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‌A human drug amid animal diseases: The ecology of globalised heparin

‌Thibaut Serviant-Fine

Historian Dominick LaCapra (2023) has stated that ‘as a rule, the problem of globalisation is confined to humans’, and this presupposition has kept research at the intersection between globalisation studies and animal studies scarce. Yet, an emerging body of scholarship has been increasingly discussing the status and significance of animal life in globalisation dynamics, for example regarding the commodification processes operating in global wildlife or pet markets (Collard 2020; Haraway 2008), the impact of the globalisation of law upon animal welfare and health (Blattner 2019; Park and Singer 2012; Sykes 2016), and the use of animal materials in the fabrication of health commodities intended for international markets (Chee 2021; Gameiro and Quet 2023). In addition, the vast literature guided by the ‘One Health’ approach has explored the multiple ecological entanglements between human and non-human animal health, the most prominent of which consists of the spread of non-human zoonoses to humans (Brown and Nading 2019; Craddock and Hinchliffe 2015; Kelly et al 2018) and of the impact of such phenomena upon the structuration of global health organisations (Fearnley 2020; Kelly et al 2020; Lakoff 2008). Building on these contributions, the following chapter intends to delineate the entanglements of three features of contemporary globalisation: the worldwide extension of raw material procurement practices through increasingly long logistical chains, the geopolitical and economic readjustments between countries or geographic areas associated with the shifting meaning of expressions such as ‘Global North’ and ‘Global South’, and the industrial transformation of animal matter into key raw materials. In this effort, our guiding interrogation is about the role of animals in the fabrication of globalisation processes: to what extent do animal populations, especially through epidemic episodes, contribute to shaping the practices of procurement and, in turn, the relations of dependence and domination between countries labelled as belonging to the Global South or the Global North? In order to answer this question, the chapter discusses the evolution of global procurement practices pertaining to heparin, an anticoagulant drug, for its production.

The world’s consumption of heparin requires vast quantities of animal matter for its manufacturing – two-thirds of which originate from the bodies of Chinese non-human animals, a factor that is crucial to understanding the global pharmaceutical industry’s growing dependence on factory farming through transnational supply chains. In spite of their predominant role, the importance of animals and animal matter in this globalisation phenomenon is barely acknowledged. In global trade statistics, they exist only as pharmaceutical components, and drug manufacturers consider them as inputs. There are, however, moments when this importance gets the attention it deserves: when animals fall sick. The biomedical operations that support human health using heparin increasingly rely on the industrialisation of animal life, which has led to production on unprecedented scales, and depends upon complex and highly international sourcing operations. The growing exploitation of non-human animals for a global market has heightened the risk of emerging diseases and paradoxically increased the vulnerability of the heparin supply chain. These animal diseases have had major consequences on the global heparin supply in three recent successive episodes, which inform the chronological structure of this chapter. The first episode was the epidemic of bovine spongiform encephalopathy, or mad cow disease, in the 1990s. The second was the scandal of adulterated heparin originating from China, in 2007–2008. The last episode pertains to the global effects of the African swine fever pandemic, which have been growing since 2018. Each episode changed the patterns of heparin production and circulation; it impacted as well as it reflected the structuration of global pharmaceutical markets. The first occurred at a time when globalisation was triumphant and long-distance outsourcing relatively unquestioned in dominant discourses. With the 2008 scandal, doubts emerged regarding pharmaceutical markets, which appeared to be globalising rapidly and perhaps uncontrollably. Finally, the third episode saw the mainstream consolidation of more direct criticism of global pharmaceutical flows, amid shortages and supply chain disruptions.

Animals are not the only actors in this story: the Chinese pharmaceutical and agro-industrial companies have developed greatly over the last 30 years and have now become the main suppliers of active pharmaceutical ingredients worldwide, from multinational companies in the North to Indian generic companies, and consolidated large companies innovating with new finished drugs (Zhang and Bjerke 2023). The country’s pig farmers, once food producers, have become key suppliers of the global pharmaceutical industry, competing with the animal industries of Iowa, in the USA, and Brittany, in France. Once considered subaltern actors, these companies have become major players in the global heparin industry. Highlighting the Chinese industry’s position as the hub of polycentric flows helps us nuance the conventional representation of South-to-North supply circuits and demonstrates how technological and regulatory change on a global scale can also be triggered by formerly dominated actors. Through this perspective, the ecological interconnections required by heparin production bring attention to the ways in which the material products that ensure human health, their sourcing, and the flaws related to their procurement influence the globalisation of pharmaceutical markets and alter conceptions of North and South as dominant/dominated or emerged/emerging entities.

This chapter results from research conducted from 2021 to 2023 within the Anipharm project,1 which analysed the pharmaceutical uses of animal life. It relies upon a systematic analysis of the grey documentation pertaining to global heparin markets, as well as a collection of media reports documenting the impact of zoonotic crises upon heparin procurement and production. After a section introducing heparin as a global medicine, each of the three next sections discusses one epidemic episode and analyses the articulations it revealed between animal populations, procurement chains, and geopolitical power relations. Exploring the dependence of the heparin supply chain on industrialised animals will eventually raise the question of the conditions needed to maintain the supply of and access to this drug for a large population, and the environmental sustainability of its mode of production.

Heparin: Animal matter as a global medicine

Historically, non-human animal matter has been widely processed to produce therapeutic products, across different geographical and cultural contexts. But acknowledgement of the fact that animals are still ubiquitous in human medicine today is not a given. The use of laboratory animals has long been publicised, which has led to many changes. However, the continued use of animals as drug production material is less recognised. The discovery of this persisting presence often prompts a puzzled response in Western biomedical settings. The use of animals in medicine is usually seen either as a relic of the past or as the preserve of so-called traditional medicine. Over the last century, the advancement of synthetic chemistry and subsequently biotechnology gradually reduced the use of animals as a primary source of matter for drug production, and more generally decreased dependence on harvesting natural resources for healing (Schwerin et al 2013). In parallel, rising concerns about animal welfare have also fuelled efforts to minimise animal use. However, in spite of these developments, animal use in human medicine has continued to grow. The linear narrative of therapeutic progress moving away from old remedies must be nuanced in order to account for the hidden persistence of animal matter in biomedicine. Heparin is a particularly apt example of this persistence, as its production did not follow this downward trend but quite the contrary.

Starting in the nineteenth century, the advent of new chemical tools gradually led to the analysis and processing of natural resources, driven by a quest for physiologically active materials, purified extracts, or isolated substances. At the turn of the twentieth century, with the emergence of new biochemical methods, many animal extracts were being tested for their physiological activity. These extracts often originated from slaughterhouses, at a time when the uses of animals for human nutrition were starting to be deeply transformed by the rise of the industrial food system (Lee 2008; Specht 2020). Readily available animal matter from slaughterhouses, combined with improved technical methods for extraction and standardisation, provided experimental material for the advancement of physiology and endocrinology. This led to the discovery of hormones, the therapeutic production of which relied on the interconnection between growing pharmaceutical companies and food industries (Clarke 1995; Oudshoorn 1994). The most well-known and impactful discovery in this field was insulin, in the early 1920s, but heparin was also one such substance extracted from animals. First identified in the 1910s in dogs’ livers, heparin consists of a family of very large molecules of close but variable compositions. As the first preparations were quite toxic, heparin only began to be used reliably in clinical settings after its preparation was improved, in the 1930s in Toronto, by the research group that had first prepared and used insulin. It was developed into an essential anticoagulant drug to prevent and treat embolism; prevent blood clotting in surgery, blood transfusion, and dialysis; and for other specific indications. Heparin is also used as a reagent in test tubes for a range of laboratory analyses of blood to prevent the clotting of samples, or in heparin-coated catheters, aptly illustrating how animal matter may be hidden deep within routine and essential biomedical infrastructure.

At present, heparin-based drugs are mostly manufactured using byproducts of industrial pig farming, and beef production to a lesser extent. While close to two-thirds of the global heparin supply comes from China (Agence Nationale de Sécurité du Médicament 2014: 2), it is also produced in other countries, such as the USA, Brazil, Argentina, India, France, Spain, Italy, and Germany. The distribution of the contemporary geographies of heparin production and consumption between the Global North and the Global South has become increasingly complex: a French industrial site may process raw heparin sourced either locally, from China, or from the USA to make an intermediary product, which it will then send to Singapore for the preparation of the finished drug. Likewise, raw heparin extracted in Iowa may be sent to the Netherlands for purification, then to another French factory for processing into another heparin-based drug, and Chinese raw heparin is supplied to Indian companies that manufacture generic heparin for Asian and African markets.

Over the course of the twentieth century, while the use of animal resources to prepare drugs decreased, heparin followed the opposite trend and was increasingly consumed, mainly due to two factors. First, technological innovations relating to heparin expanded its usability and applications, especially in outpatient treatment. In particular, the development in the 1980s of low-molecular-weight heparins (LMWH), which weigh fractions of the larger unfractionated heparin molecules, reduced side effects and the need for monitoring of potential sudden and dire side effects such as heparin-induced thrombocytopenia. Second, the demand for heparin exploded. In high-income countries, the aging population was increasingly subject to medical conditions requiring anticoagulant drugs, while low- to middle-income countries also started adopting heparin in medical practice. However, as heparin consumption increased, a parallel unrelated development came to affect its distribution, namely the advent of mad cow disease.

Episode 1: Mad cows in the North and the turn to China

In the mid-1980s, the epidemic of bovine spongiform encephalopathy (BSE), or mad cow disease, emerged in the United Kingdom. After characterising the disease, pathologists soon noticed that the brain tissue of affected cattle presented similar lesions to those observed in sheep affected by scrapie. The cattle disease was rapidly associated with animals that had consumed meat-and-bone feed, a foodstuff made of processed offal from a variety of animals. This type of feed was promptly banned, but cases continued to soar and peaked in 1992–1993. This generated widespread fear that the disease could be transmissible to humans, even though no such cases had occurred with scrapie. Based on its histology, it seemed that BSE could be similar to Creutzfeldt-Jakob disease (CJD), a rare neurological disorder; a monitoring unit was promptly established. In 1995, a variant of the disease, shortened as vCJD, was identified when individuals younger than those usually affected by CJD started to show symptoms: vCJD in humans was associated with eating BSE-infected meat, which the UK government officially recognised just a year later, in 1996. The suspicion that the use of beef materials to make medical products could cause the transmission of vCJD to humans led to the precautionary ban of these materials for heparin production in the late 1990s, in the USA and Europe.

While beef lungs were used until the 1950s, they were not ideal material, as the processes employed to treat them could degrade heparin and their pungent rotting raised issues with local communities. Intestinal mucosa from cows or pigs, a readily available byproduct of sausage casing manufacturing, were preferred by the industry. Paying attention to the concrete matter required in production processes allows us to ground the study of pharmaceutical flows, which are often approached through the prism of their economic dimensions. In the mid-twentieth century, a truckload of 40,000 pounds of pig mucosa produced five pounds of heparin (0.0125%) (Barrowcliffe 2012; Coyne 1981). These quantities show how closely interlinked the food and pharmaceutical industries were surrounding these specific processes, as the vast amounts of materials required meant that the slaughtering facilities and processing plants needed to be in close proximity. Heparin thus strongly maintained and even extended this connection, as its production necessarily originated in countries where animal materials were readily available (United States, France, Canada, Germany, Netherlands, Denmark, etc.).

In the 1970s, sourcing became more diversified: beyond local sources, some companies started to look for countries with large pig herds, such as China (still by far the main producer of pork worldwide). When BSE struck, pig intestines were already favoured, but with the ban on beef intestines as another available source, the pharmaceutical companies concerned quickly moved to secure their sourcing of pig material. This significantly accelerated the general turn towards China and expanded the supply chain to secure the necessary materials as consumption grew. At the time, the potential risks associated with this expanding supply chain and the reduction of animal sources from two main species to one were not clearly described or questioned, as though material flows would naturally keep up with the need to source elsewhere.

The increase in heparin consumption had given rise to staggering demand for raw materials. An investigation for a French consumer magazine noted that half of global heparin production came from Chinese pigs, with an estimated 500 million intestines per year needed (Browaeys 2005). A 2014 report by the French national agency for drug safety quoted the same figure and estimated that 55–60% of these pigs came from China (Agence Nationale de Sécurité du Médicament 2014: 2). In a 2016 interview, Ruixin Miao, head of the heparin-trading company Nanjing Kaiyang Biotech, estimated that ‘owing to productivity improvements, it now takes about 1,500 intestines to produce 1 kg of heparin’ (Tremblay 2016). He estimated that 300 million pigs in China could produce 17.6 million megas (a measurement unit) of heparin, and that global demand amounted to 28 million megas. According to his estimate, the number of pigs required to meet global demand stood at 477 million, close to the figures quoted above. Comparing these numbers to the global availability of pork material gives a sense of the level of dependency on industrial farming for the production of this essential drug: while 1.3–1.5 billion pigs have been slaughtered every year since 2010, this number was closer to 1 billion around the year 2000, and if we go back to the 1960s, the 500 million intestines required would have accounted for the entire global pig population.

Episode 2: Dying pigs and deadly fraud

The second episode occurred against the backdrop of growing heparin consumption and the broader global shift toward China as a key supplier. Amid this trend, a major scandal emerged around the adulteration of heparin sources. This involved the inclusion of oversulphated chondroitin sulphate, a substance hard to differentiate from heparin. The likely motive for this adulteration was the sudden scarcity of pigs (and their materials) due to a deadly virus that severely affected the animal population in China.

By late 2007, an unusually high increase in very serious adverse effects associated with heparin treatments, including deaths, alerted the US health authorities and Baxter, the company that had produced the drugs concerned. In mid-January 2008, Baxter recalled several specific batches, then issued a nationwide recall a few days later. The FDA and Baxter were faced with a difficult decision to make, as a larger recall could lead to shortages of an important drug. Baxter sourced the active principle, raw heparin, from a Wisconsin company, Scientific Protein Laboratories, which manufactured half of its heparin from Midwestern pork and sourced the other half from a Chinese subcontractor, Changzhou SPL. In mid-February, the New York Times revealed that the FDA had never inspected this subcontractor (Bogdanich and Hooker 2008; Harris 2008).

This gave rise to a public discourse of regulatory negligence, which formed the basis of a subsequent political inquiry. The FDA organised scientific coordination to investigate issues with batches causing anaphylactic reactions; within a few weeks, this led to a consensus on the presence of an undetermined contaminant that resembled heparin. In parallel, in early March, German authorities also reported the recall of heparin batches following side effects resembling those of the US cases. These batches were linked to another raw heparin supplier, suggesting that contamination had occurred in the supply chain upstream of the Chinese subcontractor (since batches from different suppliers caused the same side effects). Recalls were issued in a dozen countries worldwide. By mid-March, the contaminant was formally identified as oversulphated chondroitin sulphate, a substance resembling heparin that is quite rare naturally, and that could not have been a result of the heparin purification process, at least not in the very high concentrations found in some samples (Guerrini et al. 2008). This array of evidence, combined with the fact that this specific contaminant could not be detected by outdated reference pharmacopeia tests, prompted the hypothesis of voluntary contamination. A month later, experiments with animal models linked the substance to the type of allergic reactions observed in patients, thus articulating the analytical hypothesis with physiological consequences (Kishimoto et al. 2008). Ultimately, within a few weeks from the first clinical reports to the recalls and then the development of analytical tests to identify contaminated batches, this major pharmaceutical scandal caused approximately 200 deaths, mostly in the USA and Germany.

The explanation for the batches’ contamination upstream in the supply chain is linked to an animal pandemic. Earlier, in June 2006, signs of the spread of a porcine disease commonly called blue ear disease had appeared in China. The Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), first recognised in the late 1980s in the USA, causes high mortality among piglets, and among adult pigs to a lesser extent. Vaccines have been developed, but the virus variants can evolve genetically in highly diverse ways and can thus escape immunity2. As with BSE, this epidemic was inextricably linked to industrialised farming. The large-scale emergence of this virus after a long evolutionary history was tied to the growth of high-density pig farms in the second half of the twentieth century, as several factors ‘radically alter[ed] the ecological niche of PRRSV and facilitate[d] an explosive evolutionary radiation’ (Murtaugh et al. 2010). The emergence of a new virulent variant induced the 2006 epidemic, which spread across half of China and, according to several teams of Chinese researchers, affected more than 2 million pigs over the summer of 2006 with a 20% death toll, amounting to 400,000 individuals (Tian et al. 2007). The virus kept circulating, and a new outbreak developed over the following summer. Circulation of the virus was now reported in most Chinese provinces, with journalistic investigations reporting numbers of devastated herds seemingly incompatible with the official figures quoted above (Barboza 2007; Cha 2007). At the same time, the numbers reported by the Chinese Ministry of Agriculture and by industry were wildly different, ranging from thousands to millions3. The epidemic had a noticeable effect on wholesale pork prices and consequently on the price of crude and refined heparin, which more than doubled between May and November 20074. As oversulfated chondroitin sulphate is far cheaper than heparin, voluntary contamination was thus economically motivated: oversulfated chondroitin sulphate was used as a substitute to reduce costs in the context of rapidly rising heparin prices.

This episode unfolded at the crossroads between this emerging disease and pharmaceutical globalisation with the turn towards China during the 2000s. In the specific case of heparin, the turn towards China was dictated by the need to find new abundant pig sources following the BSE crisis. The heparin scandal was a milestone in debates on fake medicines and pharmaceutical globalisation. While the scandal of adulterated heparin occurred in the still dominantly triumphant stage of globalisation preceding the 2008 financial crisis, for many it was a harsh wake-up call regarding the rapid mass displacement of pharmaceutical production to China and, more generally, the difficulty of monitoring increasingly complex global supply chains that rely on outsourcing and subcontractors. In the United States, critical perspectives on the uncontrolled consequences of pharmaceutical globalisation and the difficulties associated with its regulation started to crystallise within the discourses of elected officials as well as FDA scientists and administrators. Testifying at a hearing in the House of Representatives, Janet Woodcock, director of the Center for Drug Evaluation and Research at the FDA, stated:

The sites of production of pharmaceuticals have changed. […]. Over the past 15 years, the majority of active pharmaceutical ingredient manufacture and actually increasing amounts of finished drug product manufacture has moved off our shores, been outsourced. For example, generic drug applications processed in 2007 at the FDA referenced over 1,000 foreign sites; 450 of those were in India, 497 of those were in China for API manufacture of those generic drugs. And only 151 of them were in the United States. The rest were in other countries around the world. The FDA of the last century is not configured to regulate this century’s globalised pharmaceutical industry (Committee on Energy and Commerce, 2008: 45).

Alarmed commentary proliferated in the public sphere. To quote one of many examples:

Like the canary that stops singing in the coal mine, the heparin safety crisis is an early and urgent warning of the vulnerability and impending failure of our drug safety system. We must respond to this warning with an extreme sense of urgency if we are to prevent more catastrophic failures of this system as a result of either mistaken or intentional drug adulteration. (Leiden 2008: 626)

In most discourses, however, the solution identified was stricter regulation to prevent the dire consequences that could ensue from the ill-intentioned exploitation of the seemingly inevitable globalisation trend. While the heparin scandal shed stark light on the growing issue of counterfeit drugs, it also provided a ready-made solution to rescue the globalisation process – adaptation through regulation – rather than questioning the outsourcing trend and increasingly complex supply chains (Quet et al. 2018).

While the FDA was harshly criticised for failing to regulate, it was also praised for its rapid response, which prevented more deaths. The FDA was able to leverage the shocked reactions to the scandal to gain more regulatory power, particularly with the FDA Globalisation Act of 2009. In parallel, it coordinated the reviewing and strengthening of quality control testing for heparin through the development of new tests (Szajek et al. 2016).

In this episode, a set of unknown actors, upstream in a globalised supply chain, locally adapted to a large-scale pig epidemic and used technical biochemical knowledge on heparin production and regulatory testing to make a profit by introducing a deadly fraud in the commercial circuits of heparin. The dire consequences, for patients, had worldwide ripple effects on the regulation of drugs. While one can (and should) point out the dreadful impact that adulterated drugs can have on patients downstream, these consequences were also the result of an uncontrolled globalisation process in which regulation always tends to be introduced only after the realisation that something has gone badly wrong. In this particular case, the pharmaceutical companies that produced finished heparin drugs had until then been free to source animal matter from wherever it could be found:

Interviews with dozens of heparin producers and traders in several Chinese provinces, as well as a visit to a village near here dominated by tiny family workshops that process crude heparin from pig intestines, show the difficulties confronting investigators as they seek to trace the supply chain. […] The Chinese heparin market has become increasingly unsettled over the last year, as pig disease has swept through the country, depleting stocks, leading some farmers to sell sick pigs into the market, and forcing heparin producers to scramble for new sources of raw material. Traders and industry experts say even big companies have been turning more often to the small village workshops, which are unregulated and often unsanitary. […] Some experts say as much as 70 percent of China’s crude heparin for domestic use and export comes from small factories in poor villages. One of the biggest areas for these workshops is here in coastal Jiangsu Province, north of Shanghai, where entire villages have become heparin production centers. In a village called Xinwangzhuang, nearly every house along a narrow street doubles as a tiny heparin operation, where teams of four to eight women wearing aprons and white boots wash, splice, separate, and process pig intestines into sausage casings and crude heparin. (Barboza and Bogdanich 2008)

Following the scandal, the FDA launched another move to reorganise the heparin supply chain and rewire the circuits of globalisation to disentangle them from China, through the coordination of expertise from both the Global North and the Global South. A discussion to reintroduce heparin sourced from bovine materials took place in June 2015, at an FDA Science Board Public Meeting (Al-Hakim 2021). Speakers voiced their concerns regarding the stability of a supply that relied mostly on one major source, Chinese pigs, pointing either to the case of porcine disease or to geopolitical instability. Reintroducing bovine sources could provide a way to broaden the geographic distribution of the animal resources needed and reduce the risk of shortages. The first issue surrounding the reintroduction of bovine heparin was how to compare its activity profiles with heparin of porcine origin: for example, as bovine heparin is less active, doses have to be adjusted. Moreover, side effects, notably allergies, needed to be taken into account. Broadly speaking, the most recent research pertained to porcine heparin. The second issue was the possibility of contamination by prions. Proponents of bovine reintroduction, such as the FDA, advocated the reevaluation of biosecurity risks: the significant amount of knowledge on prion inactivation gained since the BSE crisis could be incorporated into heparin production processes to reduce contamination risks. The use of cattle coming from countries free of the disease could further reduce risks. The National Institute for Biological Standards and Control (UK) and United States Pharmacopeia organised workshops on the characterisation of heparin-based products in 2015 and 2017, notably convening with experts from countries that had maintained the use of bovine heparin, such as Brazil, Argentina, and India. Global South expertise is thus being used in the current reorganisation and diversification of global heparin circuits.

Episode 3: Shortage fears and synthetic hopes

Within a few years, the risk of heparin shortages soon materialised, due to yet another animal epidemic that dealt a massive blow to Chinese pig herds and stretched the heparin supply thin. This last episode relates to African swine fever (ASF). As SARS-CoV-2 swept across the globe in early 2020, various Chinese animals became the centre of attention worldwide. But starting in 2018 and 2019, another developing pandemic, African swine fever, took hold in the country and swept through pig herds. In 2010, the PRRS virus had been termed ‘the most significant swine disease worldwide in spite of intensive immunological interventions’ (Murtaugh et al. 2010: 18) because of its high economic impact. Less than ten years later, these recurring outbreaks were dwarfed by the sheer scale of the new pandemic, which kept expanding worldwide. ASF spreads in factory-farm pigs, but also in wild boars: the countermeasures that are applied in Europe to try to stop the spread are thus extending veterinary logic to the ways in which human-wildlife interactions are managed (Broz et al. 2021). Estimates vary on the number of pigs killed either by the virus or in preventive culling, but the figure is probably in the several hundreds of millions5.

ASF sparked fears of a potentially massive heparin shortage, causing many local shortages and supply chain tensions. This revealed the fragility of readily available resources (pig numbers are one thing, but the animal materials also need to be collected and integrated into complex circuits of exploitation for heparin production), and strongly supported the call to reorganise the supply chain and make it more flexible (Fareed et al. 2019; McCarthy et al. 2020; Rosovsky et al. 2020). Several countries, including France, the USA, and Brazil, are currently building new factories to manufacture raw heparin out of local sources in order to stabilise the supply. In the wake of this episode, which was further compounded by the massive global supply chain disruptions caused by COVID-19, pharmaceutical globalisation is now being directly called into question.

China continues to supply worldwide heparin, and some of its large agro-industrial companies are using the aftermath of the devastation caused by ASF to advocate gigantic new pig farms as the new global frontier of technologised exploitation of animal life, creating a breeding site for future pandemics6. Meanwhile, the supply chain of Chinese raw heparin for companies of the Global North still exists, but decades of expertise on heparin is now leading to the formation of large companies integrating the entire heparin supply chain, from animals to finished drug products. These companies produce biopharmaceuticals for the Global South and, more recently, for markets in the Global North. Additionally, they are exploring the potential development of new pharmaceuticals derived from this century-old technique7.

Since the 2008 scandal, and with greater urgency lately following the spread of ASF in China, there have been renewed incentives for the development of synthetic heparin.

To get around the problem that sourcing heparin from animals poses, one solution could be synthetic heparin or a synthetic drug that performs like heparin. Several groups of researchers around the world are trying to do just that, despite the long odds against succeeding. ‘When we first started, we tried to make heparin itself’, recalls Jian Liu, a professor at the Eshelman School of Pharmacy at the University of North Carolina, Chapel Hill, who heads a group that has been trying to synthesise heparin for more than a decade. ‘But how can you reproduce a molecule that cannot be precisely characterised and that also contains 40 sugars?’ (Tremblay 2016)

The extremely complicated chemistry of synthesising massive heparin molecules might be solved by focusing on the activity of smaller molecules. Some of them, such as fondaparinux, already exist, but they are not yet suitable for all the clinical applications of other heparin molecules. It is also hoped that biotechnological engineering could finally help design heparin that is separated from its animal origins (Baytas and Linhardt 2020). The biotechnological fix could very well come about soon and add to the list of biomedical innovations that have reduced human dependence on animals for therapeutic needs, such as insulin. But it may also never be fully successful, and the relationship between animals and human health could remain, raising a set of issues briefly outlined in the conclusion.

Conclusion: The environmental sustainability of therapeutic futures

The troubled historical and geographical life of heparin, from animal guts to human medicine, helps reveal the unseen connections between biomedical globalisation and the combined diseases of humans and non-human animals alike. By analysing episodes when silent actors came to the forefront of the global stage, this chapter has shown that exploited animals can also be direct players in globalisation – especially when they get sick (Nading 2013). Furthermore, this case study contradicts the widespread view of Southern countries and people as the overpowered figures of globalisation, and that of an ever-growing asymmetry of power between North and South, with the former reinforcing its power over the latter. As regards the globalisation of pharmaceuticals, it questions the image of the linear relationship of Northern-based Big Pharma looking at the South as mere emerging markets to conquer (or mere sites for raw material extraction). It also shows that the effects of globalisation on the construction of global supply chains in the food and pharmaceutical industries, as well as the effects of emerging diseases provoked by human action, may have the unexpected consequence of reversing global power configurations, with actors supposedly from below playing an active and privileged role that may define pharmaceutical and economic policies in the North. In that perspective, heparin is helping us to nuance our understanding of globalisation processes.

But there is even more to this story. Heparin challenges our definition of waste. This chapter started with a disease that originated from the circulation of waste, in the form of processed animal matter that had been fed to cattle in Britain, thus allowing a crossing of species barriers and the emergence of BSE. The uses of animal waste took on new proportions with the emergence of the slaughterhouse industry, with a drive to make the byproducts of food production profitable in any way possible. The existence of heparin as a drug is a consequence of the ready availability of animal waste in large quantities, as a result of the rise of industrial farming in the twentieth century. However, approaching the production of this drug as a useful outlet for matter (intestinal mucus) that otherwise serves no purpose makes it possible to ignore the environmental externalities associated with industrial farming. Heparin appears as an almost free resource, a derivative of food production processes that are already in place, and as such having no environmental footprint, or even a positive one (notwithstanding the large amounts of chemical solvents used as part of the extraction process) since it puts to use matter that would otherwise be lost.

The fears of a heparin shortage are turning this perspective on its head: What if the waste were to become the primary resource? What if, due to an epidemic or geopolitical events, pig intestines were to stop being available? The rapid succession of epidemics that has threatened heparin production may well continue to develop, and if technological solutions fail, we may still be dependent on cows and pigs for its supply for some time to come. What is the minimum number of animals needed in order to continue to produce this essential drug? Is the sustained supply of heparin compatible with a reduction of intensive farming, either forcibly because of epidemics or in a controlled way to ensure environmental sustainability? These questions become more pressing if we further consider the dimension of ethical access to drugs. Today, shortages are also linked to increased consumption due to a growing and aging population, especially in countries of the Global North, where most heparin is used.

These questions also rely on the shape that has been given to global economic exchanges during the last 40 years. Whereas Chinese pig farmers appeared in the 1990s as obvious raw material providers, the procurement crises described above obliged the richest countries to revise this assumption. Shifting conceptions of dependence and international competition have turned questions of heparin supply into a geopolitical issue. In that evolving context, the globalisation of pharmaceutical raw material supply chains has been submitted to increasing criticism. Heparin procurement offers a striking example of the reconfiguration of power relations that has been taking place during the recent globalisation phase – which might complicate the idea of globalisation both ‘from above’ and ‘from below’, offering an illustration of how economies of scale and global outsourcing have also collided with biomedical constraints and geopolitical power considerations. This could inspire further social science research that considers how seemingly dominated actors, from Global South countries and their populations to non-humans, can trigger economic and political changes at the global scale.

Endnotes‌

References

Agence Nationale de Sécurité du Médicament, État des lieux sur les heparines (2014).

Al-Hakim, A., ‘General Considerations for Diversifying Heparin Drug Products by Improving the Current Heparin Manufacturing Process and Reintroducing Bovine Sourced Heparin to the US Market’, Clinical and Applied Thrombosis/Hemostasis, 27 (2021): 107602962110522 https://doi.org/10.1177/10760296211052293.

Anderson, J. L., Capitalist Pigs: Pigs, Pork, and Power in America (West Virginia University Press, 2019).

Anderson, W., The Collectors of Lost Souls: Turning Kuru Scientists into Whitemen (Johns Hopkins University Press, 2008).

Barboza, D., ‘Virus Spreading Alarm and Pig Disease in China’, The New York Times, 16 August 2007 https://www.nytimes.com/2007/08/16/business/worldbusiness/16pigs.html.

Barboza, D., and W. Bogdanich, ‘Twists in Chain of Supplies for Blood Drug’, The New York Times, 28 February 2008 https://www.nytimes.com/2008/02/28/world/asia/28drug.html.

Barrowcliffe, T. W., ‘History of Heparin’, in R. Lever, B. Mulloy, and C. P. Page, eds., Heparin – A Century of Progress: Handbook of Experimental Pharmacology (Springer, 2012), pp. 3–22 https://doi.org/10.1007/978-3-642-23056-1.

Baytas, S. N., and R. J. Linhardt, ‘Advances in the Preparation and Synthesis of Heparin and Related Products’, Drug Discovery Today, 25.12 (2020): 2095–2109 https://doi.org/10.1016/j.drudis.2020.09.011.

Blanchette, A., Porkopolis: American Animality, Standardised Life, and the Factory Farm (Duke University Press, 2020).

Blattner, C., Protecting Animals Within and Across Borders (Oxford University Press, 2019).

Bogdanich, W., and J. Hooker, ‘China Didn’t Check Drug Supplier, Files Show’, The New York Times, 16 February 2008 https://www.nytimes.com/2008/02/16/us/16baxter.html.

Browaeys, D. B., ‘Anticoagulants: La Filière Chinoise’, 60 Millions de Consommateurs (November 2005).

Brown, H., and A. M. Nading, ‘Introduction: Human Animal Health in Medical Anthropology’, Medical Anthropology Quarterly, 33.1 (2019): 5–23 https://doi.org/10.1111/maq.12488.

Broz, L., A. Garcia Arregui, and K. O’Mahony, ‘Wild Boar Events and the Veterinarization of Multispecies Coexistence’, Frontiers in Conservation Science, 2 (December 2021): 711299 https://doi.org/10.3389/fcosc.2021.711299.

Cha, A. E., ‘Pig Disease in China Worries the World’, The Washington Post, 16 September 2007 http://www.washingtonpost.com/wp-dyn/content/article/2007/09/15/AR2007091501647.html.

Chee, L. Y., Mao’s Bestiary: Medicinal Animals and Modern China (Duke University Press, 2021).

Chess, E. K., S. Bairstow, S. Donovan, and others, ‘Case Study: Contamination of Heparin with Oversulfated Chondroitin Sulfate’, in R. Lever, B. Mulloy, and C. P. Page, eds., Heparin – A Century of Progress: Handbook of Experimental Pharmacology (Springer, 2012), pp. 99–125 https://doi.org/10.1007/978-3-642-23056-1.

Clarke, A. E., ‘Research Materials and Reproductive Science in the United States, 1910–1940 with Epilogue: Research Materials (Re) Visited’, in S. L. Star, ed., Ecologies of Knowledge: New Directions in Sociology of Science and Technology (State University of New York Press, 1995), pp. 183–225.

Collard, R.-C., Animal Traffic: Lively Capital in the Global Exotic Pet Trade (Duke University Press, 2020).

Committee on Energy and Commerce. The Heparin Disaster: Chinese Counterfeits and American Failures. House of Representatives. (2008) Hearing Serial No. 110-109. https://www.govinfo.gov/content/pkg/CHRG-110hhrg53183/html/CHRG-110hhrg53183.htm.

Coyne, E., ‘Heparin – Past, Present and Future’, in R. L. Lundblad, W. V. Brown, K. G. Mann, and H. R. Roberts, eds., Chemistry and Biology of Heparin (Elsevier, 1981), pp. 9–18.

Craddock, S., and S. Hinchliffe, ‘One World, One Health? Social Science Engagements with the One Health Agenda’, Social Science & Medicine, 129 (2015): 1–4 https://doi.org/10.1016/j.socscimed.2014.11.016.

Fareed, J., W. Jeske, and E. Ramacciotti, ‘Porcine Mucosal Heparin Shortage Crisis! What Are the Options?’, Clinical and Applied Thrombosis/Hemostasis, 25 (2019): 1076029619878786 https://doi.org/10.1177/1076029619878786.

Frutos, R., and others, ‘Emerging Infectious Diseases in Ungulates’, Frontiers in Veterinary Science, 8 (2021): 620691 https://doi.org/10.3389/fvets.2021.620691.

Gao, H., and others, ‘Diversification of Heparin Products: Past, Present, and Future’, Thrombosis and Haemostasis, 121.2 (2021): 125–36 https://doi.org/10.1055/s-0040-1716862.

García-Sancho, M., Animal Breeding in the Age of Biotechnology: The Investigative Pathway Behind Dolly the Sheep (Springer Nature, 2021).

Garritano, J., Vital Strife: Humanity and Its Discontents (Cornell University Press, 2020).

Greenwood, B., The Microbe as a Metaphor: Scientific Language and Medical History (University of Chicago Press, 2019).

Hamlin, C., Cholera: The Biography (Oxford University Press, 2009).

Hess, D. J., ‘Medical Modernisation, Scientific Research Fields, and the Epistemic Politics of Health Social Movements’, Sociology of Health and Illness, 26.6 (2004): 695–709 https://doi.org/10.1111/j.1467-9566.2004.00414.x.

Hinchliffe, S., and N. Bingham, ‘Securing Life: The Emerging Practices of Biosecurity’, Environment and Planning A, 40.7 (2008): 1534–51 https://doi.org/10.1068/a4054.

Holmes, M. C., ‘Heparin and Its Production’, in R. Lever, B. Mulloy, and C. P. Page, eds., Heparin – A Century of Progress: Handbook of Experimental Pharmacology (Springer, 2012), pp. 1–21 https://doi.org/10.1007/978-3-642-23056-1_1.

Hooper, M. J., and others, ‘Animal Models of Emerging Human Disease: An Overview of the Field’, Comparative Medicine, 55.3 (2005): 221–31.

Houck, O. A., Taking Back Eden: Eight Environmental Cases That Changed the World (Island Press, 2009).

Kirksey, S. E., Emergent Ecologies (Duke University Press, 2015).

Knapp, C. R., and others, ‘Wildlife Markets and Zoonotic Disease Risk in Laos’, Frontiers in Veterinary Science, 7 (2020): 558172 https://doi.org/10.3389/fvets.2020.558172.

Krishna, V. N., and others, ‘How We Got to Now: Historical Evolution of Heparin’, Seminars in Thrombosis and Hemostasis, 45.3 (2019): 217–21 https://doi.org/10.1055/s-0039-1684021.

LaCapra, D., ‘Globalization and Critical Animal Studies’, pp. 136–154 in Amanda Minervini, Amelie Björck, Omri Grinberg, and Amrita Ghosh (Eds) ReFiguring Global Challenges. Literary and Cinematic Explorations of War, Inequality, and Migration (Brill, 2023)

Lakoff, A. ‘The generic biothreat, or, how we became unprepared’ Cultural Anthropology, 23(3) (2008): 399-428.

Latour, B., We Have Never Been Modern (Harvard University Press, 1993).

Lawrence, T., The Heparin Story: A Golden Anniversary Celebration (Springer, 1988).

Lee, P. Y. (Ed.). Meat, Modernity, and the Rise of the Slaughterhouse (University of New Hampshire Press, 2008)

Leiden, J. M., ‘Canaries, Coal Mines and the Drug Supply’, Nature Biotechnology, 26(6) (2008): 624–626. https://doi.org/10.1038/nbt0608-624.

Lever, R., and B. Mulloy, ‘Structure and Biology of Heparin’, in R. Lever, B. Mulloy, and C. P. Page, eds., Heparin – A Century of Progress: Handbook of Experimental Pharmacology (Springer, 2012), pp. 45–71 https://doi.org/10.1007/978-3-642-23056-1_2.

Liang, L. L., and others, ‘The Role of Bovine Heparin in the Diversification of Anticoagulant Therapies’, Thrombosis and Haemostasis, 121.4 (2021): 450–60 https://doi.org/10.1055/s-0040-1717364.

Linhardt, R. J., ‘Heparin: Structure and Activity’, Journal of Medicinal Chemistry, 46.13 (2003): 2551–64 https://doi.org/10.1021/jm020566b.

Linhardt, R. J., and C. L. Gunay, ‘Production and Chemical Processing of Heparin’, in R. L. Lundblad, W. V. Brown, K. G. Mann, and H. R. Roberts, eds., Chemistry and Biology of Heparin (Elsevier, 1981), pp. 57–72.

Linhardt, R. J., and others, ‘Heparin: An Overview’, Acta Poloniae Pharmaceutica – Drug Research, 60.3 (2003): 243–47.

Luo, J., and others, ‘The Significance of Heparin in Medical Practice’, Thrombosis Research, 158 (2017): 126–32 https://doi.org/10.1016/j.thromres.2017.07.017.

Mackie, A., and others, ‘Analysis of Heparin Contamination Events’, Emerging Infectious Diseases, 13.12 (2007): 1910–13 https://doi.org/10.3201/eid1312.070303.

Marder, E. M., and others, Heparin: Structure, Function, and Therapeutic Potential (Oxford University Press, 2014).

Martin, C., ‘The Ethics of Animal Research in the Context of Heparin Production’, Journal of Bioethical Inquiry, 9.3 (2012), 317–28 https://doi.org/10.1007/s11673-012-9390-6.

McCarthy, C. P., Vaduganathan, M., Solomon, E., Sakhuja, R., Piazza, G., Bhatt, D. L., Connors, J. M., & Patel, N. K. ‘Running Thin: Implications of a Heparin Shortage’, The Lancet, 395(10223) (2020): 534–536. https://doi.org/10.1016/S0140-6736(19)33135-6.

Meyer, R., Unsettling Science: The Politics of Heparin in the Global Age (Routledge, 2017).

Mills, E., and others, ‘Risk Assessment of Heparin and Heparin-Based Products’, Thrombosis Research, 126.5 (2010): 439–47 https://doi.org/10.1016/j.thromres.2010.06.004.

Murtaugh, M. P., Stadejek, T., Abrahante, J. E., Lam, T. T. Y., & Leung, F. C.-C., ‘The Ever-Expanding Diversity of Porcine Reproductive and Respiratory Syndrome Virus’, Virus Research, 154(1–2) (2010): 18–30. https://doi.org/10.1016/j.virusres.2010.08.015.

Nading, A., ‘Humans, Animals, and Health: From Ecology to Entanglement’ Environment and Society: Advances in Research 40(1) (2013): 60-78

Oudshoorn, N., Beyond the Natural Body: An Archeology of Sex Hormones (Routledge, 1994)

Page, C. P., and others, ‘Heparin and Its Role in the Blood Coagulation Cascade’, Blood Coagulation & Fibrinolysis, 29.7 (2018): 538–48 https://doi.org/10.1097/MBC.0000000000000744.

Park, M., Singer. P., ‘The Globalization of Animal Welfare: More Food Does Not Require More Suffering’, Foreign Affairs, 91, (2012): 122.

Parker, H., Zoonotic Diseases: Challenges in the Control of Emerging Pathogens (Springer, 2018).

Phillips, A., and others, ‘Heparin and Other Anticoagulants in Cardiovascular Therapy’, Journal of Clinical Pharmacology, 56.5 (2016): 543–52 https://doi.org/10.1002/jcph.720.

Reiss, H., A History of Heparin and Its Discovery (Cambridge University Press, 2021).

Rosovsky, R. P., Barra, M. E., Roberts, R. J., Parmar, A., Andonian, J., Suh, L., Algeri, S., & Biddinger, P. D. ‘When Pigs Fly: A Multidisciplinary Approach to Navigating a Critical Heparin Shortage’ The Oncologist, 25(4) (2020): 334–347. https://doi.org/10.1634/theoncologist.2019-0910.

Sands, A., and others, ‘Investigating the Safety and Efficacy of Heparin in Clinical Practice’, Journal of Clinical Hematology, 18.3 (2019): 185–91 https://doi.org/10.1016/j.jclinhem.2019.01.003.

Schwerin, A. von, Stoff, H., & Wahrig, B. (Eds.) Biologics, A History of Agents Made From Living Organisms in the Twentieth Century (Pickering & Chatto, 2013).

Smith, M., and others, The Age of Heparin: Medical History and Development (Springer, 2016).

Specht, J., Red Meat Republic: A Hoof-to-Table History of How Beef Changed America (Princeton University Press, 2020)

Sykes K., ‘Globalization and the Animal Turn: How International Trade Law Contributes to Global Norms of Animal Protection’, Transnational Environmental Law. 5(1) (2016):55-79.

Szajek, A. Y., Chess, E., Johansen, K., Gratzl, G., Gray, E., Keire, D., Linhardt, R. J., et al. The US Regulatory and Pharmacopeia Response to the Global Heparin Contamination Crisis. Nature Biotechnology, 34(6) (2016): 625–630. https://doi.org/10.1038/nbt.3606.

Taylor, R., Biotechnology and the Rise of Heparin: Medical Impact and Cultural Shifts (Sage, 2008).

Thompson, W., Modern Medical Practices and Heparin (Beacon Press, 2020).

Tian, K., Yu, X., Zhao, T., Feng, Y., Cao, Z., Wang, C., Hu, Y., et al. ‘Emergence of Fatal PRRSV Variants: Unparalleled Outbreaks of Atypical PRRS in China and Molecular Dissection of the Unique Hallmark.’, PLoS ONE, 2(6), e526. (2007). https://doi.org/10.1371/journal.pone.0000526.

Tremblay, J.-F., ‘Making Heparin Safe’ C&EN Global Enterprise, 94(40), 2016: 30–34. https://doi.org/10.1021/cen-09440-cover.

Williams, D., and others, ‘In Vitro Activity of Heparin Derivatives in the Prevention of Venous Thromboembolism’, Clinical and Applied Thrombosis/Hemostasis, 19.1 (2013): 49–55 https://doi.org/10.1177/1076029612462510.

Wilson, S., and others, ‘Heparin: From its Discovery to Modern Medical Applications’, Journal of Anticoagulant Therapy, 21.4 (2017): 425–35 https://doi.org/10.1016/j.anticoag.2017.02.001.

Wright, M., and others, ‘Heparin and Heparin-Like Substances: Biological Implications for Medical Practice’, Scientific Reports, 7.1 (2018): 3911 https://doi.org/10.1038/s41598-017-04567-9.

Zhang, M., Bjerke, L., ‘Antibiotics “dumped”: Negotiating Pharmaceutical Identities, Properties, and Interests in China–India Trade Disputes’, Medical Anthropology Quarterly, 37/2 (2023): 148-163

Zhu, W., and others, ‘Therapeutic Uses of Heparin in Surgery’, Journal of Cardiothoracic and Vascular Anesthesia, 29.5 (2015): 1187–95 https://doi.org/10.1053/j.jvca.2015.01.023.