Tag Archives: drug-testing

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.

Tales from the Archives: Testing Drugs and Trying Cures Workshop Summary

In September 2016, The Recipes Project celebrated its fourth birthday. We now have over 500 posts in our archives and over 120 pages for readers to sift through. That’s a lot of material! (And thank you so much to our contributors for sharing such a wealth of knowledge on recipes.) But with so much material on the site, it’s easy for earlier pieces to be forgotten. So, the editors have decided that, every now and then, we’ll pull something out of the archives to share with our readers anew.

Over the next few weeks, The Recipes Project will feature a selection of case studies from the current issue of the Bulletin of the History of Medicine on “‘Testing Drugs and Trying Cures”. This special issue grew out of a 2014 workshop held at Max Planck Institute for the History of Science in Berlin. We were very lucky to have two then graduate students Ashley Buchanan and Tillman Taape, join us for and grateful that they took the time to pen the post below. It seems fitting to begin this month on testing drugs and trying cures with a revisit to their post. Elaine (editor).

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By Ashley Buchanan and Tillman Taape

What did it mean to test a drug or try a cure in the early modern world? This was the central question for a group of scholars who gathered for a workshop at Max Planck Institute for the History of Science in Berlin, Germany.  Since recipes emerged as one of the key themes throughout the workshop, and because the conference’s location in Berlin made it difficult for scholars outside of Europe to attend, we thought we might share a brief summary of the “Testing Drugs and Trying Cures” papers, in the hopes that we could bring the workshop’s key ideas and discussions to a larger audience.  What emerged from an exhilarating two days of discussion and debate was the conclusion that historians of science and medicine should not privilege experiment and experimentation as fixed categories, but should understand the multiple ways in which physicians, apothecaries, artisans, institutions, and individuals in the early modern world tested, tried, investigated, experienced, modified, observed, and measured medicinal remedies and materiae medicae.

As written forms of medical and pharmaceutical knowledge and practice, recipes played an important part in the testing of drugs and cures, and our discussion raised larger questions surrounding the nature and purpose of an early modern recipe.

705px-ScuolaMedicaMiniatura
A miniature depicting the Schola Medica Salernitana from a copy of Avicenna’s Canons.  From Wikimedia Commons.

Michael McVaugh’s paper opened the discussion by exploring how medieval physicians went about testing drugs. Learned doctors in the Middle Ages might appear helplessly hidebound, and inclined to follow ancient authorities over experimentation. In contrast, McVaugh showed how a group of Montpellier physicians in the fourteenth century established something of an experimental program. Medieval physicians, however, were not testing to find a cure, but to determine the quality, strength, and effectiveness of a drug as it pertained to a particular person’s complexion. McVaugh underscored an important difference in the purpose of medieval drug testing. Physicians tested not for universal effectiveness, but to determine the quality of a drug – was it hot, cold, moist, or dry.

Duclos-title-page
Title page of the Academy’s Observations sur les eaux minérales (1675). From http://cures.hypotheses.org/the-workshop/programme-2/bycroft-michael

Although it became clear in our roundtable discussion that we should be wary of labeling such practices as obvious precursors to the experimental philosophies of the Scientific Revolution, many of the papers showed that the importance of specific tests resonated throughout the early modern period. Evan Ragland’s paper, for example, traced the use of the phrase periculum facere (‘to make a trial’) in physicians’ writings on medicine, anatomy and chemistry. Similarly, Michael Bycroft showed that French physicians and chemical experts of the Académie des Sciences became increasingly interested in the exact composition of mineral waters. Contrived tests such as color indicators or the analysis of residues after evaporation increasingly became the touchstone of proper inquiry.

McVaugh, Ragland, and Bycroft’s papers all underscored the need to understand the specific nature and purpose of testing in each historical context. Continuing to emphasize the importance of historical context, Francesco Paulo de Ceglia’s paper showed just how different the purpose of testing could be in the context of seventeenth century blood miracles in the Kingdom of Naples. Catholics tested the liquefaction of the blood of their patron saint to explore the limits of nature. By discovering nature’s limits, you could then determine what was truly miraculous. Protestants, on the other hand, tested various materials and recipes to recreate the liquefaction of blood to cast doubt on the alleged miracle.

san-gennaro
Reliquary containing a glass ampoule of San Gennaro’s blood. From La Repubblica.

In the context of testing, drugs and cures are often under scrutiny in the form of recipes detailing their production and administration. While recipes emerged from many of the papers as very important forms of knowledge, it proved virtually impossible to define exactly what a recipe was. Recipes can be very short or very detailed, ranging from a mere list of ingredients to careful step-by-step instructions. If there is one thing recipes have in common, it is the need for testing, trying, modifying and adapting to different conditions. While constructing an all-encompassing definition of a recipe proved futile, all agreed that it was fruitful to understand recipes as an important genre in early modern science and medicine.

apotheke_enhausen_l
From http://www.gn.geschichte.uni-muenchen.de/aktuelles/archiv_2011/archiv_2013/science_and_medicine/index.html

For her investigation on the testing practices of Venetian apothecaries, Valentina Pugliano emphasized the difference between experiment and experience. Venetian apothecaries were less concerned with testing drugs (in a traditional sense) than they were with the experience or truthfulness of their ingredients. Testing by inspection, smell and taste was also important in this pharmaceutical context, to ensure that the ingredients were what the merchant had promised them to be, and not a cheap substitute with inferior properties. For Pugliano’s apothecaries, the important issue that required testing was the authenticity of the ingredients rather than the efficacy of the finished product; after all, most preparations had proved their worth since antiquity. Like McVaugh, Pugliano questioned traditional “Baconian” understandings of what it meant to experiment and test and argued for more nuanced notions of testing and trying, which included observing, measuring, evaluating, and experiencing.

Image_Samir
Title page of Johannes Christophorus Homann’s Dissertatio inauguralis medica de medicinae cum geosophia nexu quam auspice deo prpitio (Hala Madgeburica, Hendelius, 1725). From http://cures.hypotheses.org/the-workshop/programme-2/boumediene-samir

With early modern Europeans’ increasing forays into the New World, however, more and more materiae medicae were found which were absent from ancient medical writings. Pliny and Dioscorides were silent on such substances as guaiacum wood, Peruvian bark or New World balsam, so their medicinal properties had to be newly investigated. Antonio Barrera-Osorio and Samir Boumediene’s papers added America, or the New World, into the discussion. Both emphasized the role of new drugs and materia medica in the rise of European experimental practices. New drugs and new medicinal recipes required new ways of testing.

Antonio Barrera-Osorio’s paper argued for an empirical culture in the Spanish empire, which was well suited to respond to these challenges. He showed how his protagonists gathered information about New World remedies from natives or travellers and experimented with ways of preparing them. Some of these drugs and recipes were deemed so important for the economy and health of the empire that the Spanish crown ordered tests in hospitals all over Castile. Samir Boumediene’s paper elaborated on the issue of making workable recipes for newly discovered drugs. Once more, taste and smell were important assays, but drugs such as guaiacum and Peruvian bark were also tested on a larger scale. Dispensing them to the poor inmates of charitable hospitals (as happened in France and Germany) helped to determine their effect, and to establish recipes, which indicated how to adjust the treatment in individual cases.

books
Andreas Cleyer, Specimen Medicinae Sinicae (Frankfurt, 1682). From http://cures.hypotheses.org/the-workshop/programme-2/hanson-marta-and-pomata-gianna

Gianna Pomata and Marta Hanson’s paper showed how recipes also functioned as vehicles of knowledge between different cultures. Recipes, as either formula or prescription, were both found in European and Chinese medical cultures. According to Pomata and Hanson, it was the familiar genre of the recipe that facilitated the transmission of Chinese pharmacology to Europe in the second half of the seventeenth century. Similarly, Carla Nappi argued that the Manchu medicinal recipes of the Qing court were spaces of encounter and medical translation in the early modern world. Pomata, Hanson, and Nappi demonstrated how the recipe served as the common ground between European and Chinese medicine and made the translation of Chinese pulse medicine and the transmission of Chinese materia medica possible in the seventeenth and eighteenth centuries.

Although recipes are difficult to characterize as a genre, it is clear that they are fascinating objects of historical study. More often than not, they are fluid rather than fixed forms of knowledge, requiring adaptation at every turn. They bring together ingredients, practices and often practitioners from all over the world, and themselves have a tendency to aggregate into larger collections. As written manifestations of gestures and processes, they play an important part in testing, assessing and modifying drugs and cures.

On Berlin Plums: Recipes from Johannes Magirus’ Medical Diary

By Sabine Schlegelmilch

For some years now, I’ve been doing research on Johannes Magirus (1615-1697). He was a German physician, and by now has made me shake my head quite often because of a certain quirkyness his writings reveal. On the other hand: when not quarelling with his surroundings or boasting his genius (or then especially?), he makes me learn quite a lot about medicine in the seventeenth century in Germany and abroad. As a student, Magirus travelled through the Netherlands, England and France. He was stunned by the practical approach of bedside teaching he witnessed there, as it was different from any medical education he had known back in Germany.  After his return, he began to practise in Berlin in 1640, and afterwards moved to Zerbst (in Anhalt-Saxony).  He soon left the town again, steaming with anger because of a personal enemy he named the ‘Sauffteuffel’ (booze devil). Finally, he became professor of medicine in Marburg (in Hesse) and tried to implement his experience gained abroad into his own teaching.  In the announcement for his classes, he advertised to take his students to the sick whom, for demonstration purposes, he would treat for free – an early polyclinical  concept largely unknown in Germany for his time.

Titel of Magirus' Medical Diary (University of Marburg Library, Ms. 96)
Titel of Magirus’ Medical Diary [Credit: University Library Marburg]
Magirus managed to reach the respectable age of 82, although he displayed a certain proneness for self-experiment. So he couldn’t help to explore the construction of a fortress while it was besieged (!), and nearly was hit by a cannonball. In medicine, he was equally eager to gain personal experience. His special interest lay in drugs, and in particular in ‘chymical’ ones. We know this from his well-preserved medical diary and a notebook with commonplaces from his time in Berlin and Zerbst. For me, it was fascinating to see how systematical his approach was in drug-testing as a young practitioner. With each recipe he prescribed, he precisely noted its impact on the patient. With a woman in pain, he wrote in his diary: ‘after the first half of my pills, there was no bowel movement, after the second half she had a motion eight times’ or ‘before my pill, she always was in pain at two o’ clock, but afterwards at three o’ clock’. Often there are notes like ‘this is the powder I also have prescribed to the tailor in the roßstrasse’ that show how Magirus drew connections between different cases. He recorded successes as well as failures, and even tried to reduce side effects by singling out the one substance his patient showed an intolerance for, and then substituting it.

Fortunately, with drug-testing on his own body he was more cautious than in his cannonball-adventure. He surely was interested in the effect of new remedies and collected information on them. It is striking, however, that he made excerpts e.g. on mercury but, according to his diary, never used it with his patients, and never did test it on himself. Reading the excerpt in his commonplace book, one doesn’t wonder; it says that

if you use an ointment with mercury, it will cause convulsions, and the patients will get blisters in their throat, their uvula will fall off, they will develop ulcers, all teeth will beginn to loosen and  get black, and a huge amount of stinking spittle will run out of their mouth.

With less dangerous drugs, though, he experimented on himself and noted his personal experience. So we read that some aloe rosata ‘had dried up my stomach and I felt even worse than before’. When one of his colleagues prescribed a plum puree to one of his patients, Magirus took some of it to try it himself. He didn’t like the effect very much, as he ‘felt  a pain and rumble in my left hypochondrium’, and therefore came to the conclusion: ‘so it’s true: sugar and everything sweet are noxious for a spleen condition’. As unpleasant as this plum-related experience was for him, as rewarding was another: one of his patients, an advocat also named Johannes Magirus, obviously had told our Magirus how to prepare a formidable plum-juice with raisins, senis-leaves and fennel-seed that did wonders as a purge. Magirus must have tested this juice, as we can see that in the following time he began to prescribe it to his patients.

MS. 96, p. 22: Magirus crossed out the ingredients of his recipe that he pharmacy couldn't provide and that he had to add from his own stock (addantur in aedibus meis).
Magirus crossed out the ingredients that the pharmacy couldn’t provide and that he had to add from his own stock. [Credit: University Library Marburg]
I imagine Berlin at this time, i.e. just around the end of the Thirty-years-war, as a rather shabby place. Contemporary sources tell us that the elector was absent for most of the time and swine were roaming the mudden streets of the town outside the court-buildings. Magirus’ notes reveal that even the court-pharmacist was not able to provide some of the more sophisticated ingredients for his recipes. So it takes no wonder that something as simple as plums grew essential to his Berlin practice.