4 Peruvian Bark: From Specific Febrifuge to Universal Remedy Introduction Most histories of therapeutics, and of medicine in general, mention the introduction of Peruvian bark in the seventeenth century as an important event. 1 There are chiefly three reasons for this attention. Firstly, Peruvian bark (Cinchona officinalis Lin.) was the predecessor and source of the therapeutically effective alkaloid quinine. Secondly, it was the prototype of a “specific” remedy (against intermittent fevers, i.e. malaria), which challenged the principles of traditional, Galenic therapy. And thirdly, it was an example of the transfer of medical knowledge and drugs from the New to the Old World. That there must have been considerable need for remedies against the “intermittents” is clear from the high prevalence of malaria in Europe in the seventeenth and eighteenth centuries. Not only the Mediterranean countries were affected, but also those further north, including England, especially the marshy regions. Moreover, malaria was a serious problem for many colonial settlements. 2 The disease was generally explained with the classic theory of miasms, or bad airs, which led to corruption of the humours. Various forms were distinguished: tertian fever, with a febrile paroxysm on the “first and third” days (i.e. every second day), thought to be caused by corrupted “yellow bile”; quartan fever, with fever attacks on the “first and fourth” days (i.e. every third day), attributed to changes of the “black bile” of the spleen; and various mixed forms, such as semitertian, impure tertian, or double quartan fevers. Especially feared was a malignant form, in which the fever returned every day. 3 Whereas the relevance of Peruvian bark for the history of medicine has been widely acknowledged against these backgrounds, only few scholarly studies have actually examined the subject in any detail. In 1941 Alec W. Haggis provided a careful analysis of the pertinent seventeenth- and early eighteenth-century sources. 4 He 223 Andreas-Holger Maehle - 9789004333291 Downloaded from Brill.com09/28/2021 01:19:00AM via free access Peruvian Bark exposed “fundamental errors” in the early accounts of the bark, that had been perpetuated through the centuries. The probably most important of these “errors” concerned the confusion about the botanical origin of the drug. Haggis demonstrated that up until Charles Marie de La Condamine’s description of the cinchona tree in 1740 (sent from his South American expedition), its bark was often mixed up with that of the Peruvian balsam tree (Myroxylon peruiferum Lin. fil.). The chances of confusion were especially great, because the bark of both trees was known under the same indigenous name, “Quina-Quina”. Moreover, since the beginning of the seventeenth century, Jesuit missionaries in South America had been sending the bark of the balsam tree as a febrifuge back home to Rome, as they did the cinchona bark from the 1630s. Haggis furthermore showed that the famous story of the “discovery” of the healing power of cinchona bark – through curing the wife of the Viceroy of Peru, the Countess of Chinchon, 5 from a tertian fever – did not match authenticated events and must therefore be regarded as a fable. A few years after Haggis, Jaime Jaramillo-Arango examined many of the same sources and problems and confirmed the former’s main conclusions. 6 Around the same time M. L. Duran-Reynals published a popularly written history of Peruvian bark and quinine from the beginnings in the seventeenth century up to 1945. However, lacking exact references, this work is only of limited value to the historian. 7 This first group of relevant publications had in part been stimulated by the military importance of malaria control and quinine therapy during the Second World War. In the following four decades various aspects of the history of Peruvian bark found further attention, sometimes in studies of closely related areas, such as the history of malaria and of “fevers”. 8 But only in 1993, with Saul Jarcho’s book Quinine’s Predecessor , another major specialist study has come out. Based on an admirable amount of primary sources from the seventeenth and early eighteenth centuries, Jarcho traces the introduction of cinchona bark into European medicine and the controversies linked with this process. His account elucidates the crucial role that the Jesuit order played in the distribution of the drug (hence also called “Jesuits’ bark” ), and it gives many insights into how physicians used the new medicine in treating intermittent and other fevers. In particular, he analyses the Therapeutice specialis (1712) of the Modena professor of medicine Franceso Torti, an influential work, which classified fevers in view of their suitability for treatment with cinchona. As an appendix to his study, Jarcho summarizes a 224 Andreas-Holger Maehle - 9789004333291 Downloaded from Brill.com09/28/2021 01:19:00AM via free access Peruvian Bark selection of concepts of intermittent fever from Galen to the beginning of the eighteenth century, providing thus a useful addition to the historical studies of theories of fevers edited by Bynum and Nutton in 1981. 9 The present chapter partly attempts to provide a follow-up to Jarcho’s account of the use of Peruvian bark as a febrifuge, by studying important developments in the late seventeenth and in the eighteenth centuries, up to the isolation of quinine in 1820, which forms a “natural” end. As in the “cases” of opium and lithontriptics, contemporary medical and scientific interest in the Peruvian bark is reflected by the vast amount of literature that has been produced on this drug: Edward John Waring’s Bibliotheca therapeutica lists (under the heading “Cinchona”) internationally 33 monographs from the seventeenth century, followed by another 187 titles published between 1700 and 1820. 10 While my discussion of works on the bark’s febrifugal powers will be selective, my focus will widen to include literature on the drug’s “new” therapeutic uses. For example, the treatment of “gangrene” with cinchona, which was introduced in the 1730s, will be studied in some detail. In general, attention will be given to experimental investigations of the bark and their consequences for pharmacological theory and therapy. Experimental aspects do not figure largely in Jarcho’s book, Quinine’s Predecessor . Yet in 1992 he edited a late seventeenth- or early eighteenth-century manuscript on Peruvian bark, which among others mentions some contemporary trials. 11 This text forms thus an interesting reference for my account of pharmacological experimentation with the drug around 1700. Early Controversy on the New Febrifuge Regular shipment of the bark from Peru to Rome was established by the Jesuit order during the 1640s. It was also a prominent member of this order, the Spanish-born Cardinal Juan de Lugo (1583-1660) in Rome, who is said to have initiated first “tests” of the drug in fever patients after 1645. 12 At de Lugo’s request, the personal physician to Pope Innocent X, Gabriele Fonseca (d. 1668), tried the bark in “own experiments” (“propriis experimentis”) and found it “not only harmless, but most beneficial” (“ non modo ... innoxium, sed etiam saluberrimum”) – according to a later Jesuit defender of the medicine.13 No further details about the nature of these “experiments” are known. According to the same source, several thousand people in Rome had been treated with the bark, in 1653 alone, without harmful effects. 14 De Lugo and the keeper of the 225 Andreas-Holger Maehle - 9789004333291 Downloaded from Brill.com09/28/2021 01:19:00AM via free access Peruvian Bark apothecary’s shop of the Jesuits’ Collegium Romanum, Pietro Paolo Puccerini (1600-61), seem to have been the main distributors of the remedy in these early years. A pharmaceutical handbill, the so-called Schedula Romana , advised about dosage and method of administration. In patients with tertian and quartan fevers two drachms of pulverised Peruvian bark, macerated in white wine, should be given at the beginning of the fever paroxysm. “According to experience”, it said here, “almost all” who took the powder were freed from their fever, if they had been well purged beforehand and abstained from other medicines during the following four days. However, the bark should not be taken, said a final warning, without previous consultation of a medical man, who judged about the right time and mode of administration. 15 By the early 1650s the use of Peruvian bark had spread to other European centres. Yet this was also the time when a first public dispute about the efficacy and harmlessness of the new drug flared up. Immediate cause was the case of the Archduke of Austria and Governor of the Spanish Netherlands, Leopold Wilhelm (1614-62). In 1652 he was diagnosed with a “false” (impure) tertian fever, which turned into a “double” quartan. The physician in charge, Jean- Jacques Chiflet (1580-1660), reluctantly yielded to the pressure of bystanders and gave – as prescribed in the Schedula Romana – two drachms of powdered bark in white wine. The Archduke became subsequently free of fever, but thirty-three days later he had a relapse. Having received a letter from his brother, the Holy Roman Emperor Ferdinand III, which advised against the use of the bark, he further refused to take the bitter medicine again. By order of his noble patient, Chiflet published, in 1653, a tract against Peruvian bark. All patients with quartan fever in Brussels who had taken the drug, he stated, had suffered relapses. The medicine merely extended the interval between the paroxysms. In Galenic fashion he further speculated that the humours might be thickened by the bark, giving thus rise to prolonged and fatal disease. Chiflet therefore recommended traditional European febrifuges, such as gentian. 16 The message of the Archduke’s physician appears to have been well received among the conservatively minded medical élite of Paris, who had his text reprinted for “the benefit of the public”.