Category Archives: Medicine

SUGAR VERSUS HONEY IN BYZANTINE RECIPES

By Petros Bouras-Vallianatos

The Byzantine Empire, with its capital in Constantinople (now Istanbul), then a mainly Greek-speaking region, constituted a natural crossroads between East and West for more than a millennium (AD 324–1453). Its history is an indispensable part of the medieval period in both Europe and the Middle East. In the field of medicine, for example, we can attest to widespread interactions with the Islamic tradition.

The most dynamic part of Byzantine therapeutics was pharmacology. We are privileged to have several surviving pharmacological manuals, especially dating from the later period, i.e. from the twelfth to the fifteenth centuries, which provide us with a unique testimony to Byzantine composite drugs. Here I have selected the example of sugar-based potions, as it offers an excellent case-study that helps us to better understand the way Byzantine recipes were developed through a process of both practical experimentation and influence from outside.

Before the introduction of sugar, people relied on honey to make medical potions sweet. Greek and early Byzantine medical authors referred to honey-based drugs such as oinomeli (a mixture of honey with wine), hydromeli (a mixture of honey with water) or oxymeli (a mixture of honey with vinegar). For example, Paul of Aegina (fl. first half of the seventh century) recommends the following recipe for those suffering from calculi:

One ounce[1] each of saxifrage, betony, dog’s-tooth grass, maidenhair fern, spikenard, carpesium, hazelwort, and eryngo; one half ounce each of Macedonian parsley and seed of rue; two ounces each of green fennel, iris, baked squill, and periwinkle; three ounces of bark of the root of capper; two ounces of water-parsnip; and two sextarii[2] each of water, vinegar, and honey.[3]

Meanwhile, the cultivation of sugarcane gradually spread throughout the Islamic East from the seventh/eighth century onwards. Sugar was used as a simple drug, for stomach ailments and the relief of pain in, for example, the chest and kidneys. However, it also became popular as an excipient in liquid pharmaceutical dosage forms, used as a sweetener and preservative, initially supplementing and gradually replacing the use of honey for pharmacological purposes in the Islamic world. Sugar is of higher purity than honey, thus a smaller quantity has a stronger preservative action; it is also less susceptible to changes of temperature and ensures greater homogeneity into the final product. Among the most commonly used potions in Islamic medicine are the so-called julep (julāb) and syrup (sharāb), both of which consisted of sugar and one or more kinds of fruit juices or extracts of flowers.

Figure 1. Medieval, cone-shaped earthenware devices for the refining of sugar from Cyprus. Courtesy of Bank of Cyprus Cultural Foundation.
Figure 1. Medieval, cone-shaped earthenware devices for the refining of sugar from Cyprus. Courtesy of Bank of Cyprus Cultural Foundation.

By the eleventh century sugarcane cultivation was thriving in Syria and Palestine, eventually reaching the large Mediterranean islands of Cyprus and Sicily. Western merchants, such as the Genoese and the Venetians, played an important role in the distribution of this commodity throughout the Mediterranean, including Byzantium. For example, sugar is mentioned among the main supplies for the newly established Byzantine hospital (xenon) of the Pantokrator Monastery in Constantinople in the early twelfth century, but it was not until the late thirteenth century that sugar became widely available in the Byzantine world.

At the same time, we can observe the transfer of medical knowledge to Byzantium through translations of Arabic and Persian works into Greek. The earliest text of this kind, which preserves a large number of references relating to the various kinds of sugar-based potions, is the Greek translation of Ibn-Jazzār’s (fl. tenth century) Ephodia tou Apodēmountos (Zād al-musāfir wa qūṭ al-ḥāḍir/Provisions for the Traveller and Nourishment for the Sedentary), which must have been translated in the late eleventh/early twelfth century by scholars working in Southern Italy. By the early fourteenth century recipes for sugar-based potions had become very common in Byzantine manuals. The Constantinopolitan medical author and practising physician John Zacharias Aktouarios (ca. 1275–ca. 1330) provides an extensive list consisting of about thirty recipes, and he often explicitly acknowledges that he was introducing a new recipe. For example, he gives the following recipe for a julep for heart palpitations:

One hexagion[4] of the three sandalwoods; three hexagia of violet; two hexagia of basil seed; two hexagia of rose; five hexagia each of bugloss and ox-eye flowers; two hexagia of aloeswood; one hexagion of ambergris; two hexagia of saffron; three hexagia each of dried flower-buds from the clove-tree and nutmeg; one hexagion each of cinnamon, anise, caraway, and fennel seed; five grains of musk; one hexagion of poppy seed; three ounces of the juice of sweet apples; one ounce of rosewater; five ounces of distilled endive water; one ounce each of the roots of fennel, wild celery, and chicory; three hexagia each of marjoram, chamomile, and wormwood; and three ounces of sugar.[5]

Figure 2. A julep recipe added in the lower margin of a fifteenth-century medical manuscript, MS.MSL.52, f. 143v. Courtesy of the Wellcome Library, London.
Figure 2. A julep recipe added in the lower margin of a fifteenth-century medical manuscript, MS.MSL.52, f. 143v. Courtesy of the Wellcome Library, London.

In this recipe, in addition to sugar, we can also see ingredients from Asia and the Far East, such as musk, amber, and sandalwood, which became common in European pharmacology, especially during the thirteenth and fourteenth centuries after the Mongols’ conquests in Eurasia that led to the Pax Mongolica and the resulting improvements in trading conditions. To sum up, the fact that Byzantine physicians were aware of the usefulness and effectiveness of these sugar-based potions and made extensive use of them is at odds with the established view that Byzantine society was not very open to outside influence. Nowadays sugar is omnipresent and often replaced by sugar substitutes for the sake of diabetics and the diet-conscious; but once it was a novelty and highly desirable!

[1] One ounce is equal to 27.288 g.

[2] One sextarius is equal to 54.58 g.

[3] Ed. J. L. Heiberg. Paulus Aegineta, vol. 2 (Leipzig-Berlin: Teubner, 1924), 309, 1-6.

[4] One hexagion is equal to 5.166 g.

[5] Vindobonensis med. gr. 17 (first half 15th c.), f. 118r, lines 4-11.

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Petros Bouras-Vallianatos studied pharmacy, ancient and Byzantine history, before completing his PhD on the late Byzantine medical author John Zacharias Aktouarios; a revised version of his doctoral thesis is to be published soon. He is Wellcome Trust Research Fellow in Medical Humanities in the Department of History at King’s College London, where he is working on a three-year project entitled ‘Experiment and Exchange: Byzantine Pharmacology between East and West (ca. 1150-ca.1450)’. He has published several articles on Byzantine and early Renaissance medicine and pharmacology, the reception of the classical medical tradition in the Middle Ages, and palaeography, including the first descriptive catalogue of the Greek manuscripts at the Wellcome Library in London. He is also co-editing the Brill’s Companion to the Reception of Galen.

The Live Chicken Treatment for Buboes: Trying a Plague Cure in Medieval and Early Modern Europe

By Erik Heinrichs 

Titlepage of Philippus Culmacher’s plague treatise, Leipzig: circa 1495
Credit: Wellcome Library, London.

While researching German plague treatises I became fascinated by one odd treatment for buboes that appeared again and again, despite sounding so far-fetched. One sixteenth-century version calls for plucking the feathers from around the single hole in a chicken’s backside, then placing it on a person’s bubo. The instructions say to hold the chicken on the bubo until it dies, when it must be replaced with a new chicken, similarly plucked. I soon dubbed this the “live chicken treatment for buboes” and after years of casual encounters I began to track the recipe more systematically. As strange as it sounds, versions of this “live chicken treatment” were fairly common in plague writing, beginning with the Black Death and lasting, amazingly, into the eighteenth century. Tracing the long history of this recipe led me to explore questions such as: Where might this come from? Why chickens? Why might healers think that this was a good idea? Did anyone actually try this or is this all theoretical? As a historian, I was also interested in change over time within the recipe. Here I found much to explore, as I followed the recipe’s twists and turns over a seven-hundred year period, roughly 1000 to 1700.

The “live chicken treatment” turns out to have a long history, indeed. Its origins seem to lie in Avicenna’s Canon of Medicine, although it may be older than that. Chickens and chicken broth were a common source of medicine in early times, probably because chickens were such ubiquitous and useful animals since antiquity. Not only did Avicenna praise chicken broth for its general benefits for the body, but he also recommended placing a cut chicken on a poisonous bite or sting in order to fight poisons. In later centuries European physicians turned to Avicenna’s advice when they faced the mysterious and devastating epidemics of the fourteenth century. As Europeans emphasized the poisonous nature of the plagues around them, older treatments for poisons drew new attention. The first mention of using a chicken rump to draw poisons out of a bubo appeared in the very first plague treatise of 1348, coming in response to the so-called Black Death. Here the Catalan author Jacme d’Agramont seems to have introduced a novel and lasting adaptation of Avicenna’s recipe, although the “cut chicken” version persisted in plague treatises for centuries to come.

Most interesting for the history of trying and testing cures are the many variations of the “cut chicken” and “chicken rump” versions of the treatment, as well as physicians’ comments about how effective they are. Especially after 1400, physicians seem to be thinking about this recipe quite often as they seek practical treatments for the plagues of the time. Physicians were preoccupied with altering the recipe in order to reason out the nature of the mysterious poisons underlying the plague. Some add substances to the process, such as salt placed on top of the chicken as it is placed on the bubo. During the fifteenth century, a number of German physicians began to explain the treatment’s workings in a strikingly physical way—that the chicken breathes through its backside and thus pulls the bubo’s poisons into itself. This change led to the suggestion to hold the chicken’s beak shut during the treatment in order to force the chicken to breathe from below. My article (accessible here) show how all aspects of the treatment changed over time as physicians engaged with the recipe, including the quantity of chickens used, the amount of time required, and even the type of animal in question. This work demonstrates the importance of the recipe itself as a platform for thought, experimentation, and communication among physicians.

Perhaps a surprise to modern readers, many physicians praised their version of the “live chicken treatment,” describing it as effective and desirable. Such comments multiply after the introduction of print, which encouraged the production of plague treatises, some fitted with fetching cover illustrations for the marketplace (see image below of Philippus Culmacher’s treatise of circa 1495). In German-speaking lands especially, sixteenth-century physicians used their printed plague treatises to promote their own services and expertise at a local level.[1] This brought about a change in the genre whereby physicians seem more eager to discuss their own experiences with effective recipes in order to appeal to the practical interests of a broad audience. Amidst this change comes evidence that some German physicians witnessed first-hand the successful use of the “live chicken treatment.” Another interesting change during the sixteenth century is the increased attention to the bodily warmth of the chicken as the treatment’s active healing force. These emergent views provide a tantalizing link to modern medicine, since moist heat remains one of the treatments for buboes today. For more information, please read my article.

Erik Heinrichs is an associate professor of history at Winona State University (Minnesota). His interests are the history of medicine and religion in the late medieval and early modern periods. His book Plague, Print, and the Reformation: The German Reform of Healing, 1473-1573 will be published by Routledge this November.

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[1] For a survey of German plague treatises from the first century of print, see: Erik A. Heinrichs, Plague, Print, and the Reformation: The German Reform of Healing, 1473-1573 (London: Routledge, 2017).

True but not Tested: Experimentation in the Apothecary’s Shop

By Valentina Pugliano

Testing and standardization are firmly entrenched in the pharmacological imagination of western biomedicine and its public. Before a new drug can be put on the market, the U.S. Food and Drug Administration demands five rounds of trials. Approximately 70% of new ‘recipes’ fails to pass the first round. Similarly, the European Medicines Agency maintains a database of adverse drug reactions (EudraVigilance) which, growing of one million entries yearly, is used to monitor all pharmaceuticals on sale across the European Economic Area. Meanwhile, the media seizes upon the perils of untested cures as if on morality tales, policing the boundaries of modern science from potential intrusion from the miraculous and the charlatanesque.

Yet, can the same be said of premodern drug manufacturing? Was a drug’s efficacy established by testing? And what did ‘testing’ recipes even mean in the sixteenth and seventeenth centuries? When these questions were suggested at Elaine Leong and Alisha Rankin’s Testing Drugs, Trying Cures Workshop in 2013, I began to look for answers among those early modern medical practitioners who most closely resemble the pharmaceutical industry of our times, combining the manufacturing of a Glaxo Smith-Kline and AstraZeneca with the retailing of Boots and Walgreens: apothecaries. [1]

Pharmacy shop, Tacuinum sanitatis, 16th century (BNF, MS Latin 9333, fol. 51v).

While not corporate giants, apothecaries thrived in every large hamlet and town of Italy, reaching spectacular numbers in metropolises like Rome, Naples, and Venice. Unlike free-lance alchemists and empirics, they belonged to the city’s official infrastructure of healthcare: they worked from a licensed shop, trained through formal apprenticeship and, like physicians and surgeons, belonged to a professional association or arte. This ‘trade brotherhood’ gave them bargaining powers but also subjected them to standardization rules and quality controls. As disgruntled masters testify from the archives, in severe cases of infraction the apothecary could see the remedies he had belaboured on for weeks thrown into the gutter or burnt to ashes.

So what did it mean to have ‘correct’ remedies that passed the test of shop inspections and satisfied “God and the public good”? As a historian of artisan knowledge I have learnt that infractions, those occasions when things go (deliberately) wrong, sometimes provide the best clue to understanding which methods of doing things were considered orthodox in the crafts. Apothecaries loved to speak of the abuses supposedly perpetrated by their colleagues. In Florence, for example, they conned customers by mixing expensive guaiac wood with the bark of mulberry trees. In Mantua and Padua, those with a fever and a bad stomach better beware the Lenitive Electuary, regularly adulterated with black sugar (instead of its fine white variety) and counterfeit tamarinds (mimicked by a paste made of old cassia and badly preserved dates ).[2]

Tamarinds

These complaints were not the only ones to be voiced, but they are telling. They are not motivated by protestations from patients, who are remarkably absent from the writings of early modern apothecaries. Nor are they driven by doubts about the method employed to make the remedy from a set of instructions. While household experimenters and professors of secrets were always seeking new formulas and ways to stabilise them, the corpus of remedies sold in sixteenth-century Italian pharmacies was fairly stable, and so were their recipes.

What these criticisms suggested, rather, was that medicinal ingredients possessed a purity, and that this purity had been tainted. The rogue apothecary had played around with the ‘honesty’ of simples, diluting their strength or altogether replacing the ‘sincere originals’ prescribed in the recipe with fraudulent alternatives (often from the kitchen pantry).

With this concern for authenticity in mind, I returned to the apothecaries’ writings, and especially to two bestselling pharmacopoeias, Girolamo Calestani of Parma’s Observations on the Antidotes and Medicaments Most Used in Italy (1562), and Giorgio Melichio of Venice’s Warnings on the Compound Remedies in Use in Pharmacy (1575). Leafing through these texts, I made a curious discovery. Repeatedly, key plant and mineral ingredients in their recipes were referred to according to their reputed truth or falsity: e.g. “true cinnamon”, “true rhaponticum”, “false stibium”, “false balsam”. Repeatedly, apothecaries stressed the importance of sourcing these authentic materials, while their absence was said to ruin the preparation.

Even the use of substitutes began to be criticised. The practice of substituting one ingredient with another possessing similar qualities (quid pro quo), usually a local simple for an exotic import difficult to acquire, had been necessary since antiquity. Yet, the changing attitude to substitutions in the sixteenth century is summarised well by the Neapolitan physician Bartolomeo Maranta: “Substitutes are an abuse.” Never more so than for Theriac, the most celebrated antidote of Italian pharmacy and the toughest to prepare with over sixty ingredients. A Theriac with substitutes instead of true ingredients, Maranta declared, “will be itself in a certain way sick”.[4]

How should we interpret such appeal to the truthfulness of ingredients? At a superficial level, we can understand the apothecary wanting to reassure the public of the genuineness of his wares. After all, practitioners of pharmacy were often portrayed as profiteers and cheats. But, as I argue in my article “Pharmacy, Testing and the Language of Truth in Renaissance Italy,” something else had changed between the medieval period and the 1540s, when this terminology of trues and falses appears: Greek and Roman books on materia medica were reintroduced into western Europe. It is well known that the reappearance of Dioscorides’s On Medicinal Plants, Theophrastus’s On Plants and Pliny’s revised Natural History created as many problems as it solved for those who wished to implement their teachings. Many of the Mediterranean and Levantine simples described in them remained entirely unavailable during the sixteenth century, while many others were plagued by problems of identification and nomenclature.

My sense is that this ‘Language of Truth’ was an intervention into this state of affairs. It helped the apothecaries get a grip on which was which among rare ingredients, and reflected their aspiration, shared with many contemporaries, of restoring the wisdom of the ancients. It also showed the increasing influence on pharmacy of the contemporary botanical renaissance and the ethos of naturalists who, for the first time, put nature in the foreground, liberating flowers, trees, animals and rocks from the need to be useful.

Crucially, authenticity came to replace experimentation. As ingredients acquired more importance in the apothecary’s mind, the efficacy of the recipe began to be pegged to their presence and quality. Providing the remedy contained the true, correct ingredients its efficacy and fitness for human consumption would be guaranteed, with no need to involve test subjects or pursue the feedback of patients and colleagues. How much this ‘testing by truth’ differed from modern-day trials becomes clear when we turn to the contemporary idiom of the pharmaceutical industry: it is as if the apothecaries’ R&D stopped at the preclinical stage.

 

Notes:

[1] V. Pugliano, “Pharmacy, Testing and the Language of Truth”, Bulletin of the History of Medicine 92/2 (2017): 233-273. See also the other articles in the same issue of BHM.

[2] Ricettario Fiorentino dell’Arte dei Medici e Spetiali di Firenze (Florence, 1574), pp. 45, 74; Giovanni Antonio Lodetto, Dialogo degl’inganni d’alcuni malvagi speciali (Padua, 1572), pp. 21-22.

[3] Giorgio Melichio, Avvertimenti nelle compositioni per uso della spetiaria (Venice, 1601), pp. 27-28.

[4] Bartolomeo Maranta, Della Theriaca et Mithridato libri due (Naples, 1572), p. 33.

 

 

When Does a Drug Trial End?

By Justin Rivest

An eighteenth-century proprietary medicine vendor. Detail from “Le Charlatan, 1785.” Hand coloured etching and aquatint. Antoine Borel after J. Augustin L’Eveillé. Source: Wellcome Images.

The question I’d like to begin this post by asking is, When does a drug enter “normal use”? Is a trial a “provisional” phase, that reaches a definitive end, say when “proof” is found, or when the relevant authorities are convinced? Or in an age where drug monopolies were insecure and difficult to enforce, was the state of trial—l’épreuve—always ongoing?

This question first crossed my mind while preparing my contribution for the recent special issue of the Bulletin of the History of Medicine, “Testing drugs and trying cures,” edited by Elaine Leong and Alisha Rankin. My article focuses on the role of patient trials in granting monopoly privileges for proprietary drugs in eighteenth-century France. These royally-granted privileges were the distant ancestors of modern drug patents. They gave their inventors a legally enforceable monopoly over the drug in question by enabling them to fine counterfeiters.

Even after they were granted monopoly privileges, drug vendors continued, almost compulsively, to gather further evidence of the effectiveness of their drugs. This evidence often took the form of an attestation or certificat. These documents could take several forms: some were notarized statements, made by a patient declaring that he or she had been cured of this or that condition. Others were endorsements signed by an expert practitioner—a famous doctor, a representative of a local college or guild—who had personally witnessed the drug’s effects.

In this post, I will use the practice of what we might call “cure attestation collection” to question whether “trials” (épreuves) of a drug really had an end from the perspective of early modern drug monopolists.

The most important reason to continue gathering documentation of the effectiveness of their drug was to convince authorities to renew their privilege at a later date, as most monopoly privileges had fixed terms of three, ten, or fifteen years. But even within these term limits, they did not have perfect guarantees. Early modern drug monopolies were tenuous. Vendors knew that they might even have to re-submit both their drugs and their documentation for arbitrary re-examination by the authorities.

Even barring arbitrary re-examinations, the multi-generational duration of many early modern monopolies meant that they would be evaluated more than once by the authorities. The drug monopoly I studied in my article, the poudre fébrifuge of the Chevalier de Guiller, was particularly long-standing, extending across four generations. As a febrifuge, the drug was targeted at “intermittent fevers,” an important cause of mortality in the French army in this period. The drug was first awarded a monopoly privilege in 1713, at the end of the reign of Louis XIV. Its inheritors faced various challenges in exploiting it over the coming decades, but they consistently managed to get the privilege renewed. By the 1770s, in fact, the latest inheritors, the sisters Marie-Thérèse and Marie-Victoire de La Jutais, had accumulated a veritable archive of attestations in favour of their drug, spanning over sixty years.

Most of these documents were cure attestations and endorsements from patients, and prominent medical practitioners. A signed personal endorsement of the drug from the supervising practitioner was often the most important result of a hospital trial. Vendors who sold drugs in bulk to the state, especially to the military, could appeal to a special type of attestation. The La Jutais sisters, for instance, did not just rely on the documents that had been handed down to them through their family. They also went to government archives—much as historians do today—looking to collect documentation that might endorse their drug. They paid the navy office to make official copies of fifty-year-old correspondence concerning their drug so that they could submit it with their petition to renew their monopoly.

Monopolists were not, however, impartial researchers. The La Jutais sisters seem not to have collected any documentation which might cast their drug in a negative light—or at least, if they came across such evidence, they avoided disseminating it. Indeed, during my research I came across several documented cases of ambiguous or negative patient trial results of the poudre fébrifuge. In one 1714 trial involving “twenty or thirty” patients at a navy hospital, the drug was deemed to be too inconsistent in its effects and was dismissed as a violent purgative rather than a true febrifuge. It seems at least plausible that the La Jutais sisters’ archival searches might have drawn up this material as well. Nonetheless this report is notably absent from their petitions for monopoly renewal in the 1770s.

The “selective archive” of positive attestations that the La Jutais sisters assembled helped them to renew their monopoly privilege in 1775. We can see from their case that early modern drug monopolists had good reasons to keep collecting cure attestations wherever they could get them. They had the effect of turning the drug’s everyday use into a form of legally acceptable evidence, making a successful trial out of every cure.

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Justin is a postdoctoral researcher at the University of Cambridge and his work focuses on early drug monopolies and the role of bulk drug producers and consumers in the early modern medical marketplace. He recently co-wrote a short piece in The New England Journal of Medicine with Alisha Rankin on this topic, as well as an article in the Canadian Journal of History on one particularly successful drug entrepreneur, Adrien Helvétius (1662-1727), who sold massive quantities of his drug against dysentery to the French state for use in the army and rural poor relief efforts. His research has shown that trials on patients played a critical role in licensing early drug monopolies as well as in helping entrepreneurs secure lucrative supply contracts with the state.