Category Archives: Pre Modern

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.

Testing Drugs and Trying Cures

By Elaine Leong and Alisha Rankin

Miniature (no. 37.181) from 15th century manuscript in Dresden: Galen, and assistant with a pestle and mortar, and a scribe in an apothecary’s shop. © Wellcome Images

As readers of this blog well know, early modern Europe was aflood with recipes and drugs. One central question has long preoccupied many of us –  just how did our historical actors assess, test and try out recipes, drugs and materia medica? A few summers ago, a group of historians of science and medicine gathered to discuss just this question. This month, we present our ideas and findings in a special issue of the Bulletin of the History of Medicine. To celebrate the launch of the special issue, several authors of the volume will share their work on The Recipes Project. Tuesday’s post revisited Ashley Buchanan and Tillmann Taape‘s report on the original 2014 conference. Over the next few weeks, we’ll learn more about the research of Erik Heinrichs, Valentina Pugliano, Alisha Rankin and Justin Rivest. Finally, Tillmann Taape, who just completed his PhD at the University Cambridge (congrats!) also adds his voice to the series by reflecting on how theme of drug testing features in his doctoral dissertation.

To get us started on our month of ‘Testing Drugs and Trying Cures’, we wanted to say a few words as the organizers and editors of the project. First, you might ask, what do we mean by ‘Testing Drugs and Trying Cures’? Over the course of the project, we found that it was useful to view ‘testing drugs’ and ‘trying cures’ as two overlapping but distinct phenomena.

As the essays in the special issue show, physicians and apothecaries developed clear rules and practices for testing drugs as materials – from sensory analysis of materia medica to chemical analysis of substances like mineral waters or alchemical medicines. This kind of ‘testing drugs’ largely focused on gaining knowledge on the substances’ medicinal properties and played a particularly significant role in the discovery and adoption of materia medica from the New World and in assessing and establishing authenticity of exotic and/or expensive medicaments.

Paolo Antonio Barbieri, The Spice Shop, 1637. Image from Wikimedia.

‘Trying cures’, on the other hand, describes the widespread practice of trying remedies and other kinds of cures on human bodies. If ‘testing drugs’ was mainly conducted by learned physicians and apothecaries, ‘trying cures’ was performed by a broad range of healers. Within the home, women and men applied and observed the effects of remedies on family and household members. Likewise, physicians and other practitioners prescribed diets, medicines and other cures to their patients, again observing and recording the effects. Ample evidence of this kind of ‘trying cures’ survive in a range historical sources from the use of ‘probatum est’ to expressions of personal experience, customisation and rejection of recipes in household recipe collections (for more on this, see posts here and here).

For us, these two categories ‘testing drugs and ‘trying cures’ serve as helpful heuristic tools to untangle the assessment practices used by early modern practitioners. We see the two categories not as separate boxes but rather as overlapping and often intertwined practices. Many healers merged testing and trying by using patient tests to determine a substance’s properties or to refine methodologies in both drug production and application. These themes of testing and trying occupied a central place in the making of medical knowledge across a vast chronological span and broad geographical regions and social contexts. The essays in the special issue examine these crucial knowledge practices in Europe c. 1300-1800 (go here for a table of contents).

Several main themes emerged from this collaborative project. First, medicine was always an experiential art and the essays in the special issue demonstrate clear continuities between the learned physicians’ uses of experience/experiment in the Middle Ages and early modern experimental interests. Learned medicine made deliberate use of experience from a very early date and pharmacy was an area where the gathering of experiential knowledge was particularly pronounced. The senses – touch, taste, smell, sight and hearing – played vital roles in determining the properties of drugs and their effects on the human body.

Concurrently, as many essays in the volume demonstrate, structured drug testing had a long history. Medieval physicians developed meticulous rules for drug testing, as Michael McVaugh’s essay shows, although they left no record of actual medical trials. This focus on establishing protocols for drug testing continues throughout the medieval and early modern period, with significant expansion in scale and scope. By the eighteenth century, the testing of mineral spa waters (in Michael Bycroft’s essay) or proprietary drugs (in Justin Rivest’s essay) became large-scale undertakings situated in learned academies and hospitals.

When taken together, the essays in the ‘Testing Drugs and Trying Cures’ special issue collectively argue that ‘experimental thinking’ played a crucial role in learned assessments of medicine and drugs throughout the Middle Ages and early modern period. From the time of Galen, drug testing was structured and evidence-based with an aim to produce transferable results. For us, this fascinating and multifaceted story of premodern drug testing enriches and extends current histories of experimentation and we hope that our explorations into topic will inspire others to join us too!

Further Reading and Acknowledgements:

This post is a very condensed version of Elaine Leong and Alisha Rankin’s ‘Testing Drugs and Trying Cures: Experiment and Medicine in Medieval and Early Modern Europe’, Bulletin of the History of Medicine, 91 (2017), 157-182. The full version of the article is available here. The entire special issue is available here.

The ‘Testing Drugs and Trying Cures’ project was funded by the Max Planck Society as part of the Minerva Research Group’s ‘Reading and Writing Nature in Early Modern Europe’.  We also extend our grateful thanks to all the participants of the 2014 workshop, the editors of the BHM and the anonymous reviewers of the articles in this special issue.

Distilling and Deflowering

A friar in an apothecary
Credit: Wellcome Library, London.

By Peter Murray Jones

Between 1416 and 1425, English friars put together a Latin medical handbook. This handbook, called the Tabula Medicine (‘Table of Medicine’), mostly consisted of remedies, arranged alphabetically by name of ailment, instead of the head to toe order of the standard medical Practica. The friars seem to have assembled the text by accumulating remedies in a sort of medieval Wikipedia. Some copies preserve the ‘open’ format by leaving room for additional remedies under each heading.[1]

Many remedies are medicinal recipes culled from books. Most often they cite the works of Avicenna, Galen and native authorities, Gilbertus Anglicus, Bernard de Gordon, John of Gaddesden, and John Arderne. But a lot of other remedies are attributed to English friars who flourished c.1370-1420.[2] The friars mentioned were identified as authorities (expressed as “per fratrem Peter Russell”, for example) for recipes of all kinds. But they had a particular fondness for distillations. Under the heading “Gutta arthetica” (Gout of the joints), we find:

King’s MS 16, fol.1. The opening of the Tabula medicine

“According to brother William Holme, for cold gout take the dregs of a pottle (two quarts) of beer; boil down a pennyweight of boar’s flesh for a day, stirring it with a ladle; and take a handful each of chamomile, pellitory, cowslip, lavender, honeysuckle, and marjoram. Cut up the cooked meat and the herbs into tiny pieces and distill together with the dregs in an alembic. The water collected in a glass can be kept and used as wanted.  Apply it warm, and it is called flesh-water.”

Holme, like Hieronymus Brunschwig, held that distillation ensured your remedy did not go off.

More ambitious distillations aimed at producing the heavenly quintessence, or at the very least aqua ardens (burning water). The friars must have had a copy of John of Rupescissa, Liber de consideratione quintae essentie to hand, for they quote from it accurately under headings for “Cor” (Heart), “Demon,” “Facies” (Face), “Frenesis” (Frenzy), “Melancholia,” “Spasmum” [Convulsion] and “Venenum” (Poison). They never identify him by name, although Rupescissa was a Franciscan friar, writing from prison in France c.1350. Under the heading “Facies”, they tell us that wild strawberries are a hundred times more powerful against outbreaks of pustules on the face if administered as a quintessence. Rupescissa uses exactly the same words at two points in his text. We are not told in the ‘Table of Medicine’ how to extract a water from wild strawberries and combine it with quintessence, although Rupescissa does give a recipe.

The only heading in the ‘Table of Medicine’ that names a remedy instead of an ailment is “Balsamum” (Balsam). Native balsam was extraordinarily rare and expensive in late medieval Europe, in all its three forms, and friar William Holme is credited with two different recipes for making an ‘Artificial Balsam.’ One simply requires powdered exotic spices to be put successively into hot but not boiling oil. The second requires small quantities of natural balsam, as well as twenty-five other ingredients. They are mixed and pulped in a mortar before distillation. This distillate comes in three degrees of strength, and is said to be just as effective as the native kinds in treating a long list of ailments. Holme is the only one of the friars mentioned in the ‘Table of Medicine’ who can now be identified as author of a surviving text, De simplicibus medicinis (‘On medicinal simples’) of 1415. This was “deflowered” as the bibliographer John Bale later put it, by Holme “from twelve doctors of medicine”. The ‘Table of Medicine’ itself went in for “deflowering”, though it also credited experienced friar practitioners.

King’s MS 16, fol. 144. Wistanton’s recipe for distilling blood and Forman’s hand in the margin.

Friar Robert Wistanton gives a recipe to make use of distilled human blood in surgery. The blood is kept for forty days in a glass vessel under dung, then cooked in a copper pot for a day, cooled, then skimmed. Afterwards it is distilled with a filter, mixed with aqua ardens, then distilled again with an alembic, and that distillate is the best of all waters. It will consolidate a wounded limb within three days and heal the sick. What remains in the bottom of the vessel should be kept, cooled and dried, and the resultant powder is best for fractured bones. Friars were not supposed to dabble in alchemy and surgery, but that does not seem to have stopped Wistanton and his brothers.

King’s MS 16, fol. 8b. Insert in Forman’s hand on Catalepsis.

In 1574 Simon Forman, astrologer and alchemist, purchased a manuscript of the ‘Table of Medicine’ in Oxford. He added recipes drawn from his own experience, or from Andrew Boorde’s Breviary of Healthe (1557), in the margin opposite the entries for particular illnesses. He also interleaved the manuscript to add remedies for illnesses not covered in the ‘Table of Medicine’. In this enhanced form the text continued in use into the seventeenth century.[3]

[1] Peter Murray Jones, “The ‘Tabula medicine’: an Evolving Encyclopedia,” English Manuscript Studies 1100–1700, vol. 14, Regional Manuscripts 1200-1700, ed. A. S. G. Edwards (2008), 60-85.

[2] Peter Murray Jones, “Mediating Collective Experience: the Tabula Medicine (1416–1425) as a Handbook for Medical Practice,” in Between Text and Patient: The Medical Enterprise in Medieval & Early Modern Europe, ed. Florence Eliza Glaze and Brian K. Nance (Florence: SISMEL-Edizioni del Galluzzo, 2011), 279-307.

[3] Cambridge, King’s College MS 16. See Lauren Kassell, Medicine and Magic in Elizabethan London. Simon Forman: Astrologer, Alchemist and Physician (Oxford: Clarendon Press, 2005).

Peter Murray Jones: I am Fellow Librarian of King’s College, Cambridge and a historian of medieval medicine. I have a particular interest in relations between knowledge and practice as expressed through recipes. My current project is on the contribution of friars to practical medicine and science in late medieval England.

Living in Seasons: Mulberry Wine, or the Moral Perils of Recipes in Times of Austerity

By He Bian

April and May on the US east coast = temperature swings = confusing and sickly weather. This year especially reminds me of the sobering admonition from the ancient Chinese classic of medicine, <The Yellow Emperor’s Inner Canon>: “when there is damage from cold in winter, one suffers from warm diseases in spring (Dong shang yu han, chun bi bing wen)” (see Marta Hanson’s insightful book on this subject). Seasonality is well known as a central preoccupation in the Chinese medical tradition: the cosmic resonance of the body and the larger world according to the quadruple division of the solar year – the cyclic fluctuation of temperature, directionality of wind, and the loci of corporal vulnerability that furnished essential cues for a master practitioner of medicine.

But if etiology in Chinese medicine is classically understood as seasonal, surely the therapeutics should also follow a seasonal rhythm? To my surprise, a search for pre-modern monographs that contain the keyword “four seasons” (sishi) yielded few results. In addition, they tend to focus on agriculture (which of course also follows a seasonal rhythm) or popular festivities around the year. I decide to take a closer look at the latest text that featured “four seasons” in its title – a title attributed to Qu You (1341-1427), Si shi yi ji (Auspicious and Inauspicious Deeds in Four Seasons). I thought this text might teach me something about how a learned scholar approached the notion of seasonality in the early fifteenth century, and how that might align or depart from the canonical medical model of seasonality.

The book consists of twelve chapters, each describing the dos and don’ts for a specific month. I flipped to the chapter on the fourth month (which corresponded roughly to this present moment in Western calendar). I learned, to my surprise and delight, a ton of practical advice with specific recipes: how to properly dry and insulate book and painting cases before the advent of rainy season; “use eels that have been sun-dried, burn them inside the house to thwart the thirst of mosquitoes” (seems appropriate for New Jersey habitat); “wrap your battle gears along with Sichuanese peppers (huajiao) or powder of Daphne flowers (yuanhua) to prevent worm damage… wrap windshield collars and earmuffs and store them in a vat, tightly seal it up, so as the fur will not fall off.” After the first full moon this month, one “should drink mulberry wine” to prevent “wind heat” illnesses (see Shigehisa Kuriyama’s discussion of wind in classical Chinese and Greek medicines). The recipe goes as follows:

Use Mulberries, get its juice of three dou (1 dou ~ 18 liter). White Honey four ounces (liang); Butter (suyou) one ounce; raw ginger juice two ounces.

Bring mulberry juice to a boil in a pot, and reduce its volume to three sheng (1 sheng = 1/10 dou), and then add honey, butter, and ginger juice. Add three drachm (qian) of salt and keep boiling till the texture is thick.

Store in porcelain utensils. Each time, take a small cup with wine. This effectively cures various wind-induced illnesses.

Not only does this sound completely delicious and doable to me, I also realize how recipes like this are in fact completely grounded in the seasonal rhythm of biological life (I just saw a friend posting the harvest of fresh mulberries in her backyard in China).

In sum, what Qu You did in this book was to cull from a wide range of medical and non-medical sources (a rough count yielded over 60 different titles) for hints and tips on how to live according to the seasons. Some of his references were archaic almanacs that offered divinations on the most auspicious dates to travel, have sex, trim your nails, or remove grey hair, as well as dates one should abstain from such activities. Some were quasi-ethnographic accounts of “customs” (fengsu) in ancient cities that still lend to a viable reading as practical guides to festivities. Still others draw from esoteric Daoist literature on the preservation of vital essence (I have blogged on a related topic here), a decision on Qu You’s part that raised many eyebrows both during his lifetime as well as centuries later.

A Daoist talisman in Qu You, Si shi yi ji (1920 reprint of an 1836 edition).

We must remember that Qu lived through the Ming dynasty’s founder, Hongwu emperor’s reign (1368-1398) – a period known for its austere message of moral purity and simplicity. His fourth son, who usurped the throne shortly after Hongwu’s death to become the Yongle emperor (r. 1404-1424), was not exactly friend of the letters either. Those were not easy times for a literary aficionado with keen interests in morally dubious subjects, and yet Qu You continued to compose and comment on poetry, wrote short stories featuring ghosts and women, and collected esoteric recipes. He even managed to publish those works, prefacing them with loud self-defense of his moral stature. Qu eventually got into trouble, endured decades of exile in the north, and yet again outlived the Yongle emperor, who threw many a undisciplined scholars like him into jail, by three years.

Perhaps the seasonal recipes did work well for him after all?