Cheryl Lopate, MS, DVMDiplomate, American College of Theriogenologists Pyometra in the Bitch Pyometra is a condition that affects intact bitches, causing a variety of clinical signs and symptoms. Pyometra is typically pre-empted by pathologic changes in the uterus. The Greekderivation of pyometra is: pyo = pus and metra = uterus, so pyometra = an accumulation of pus inthe uterus.
469284 57.79East Asian Science, Technology and Society: An International Journal (2014) 8:57–79DOI 10.1215/18752160-2406053 The Reformulation Regime in Drug Discovery: RevisitingPolyherbals and Property Rights in the Ayurvedic Industry Laurent Pordie´ and Jean-Paul Gaudillie re Received: 21 March 2012 / Accepted: 29 May 2013q Ministry of Science and Technology, Taiwan 2014 Abstract In so-called traditional medicine in South Asia, substances have not ordi-narily been prescribed or consumed in isolation, yet the transformations of compoundformulations have been comparatively little studied from any position within anthro-pology or history. Since the early twentieth century, ayurvedic formulations haveoften been redesigned to address the biomedical disorders of a new global clientele.
This has involved overlapping medical cultures and the creation of heterodox epis-temologies, which have then allowed the creation of new "traditional" products thatsuit the demands of the market. In India, these new formulations fall under the cat-egory of "Ayurvedic Proprietary Medicines," which are distinct from classical, tex-tual (shastric) formulations already in the public domain. Proprietary medicines arethe object of specific systems of appropriation and protection, which have not onlygained central stage in the country but also influenced international regulatory bodies.
This article seeks to explore the way in which the "reformulation regime" has fosteredthe emergence of alternative models of property rights, and their global acceptance, aswell as how, in turn, these new forms of property have today come to drive pharma-ceutical innovation itself. By analyzing this "looping effect," this article sets outprospective avenues to study the industrialization of traditional medicine and thecomplex interface between regulatory systems, innovation processes, and the market.
Keywords Reformulation regimepharmaceutical innovationproperty rights L. Pordie´ (*)National Center for Scientific Research (CNRS), Research Unit on Medicine, Science, Health and Society(Cermes3), Parise-mail: l[email protected] J.-P. Gaudillie re (*)National Institute of Health and Medical Research (INSERM), Research Unit on Medicine, Science, Healthand Society (Cermes3), Parise-mail: [email protected] L. Pordie´ and J.-P. Gaudillie re In the past fifteen years, the present and future status of the pharmaceutical industryhas been at stake in many a controversy and public debate on intellectual property,therapeutic evaluation methods, the procedures governing access to drugs, marketregulation, iatrogenic risk prevention, and adverse effects. This technoscientific sectoris so greatly affected by the current tensions in the relationships among knowledge,medicine, economy, and society that its ways of mobilizing knowledge for half acentury have increasingly been called into question. Before the turn of the twenty-first century, such questioning of pharmaceutical research and development hasmostly come from practitioners and public health authorities in economically "devel-oping" and "emerging" countries, and more recently by user and patient organiza-tions. It is now also being questioned by companies and regulation authorities inhighly industrialized countries, highlighting what is increasingly labeled as a "crisisof innovation." The main signposts of this crisis are the declining number of newmolecular entities being put on the market and an increasing attrition rate.1 Manyobservers are now underscoring that the screening model that has dominated the sectorsince the end of World War II (large-scale chemical syntheses and standardized clini-cal trials) has run its course and that the therapeutic results of genetic biotechnology,which were in the 1980s and 1990s seen as the main source of renewal for the model,remain limited.2 The dominant innovation regime in the pharmaceutical milieu based on the chemi- cal synthesis of active substances and on a patent-based economy has itself entered aprofound crisis due to rising costs and declining returns of investments in chemicalscreening Large companies, aware that the patentsprotecting most of the molecules currently generating huge profits (so-calledblockbusters) will soon be in the public domain, have implemented a variety ofresponses—sometimes contradictory—by, among other actions, making intellectual-ownership standards more stringent, intensifying bioprospecting practices, andresearching new indications for molecules that have already been marketed. Thefragile situation of a flagship sector of the "knowledge economy" is not, however,exclusively of industrial origins. It has been made more acute by changes in medicaland clinical practices. What is in question is not only the effects of treatments that, inthe industrialized countries, have significantly extended life expectancy and thereforechanged the incidence and visibility of a whole series of chronic diseases, but also thefact that the boundaries of medicine have shifted, for example by giving greaterimportance to working "on" symptoms rather than identifying a nosological category.
Against this background and heightened by globalization processes, the pharma- ceutical innovation issue in India has moved radically away from the transfer modelassociated with postwar development strategies. The industrialization of India's scho-larly medicines and the institution of pharmaceutical infrastructures, which started inthe early twentieth century, are experiencing unprecedented developments today. Theemergence of a world specialized in the production, sometimes in the invention, and in 1 This decrease is even sharper when considering the molecules identified by drug-regulation agencies as sources of significant clinical improvement.
2 The works that have contributed to historicizing the screening model show that it was only a marginal form of innovation until World War II The Reformulation Regime in Drug Discovery the marketing of therapeutic specialties conveys a radical change in the nature and thescale of the "formulation" practices associated with ayurvedic medicine. However, theextension of procedures for pharmaceutical production and for standardizing labora-tory practices in India is not a replica of the dominant innovation model in highlyindustrialized countries. The innovation processes of the Indian ayurvedic industryindicate a form of alternative modernity that differs from the develop-ment models focused on knowledge and technological transfers by drawing from othertypes of knowledge than that of the molecular paradigm that has been prevalent inpharmaceutical research since the mid-twentieth century. The reformulation strategiesof traditional preparations promoted by Indian firms and researchers are in theiressence foreign to the chemical-screening model—a model that appears to be "anintellectually reductionist approach" when it is applied to the complexity of herbalsubstances and the learned knowledge of ayurveda Likebioprospecting, which was revived by the rapid growth of biotechnology, Indian firmsfavor the use of medicinal plants, but unlike the former, the purpose is less to purify theactive principles than to exploit the properties of polyherbal compositions.
In a context of accelerated industrialization, the ayurvedic industry is reinventing its remedies and in doing so is borrowing from various medical schools of thoughtand various techniques such as modern galenics, biomedicine, and traditionalmedicine as formalized in the framework of professionalization and the integrationpolicies implemented since Indian independence. Essentially based on what its actorscall "reverse engineering," this regime consists in reformulating and simplifyingayurvedic medicinal compositions in order to create new "traditional" drugs for thebiomedical disorders of an international as well as Indian clientele. This approachentails a deep change in ayurveda, because it supposes not only industrializationand moving to mass production, but also the emergence of a world of ayurvedicpharmacy focused on the collection and manipulation of medicinal plants in a spherethat had thus far been medical and clinical, claiming a "holistic" and individualapproach to illnesses.
The "reformulation regime" characteristic of the ayurvedic industry constitutes the example selected for this article.3 We have coined this expression to qualify contem-porary manufacturing and production practices in this industry, as well as their centralrole in reshaping the way traditional knowledge-based pharmaceutical innovationsare appropriated and protected by law. The reformulation regime therefore deeplyquestions the economic, epistemological, and regulatory context of pharmaceuticalinnovation. It is affected by fundamental tensions related not only to the epistemicstatus of the products and their problematic relationship with the ayurvedic texts andpractices, but also to their exploitation conditions. This article is divided into threemain sections that render these tensions especially visible. We tackle issues pertaining 3 In India, the existence of various differing innovation regimes reflects the existence of various types of medicine as well as of a hierarchy marked by the domination of biomedical knowledge that has prevailedsince the colonial age It should be said, however, that the "cultural authority ofbiomedicine" is not undivided. Work on intellectual property rights as applied tolocal knowledge indicates that hierarchies can be turned upside down, or at least used to the benefit of thelatter. For traditional practitioners, bioprospecting and ethnopharmacology, for example, legitimize theirown knowledge, underscoring the validity of their drug formulations ( L. Pordie´ and J.-P. Gaudillie re to the recombination practices—that is, the practices of reformulation themselves—tostandardization, and to the dynamics of property rights.
The reformulation regime can only be understood by studying all the factors, local and global, converging to determine these new practices. To these ends, we examinethe social dimensions of the drug-object in association with the technical dimensionsof the drug-in-society and use reformulation practices as a prism to do so. For instance,raising the technical threshold for patenting in India, which makes it more complicatedfor ayurvedic pharmaceutical companies to file patents is part of thepolitical and economic strategy of the country, which is keen to harmonize its pro-ceedings so it is able to comply with the Agreement on Trade-Related Aspects ofIntellectual Property Rights (TRIPS) and the international harmonization of intellec-tual property rights, while at the same time claiming to protect traditional knowledgeagainst "biopiracy." Even if local patenting practices are still more "open" than thoseof European or American patent offices, Indian companies producing plant-basedpreparations are part of a globalized system that is centered on the development ofnew markets expressed through the global regulations of therapeutic agents and thatalso seeks responses to the crisis of drug innovation and to mounting critiques ofits operations. Indian companies are also trying to expand their domestic market,which is targeted to the country's urban populations, by exporting products or drugsto the United States, Australia, the Middle East, Central Asia, Japan, and a number ofEuropean countries. These products are now part of the fuzzy array of "alternativetherapies and supplements." International marketing and diffusion of ayurvedic drugsare leading to a deep reconfiguration of the "traditional" recipes and remedies pro-duced by the industry.4 This article proposes to set out a number of avenues for research on these trans- formations. It explores new knowledge-building schemes in India, a country playingan ever greater role in the pharmaceutical sector and, more broadly, in the globaleconomy and its regulation.
1 Pharmaceutical Globalization Economic globalization is often approached as a worldwide unification of markets andthe generalization of neoliberal regulations and forms of governance. In pharmaceu-tics, a new phase in this complex process began with the changing role of the WorldHealth Organization (WHO) in the mid-1980s and the TRIPS agreement. This resultedin the international diffusion and recognition of drug patents includingin India, a country that had excluded therapeutic agents (as well as food) from thesphere of patentability in the 1970s in order to guarantee access to drugs (propertyrights were seen as leading to monopolies and price increases) and to maintain thefreedom to copy foreign technology and strengthen its industry.5 The United Statesinitiated the globalization of pharmaceutical patents to put an end to "pirating" by 4 On the globalization of Indian medicine, read, for instance, 5 For the paths and practices that brought medicine back into the domain of patentable inventions, read The Reformulation Regime in Drug Discovery countries like India—where copying was completely legal for the reasons justmentioned—and to generate incentives to develop local research that could thenbe appropriated.
Economic reasoning plays an essential role in the realm of pharmacy, including "indigenous pharmacy" but does not explain all the changes engenderedby pharmaceutical globalization. Understood less restrictively as a twofold move-ment—to extend circulation (of commodities, persons, or knowledge) and to set upprocedures to govern it—globalization has reconfigured "relations between the singu-lar and the collective, deeply affecting ways of thinking and of acting in all corners ofthe world" In pharmaceutical globalization, interconnections reachbeyond just market trading. Changes in the world of pharmacy in fact are not onlyrelated to trade and intellectual property but also have to do with standardizingresearch and production practices, with the nature of products judged to be usefuland useable, and with their use. The extension of circulation thus modified pharma-ceutical practices by imposing, for instance, the requirement to adapt products orig-inating in Asian medicine to the regulatory frameworks of certain European and NorthAmerican countries and to the expectations of consumers in those parts of the world.6As a result, the nature of these pharmaceutical goods, as well as their mandatoryproduction and evaluation standards, underwent radical transformation. In India,biotechnology and pharmaceutical laboratories have wished to demonstrate theirexcellence by complying with "good manufacturing practices"; they have soughtWHO and FDA certification and entered into vast transnational networks includingEuropean or American laboratories (academic and industrial).
Like previous waves of globalization, for instance the rise of international public health under the leadership of WHO and other UN agencies, however, contemporaryglobalization processes have met with resistance and alternatives to the innovationmodels encouraged by pharmaceutical multinational corporations or by European andNorth American countries. An immediate explanation—powerfully illustrated by the1970s debates at WHO—is that the innovations resulting from biomedical researchare targeted to health needs that are very distant from those considered as public healthpriorities in the countries of the "Global South." Contemporary resistance has alsobeen directed against initiatives aimed at bringing intellectual property procedures,and those used for the development of biological resources and for evaluating thera-peutic efficacy, into line with those of the United States and Europe. In the name ofa more "holistic" medicine, which is more sensitive to individual variations and lessfocused on the purity and properties of isolated molecules, opponents are demandingdifferent evaluation procedures from those used in countries of the North to testtoxicity and efficacy.
Despite these changes, literature on pharmaceutical innovation in the South is still mostly concerned by technological dependence and technology transfers from lab-oratories in the North Thus theestablishment of an Indian public and private pharmaceutical sector and the low levelof patent protection have led investigators to study the learning methods used forcopying technologies and adapting them locally 6 See for the case of Tibetan medicine in Great Britain.
L. Pordie´ and J.-P. Gaudillie re The research underlying this article looks at other dynamics inpharmaceutical globalization by focusing on the local production of knowledge.7While patenting remains an option, albeit less sought after, new innovation "regimes"and new "modes of regulation" are being developed outside of the pharmaceuticalproprietary economy.8 2 The Reformulation Regime To understand the magnitude of the change bearing on ayurveda today, a brief remind-er of this medicine will be useful here. The "science (veda) of life (a¯yus)" is a form oflearned medicine originating in Brahmanic tradition and set in Sanskrit texts as farback as the early centuries of the Christian era. The medical theory is based on humoralphysiological and pathological principles that explain both the healthy body and itsmalfunctions. The "therapeutic sections" (cikitsa¯stha¯na) in the ayurvedic texts men-tion the pharmaceutical uses and properties of a number of plants, parts of plants, anddrug formulations. Ayurvedic pharmacopoeia was fully expressed, however, in the laterliterary genre constituted by the Sanskrit materia medica dictionaries (nighantu). The pharmacopoeia is also a general taxonomy of living beings, ordered according toHindu cosmogony. Man and disease cannot be dissociated from their ecologicaland social context, which makes ayurveda more than simply medicine as generallydefined in the West Although this medicine is based on anenormous amount of literature, the texts do not constitute the only authority in medicalpractice and are, besides, the object of multiple interpretations by the therapists, whichleads to rather heterogeneous practices. Ayurveda is traditionally learned over manyyears from a master who acquired his knowledge by lineage, but this way of trans-mitting knowledge is now disappearing. Masters are being replaced by therapists whohave received shorter and less complete educations in the many ayurvedic collegesbuilt by the government since the 1950s. This form of medicine has been completelyintegrated into national health policy since the mid-1970s. The institutional curriculaand individual practices have both strongly integrated the concepts, tools, diagnosticmethods, and nosological and etiological categories of biomedicine.9 Medicalresearch and some forms of clinical trials aiming to certify the therapeutic efficacyof ayurvedic practices are now being widely promoted The mass production of drugs and derived products, a large part of which 7 This research was funded from 2009 to 2013 by the French National Research Agency in the framework of PHARMASUD, a multidisciplinary program that was developing a comparative approach to pharma-ceutical innovation processes in India and Brazil. Over the course of this program, the authors have con-ducted research in two private ayurvedic pharmaceutical firms, as well governmental institutions and officesand public and private research institutes.
8 For the concept of knowledge-production regimes in general, see For the concept of "ways of regulating" in the history of drugs and pharmacy, see 9 Integration of subjects from European medicine such as modern anatomy into institutional training was already noteworthy in the colonial era, which was marked by some hostility to Indian medicine. The growinginfluence of nationalist discourse in the pre- and post-independence periods prompted traditional therapiststo mobilize. Colleges and (small and medium-sized) pharmaceutical companies were then instituted andmany aspects related to the traditional sciences were removed from the curricula, which otherwise stressedthe importance acquired by the materia medica.
The Reformulation Regime in Drug Discovery are export oriented, has put Indian medicine at the heart of the global market of alterna-tive therapies. As such, ayurvedic drugs are subject to specific authorization and mar-keting mechanisms that include toxicity-testing procedures, and often efficacy testing aswell, that are consistent with the techniques and institutional system of biomedicine.
These procedures are gradually penetrating the world of reformulation, in some casescompletely. Companies and the government are unquestionably looking beyond justintegrating ayurvedic practitioners into health centers: they are increasingly concernedwith building pharmaceutical markets ().
Innovation through reformulation must be understood in this wider context. How- ever, the reformulation regime consists neither in integrating plant preparations intobiomedicine nor in adapting traditional practices into an industrial context; it consistsin reinventing a "traditional" drug by borrowing, for its development, from sometimesvery distant medical paradigms. The reformulation regime is a work involving arecomposition based on unique knowledge-prospecting mechanisms and singularindustrialization schemes for the remedies. Thus understood, drug "reformulation"redefines knowledge and preparation practices, focusing on the properties of complexmedicinal materials produced and sold on a mass scale for uses in which medicalcultures are mixed. An essential aspect of reformulation is that it feeds the emergenceof an autonomous "pharmacy" (in the sense of a world exclusively devoted to thera-peutic substances) that breaks with ayurvedic clinical practice both from a sociologi-cal point of view (preparations are no longer made by doctors but by personsspecializing in medicinal plants and their manipulation) and from an epistemicpoint of view (formulations are ready-to-use mixes for specific indications, no longerad hoc mixes that are part of an individualized treatment regime). Largely overlookingindividual humoral variabilities, the mass production of drugs thus tends to simplifyand depersonalize the act of healing. This process objectifies medicine by placing thedrug at the center of the clinical relationship . These changes coincideperfectly with the needs of the market.
The term reformulation thus not only aims at highlighting the fact that this form of industrialization combines Indian knowledge and practices with elements of biomedi-cine, but also underscores the importance of drug formulation in these changes. Thereformulation of drugs is thus both the object and the product of industrial practicesaiming to produce new drugs based on natural substances and on clinical practices thatare deeply modified, given that it links the prescription of these therapeutic agents tothe diagnosis of good "indications" by drawing extensively on biomedical categories.
In the reformulation regime, industrially targeted "prospection" of the body of tra-ditional literature plays an important role. Its goals are (a) to homogenize and controlconventional preparations that are formulations containing as many as several dozeningredients; (b) to simplify formulations in order to adapt them to mass production—either by respecting that they are mixtures or by simply promoting the use of singleplants—and to define therapeutic indications that combine, to some extent, ayurvedicand biomedical descriptions of the diseases; and (c) to change the formulations toadapt them to the global market and possibly isolate active chemical fractions forbiomedical research—sometimes done within the ayurvedic industries themselves.
We should not confuse the reformulation regime and its industrial nature with other forms of "reformulation" that characterize individual therapists and are fostered by theavailability (or lack thereof) of medicinal materials and the need to find substitutes, by L. Pordie´ and J.-P. Gaudillie re individual preferences, or again by economic constraints. The reformulation regimewe consider in this article is not a local or individual adaptation of drugs' composition.
Likewise, this regime takes as a basis the formulations and descriptions of plantproperties fixed in ancient texts (s´a¯stra), but its singularity comes from the factthat the aim is the industrial reformulation of remedies. This reformulation involvesmultiple translations in order to create new, ideally global, ayurvedic medicines forbiomedically defined ailments. The industry then "stabilizes" these new formulas forand through mass production as well as through appropriation and registration astrademarks under the label "Ayurvedic Proprietary Medicine"—which, comparedto patent, for example, appears to be the quickest and most cost-efficient means toenter the Indian market.
In a remarkable parallel with the vocabulary of chemists, certain actors of the industrialization of ayurvedic preparations speak of "reverse engineering" when refer-ring to the development of new drugs based on ayurvedic knowledge. A typicalsequence consists of identifying symptoms (and biomarkers) associated in the biome-dical literature with the targeted indication (or disease), seeking an equivalence inayurvedic medicine entities, listing all the formulations mentioning these entities inthe s´a¯stra, defining a simplified consensus formula (containing half a dozen ingredi-ents at most), and selecting a protocol to produce and test (possibly biologically) thisformulation. Such is the case for the drug named Diabecon, invented by the HimalayaDrug Company in Bangalore (see below). As the name suggests, this medicine isindicated for the biomedically defined diabetes (insulin-dependent or not), the symp-toms of which find their equivalent in an ayurvedic-defined disease called prameha (ormeha), which translates as "urinary disorders."10 The ayurvedic physician leading thedrug discovery department in this company told us that this ayurvedic disorder wouldcorrespond to polyuria, which includes diabetes (or, according to biomedical nosolo-gy, reveals the existence of diabetes). The classical formula used in the treatmentof prameha stems from a Sanskrit textual source from around the sixteenth centuryAD, namely, Bhai_sajyaratna¯valı¯, and comprises, among numerous other things, two important triads of plants: the three myrobolans (Terminalia chebula, Terminaliabelerica, and Embelica officinalis) and the three spices (Piper nigrum, Piper longum,and Zingiber officinale). These triads, as well as the main component in the classicalformula (the plant guggulu, Commiphora sp.) and the paste Vidanga¯di lauham (inwhich the plant Embelia robusta is the main component), remain as such in the newlyformulated Diabecon, which counts a total of thirty-three ingredients against a highernumber in the original, shastric formula. The new formulation has been chosen amongvarious others, which where all subject to toxicity and efficacy essays (animals andin vivo). The selected formulation then went to the Department of Formulation Deve-lopment, where it has been stabilized (through galenics) and rendered compatible tomass production. Since it is marketed, the mode of action of Diabecon is presentednot in ayurvedic language but in exclusively biomedical terms.11 10 We refer to as well as to the many personal communications we had duringinformal and formal meetings under the PHARMASUD program in Paris and elsewhere.
11 We read on the company website: "The natural ingredients in Diabecon increase insulin secretion in thebody. By reducing the glycated hemoglobin level (form of hemoglobin used to measure glucose content inthe blood) level [sic], normalizing microalbuminuria (a condition which is an important prognostic marker The Reformulation Regime in Drug Discovery This kind of necessarily approximate approach (incommensurability of medical paradigms, linguistic-translation difficulties and problem of conceptual equivalence,variability of botanical identifications in the reference texts, etc.) is systematicallyreduced to an ethnopharmacological exercise,12 renamed for the occasion "reversepharmacology" in the specialized literature.13 Contrary to what the authors suggest,reverse engineering is not self-evident. It is a very complex approach involving manyshifts from one range of knowledge to another (and therefore a chain of translations),each step of which requires scrupulous study at the practical, cognitive, and epistemo-logical levels.
A good example of the complexities of the reformulation regime is provided by the activities of companies like Arya Vaidya Sala (AVS), set up in 1903. The firm has botha production and research site and a network of clinics. Clients are patients who areoffered a course of treatment, the content and progression of which is defined by one ofthe firm's practitioners on the basis of a questionnaire (that can be filled out online) anda consultation (pulse-taking, constitution assessment, and diagnosis of humoral imbal-ances). AVS offers its clients formulations integrated into a therapeutic regime thatunderscores the traditional nature of administering preparations and their associationwith nondrug prescriptions, including diets, purging, enemas, or massages. AVS is,in fact, known to produce "traditional" ayurvedic drug recipes that is,recipes that are formulated in detail in very ancient texts: indications, content, dosage,the manufacturing principle for mixtures and associations—or yogam (union)—of theraw materials. AVS literature also underscores the traditional roots of the procedures,their relationship with the fundamental texts, their adaptation to the individual, andtheir cultural and symbolic significance calling on the relationship between micro-cosm and macrocosm. The drugs draw their legitimacy both from the authority of thetexts and increasingly from the development of new forms of knowledge. As far asmanufacturing is concerned, powder-reducing techniques and, more generally speak-ing, the production techniques did change in the course of the twentieth century. Thisevolution was characterized by the advent of mechanization, the use of evaluationmethods for product quality based on chemistry and physics or borrowing from mod-ern galenics. AVS also claims that its services are "modern" and "scientific" in thesense that they apply all the criteria of objective demonstration of the pharmacologicalefficacy except for statistical clinical trials. On the clinical side, the care of chronichealth conditions has come to the fore, combining in the same statements entities frombiomedicine (diabetes, hyperlipemia, and hypertension) and terms from humoral and for kidney disease in diabetes mellitus) and modulating the lipid profile, Diabecon minimizes long-term diabeticcomplications. The drug also increases hepatic and muscle glycogen content, which enhances the peripher-al utilization of glucose" (http://www.himalayahealthcare.com/products/pharmaceuticals/diabecon-tablet.
htm, accessed 29 January 2013).
12 Ethnopharmacology is a specialized branch of medicine born in the late 1970s. Its aim is to study carepractices, to contribute to their regulation and standardization, to evaluate the biological efficacy of itspharmacopoeia, and above all, to discover new drugs in it. Although there are very inclusive definitions ofethnopharmacology (the science is essentially based on theplants used in traditional medicine and on identifying active substances (13 See, for instance, for the most important teams in India, and L. Pordie´ and J.-P. Gaudillie re constitutional imbalances. AVS consultants are graduates of ayurvedic colleges, thecurricula of which systematically include a substantial biomedical part. Their clientsalso often come with previously established biomedical diagnoses and sometimesmanage a combination of treatments.
Procedures for reformulation and the industrialization of ayurveda are extremely diverse. The case of AVS is only one along a broad range of positions. The HimalayaDrug Company in Bangalore illustrates the other end of the spectrum. Set up in 1930,the firm distributes its products worldwide and has branches in Europe, the UnitedStates, the Middle East, and several countries in Asia. It does not operate like bio-technology firms, seeking only to isolate and synthesize the active molecules of plantpreparations; it revisits and adapts traditional formulations according to the principleoutlined above or, indeed, invents brand-new plant combinations or uses laboratoryprocesses to isolate and concentrate a particular fraction of the plant (then called"active marker") in order to enrich the preparation. The firm also underscores itsprofessional, "scientific" relationship with the prescribers. The Himalaya Drug Com-pany thus decided to build a market for its products by relying largely on scientificmarketing to biomedical professionals, pitching its practice of laboratory research andclinical trials, and using the positive results of controlled therapeutic trials conductedoutside the firm. Himalaya publishes several journals targeted to doctors in which partof its scientific work is presented—the rest of it being mostly published in biomedicaljournals.
One important question raised by this reformulation regime is therefore whether the globalization of ayurvedic preparations also changes biomedical practices, and howmuch. This question needs to be approached in two ways: on the one hand, by fol-lowing how certain products of the Indian companies become an integral part ofthe range of products prescribed by biomedical physicians in India (60 percent ofthe drugs produced by the Himalaya Drug Company are prescribed by biomedicaldoctors) and elsewhere in the West, in the latter case most often as an "alternative andcomplementary" therapy; and on the other hand, by following the research conductedin India, the United States, or Europe to turn certain preparations into targets formolecular innovation. The first configuration can be illustrated by one of the recentproducts marketed by the Himalaya Drug Company. Menosan targets the market formenopause hormone-replacement therapy, which went into crisis after the 2002 pub-lication of important statistical trials showing that using synthetic estrogen increasedthe risk of breast cancer and adverse cardiovascular events Menosan is a completely new, plant-based preparation whose invention fol-lowed the model of reverse engineering, that is, beginning with the mining of ancienttexts in search for menopause-like symptoms and their treatment. It is presented as a"phytoestrogenic" drug for which its efficacy on menopause symptoms is guaranteedby statistically controlled trials conducted under FDA standards but leaving out theexamination of biological end points in favor of well-being criteria. Although themarketing of the drug at the time of the debates and controversies that surrounded theuse of synthetic estrogens is fortuitous, for the Himalaya Drug Company, Menosan is a"natural," "traditional" response to the impasses of conventional pharmaceutical inno-vation, in particular to the multiplication of undesirable events among millions ofpatients resulting from the long-term use of risk-prevention substances.
The Reformulation Regime in Drug Discovery The second configuration is illustrated by the developments of a plant like guggulu (a local species of Commiphora) used locally to treat a variety of diseases, which hasbeen reconfigured as an anti-obesity drug. There has been a lot of research on guggulu.
In India as well as in the United States, preparations based on this plant have beenredefined as lowering serum cholesterol and lipoprotein. Their composition has beenanalyzed and reduced to a combination of sterones capable of binding a steroid recep-tor protein. The fate of these studies, however, reveals typical tensions of the refor-mulation regime. Although the animal modeling of the effects of guggulu resin hadbeen convincing as to their positive effect on the accumulation of lipids, the results ofcontrolled clinical trials mostly performed in India did not trigger the same consensus.
It gave rise to a controversy, not only about the validity of the statistical proceduresemployed but also about the way these studies are ranked and evaluated in the UnitedStates, without taking into account the links between the effect of extract adminis-tration and the food regimen and without considering the comprehensive nature ofayurvedic treatments These newly formulated ayurvedic drugs circulate within the sociotechnical net- work of contemporary ayurveda—a network that includes vaidyas (ayurvedic prac-titioners) as well as pharmacologists, pharmacognosists, chemists, graphic designers,salesmen, patent examiners, public health administrators, and so on. Although suchconstellations involve biomedical specialists, speaking of a "re-networking" of ayurvedic drugs in the sphere of biomedicine would miss the originality ofthe situation. A fundamental reason for that is surely the historical roots and strongidentity of the two above-mentioned firms in ayurveda and their reiterated claims tocompete with, and therefore resist, biomedicine. Most important, however, is the factthat the forms of innovations that create novel Ayurvedic Proprietary Medicines areexclusively based on plant compound formulations or single-plant fraction extracts.
They provide an escape to the biopharmaceutical innovation paradigm and the use ofsingle molecular entities and therefore make difficult, if not impossible, to "materiallyreducing [these] drugs into the constituents of [the biomedical] network" (ibid.: 345).
These new medicines offer a critical alterity to biomedicine: they are conceived,marketed, and consumed as ayurveda, in spite of the effort conducted to "modernize"it. This shows a clear distinction with the "Chinese propriety medicines" studied byElisabeth which include not only plant preparations in the form of com-pounds but also and increasingly often isolated molecules, as in the case of the anti-malarial artesunate. In this case, Chinese propriety medicines cross the biomedicalline, so to speak, and fail to provide the same kind of critic and alternative.
3 Alternatives to the Globalization of Patents on Drugs? The reformulation regime raises a second category of questions insofar as it is builtas an alternative, when not in opposition, to the proprietary economics of drugs;appropriation practices in this regime build property in a different way than that ofpharmaceutical patents, as in the case of "proprietary medicines." For ayurvedic prac-titioners and industrialists, the idea is to protect traditional knowledge from being filedfor patents (in Europe and in the United States), covering uses of biological resourcesas well as the preparation of plant-based therapeutic formulations. In practice, it is L. Pordie´ and J.-P. Gaudillie re state administrations (federal and regional) that are defending the stock of traditionalknowledge as "commons" by organizing the inventory and codification of "Indian"therapeutic knowledge. Firms, on their side, consider this knowledge as a resource forinventing, industrializing, and marketing preparations. To build their markets, theyare filing applications for both trademarks and (Indian) patents on formulations notrecorded in the classic texts.14 Compatibility between these patents and the claimsabout protecting traditional knowledge against appropriation hangs on two specific-ities of this mode of appropriation: first, patent applications are filled for "national"rather than international appropriation, thus leaving room for international campaign-ing against biopiracy; second, the patents seek intellectual property rights on thereformulations and not on the recipes included in the classical texts.
This conjunction between protection, access, and exploitation is now at the core of the attempt by the Indian government to foster international laws on the protection oftraditional knowledge. The exploitation of plants from India by a number of Westernpharmaceutical companies in the late twentieth century triggered a sharp reaction inthe country over intellectual property rights and biological heritage. The main episodeinvolved the neem tree (Azadirachta indica), a common tree with medicinal qualitiesthat is held in high esteem in India. In the mid-1990s, the US Department of Agri-culture and the pharmaceutical company W. R. Grace studied the local uses of the treeand eventually filed for a patent on the use of extracts that had pesticidal properties.
The American patent, which W. R. Grace tried to extend to the European Patent Office,was on the technical procedure used to obtain the extracts (the claimed innovation wasto have obtained an active composition without azadirachtin, the substance that hadthus far been held responsible for pesticidal activity) and not on the neem tree as such.
In India, however, it was considered that the original knowledge belonged to thecountry. From the Indian point of view, the commercial use of the patent constituteda wrong, one compounded by the fact that this was no ordinary tree. Locally, the neemtree is a sacred tree associated with a number of divinities. Its leaves, for instance,are used to decorate pilgrims' buses. It is used as a home remedy and appears in thecenturies-old pharmacopoeias of scholarly medicine; its therapeutic use covers infec-tious, parasitic, and dermatological diseases. Moreover, the neem tree is part of thecomposition of a remarkable number of modern cosmetic and hygiene products;villagers use it to smoke dwellings in order to keep harmful insects away. So thewhole of India, it was said at the time, was concerned. India made this tree a symbol ofits sovereign rights over its biological resources and its national medical knowledge.
The country took the case to court, in India and internationally. It took several years to build a convincing legal case, and the cost of the lawsuit went into millions ofdollars.15 In 1997, an objection procedure was taken to the European Patent Office(a procedure that does not exist in the United States) by the Indian alterglobalist 14 The Himalaya Drug Company thus diversifies the means to protect its products. For example, the drugDiabecon we mentioned earlier, as well as all other drugs created by the company, is registered undertrademark as an Ayurvedic Proprietary Medicine, but this does not preclude the fact that the firm may alsoattempt to apply for a patent in India or abroad—as it goes global, Europe- or US-based patents areincreasingly sought after. Over the last nine years or so, this firm has filed eighty-five patents, with eightgranted so far for innovations in therapeutic and personal care products.
15 This sum also covers expenses for the defense of two other similar cases, involving basmati rice andturmeric (Curcuma longa).
The Reformulation Regime in Drug Discovery activist V. Shiva, the European Green Party, and a European organic-farming non-governmental organization (NGO), with indirect support from the Indian PatentOffice.16 The opponents' arguments met with two difficulties: the first was relatedto the technical (molecular) definition of the invention, which had to do with theproduction of a new type of extract and not with its uses; the second difficulty wasthe absence of "scientific" sources that were acceptable to the patent office and couldprove that uses of the neem tree as a pesticidal or therapeutic agent were in fact drawnfrom "traditional" knowledge. The proceedings lasted eight years and in the end led tothe cancellation of the European patent on the neem tree based on the argument that theprocedures used by W. R. Grace were not innovative because the claimed protocol hadalready been used in India, completely bypassing the question of traditional knowl-edge This mixed success was read in different ways.
For many NGOs, the episode has become an exemplary case of unfair trade associ- ated with new forms of prospection for biological resources, but also an example ofsuccessful opposition to patenting and defense of a form of traditional knowledgeagainst wrongful appropriation, ironically conducted, in this case, in the name ofsustainable, "green" development. As for the Indian government, it concluded thatthe present working of the international patent system is ineffective for preventing"biopiracy." It gradually developed a specific policy fleshed out with local laws andinternational pressure for an agreement on the trade, use, protection, and preservationof traditional knowledge and phytogenetic resources (17 More generally, indigenous assets and knowledge acquired a central place innational conservation policies 101). In India, the initial administrativeresponse to the neem tree case consisted in setting up a new task force comprising thepatent office, the industrial-research advisory board, and the ministry of health. In2000, this task force recommended the constitution of a vast databank, the TraditionalKnowledge Digital Library (TKDL), aimed at making Indian therapeutic knowledgeand practices (ayurveda, unani, siddha, and yoga) available in a form that could beused by intellectual property management institutions so that it could be taken intoaccount during a prior art search. Begun in 2001, the TKDL staff's work consists in"transcribing" in a form adapted to patenting procedures the thousands of medicinalformulations described in the fundamental works used in the colleges that trained thepractitioners of Indian medical systems. This translation supposes a set of scarcelyobvious equivalences between the vernacular denominations of medicinal materialsand the botanical or geological denominations, on the one hand, and the etiologicaland nosological categories of the various therapeutic sets involved, on the other. Thedigital library currently presents in five languages thousands of plants and substancesused in the local pharmacopoeia and more than 230,000 drug formulations. The Euro-pean Patent Office has been authorized to consult it since February 2009.
16 Significant documentation regarding the Grace patent (EP90250319) and the opposition procedure isavailable on the EPO website (http://www.epo.org, accessed 6 February 2013).
17 Since that period, India has also intensively pursued research and development activities in the pharma-ceutical and chemical sectors with a view to improve their competitiveness L. Pordie´ and J.-P. Gaudillie re This formalization option is not purely an Indian phenomenon. It has been strength- ened by relations between India and the World Intellectual Property Organization(WIPO). The Indian experience is, in fact, at the core of WIPO attempts to set a legalframework for traditional knowledge. The intergovernmental work group, which wasset up in 2000 to develop a framework that could make compatible intellectual prop-erty rights, protection of biodiversity (as per the terms of the Convention on BiologicalDiversity), and profit sharing with societies whose traditional knowledge is industri-alized or marketed, not only upheld the Indian project but also adopted its forms ofinventory and categorization of traditional resources as a basis to amend the inter-national classification of inventions, which is currently used by patent offices. Moregenerally, WIPO developed a discourse on the nature of traditional knowledge and onthe need and the way to protect it, which favors the Indian positions on changes to thelaw on patents over those of Latin American countries on the institution of an entirelynew system of rights For the WIPO as well as for the Indianauthorities, recognition and protection of knowledge must be made compatible withtheir marketing and the appropriation of "substantial" innovations through patents(especially those dealing with technological or methodological procedures drawnfrom traditional knowledge).
Official WIPO documents consider traditional knowledge as radically different from "scientific knowledge." Traditional knowledge is given a holistic character,and its learning is seen as relying basically on oral transmission 18 Traditional knowledge is also held to be rooted in "communities" (in general,undefined) and in collective-property systems, warranting their protection throughtheir registration in the public domain. For the WIPO, specific rights need to beinvented that are compatible with commercial uses and the patent system. The privi-leged tools for this protection would be contracts certifying that the holders of tra-ditional knowledge consent to their use and ensuring a fair distribution of profits.
These considerations and developments are partially congruent with the Indian gov-ernment's intent as well as that of some ayurvedic pharmaceutical companies. Theselatter are claiming the "common" nature of the classical recipes so that they willremain accessible and open to mining by all Indian producers.
This definition of traditional knowledge and protection through collection and documentation agreements and the formalization of profit sharing with the local com-munities recognized as holders of traditional knowledge (the so-called benefit-sharingagreements introduced within the framework of the Convention on Biological Diver-sity) has at first sight no relevance to ayurvedic written and public formulations.
However, in the world of reformulation, there is not always a clear distinction betweencollection, protection, and exploitation, between indigenous and scholarly traditions.
A good example is in the invention of the Jeevani preparation marketed by the firmArya Vaidya Pharmacy. This new formulation with antiasthenic and immune-system-modulation properties originated in the ethnopharmacological prospection activitiesof the researchers at the Tropical Botanical Garden (TBG) in Trivandrum among 18 For more information on WIPO's work on traditional knowledge, see http://www.wipo.int/tk/en/tk/index.html.
The Reformulation Regime in Drug Discovery the Kani people in Kerala. The therapeutic properties of aarogyapacha (Trichopuszeylanicus), one of the plants in the composition of Jeevani, were known only to theKanis until the early 1990s. Informed by the Kanis, TBG researchers confirmed thepharmaceutical interest of aarogyapacha through a series of laboratory studies inanimals. They then proposed an ayurvedic identity for the plant and chose to includeit in an antifatigue formulation aimed at strengthening the effect of aarogyapachaextracts. For this purpose, they associated it with three more ingredients that werewell known in ayurveda and had effects that were judged to be complementary: longpepper (pipli, Piper longum), Indian ginseng (ashwagandha, Withania somnifera), andshankhpushpi (Evolvulus alsinoides). The first was chosen because of its ability to playthe role of adjuvant; the two others, because of their status of rejuvenating remedies.
The agreement among the researchers and the Kanis became an international model ofbenefit-sharing dynamics, and its uneven consequences have been widely discussedThe system of property rights associated with this reformulation isnevertheless not limited to the (formal) recognition of Kani knowledge and its con-tribution. It includes the patent on the formulation, obtained by the TBG researchersalone; the exclusive license they granted to the ayurvedic firm; and the certification bythe Kerala state controller of Jeevani as a proprietary ayurvedic remedy.
Another dimension of the appropriation logic and market building related to refor- mulation practices has its origin in the conflicts between conservation and collectionThe existence of a crisis in the supply of medicinal plants causedby the rapid growth of the market in the past fifteen years and the massive collection(80 percent of the total supply) of "wild" plants is being highlighted by the firms,international bodies specializing in environmental conservation like the InternationalUnion for Conservation of Nature (IUCN), local NGOs, and Indian regional andfederal administrations Many plants used in ayurveda arethreatened with exhaustion and even extinction. Theoretically, the sustainable solu-tion would be to move to in situ or ex situ culture. In 2000, the Ministry of Industry thusdecided to set up a public-private partnership for the management of medicinal plants.
The goal of the National Medicinal Plant Board (NMPB) was to organize the whole"chain" and in particular to increase supply to the market. The NMPB's initial selec-tion of three dozen strategic plants thus includes a majority of plants that are in highdemand on the market, for which the idea is either to improve and standardize culti-vation (when existing) or to promote domestication. In addition, the NMPB managesfinancial incentives to grow species that already are agricultural products. The impactof the program seems, however, limited due to a relative lack of resources and, moreimportant, to the internal contradictions of the domestication paradigm.
The Jeevani/aarogyapacha example is also telling here Tricho- pus zeylanicus is a species endemic to the reserved parts of the Keralese forest wherecollection is closely monitored by the government and is limited to the needs of tribalcommunities. Aware of the raw materials problem, the inventors of Jeevani thereforetried cultivating Trichopus zeylanicus, the predominant plant of the preparation. Theobjective was to allow the Kanis to grow aarogyapacha and to stop forest collection.
Experimental cultivation in open fields succeeded but at the cost of losing the thera-peutic properties of the extracts. Although the botanical garden researchers were notable to explain why, only the plants grown in situ, beneath the forest cover, preservedtheir active properties and could be used to produce Jeevani. The cultivation project L. Pordie´ and J.-P. Gaudillie re then faced issues related to rights to forest resources. In charge of a dual mission withthe aim of protecting and exploiting the resource, the Forest Department in Keralaopposed the cultivation in situ of aarogyapacha, taking the product of the firsttwo harvests and putting an end to the rise of Jeevani production. While it has beengoing on for ten years, this conflict may be now resolving with the negotiation ofan agreement authorizing the Kanis to grow the plant on condition that they keep itto forest edges.
Patenting Ayurvedic Proprietary Medicine is not unique to the trajectory of Jee- vani. The scientists working at TBG hold five patents granting them exclusive rightof use of the new formulations they have designed, which include aarogyapacha andayurvedic plants found in classical texts, among them an anticancer combination.
More generally, a simple survey of the Indian Patent Office website shows that duringthe past ten years, this institution has granted dozens of similar property rights. Theoffice has thus established a practice that actually grounds a new interpretation of theIndian patent law. At the time of its 2005 revision, whose main aim was to align thenational law on the international TRIPS agreement, the law quite clearly excludedpatents on traditional knowledge. Although understanding reformulations as noveltiesis not far-fetched reasoning for patent examiners, the IPO jurisprudence is a significantdisplacement: it potentially gives Ayurvedic Proprietary Medicines an industrial andlegal status akin to that of biotechnological inventions based on natural products. Thisform of appropriation may result in a "looping effect" bearing stronganalogies with the situation created by the US and European patent offices in the late1980s and early 1990s when they started on a routine basis to grant intellectual rightsover the "invention" of genes, arguing for the novelty and industrial utility of isolatedand chemically characterized DNA sequences The existenceof patents on reformulation is accordingly likely to trigger larger investments inreformulation work, which will in turn favor the appropriation of formulas.
The constitution of a right protecting knowledge drawn from Indian medicine is thus not only opposed to but also articulated with intellectual property rights and withthe building of new markets. The industrialization of ayurveda thus fosters irremedi-able tensions between firms, collectors, practitioners, and local governments.
4 Producing Standardized and Certified Drugs for the Global Market One additional specific aspect of the reformulation regime is the problem of standardi-zation. The standardization of traditional preparations and medicinal plants in Indiais one of the effects of the transition to industrial mass production. It is the source oftensions related to whether such homogeneity of products is needed, to the nature ofthe standardization procedures envisioned, and to the compatibility of these practiceswith the particularities of traditional formulations.
The discourse on standardization of preparations based on Indian medicinal plants is recurrent. It originates in firms, the Indian government, and a number of NGOs andinternational organizations. This is not surprising, as we are dealing with productsintended for circulation at the regional, national, and international scales, the distri-bution of which is increasingly bounded by debates about quality, toxicity, and control.
This situation is nonetheless problematic in view of the status claimed for preparations The Reformulation Regime in Drug Discovery drawn from Indian medicine, which involve complex mixtures whose production mustpreserve the synergies among constituents deemed essential to their efficacy and theirability to take patients' individual health needs into account. The discourse on stan-dardization is shared, but it covers a variety of different practices and goals.
For the AYUSH department, which is in charge of "Indian medicine" at the Min- istry of Health and Family Welfare, respecting formulations, developing the market,and making available products that are free of toxic contaminants are all part of publichealth policy.19 This approach considers the preparations themselves as free of majorside effects, as would seem to be indicated by their centuries of use. Added to this is theexport concern and the risk of having a marketing permit refused (in particular in theUnited States) because of possible contamination of the preparation by heavy metals,bacteria, and the like.20 Although oversight of the products is limited to their regis-tration in order to determine their tax status (traditional remedies benefit from total taxexemption or a reduced tax rate), the Department of AYUSH has published GoodManufacturing Practice guidelines, and registration of firms has become mandatory.21 The globalization of traditional medicines has also had the effect of strengthening WHO involvement. The organization has adopted a strategic plan for their develop-ment in which standardization has been selected as the means and condition of their"integration" into health systems and of their "universalization" Ratherthan promoting traditional medicines, which has been on the WHO agenda since theAlma-Ata conference in 1978, this choice extends a long tradition of intervening in thestandardization of biological products. The various WHO bodies have thus developedstrategic plans to simplify and generalize the procedures for toxicological or pharma-cological testing and adapt them to the approval of plant preparations One of the indicators of the conflicts between reformulation and standardization is thusthe question of the acceptable number of plants: for the WHO or the European Union,and unlike the Indian authorities, there can be only half a dozen at the most; otherwise,safety control and guarantee are impossible. This had direct implications in thereduction of ingredients in the new formulas drawn from the reformulation regime.
It is in the firms themselves that the discourse on standardization is most closely geared to the practices. For the industry, it is not just about ensuring marketing poten-tial, productivity, and quality by avoiding contaminants; raw materials also have tobe controlled. Although the health department had drawn up a reference list for tra-ditional preparations since the 1970s, several professional initiatives have recentlyextended this normalization arena with the writing of professional standards: theIndian association of engineers in the industry has produced its own pharmacopoeiawhile the National Institute of Industrial Research has established areference list for the plants used by the firms (These corpora refer tothe same problematic translations involved in reverse engineering or in the TKDLtranscriptions of recipes. In practice, what is being done? What are the targets, thecriteria, and the procedures of this standardization of the complex and the traditional? 19 This department was set up in 1995 as the Department of Indian Systems of Medicine and Homeopathy.
In 2003, it was renamed AYUSH, which stands for Ayurveda, Yoga, Unani, Siddha, and Homeopathy.
20 About the debates and controversies on the presence of heavy metals in drugs derived from Indian drugs,see 21 There is, however, no real knowledge as to whether these measures are applied and in which way.
L. Pordie´ and J.-P. Gaudillie re Two distinct aspects of company activity need to be considered: the organization ofmass production and the management of plants.
Let us go back to the example of AVS. Mass production favors the values of product homogeneity, reproducibility, and control of protocols. AVS thus combines two typesof procedures that are emblematic of the "pluralism" of this new pharmacy: on the onehand, those of a "traditional" workshop consistent with the recommendations of clas-sical ayurvedic pharmacy; on the other hand, those of a factory extensively usingmechanical innovations, machines to cut, dry, encapsulate, package, and so on—afactory complying with the ISO standards of the pharmaceutical sector, where everybatch is traced and tested for a small number of quantitative and qualitative criteria.
Under these conditions, what is standardized, and how is this done? What happens, forinstance, to elements such as the rasa, the taste of the remedies? These are at the coreof the pharmacological judgment of ayurvedic practitioners; they were codified andrelated with evaluations of chemical and biochemical composition as early as the1950s. Their status is now the subject of a new wave of "scientification." AVS isthus associated with a project aiming at the standardization of tastes supported bythe Institute for Ayurveda and Integrative Medicine, formerly the Foundation forRevitalisation of Local Health Traditions The issue here is notonly to standardize the organoleptic judgment for industrial quality control (as inthe food industry), but also to stabilize relations between therapeutic activity andsensory properties. These properties are used not to determine a drug's compositionbut as signatures of a specific therapeutic action, insofar as the five fundamentalproperties of the materia medica can ideally be derived from sensory attributes(taste, color, texture, smell).
Another specificity in AVS standardization compared to what is done in a bio- pharmaceutical or biotechnology company is the way it manages raw materials byunderscoring a "holistic" approach to plant properties, which is a correlate of usingentire parts of plants in the formulations. There are two dimensions here. The firstone is the conventional approach to control the collection, and in particular tohomogenize the evaluation of the quality of the plants collected for AVS usingbiological and/or botanical criteria. A second dimension of this form of standard-ization has taken the shape of specific research to reformulate traditional knowledgeas agroecological knowledge, integrating the plants into their ecosystem andexploring and objectifying the links among growing conditions, the dynamics ofthe plant populations, and therapeutic efficacy in order to avoid the domesticationdrama illustrated by the loss of efficacy in open-field cultivation of aarogyapatcha.
In line with these two approaches of standardization, AVS widely publicizes itsinvestments in (a) a conservatory garden containing seven hundred species; (b) alaboratory for in vitro culture and for the constitution of so-called reference chemi-cal fingerprints to evaluate the composition of the plants intended for production;and (c) a biobank (partly financed by a Canadian foundation) storing DNA, celllines, seeds, and computer data on the genome belonging to a few dozen speciesjudged to be strategic.
Discourses of standardization are thus particularly revealing of the underlying epistemic, technical, and social tensions in the governance and mobilization of tra-ditional medical knowledge. To explore them, more attention should be given to whatis done in practice, to the firms' operations in particular.
The Reformulation Regime in Drug Discovery The idea of reformulation regime we propose in this article questions the production ofnew forms of knowledge in the pharmaceutical field, as well as the reinvention ofmedical traditions—a term obviously inspired by the famous book by Eric The reformulation regime distinguishes itself from clas-sical formulation and practices but sees in these traditions the foundations of itslegitimacy.22 For Hobsbawm and Ranger, traditions are inventions of the presentday that relate systematically to the past. They are ubiquitous and serve primarilyideological or political aims. These traditions emerge more easily in periods of accel-erated social change, as these transformations threaten "ancient traditions." Whilethere is a political and ideological component in the new traditions issuing frompharmaceutical innovation in ayurveda—such as the revitalization of Indian traditionsconsidered to be threatened or lost—they cannot be reduced to it. These new tra-ditional drugs are essentially invented to meet consumers' needs and to enter drugmarkets. This article also highlights another dimension by considering the changesin the contemporary pharmaceutical milieu as likely to create new codes and newparadigms within the context of globalization and in response to it.
By focusing on the invention of complex extracts and plants combinations, the reformulation regime reorganizes practices around the identification, preparation,evaluation, and mass production of materia medica. It creates a world of experts,manufacturers, and consumers whose actions revolves around medicinal plants: froman increasingly problematic collection of raw materials to the multiple translationsat stake in the definition of medical uses predicated (or not predicated) upon a physi-cian's diagnosis and prescription. The new world of ayurvedic pharmacy thus stands atodds with the clinical practice of ayurveda—as revealed by the marginal status of theayurvedic nosology in the choice of indications—but it also stands at odds with thebiomedical world of pharmacy, which, when it comes to the uses of plants, remainscentered on the bioprospection model, that is, the mining of local resources in order toselect research materials, to identify and purify active molecules, and to make themavailable through chemical synthesis. The general framework for interpreting con-temporary changes in the Indian ayurvedic industry presented in this article thusconsiders innovation processes in this area as a form of modernity alternative to thedevelopment models based on Western knowledge and technological transfers. Thereare two reasons for this: reformulation draws from other types of knowledge than thatof the molecular paradigm that has been prevalent in pharmaceutical research sincethe mid-twentieth century; and reformulation is rooted in enlarged circulations fromSouth to North as well as between southern countries.
Exploring the reformulation regime therefore discloses conflicting issues related not only to the epistemic status of the drugs and their relationship with the ayurvedictextual sources and practices, but also to the conditions by which these products areexploited. These tensions are especially visible in the areas of standardization, oftoxicity (or efficacy) trials, and, above all, of property rights with the association of 22 This is a common feature in neotraditional therapies, which use "tradition" systematically to legitimatenew practices. For details, see and L. Pordie´ and J.-P. Gaudillie re systematic documentation practices in the name of protecting traditional knowledgeagainst "biopiracy" and appropriation strategies pertaining to national trademarks andpatents. A loop, which links reformulation and the granting of patents over AyruvedicProprietary Medicines, has thus been established. In the near future, such loopingeffects may lead to significant changes in the precarious balance between the inven-tion, protection, and appropriation of medical knowledge deemed traditional.
The reformulation regime is based on knowledge-production procedures that link the local with the global in a new way, since the idea is to create new "traditional"drugs for the biomedical disorders of a cosmopolitan clientele. Rather than turningayurvedic medicine into a local and marginal form of biomedicine, the practices ofreformulation accordingly reveal heterogeneous but deeply rooted processes ofspecialization, which isolate the manipulation of the materia medica, the designand production of polyherbals, from the clinic. Indeed, rather than looking at theseprocesses in terms of "biomedicalization" observers of contem-porary ayurveda may consider them as a form of "pharmaceuticalization." Introducedinto the study of Indian medicine by Madhulika and to insist onthe pharmaceutical and commercial status of industrialized ayurveda, this term mayalso be used to denote the cognitive and social dynamics of reformulation and, therein,its peculiarities. However, what is at stake with the "pharmaceuticalization" of ayur-veda is not the disappearance of Indian traditions in the drugs themselves. Accordingto "Ayurvedic pharmaceuticals become undistinguishablefrom any other pharmaceutical. They neither continue to carry the distinctive marks oftheir original knowledge system nor require their specific context to be effective. Thusthe capacity of Ayurveda to be able to pose an ‘alternate' system is being graduallyeroded." As indicated in this article, these claims do not stand when one closelyexamines the range of knowledge involved, the practical work of reformulation,and the products it delivers. What we are witnessing today is rather the emergenceof a new configuration of ayurveda.
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Laurent Pordie´ is an anthropologist; senior researcher with the French National Center for ScientificResearch (CNRS) at the Cermes3, a unit focused on medicine, science, and society; and a member of theCenter for South Asian Studies at the E ´ cole des Hautes E´tudes en Sciences Sociales (EHESS), both in Paris.
Jean-Paul Gaudillie re is a historian of science, a research professor at the Institut National de la Sante´ etde la Recherche Me´dicale, and director of the Center for Research on Science, Health, Medicine and Society(Cermes3) in Paris.
Cuando despertaron la mañana del 2 de noviembre de 2004, millones de votantes del Partido Demócrata norteamericano contemplaron un nuevo orden. El humo de las hogueras neoconservadoras se elevaba sobre todas las ciudades del Sur y del Este. Las peludas hordas del fun- damentalismo cristiano, las legiones de obreros y campesinos blancos y de otras culturas visigodas se agitaban detrás de sus remotas trincheras.