: This essay approaches the eighteenth-century novel via debates in twentieth century theories of representationalism. At the core of these debates is a critical genealogy stemming from Michael Fried's "Art and Objecthood" (1967), one whose commitments are most powerfully on display in Steven Knapp's neglected Personification and the Sublime and its transformation of the anxiety about literalist art into an anxiety about allegory. What made eighteenth-century writers uncomfortable about Miltonic allegory, says Knapp, was its literalism; and thus the category of "literature" came to be defined by its power to defeat allegorical personhood. Angus Fletcher had made a similar claim about the realist novel in Allegory: Theory of a Symbolic Mode (1964). For Robbe-Grillet, however—whose Pour un nouveau roman precedes "Art and Objecthood" by four years, anticipating Fried's claims but on behalf of objecthood—the realist novel's attention to detail is the apotheosis of allegorical literalism. This is how and why Kafka is a realist. It is also, I argue, the realism of Jane Austen. Zadie Smith influentially sketches out two paths for the novel, with Robbe-Grillet and Austen moving along vectors that will never meet. But there is only one path for the novel.

Essays from The English Institute 2017:Scale Sandra Macpherson and Meredith Martin introduction The essays collected in this special issue of ELH represent a conversation that happened on the West Coast of the United States for the first time in the English Institute's 76-year history. The shift in geographic scale was salutary in every possible way. Among the attendees were faculty and students from schools that had never before been represented at the annual meeting—scholars from throughout the UC system, from Cal State Long Beach and San Diego State, from the Claremont Graduate School and Chapman University, from the University of Texas and Texas A&M, from the University of Washington and the Pacific Northwest College of Art. The latter contingent enjoyed their experience so much that they followed the English Institute to Yale in 2018, and plan to travel to Chicago in the fall of 2019. This is exactly the sort of expanded community we'd hoped for when setting the English Institute on the move. The scale of Irvine itself—its emphatic horizontality—lent the proceedings an unprecedented intimacy. There have been other venues for thinking and talking about scale, of course: Ted Underwood and James English's volume of MLQ, Scale and Value: New and Digital Approaches to Literary History (September 2016); Rebecca Walkowitz's forum in Modernism/modernity, What is the Scale of the Literary Object? (February 2019); the ongoing project of conceptualizing Anthropogenic climate change. What's unique about the occasion captured in these pages is not so much its face-to-faceness as the anchoring of disparate approaches to a question in a shared reading designed, as our tagline puts it, to produce seven talks but one conversation. The text for the conversation at Irvine was Claude Lévi-Strauss's "The Structural Analysis of Myth" (1955), a piece whose startling relevance to a number of the talks was all the more surprising given how little attention structuralism has received in recent scale talk. Walkowitz argues that for modernist studies "the turn to scale began [End Page 267] geographically at least 15 years ago, with the new theories of world literature," and that if "global modernism" is "part of a first re-scaling in modernist studies," the second, happening in the forum she introduces, turns its attention instead to "middle scales" and to "the mechanisms that get us from one scale to another."1 According to Underwood and English, however, moving up and down in scale—and meta-critical attentiveness to this movement—has been a central feature of the history of criticism writ large. They observe that "scalar constructs" both large ("temporal spans" and "geo-cultural categories") and small ("formal entities") "organize our research projects and structure our intellectual and institutional divisions of labor."2 And the disciplinary history they chart moves back and forth from the relatively large-scale project of philology to the "scalar contraction" of New Criticism to the scaling up of "Always Historicize!" to the "gigahistoricisms" of distant reading, deep time, and the world literary system, back down to "close but not deep" and "too-close" reading.3 One might imagine Lévi-Strauss's goal of creating a method adequate to the vast temporal and geographical scales of myth-making—and his instinct that such a method would require machine learning—might have a place in this story. Perhaps the technical intricacy of linguistic morphology has been too rebarbative. Or perhaps, as one attendee observed, to perform a structural analysis of even one myth and all its variants one would need not a machine but an army. (And even if one had an army of coders, another pointed out, "none of it [would be] operational because its units aren't discrete enough to be coded."4) Yet another observed that ethnography won out over structural analysis in anthropology, and this preference for particularity over and against abstraction has been powerfully present in our own discipline as well. It was present in the conversation too: over and over again there was an expressed worry about the way in which a method grounded in repetition might flatten difference. Yet in its focus on what Lévi-Strauss...

ion of “Coleridgean” criticism, and his claim that Chicago School critics “are interested in lyrics not as exemplars but as objects,” where the object is “not a universal form or value reflected in the poem but the poem itself in its wholeness and particularly as a structure of mutually appropriate parts” (128). Burke offers a quote from Norman Maclean that encapsulates the particularism of the Chicago method: “The obligations resting upon this kind of criticism are twofold: to discover the parts of a poem and to render an account of their relationships” (131). For Burke, to speak of part/whole relations is to presume taxonomic categories that exceed the poetic object. “One does not place a form in isolation” (135), he asserts. “There is, of course, a sense in which every work is unique, since its particular combination of details is never repeated. But is the emphasis upon this fact feasible if one would develop an ‘Aristotelian’ poetics of the lyric, treating lyrics as a class?” The answer, it appears, is no: “a mere concern with one lyric, then another lyric, then another would not yield the kind of observations needed to treat of lyrics as a class. For to treat lyrics as a class, one must examine individual lyrics from the standpoint of their generic attributes. And to do this, one must have terminological prepossessions, prior to the analysis, even before one can select a poem that he considers representative of the lyric” (135). Burke is suggesting that in its particularism the Chicago School fails to be a proper formalism. And Wimsatt agrees, complaining that its practitioners seem to think there cannot be a “general” discussion about anything: “You have to divide it into its parts”; “If you try to pick up a pie whole it will melt into a plan for a pie or the taste of a pie. If you cut it into slices it will remain pie and whole pie” (57). This might make sense, he says, if one really couldmaintain a literal equation of aesthetic object with physical object. Then, if one were somehow constrained to talk in general terms about artifacts and not about “houses” or “hammers,” it might be true that such talk would “lose tangibility and become just qualities or, by a further slip, just human aims and methods” (57). Wimsatt of course rejects the notion that poems are physical artifacts, and derives their tangibility from their status as verbal acts. But he also thinks that Chicago Critics themselves aren’t really interested in houses, hammers, or poems qua poems. They are, he suggests, ultimately focused precisely on human aims andmethods. Crane’s literalism andmaterialism is like saying that “the shape and function of a saw are determined by the steel of which it is made” rather than the sawness of the saw being “determined by the steel fashioned in a certain shape” (63). And although for his part, Wimsatt thinks that the shaping of words makes them meaningful— that shape entails meaning—this isn’t really his main concern. Instead he notes (again, rightly) that whereas a formalist might want to talk about what makes a saw cut (“that is, what the saw itself is”), Chicago School critics are 496 M O D E R N P H I L O L O G Y preoccupied with “what made the saw become what it is”—that is, with intention and reception (63). Or in other words, withfinal causation over and abovematerial or formal causation. At one point in his essay on Empson, Elder Olson announces: “All poetic theory is a form of causal explanation; and such explanation must comprise all the causes requisite to make a thing what it is. Unless the causal account is complete, the explanation is inadequate.” “The theories of the early Greek physicists offer an example,” he observes: “Thales . . . thought to account for the phenomenal universe in terms merely of its material causes, the principle of water; but, as numerous philosophers have pointed out, this would at most account for the substrate.” “Modern criticism is very much in the condition of Thales” (40), he concludes tersely. Semiotics cannot be the substrate of poetic objects as there is no attribute of poetic language “which cannot also be found, and that abundantly, in other forms of discourse” (41). To imagine otherwise, Olson says, is “like arguing that ice is ice because it is water; they are attempts to derive the form from the matter. All such argument runs, obviously, in the wrong direction; it would infer the design of a house from the shape and weight of the bricks. No product is what it is simply because its matter is such-andsuch; its matter is indeed a necessary, but not a sufficient, condition of its existence and nature” (41). Crane agrees that the “formal nature” of a thing ismore important than the “material nature” because the “‘form’ of any individual object, such as a man or a couch, is the principle or cause ‘by reason of which the matter is some definite thing’” (150). Now one could stop here, as I would like to stop, and think about how to conceive of literary objects with the perspicuity and immediacy with which one understands the relationship between the couch form and its materialization in leather or wool. What is the form and what the matter in a literary object? Fourteen lines of iambic pentameter verse? The marriage plot with its infinitely replaceable variables? But Crane does not stop. Instead he goes on to say, “We understand by form that principle, or complex of principles, which gives to the subject-matter the power it has to affect our opinions and emotions in a certain definite way such as would not have been possible had the synthesizing principle been of a different kind” (166). Thematter thatmatters to Chicago School formalism is subject matter, or, in violation of any rigorously formalist formalism, what onemight otherwise call content. The definingmethod of the Chicago School is to make visible “the shaping principle of form and emotional ‘power’ without which no poem could come into existence as a beautiful and effective whole of a determinate kind” (185). And according to Wimsatt, this means that despite a rigorous critique of anything that would tend toward “psychologism” (45), in their focus on the pleasure Sandra Macpherson ◦ The Object of Literal Criticism 497 and purpose of aesthetic objects Chicago School critics are more invested in intentional and affective fallacies than they care to admit. In his contribution to the edited volume Aristotle’s “Poetics” and English Literature (1965), for example, Olson argues that a properly Aristotelian poetics will center on what he calls the synolon, a combination of form and matter that constitutes the identity of any poetic object. The synolon does not describe the ontology of that object as object, however. It is “what is made by the artist”: “the sculptor makes neither the marble which is his material nor the human form which he gives it, but the statue, which is the human form imposed on upon the marble; the ironworker makes neither the iron nor the spherical form, but the iron sphere, a concretum of form and matter.” The conflation of natural and aesthetic objects that so worries Wimsatt, it turns out, is only a temporary step in the critical logic: “while natural things are defined by a two-part definition consisting of genus (matter) and difference (form), artificial things must be defined by enumeration and differentiation of the various causes that make them what they are.” AsMcKeon explains later in the volume, “Aesthetic objects are ‘concrete objects’” like natural objects, “and as such analyzable in terms of form and matter.” But unlike natural objects, “form and definition . . . are determined ultimately not only by the potentiality of the artistic material but by the nature of the artist and the susceptibilities of the audience.” In his dense and borderline incomprehensible essay “The Philosophic Bases of Art and Criticism,” McKeon repeats this move toward intention and reception by describing “literal criticism” as an attempt “to set forth the nature and achievements of the arts literally in terms of the objects produced by artists and appreciated by audiences.” (Early in “The Fallacy of the Neoclassic Species” Wimsatt enters “a strong preliminary complaint against the frequent opaqueness of McKeon’s writing, his absentmindedness, as it were, his neglect to make details of comparisons and antitheses go together” [43], and bemoans the fact that he “looms massively and portentously behind thewhole Chicago effort” [42].)McKeon exhaustively delineates six “modes” of literal criticism—dialectical (Plato, Whitehead), scientific (Aristotle), poetic (Longinus), scholarly (Dover Wilson), technical (Horace, Boileau), and formal (Demetrius, I. A. Richards, and 6. Elder Olson, “The Poetic Method of Aristotle: Its Powers and Limitations” (1952), in Aristotle’s “Poetics” and English Literature: A Collection of Critical Essays, ed. Elder Olson (University of Chicago Press, 1965), 180.

What kind of action is literary criticism? In literary criticism: a concise political history, Joseph North tells us up front: it's political action. His history “is explicitly motivated by present concerns: one has something like a goal, and something like a plan for reaching it,” and his goal is to persuade “readers on the radical left” that there is something at stake for them in “an extended discussion of matters literary, aesthetic, and methodological” (viii, ix, x). Or, rather, his goal is to persuade both readers on the left and “readers within and around academic literary studies” that their interests align: that the “materialist account of the aesthetic” at the root of close reading is “properly understood as part of a longer history of resistance to the economic, political, and cultural systems that prevent us from cultivating deeper modes of life” (x).

A Little Formalism Sandra Macpherson My title comes from Barthes’s well-known parody of a well-known saying trotted out whenever one is asked to talk about form: “I shall say that a little formalism turns one away from history, but that a lot brings one back to it.”1 When in 1988 Caroline Porter asked “Are We Being Historical Yet?” and answered “no,” expressing from within New Historicism the wish for a “genuinely historicist critical practice” that would finally escape the “formalist legacy,” she perhaps missed Barthes’s point: that a committed formalism is historicist, that the legacy of formalism is historicism.2 The new formalism takes this legacy for granted. Indeed, in Susan Wolfson’s Introduction to the Modern Language Quarterly issue meant to capture the rebirth of formalism from among the ashes of cultural studies, Barthes “famous aphorism” is offered as shorthand for the argument of the volume: that “to set formalist attention against claims of contextual determination [obscures] the way formal choices and actions are enmeshed in, and even exercise agency within, networks of social and historical conditions.”3 Although Wolfson goes on to say that none of the essays to come “tries to justify or rehabilitate formalist criticism in the year 2000 by cross-dressing it as a version of historicist criticism and pleading for it on that basis, as if that were the only legitimacy,” it is my sense that much of the new formalism does precisely that—ransoms form with history.4 Given this, a better question might be: “Are We Being Formalist Yet?” And the answer, once again, is no. What follows expresses my own wish: for a genuinely formalist critical practice, a little formalism that would turn one away from history without shame or apology. But if even Barthes’s formalism is too big to serve as a model, it’s hard to know what a little formalism might look like. This is not only because, as Marianne de Koven points out, Mythologies was seen by key players in the movement as “an initiatory and paradigmatic text of cultural studies”; but also because when you look at Barthes closely, the opposition between formalism and historicism is superseded by a more perplexing one between form and formalization. And I am quite confused about form.5 [End Page 385] I can date that confusion precisely: to the wonderful English Institute meeting in 2009 on the topic of genre. There I realized three things that came to shape my future work: firstly, that although the book I had just published had the word “form” in its title, the term was massively underelaborated, weakly synonymous with “plot” or “structure”; secondly, that my formalism was therefore also rather thin, registering an interest in a determinism equated with formalism but lacking any rigorous discrimination between form, structure, and necessity; and finally, that after listening to two days of brilliant talks and stimulating conversation, I had no idea what distinguished form from genre.6 A recent perusal of the publication issuing from that meeting—The Work of Genre—reinforced my befuddlement. Jonathan Culler and Wai Chee Dimock call lyric a “genre,” and I have always thought of lyric as form-like—distinct from an ode, say, which is often described as a “genre,” and moreover a genre of lyric. Deidre Lynch begins by calling the novel a “form” and ends by calling it a “genre.” Alex Woloch calls the novel a form as well, but form looks a lot like genre; both are kinds of constraint placed upon a third term, “representation.” Craig Dworkin—who admits to wanting to “think through the dynamic of form and genre”—moves between calling prose a “form,” a “format,” and a “genre,” and calling both poetry and lyric “genres.”7 Such conflations of form and genre might be quite irrelevant to the nuanced arguments in which they occur and whose stakes lie elsewhere. Dworkin’s concern, for instance, is to make us see that whatever we happen to call poetry or prose, they tend to be distinguished from one another on the basis of lineation, and prose too is lineated. His is a materialist formalism that operates under the motto: “form...

Conventional studies of the 18th-century novel link the form's evolution to the emergence of a modern liberal subject whose actions and attachments are imagined to be voluntary and intentional. Sandra Macpherson challenges this account of modernity, arguing that accident and injury are central to the way the early realist novel conceives of personhood and belonging. Macpherson's unique approach connects the rise of the novel to contemporary developments in liability law-in particular, to legal principles of strict liability that hold persons accountable for harms inflicted upon others in the absence of intention, consent, direct action, or foreknowledge. In fresh readings of Defoe, Richardson, and Fielding, she shows that these laws share with the novel the view that the state of a person's mind is irrelevant to the question of her responsibility for her actions. Macpherson urges readers to rethink the ancient consensus that the novel differs from tragedy in its elevation of character over plot. She concludes that the realist novel is ultimately a tragic form, committed to holding persons accountable for accidents of fate. Macpherson's original insights will have a broad and lasting impact on the study of the 18th-century novel.

In 1865 a pornographic novel called The New Epicurean was published anonymously (it is now thought to be by Edward Sellon) with a title page calling the text a "reprint" of an edition dated 1740. Historicism and anachronism are commonplaces in European pornography, but rarely is the periodization quite so explicit or so precise. The date conspicuously precedes Cleland's Memoirs of a Woman of Pleasure (1749), the first pornographic novel in English, and invokes instead Pamela—like The New Epicurean, a collection of letters published anonymously in 1740. The Richardsonian pedigree is enhanced by a number of narrative details: the title, The New Epicurean: or, the Delights of Sex . . . in Graphic Letters echoes Pamela: or, Virtue Rewarded, in a series of Familiar Letters; the protagonist is a man named Sir Charles, a Grandisonian landlord; and the orphaned girls whom he benevolently "saves" from penury are overseen by a Mrs. Jukes, a figure at once Mrs. Jewkes and Mrs. Jarvis, and by a Mrs. J, who resembles Clarissa's Mrs. Sinclair. By invoking Richardson, Sellon self-consciously places himself within an anti-Pamelist tradition stemming from Fielding to Sade, one that insists upon an intimate connection between the sentimental and the pornographic novel and calls into question sentimental literature's claim to be something other—better—than pornography. Historians of the novel from Ian Watt to William Warner reiterate the anti-Pamelist emphasis on Richardson's exploitation of readerly desire and the conventions of amatory fiction. For Watt, Richardson's "verbosity" makes his erotic scenes "much more suggestive than Boccaccio's": we "know Richardson's characters, and his exhaustive treatment of their reactions to each incident makes us imagine that we are participating in every fascinating advance and retreat as it is reflected in Pamela's excited sensibility."1 Or, as Fielding's Parson Oliver puts it: notwithstanding our Author's Professions of Modesty . . . I cannot agree that my Daughter should entertain herself with some of his Pictures; which I do not expect to be contemplated without Emotion, unless by one of my Age and Temper, who can see the Girl lie on her Back, with one Arm round Mrs. Jewkes and the other round the Squire, naked [End Page 471] in Bed, with his Hand on her Breasts, &c. with as much Indifference as I read any other Page in the whole Novel.2 Recent work on the history of pornography likewise gives Richardson pride of place in the development of the genre in its novelistic form: according to Bradford Mudge, Cleland's Memoirs of a Woman of Pleasure and Memoirs of a Coxcomb "have to be considered as important 'anti-Pamelas,'" and Justine: or, Virtue Well-Chastized is "the most devastating" anti-Pamela of them all.3 Sellon's invocation of Richardson, then, is not surprising: allusions to Richardson seem to be a necessary feature of the pornographic novel from its inception. The answer to the question "Why 1740?" cannot, therefore, end with the observation that the date invokes Pamela and anti-Pamelism. I am interested in more subtle moments of eighteenth-centuriana in the text—in particular the fact that Sir Charles's estate is a "villa at Twickenham."4 The Twickenham context suggests a new literary genealogy for pornography; for while critics agree that Richardson's formal innovations "make possible the novel's role as a popular purveyor of vicarious sexual experience and adolescent wish-fulfillment," no one has thought to trace a line of inheritance from Pope to porn.5 There is, of course, the Essay on Woman. John Wilkes and Thomas Potter's satire on Pope's Essay on Man, and Wilkes's trial for obscenity and blasphemy, are important moments in the history of pornography in England.6 But Wilkes and Potter are not suggesting that there is something pornographic about the life and work of Alexander Pope. Indeed, what's amusing about the Essay on Woman is the presumed disparity between the original and its imitation: as Arthur Cash points...

This essay attempts to explain the function of the most famous entail in literary history. The essay begins with a brief survey of the legal history of entailment, focusing in particular on the contradictory notions of agency and obligation embedded in the English fee. The author argues that Austen is familiar with this history and these contradictions, and that in Pride and Prejudice, the entail - which had seemed a threat to social obligation - becomes a model form of sociability. What is entailed in Pride and Prejudice, she concludes, is an argument about short- and long-term obligations: an argument on behalf of a model of obligation whose durability and impersonality is enabled by the technology - at once conceptual and historical - of entailment.

Previous articleNext article No AccessBook ReviewsThe Sodomite in Fiction and Satire, 1660-1750. Cameron McFarlane Sandra MacphersonSandra Macpherson Search for more articles by this author PDFPDF PLUS Add to favoritesDownload CitationTrack CitationsPermissionsReprints Share onFacebookTwitterLinkedInRedditEmail SectionsMoreDetailsFiguresReferencesCited by Modern Philology Volume 98, Number 3Feb., 2001 Article DOIhttps://doi.org/10.1086/492983 Views: 2Total views on this site Copyright 2001 The University of ChicagoPDF download Crossref reports no articles citing this article.

Lovelace, Ltd. Sandra Macpherson “What did the man mean!” Arabella Harlowe complains of Lovelace in the opening pages of Clarissa; “a woman should be put out of doubt, early, as to a man’s intentions in such a case as this, from his own mouth.” 1 The “case” she refers to is the question of whether Lovelace intends to ask her to marry him—of what signifies a binding matrimonial obligation—a question that appears to be resolved later in the narrative by her uncle Anthony Harlowe, who implies that Arabella’s confusion is merely the effect of Lovelace’s peculiar brand of obscurantism. “I resolved to write,” he recounts of his own, exemplary, proposal to Mrs. Howe, “that my writing may stand, as upon record, for my upright meaning; being none of your Lovelaces; you’ll mark that, madam; but a downright, true, honest, faithful Englishman” (625). Harlowe’s confidence in the capacity of written stipulation to make clear and incontrovertible the meaning of various acts or utterances, and the way in which such contractualism is set up as anti-Lovelacian and therefore seemingly representative of the author’s own ideology of representation, has made Clarissa a favorite text for post-structuralist critics interested in the persistence of Arabella’s initial quandary: how does one determine what Lovelace means? In the deconstructive account of the novel, Lovelace’s impenetrability is mapped onto the rape scene, his violation of Clarissa’s unconscious person seen as an objective correlative for the way in which other people’s interpretive agency continually violates Clarissa’s “sense of the meaningful.” 2 Indeed, Terry Eagleton goes so far as to suggest that because language has “a ‘body,’ a material weight of connotations, which outstrips authorial meaning”—because the attempt to signify only one thing by using a given word is undermined by the way in which past meanings accrue to a linguistic object—language itself is stripping and raping Clarissa. 3 While such a suggestion has understandably disturbed many readers of the novel—in particular, feminist critics committed to preserving a distinction between rape and representation—post-structuralism’s primary insight and inescapable legacy in moments such as this is to have foregrounded the problem of intentionality as central to Richardson’s literary project. 4 Having done so, however, critics like Eagleton, Warner, [End Page 99] and Castle go on to mistake what is an epistemological problem in Clarissa (the difficulty of determining what a person means to do or say, or means to be held accountable for doing or saying) for an ontological one (the impossibility of intentional agency and therefore of accountability). The assumption that problematizing intentionality involves problematizing accountability, that because language is “entirely free with regard to referential meaning” an individual cannot be held accountable for the accidental effects of what she does or says, derives from Paul de Man’s claim in “The Purloined Ribbon” that guilt “can always be dismissed as the gratuitous product of a textual grammar or a radical fiction”—that language itself, and not Rousseau, is responsible for the accident of saying “Marion.” 5 (De Man is concerned here with the moment in the Confessions where Rousseau claims responsibility for the consequences of having unintentionally accused a young serving-woman of stealing a ribbon he himself had taken: “Never was deliberate wickedness further from my intention than at that cruel moment,” recounts Rousseau; “The memory tortures me less on account of the crime itself than because of its possible evil consequences . . . [and] it has secured me for the rest of my life against any act that might prove criminal in its results.” 6) What is interesting to me about de Man’s insistence that Rousseau could not be responsible for what he did not intend is the extent to which such a claim remains committed to an intentionalist account of meaning, to judging the meaning of an act with respect to its intentionality or lack of intentionality (no intention, no meaning). 7 And it is interesting precisely because de Man’s argument is the ground for what post-structuralist critics suppose is an anti-intentionalist critique of Clarissa’s, and ultimately Richardson’s own naïve...

GMDP (glucosaminylmuramyl dipeptide) is a promising orally active immunomodulator. It is undergoing phase II trials as an adjunct to chemotherapy for metastatic breast and colorectal cancer, as prophylaxis against post-operative infection, and as antipsoriasis therapy. In an interview with Inpharma ®, Dr Philip Ledger, Managing Director of Peptech (UK), said that the preliminary results with GMDP are encouraging enough for Peptech to be confident of a promising future with this agent.

The first drug to be manufactured in genetically engineered animals will go into full-scale production this year. It is hoped that this new production technique will make it possible to treat diseases for which drug therapy has thus far been unavailable, inadequate or prohibitively expensive. Drugs manufactured in this way may also offer stiff competition to pharmaceuticals that are produced by more conventional technology. So should the pharmaceutical industry be worried? ‘ No ’, says commercial director of the UK-based company PPL Therapeutics, Dr Martyn Breeze, ‘ It should be excited ’. The technology involved in this new method of drug manufacturing, and the implications that its use may have for the pharmaceutical industry are discussed below, following an interview with Dr Breeze.

Sometime this year a human being is likely to receive a replacement organ from a pig genetically engineered for this purpose. It will not be the first time that animal organs have been used in an attempt to prolong human life. The first xenotransplantation procedures were conducted as early as 1964. So far, none can be considered successful - most recipients died within days, or even hours. The key problem is hyperacute rejection. This highly aggressive immune response can destroy the transplanted organ completely within minutes, and it cannot be controlled by immunosuppressive drugs. However, progress has been made. In this article, Inpharma ® looks at research that has led to successful pig-to-monkey transplantations, and examines the implications of this research for future transplantation practice in humans.

Sumatriptan has been the gold standard of migraine treatment since its launch 5 years ago. However, it accounts for only 8.5% of all migraine therapy prescriptions worldwide. The drug is not an option for some patients due to its high cost. For others, it is ineffective or unacceptable in available formulations. Further to this, sumatriptan will soon face competition from a number of new serotonin agonists that are reaching the final stages of development. The latest data on these competitors were presented at the 3rd European Headache Conference [ Sardinia; June 1996 ].

The second-generation cholinesterase inhibitor galanthamine is a promising treatment for the symptoms of mild to moderate Alzheimer’s disease. Preliminary studies suggest that it offers at least equal efficacy to that of Warner-Lambert’s tacrine, but without the risk of hepatotoxicity. Large pan-European phase III studies are now underway. Clinicians believe that if these trials confirm earlier findings, galanthamine will prove to be a major advance in the treatment of Alzheimer’s disease.

The market for hormone replacement therapy (HRT) products is vast and largely untapped. Two new concepts in HRT, recently launched in the UK, are hoped to realise that market by giving women easier, more palatable options for therapy. There are also plenty more ideas in the pipeline. One of the recently launched products is ‘Tridestra’. It is the first HRT product to be taken in 91-day cycles, resulting in 4 periods of withdrawal bleeding per year, rather than 13. It is licensed for the treatment of menopausal symptoms in peri- and postmenopausal women, and the prevention of postmenopausal osteoporosis.

Cabergoline, already used successfully as a treatment for hyperprolactinaemic amenorrhoea and the inhibition of lactation, is now awaiting approval as a treatment for Parkinson’s disease. It is the first long-acting dopamine agonist to be developed for this indication. Treatment with cabergoline appears to delay the need for levodopa in newly diagnosed patients, and reduce the amount of levodopa necessary for symptom control in patients with more severe disease. It has also been used to reduce symptom severity in patients with levodopa-associated motor complications. Results of the studies used in the European license application were presented at the First Congress of the European Federation of Neurological Societies [ Marseilles, France; September 1995 ].

Candoxatril increased exercise tolerance and reduced symptoms in a study involving 59 patients with mild congestive heart failure (CHF). This is thought to be the first study to demonstrate the effects of a neutral endopeptidase inhibitor on CHF symptoms. The results, which were presented at Heart Failure ’95 [ Amsterdam, The Netherlands; April 1995 ], led researchers to say that candoxatril could be used as first-line therapy in mild CHF, or as adjunctive therapy in more severe cases of disease.

Digoxin may be on the verge of a revival as a key treatment for congestive heart failure (CHF). During the last 2 decades, its efficacy in CHF was questioned, and concerns were raised over its effect on mortality. But now, there is increasing evidence to suggest that digoxin provides substantial benefit in terms of morbidity. The data were presented to delegates at Heart Failure ’95 [ Amsterdam, The Netherlands; April, 1995 ], along with details of a large trial that is expected to clarify digoxin’s effects on mortality once and for all.