetic information that (...) underpins developmental ontogeny and the differences between species, ecotypes and individuals. It is also evident that RNA editing is a primary means by which hardwired genetic information in animals can be altered by environmental signals, especially in the brain, indicating a dynamic RNA-mediated interplay between the transcriptome, the environment and the epigenome. Moreover, RNA-directed regulatory processes may also transfer epigenetic information not only within cells but also between cells and organ systems, as well as across generations. (shrink)

Having adequate knowledge of the world is not just a matter of survival but also one of obligation. This obligation to "know well" is what philosophers have termed "epistemic responsibility." In this innovative and eclectic study, Lorraine Code explores the possibilities inherent in this concept as a basis for understanding human attempts to know and understand the world and for discerning the nature of intellectual virtue. By focusing on the idea that knowing is a creative process guided by imperatives (...) of epistemic responsibility, Code provides a fresh perspective on the theory of knowledge. From this new perspective, Code poses questions about knowledge that have a different focus from those traditionally raised in the two leading epistemological theories, foundationalism and coherentism. While not rejecting these approaches, this new position moves away from a primary concentration on determinate products and towards an examination of ever-changing processes. Arguing that knowledge never exists as an ungrounded abstraction but rather emerges through dialogue between variously authoritative "knowers" situated within particular social and historical contexts, she draws extensively on examples from lived social experience to illustrate the ways in which human beings have long tried to recognize and meet their epistemic responsibilities. This edition of Epistemic Responsibility includes a new preface from Lorraine Code"--Provided by the publisher. (shrink)

Fifteen essays examine the work of German philosopher Hans Georg Gadamer to provide feminist interpretations of his views on science, language, history, ...

In this lively and accessible book Lorraine Code addresses one of the most controversial questions in contemporary theory of knowledge, a question of fundamental concern for feminist theory as well: Is the sex of the knower epistemologically significant? Responding in the affirmative, Code offers a radical alterantive to mainstream philosophy's terms for what counts as knowledge and how it is to be evaluated. Code first reviews the literature of established epistemologies and unmasks the prevailing assumption in Anglo-American (...) philosophy that "the knower" is a value-free and ideologically neutral abstraction. Approaching knowledge as a social construct produced and validated through critical dialogue, she defines the knower in light of a conception of subjectivity based on a personal relational model. Code maps out the relevance of the particular people involved in knowing: their historical specificity, the kinds of relationships they have, the effects of social position and power on those relationships, and the ways in which knowledge can change both knower and known. In an exploration of the politics of knowledge that mainstream epistemologies sustain, she examines such issues as the function of knowledge in shaping institutions and the unequal distribution of cognitive resources. What Can She Know? will raise the level of debate concerning epistemological issues among philosophers, political and social scientists, and anyone interested in feminist theory. (shrink)

Feminist epistemologists who attempt to refigure epistemology must wrestle with a number of dualisms. This essay examines the ways Lorraine Code, Sandra Harding, and Susan Hekman reconceptualize the relationship between self/other, nature/culture, and subject/object as they struggle to reformulate objectivity and knowledge.

Abstract Taking my point of entry from George Eliot's reference to ?the power of Ignorance?, I analyse some manifestations of that power as she portrays it in the life of a young woman of affluence, in her novel Daniel Deronda. Comparing and contrasting this kind of ignorance with James Mill's avowed ignorance of local tradition and custom in his History of British India, I consider how ignorance can foster immoral beliefs which, in turn, contribute to social-political arrangements of dominance and (...) subordination. Yet I ask, too, how judgements of culpability can be sustained when ignorance is culturally induced. (shrink)

In a remarkable development, I have constructed a new definition for a self-delimiting universal Turing machine (UTM) that is easy to program and runs very quickly. This provides a new foundation for algorithmic information theory (AIT), which is the theory of the size in bits of programs for selfdelimiting UTM's. Previously, AIT had an abstract mathematical quality. Now it is possible to write down executable programs that embody the constructions in the proofs of theorems. So AIT goes from dealing with (...) remote idealized mythical objects to being a theory about practical down-to-earth gadgets that one can actually play with and use. (shrink)

Arguing that ecological thinking can animate an epistemology capable of addressing feminist, multicultural, and other post-colonial concerns, this book critiques the instrumental rationality, hyperbolized autonomy, abstract individualism, and exploitation of people and places that western epistemologies of mastery have legitimated. It proposes a politics of epistemic location, sensitive to the interplay of particularity and diversity, and focused on responsible epistemic practices. Starting from an epistemological approach implicit in Rachel Carson’s scientific projects, the book draws, constructively and critically, on ecological theory (...) and practice, on (post-Quinean) naturalized epistemology, and on feminist and post-colonial theory. Analyzing extended examples from developmental psychology, from medicine and law, and from circumstances where vulnerability, credibility, and public trust are at issue, the argument addresses the constitutive part played by an instituted social imaginary in shaping and regulating human lives. The practices and examples discussed invoke the responsibility requirements central to this text’s larger purpose of imagining, crafting, articulating a creative, innovative, instituting social imaginary, committed to interrogating entrenched hierarchical social structures, en route to enacting principles of ideal cohabitation. (shrink)

The arguments in this book are informed at once by the moral-political implications of how knowledge is produced and circulated and by issues of gendered subjectivity. In their critical dimension, these lucid essays engage with the incapacity of the philosophical mainstream's dominant epistemologies to offer regulative principles that guide people in the epistemic projects that figure centrally in their lives. In its constructive dimension, ____Rhetorical__ ____Spaces__ focuses on developing productive, case-by-case analyses of knowing other people in situations where social-political inequalities (...) create asymmetrical patterns of epistemic power and privilege. (shrink)

This essay extends my engagements with questions of epistemic agency and the politics of epistemic location, in Epistemic Responsibility and in Ecological Thinking to consider how questions of understanding and of certainty play diversely into human and other ecological circumstances. In so doing, it opens lines of inquiry not immediately available in standard western-northern approaches to epistemology with their concentration on medium-sized physical objects in their presupposed neutrality and replicability. Working from a tacit assumption that knowing and knowers are always (...) situated, and that they are enabled or restricted in so being, the book engages with specific epistemic situations in order to show how “situatedness” indeed makes knowledge possible, while regarding it as an enabling rather than a constraining modality. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:Women Philosophers: Genre and the Boundaries of PhilosophyLorraine CodeCatherine Villanueva Gardner. Women Philosophers: Genre and the Boundaries of Philosophy. Boulder, CO: Westview, 2003. Pp. xv + 198. Paper, $22.00.In a tradition which "trains us to read purely for content" (xii), Catherine Gardner wonders how to read the philosophy of five women who write in "non-standard philosophical forms" (xiii): Mechthild of Magdeburg's poetry, Christine de Pisan's allegory, Catharine Macaulay's (...) epistolary form, and Mary Wollstonecraft's and George Eliot's fiction. Asking how these authors' gender and their works' genre bear on their exclusion from canonical philosophy with its reliance on rigorous argument unsullied by stylistic considerations, she argues that form is integral to understanding philosophy, and can impede its recognition as philosophy. Specifically, she wonders what these historical writings can offer present-day feminist ethics?Gardner's readings and her thesis about style and genre as conditions of philosophical legitimacy are provocative. She urges "reading past" forms deemed inhospitable to moral truth—such as Macaulay's epistolary style (44-45)—to encounter the author as moral philosopher, and explain her invisibility as such. Eliot's philosophy "demands the form of a novel" (123), she proposes, and Wollstonecraft's principles of style "are ultimately principles of morality as well" (92). More complex is the poetically articulated moral epistemology in Mechthild's The Flowing Light, with God, speaking through Mechthild, as its author (154-56). Because these forms—epistolary, allegorical, mystical-poetic, fictional—have been most accessible to women, Gardner urges feminists to consider how these authors' gender bears on their exclusion from moral philosophy. Owing to women's "greater capacity for emotion and... weaker capacity for reason" (155), mystics such as Mechthild were deemed well-suited to write as they did; yet works attributed to God stand immune to philosophical argument. Macaulay's thoughts on government and social reform were judged secondary to her "feminine" ones about educating women for marriage and domesticity (26-27). Gardner is persuaded and persuasive about the philosophical stature of the works she discusses. Yet if a thinker's gender denies her philosophical status, how can she bypass those exclusionary structures—even if, like Eliot, she chooses a male name? If a work's genre removes it from the sustained argumentative debate that is the hallmark of western philosophy, how can it claim a place there?There are no easy answers, but the questions spark numerous others. Perplexing is Gardner's contention that these women are ignored because they defy norms of style and method. But how would she classify Plato's dialogues, Voltaire's Candide, Pascal's and Nietzsche's aphorisms, Wittgenstein's numbered propositions,or Sartre's, Camus' (and Beauvoir's) philosophical novels, given their maverick styles? Style alone cannot effect or explain the exclusions she deplores. More puzzling are Gardner's conceptions of standard method and dominant form (e.g., 24, 120, 175), since she does not elaborate, apart from indicating that both require rigorous prose argument. But formal and methodological orthodoxy varies historically, as in the influence of scholasticism, for Christine, which receives no mention, or Gardner's ahistorical suggestion that the absence of a "normative subject as an independent, autonomous individual" (171) is a lacuna in Mechthild's work. Why would a thirteenth-century writer presuppose an Enlightenment subject? These issues demand attention in a work of historical scholarship.A different question troubles the method discussion. The author regrets certain women's exclusion from the canon despite the philosophical nature of their work, maintaining that [End Page 215] works whose styles/forms diverge from the standard count, nonetheless, as philosophy. These women demonstrate that philosophy need not be couched in formal argument: poetry, allegory, novels can also articulate philosophical theories. But—if my reading is correct—here Gardner is inconsistent. She commends the philosophy in Macaulay's Letters, claiming it "can and does contain the sort of sustained argument... uncontroversially identifiable as... philosophical" (44), and makes similar claims for Wollstonecraft and Eliot. But in legitimating these works by received standards of argument after all, Gardner weakens the force of her claims that philosophy—good philosophy—need not be presented in orthodox form, thus... (shrink)