Category Archives: Early 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.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

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.

‘This one is good’: Recipes, Testing and Lay Practitioners in Early German Print

By Tillmann Taape

Title illustration from Brunschwig’s Small book of distillation. © Wellcome Images

Having recently finished my doctoral thesis on the printed works of Hieronymus Brunschwig, which have previously featured on the Recipes Blog (here and here), I am delighted to contribute to this series of posts on testing and trying (for an overview, see our re-posted summary of the Testing Drugs and Trying Cures conference). What better opportunity to share how it all came together, and reflect on the role of recipes and testing in the narrative.

Hieronymus Brunschwig (c.1450–c.1530), a surgeon and apothecary from Strasbourg, wrote the first printed books on surgery and distillation. In my thesis, Hieronymus Brunschwig and the Making of Vernacular Medical Knowledge in Early German Print, I read these uncommonly practical and technical books alongside records from the Strasbourg archives, about the craft guilds and medical practice. This allows us to make sense of Brunschwig’s practical vernacular medicine in relation to local intellectual trends, different forms of healing, the local milieu of guilds and artisans, and early German print culture.

Brunschwig’s first book was the Cirurgia of 1497, the first surgical manual in print. This, of course, was an opportunity to codify and re-define surgery. Brunschwig revives the medieval tradition of what Michael McVaugh has termed rational surgery (i.e. a learned as well as a practical art), to educate trainee surgeons and to present their discipline as a respectable and useful trade. Emphasising the need for skilled hands as well as a working knowledge of the human body, Brunschwig defends surgery on two fronts: against learned physicians’ rhetoric of superiority, and against other craftsmen’s deep-seated anxieties about occupations which were in contact with sick and dead bodies.

A surgeon treating an abdominal wound. Hieronymus Brunschwig, Dis ist das Buoch der Cirurgia (Strasbourg, 1497). © Wellcome Images.

The later books on distillation, published in 1500 and 1512, open up to a wider readership, including not only medical artisans such as surgeons or apothecaries, but also the ‘common man’ – a middling social layer of literate citizens, householders and other lay practitioners. This new kind of medical reader, as I have discussed in a previous post and elsewhere, is emblematised in the figure of the ‘striped layman’ which appears in numerous woodcut illustrations throughout Brunschwig’s works.

A conspicuously stripy student, from Brunschwig’s Cirurgia (1497). © Wellcome Images

Many of the recipes and instructions in the distillation books are adjusted for this type of reader. They start from scratch and are rich in technical details which are not found elsewhere in print or, to my knowledge, in manuscript. Although Brunschwig engages with complex ideas about the nature of matter and its manipulation, such as John of Rupescissa’s notion of a ‘quintessence’ in all things, he re-works them into manageable, pedestrian remedies. Rather than pursuing Rupescissa’s heavenly panacea, Brunschwig uses distillation to produce a type of middle-class quintessences: although earth-bound and imperfect, they were reliable and effective remedies in the hands of laypeople.

Detailed woodcut images of distillation apparatus and instructions for its use. Brunschwig, Liber de arte distillandi de simplicibus (Strasbourg, 1500). © Wellcome Images.

One overarching theme of my thesis is the artisan’s approach to understanding and manipulating nature. For a craftsman with no Latin, Brunschwig mined a surprising amount of knowledge from texts. But more importantly, I argue, he knew things through direct physical engagement with bodies, materials and technical processes. His books are full of instructions to probe wounds, check temperature by touch, inspect colour changes in the alembic, and smell or taste distilled remedies. His expertise was located as much in the body and its senses as in books.

Nonetheless, writing was a powerful tool for recording and communicating practical insights. From cautionary tales of exploding alembics to heroic accounts of successful cures, Brunschwig emphasises his own experience as a source of knowledge. The German term he uses for this type of knowledge, erfarung, is related to fahren, meaning ‘to travel’. In the early sixteenth century, it denoted a way of experiencing the world through one’s own senses, by moving through it or simply being in it in an active, attentive manner. Erfarung was compared, often unfavourably, to spiritual contemplation and introspection. Over time, however, doctors and students of nature such as Paracelsus came to see personal erfarung as the necessary labour of insight rather than a sinful distraction. The Book of Nature, they insisted, should be read with one’s feet. Brunschwig’s emphasis on his own and others’ erfarung was thus part of a larger vernacular culture of experiential knowledge, as well as learned debates about experientia which have often been the focus of historical accounts of a medical empiricism developing in the early modern period.

Recipes played a major part in Brunschwig’s codification of experiential medical knowledge. Some, as I have shown in a previous post, were presented in Latin pharmaceutical jargon likely unknown to laypeople. These recipes were closed to readers, who were meant to copy them out on a piece of paper and hand them to an apothecary who would manufacture the remedy according to his art and his experience. Although the great majority of recipes are in German, some of these are also presented as tried and tested, by Brunschwig himself or others, and do not call for ‘tweaking’ on the part of readers.

Other recipes, however, give alternative ingredients or leave the exact composition up to the practitioner’s judgment. Many recipes come without the author’s seal of approval, and their sheer number makes it seem unlikely that Brunschwig could have tested each one. Such ‘open’ recipes leave room for improvisation and testing. The ongoing work of erfarung runs on into readers’ own practice, and often spills out into the margins of Brunschwig’s printed books. In many surviving copies, early modern healers from different walks of life marked recipes with a magisterial probatum est, or a simple vernacular note such as ‘this one is good’.

In some of the earliest medical works in print, Brunschwig addresses a readership of lay healers and ‘common men’ which would come to represent a significant portion of the early German print market. Through his use of recipes embedded within a culture of erfarung, he involved his vernacular readers in a continued effort of empirical trying and testing.

Pursuing the themes of recipes and artisanal knowledge, I am delighted to be joining the Making and Knowing Project at Columbia University this summer, and look forward to sharing our work on making, testing, and trying, which has previously featured on this blog.

 

Anecdotes and Antidotes

By Alisha Rankin

How did early modern individuals test and try their recipes and cures? This question is at the heart of the special issue of the Bulletin of the History of Medicine, “Testing Drugs and Trying Cures in Medieval and Early Modern Europe,” in which I participated as both a co-editor and an author. My article, “On Anecdote and Antidotes: Poison Trials in Early Modern Europe,” examines the ways in which early modern practitioners tested a specific kind of cure: antidotes to poison. It contains some information I discussed in earlier posts on this blog – here and here – but adds many details and thoughts about testing in general. Most cures, I argue, tended to be tested in the course of regular clinical experience. A patient got sick; a practitioner tried a particular remedy, observed the results, and frequently shared anecdotes of success or failure. The scale of this kind of testing could be small or large, but in most cases it involved patients who were already sick.

Poison antidotes were a little different, because practitioners could actually create the condition of illness by giving poison to a test subject. In 1563, for example, the royal surgeon to Holy Roman Emperor Ferdinand I, Claudius Richardus, wrote a letter describing the marvellous virtues of bezoar stone. As avid Harry Potter readers will know, bezoar was an animal byproduct prized as a poison antidote and cure-all. Richardus recounted a series of marvellously successful tests he had conducted on bezoar at the Emperor’s behest. In two of them, patients received bezoar in the midst of a serious illness – the usual practice. In the other two, bezoar was tested in contrived trials on condemned criminals.[1]

Bezoar stones from the imperial Kunstkammer, Kunsthistorisches Museum Vienna. Photo by Alisha Rankin.

This second kind of test – which I call a poison trial – has a long history dating back to antiquity. Many ancient kings, most famously Mithridates VI of Pontos (135-63 BCE), used condemned criminals to test poison antidotes, from which he developed his famous antidote and cure-all, mithridatium. The Greco-Roman physician Galen reportedly tested theriac, a derivative of mithridatium, on roosters, and versions of this test appeared in the writings of several Arabic physicians, including Avicenna’s highly influential Canon of Medicine.[2] Medieval physicians repeated the description of Galen’s test as well. However, poison trials tended to be described as theoretical tests that one could conduct rather than as anecdotes about tests that had actually taken place, and they were mainly suggested as a means to test whether a batch of theriac was inferior, fraudulent, or old – not whether theriac actually worked. From the time of Galen, moreover, poison trials were conducted exclusively on animals, not humans. The dominant argument for the efficacy of these drugs remained anecdotal reports of their use on sick patients.

In the Renaissance, poison trials expanded significantly, as did their role in medical communication. From the 1520s, powerful rulers began to revive the gruesome tradition of using condemned criminals to test a variety of poison antidotes – not just theriac. In addition, these tests were reported and circulated as anecdotes rather than being described as theoretical suggestions. The first known example comes from Rome in August 1524, when Pope Clement VII directed his medical personnel to test an antidote oil created by the surgeon Gregorio Caravita. He granted the medics two Corsican criminals who had been condemned to death by beheading. Both prisoners were given a strong dose of the deadly herb wolfsbane (aconitum napellus). Caravita then anointed one prisoner with the oil. The other, a “savage spirit,” was given no antidote. The first man survived; the other died in much agony.

Testimonium de verissima ac admirabili virtute olei compositi contra pestem & omnia venena (Rome, 1524), BNF.

A second successful test was conducted on a Mantuan prisoner given arsenic. Soon thereafter, the medical personnel published a public service pamphlet describing these trials in detail.[3]

A shorter version of this anecdote also appeared in the famous herbal published by Italian physician Pietro Andrea Mattioli in 1544 (with a Latin version in 1554). Mattioli’s influence helped spread poison trials around Europe. From 1561-67, a number of contrived trials on condemned criminals took place under powerful princes, including Emperor Ferdinand I, King Charles IX of France, and Duke Cosimo II de’Medici. Significantly, royal physicians and surgeons spearheaded these poison trials, and they communicated the results in anecdotes that appeared both in private documents and printed books. Claudius Richardus’s bezoar trials were part of a series of such events.

These anecdotes demonstrated careful thought in how the trials were devised and conducted. They described the trials in in excruciating detail, including the number of times a prisoner had vomited and defecated as well as the hour at which these events had occurred. In some cases, physicians attempted to created conditions that would lead to a useful outcome. Richardus’s letter described how food was withheld from a prisoner before the test, “so that one could be more certain of the trial.” This step came in response to a previous case in which the physicians had trouble getting the poison to work. Finally, physicians took care in reporting and circulating their reports about the trials, clearly imbuing them with significance. A series of poison trials on dogs conducted in 1580 by a German prince circulated in both manuscript and print as a detailed Observatio, a report intended to be shared.

Poison trials represented only a miniscule part of drug testing in early modern Europe. Indeed, anecdotes about drugs used successfully on sick people helped drive the interest in new drugs from around the globe, as described in this post by R.A. Kashanipour. Nevertheless, the anecdotes about antidotes demonstrated significant developments in both testing practices and medical communication. To find out more, read my article!

 

[1] Richardus’s letter, to Archbishop Nicholas Olahus, was later published in Latin and German. Thomas Jordan, Pestis phaenomena (Frankfurt, 1576), 621–630; Johann Wittich, Bericht von der wunderbaren bezoardischen Steinen (Leipzig, 1592), 21.

[2] Galen’s poison trial appeared in the treatise On Theriac to Piso, which may be spurious. However, scholars in the Islamic world and Europe assumed it was authentic. See Robert Leigh, On Theriac to Piso, Attributed to Galen: A Critical Edition with Translation and Commentary (Leiden: Brill, 2016).

[3] The pamphlet was signed by the physician Paolo Giovio, the apothecary Tomasso Bigliotti, and the senator Pietro Borghese. Testimonium de verissima ac admirabili virtute olei compositi contra pestem & omnia venena (Rome, 1524).

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.