Category Archives: medical practitioners

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.

‘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.

 

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.

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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.

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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.

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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.

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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.

A forgotten chapter in natural history: the taxidermy of man

By Marieke Hendriksen

Having written a book on eighteenth-century anatomical collections, I know a thing or two about historical techniques for preserving (parts of) the human body. As I am interested in natural history collections more generally, I also did some research on the preservation of animal bodies, and even took a taxidermy course myself. However, recently I realised that the preservation of human and animal bodies were historically even closer connected than I had imagined. Yet ideas about which parts of the human body could and should be preserved, and how, diverged greatly, particularly when it comes to skin, or taxidermy. Taxidermy, from the Greek τάξις (taxis) and  δέρμα (derma – I am adding those for people who may not read Greek script), literally means ‘the arranging of skin’.

Fragment of an engraving of the anatomical theatre of Leiden University, early 17th century, showing visitors who appear to discuss a human skin. Contemporary engraving by Willem Swanenburgh; drawing by Jan van ‘t Woudt (Johannes Woudanus).

There are a few known cases of attempts to preserve human skins in their entirety before 1800 – for example, there was a human skin in the Leiden anatomical theatre in the seventeenth century – but that wasn’t stuffed, and such attempts appear to have been altogether unsuccessful. If human skin was preserved, it was mostly small pieces, which were used to study things like skin colour and structure, tattoos, or pathologies. By the end of the eighteenth century, the preservation of an entire human skin in a lifelike pose was of little interest to anatomists. Normal internal anatomy would be studied through dissection and the creation of preparations and skeletons, and pathologies of the skin could be preserved by making preparations of small sections of skin. As healthy skin can be studied perfectly easily in live subjects, there was little reason to pursue the taxidermy of man. This is reflected in anatomical handbooks like Thomas Pole’s 1790 Anatomical Instructor (reprinted in 1813), which gave detailed directions for numerous methods to preserve parts of the human and animal body, including entire heads and foetuses, but did not say anything about how to preserve only skin. On the contrary, Pole advised to remove the cuticle from a head that was to be preserved,  as this would give ‘a brightness to the complexion’.[1]

Jeremy Bentham’s ‘preserved’ head is not on display, but stored in an environmentally controlled safe. Copyright: UCL.

However, with the growing popularity of taxidermy – the mounting of animal skins in lifelike poses – and the rise of physical anthropology in the early nineteenth century, there were a number of experiments with human taxidermy, the most famous of which was probably Jeremy Bentham’s unsuccessful attempt to have his body made into an ‘auto-icon’ after this death. Then there was ‘el negro’ or ‘the negro of Banyoles’, whose faith was described by Dutch author Frank Westerman in his 2004 book El Negro en ik (‘El negro and I’). The remains of this young African San man were stuffed by two taxidermists, the French Verreaux brothers, in the 1830s, and remained on display in a local Museum in Banyoles, Spain, until 1997. Eventually his remains were send for burial in Botswana in 2000. Jules Pierre (1807-1837) and Jean Baptiste Édouard (1810-1868) Verreaux created taxidermy specimens of exotic animals for their father’s Parisian shop in natural historical objects, Maison Verreaux, and, as ‘el negro’ shows, used human bones for his models.

The head of the figure in ‘Arab Courier attacked by lions’ sits detached from the rest of the diorama during restoration work. Copyright: Nate Smallwood | Tribune – Review

For a long time, ‘el negro’ was the only known case of nineteenth-century human taxidermy. However, a recent discovery suggests that the Verreaux brothers used human remains more frequently. In 2016, a human skull was discovered in a mannequin that was part of an ensemble made by the Verreaux studio. Formerly known as “Arab Courier Attacked by Lions”, it was restored and returned to display at the Carnegie Museum of Natural History in Pittsburgh under the title “Lion Attacking a Dromedary”. Although apparently no attempt was made to use human skin in the Pittsburgh diorama, these cases show that there was little reticence when it came to using human materials for taxidermy displays in the nineteenth century, particularly when the human in question was considered ‘exotic’. This is supported by the fact that a popular contemporary taxidermy manual, aimed specifically at museums and travelers, opened with a paragraph on the impossibility of applying taxidermy to man successfully. The book, written by the naturalist Sarah Bowdich (née Wallis, later Lee, 1791-1856) saw six editions – the first in 1820, the last in 1843.

After listing the necessary tools and giving a number of recipes for the cleansing and preservation fluids used in taxidermy, Bowdich opened the section on ‘the preparation of mammalia’ with a somewhat disappointed-sounding statement:

1. Of man 

All the efforts of man to restore the skin of his fellow creature to its natural form and beauty, have hitherto been fruitless: the trials which have been made have only produced mis-shapen, hideous objects, and so unlike nature, that they have never found a place in our collections.

Bowdich went on to discuss the life-like wet preparations made by Amsterdam anatomist Frederik Ruysch (1638  – 1731) as ‘without doubt (…) very useful to science’, before switching to a description of a more successful practice – the preservation of skeletons. Given the tragic history of ‘el negro’ and many other violently obtained human remains in museum collections, it is a cold comfort that the naturalists of the nineteenth century failed at the taxidermy of their ‘fellow creature’.

[1] Pole, Thomas. The Anatomical Instructor ; or an Illustration of the Modern and Most Approved Methods of Preparing and Preserving the Different Parts of the Human Body and of Quadrupeds by Injection, Corrosion, Maceration, Distention, Articulation, Modelling, &C. London: Couchman & Fry, 1790: p.84.