THE RECIPES PROJECT - WHEN DOES A DRUG TRIAL END?

22/08/2017 ELAINE LEONG 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.