The influence of German science on Cinchona and quinine research in Portugal in the second half of the 19th century.

This paper examines the contribution of three Portuguese scientists to Cinchona cultivation in the former Portuguese colonies in the second half of the 19th century, while discussing the importance of their studies in Germany to their professional lives. Portuguese pharmaceutical, medical, and botanical literature from the 19 th and 20 th century was reviewed, as well as books and articles regarding the history of pharmacy and medicine in Portugal. Cinchona bark, source of the antimalarial alkaloid quinine, is obtained from a South American plant, and was an important commodity in the 19th century. Many European nations (including Portugal) tried to acclimatize and cultivate Cinchona plants in their colonies. Pharmacist Joaquim dos Santos e Silva (1842-1906) performed chemical analysis of Cinchona bark samples from the Portuguese colonies in Africa. Forester Bernardino Barros Gomes (1839-1910) wrote a book with practical instructions for Cinchona cultivation and chronicled the history of Cinchona plantations in the British and Dutch colonies. In that work he also encouraged private planters to cultivate Cinchona. Forester Adolpho Frederico Möller (1842-1920), as inspector of the Botanical Garden of Coimbra, managed Cinchona plants' cultivation in the garden's nurseries, which were later sent to the colonies, and answered queries from Cinchona planters. Silva's chemistry studies in Germany were crucial to his career and the work of the three scientists was influenced and guided by their knowledge of German science and scientific culture.

Hidroxicloroquina: Del fármaco de herencia Inca hasta la inmunología moderna / Hydroxychloroquine: Inca inheritance drug to modern immunology

Resumen La hidroxicloroquina es un antiguo fármaco proveniente del árbol de quino (Cinchona pubescens), a partir del componente químico alcaloide llamado quinina. Sus primeros usos se documentaron en el Imperio Inca del Perú. Se caracteriza por distintos efectos beneficiosos en enfermedades inmunológicas, al disminuir los procesos de autoinflamación y autoinmunidad persistente. Esta revisión se enfoca en describir los mecanismos inmunomoduladores de la hidroxicloroquina, así como los efectos del fármaco en algunas de las enfermedades autoinmunes más prevalentes: lupus eritematoso sistémico, artritis reumatoide, síndrome de Sjögren, vasculitis sistémicas, nefropatía por IgA, síndrome antifosfolípido, distintas enfermedades inmunológicas de la piel. También se revisarán los efectos adversos descritos para este fármaco, especialmente la toxicidad de retina, que es el más temido.

Abstract Hydroxychloroquine is an old drug derived from the quino tree (Cinchona pubescens), from the alkaloid chemical component called quinine. Its first uses trace back to the Inca empire of Peru. It is characterized by different beneficial effects in immunological diseases, decreasing the processes of autoinflammation and persistent autoimmunity. This review focuses on describing the immunomodulatory mechanisms of hydroxychloroquine as well as the effects of the drug on some of the most prevalent autoimmune diseases: systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, systemic vasculitis, IgA nephropathy, antiphospholipid syndrome, different skin-related autoimmune disorders. The main adverse effects will be revised, focusing in the retinal toxicity.

Quinine, Malaria, and the Cinchona Bureau: Marketing Practices and Knowledge Circulation in a Dutch Transoceanic Cinchona-Quinine Enterprise (1920s-30s).

In this study, we will show how a Dutch pharmaceutical consortium of cinchona producers and quinine manufacturers was able to capitalize on one of the first international public health campaigns to fight malaria, thereby promoting the sale of quinine, an antimalarial medicine. During the 1920s and 1930s, the international markets for quinine were controlled by this Dutch consortium, which was a transoceanic cinchona-quinine enterprise centered in the Cinchona Bureau in the Netherlands. We will argue that during the interwar period, the Cinchona Bureau became the decision-making center of this Dutch cinchona-quinine pharmaceutical enterprise and monopolized the production and trade of an essential medicine. In addition, we will argue that capitalizing on the international public health campaign in the fight against malaria by the Dutch cinchona-quinine enterprise via the Cinchona Bureau can be regarded as an early example of corporate colonization of public health by a private pharmaceutical consortium. Furthermore, we will show how commercial interests prevailed over scientific interests within the Dutch cinchona-quinine consortium, thus interfering with and ultimately curtailing the transoceanic circulation of knowledge in the Dutch empire.

On the history of Cinchona bark in the treatment of Malaria.

How and when the medical value of Cinchona bark was discovered is obscure, but it is said that the powder was given to a European for malaria for the first time in the 1630s. The bark was brought to Europe by Spanish missionaries and it was recommended by the cardinal Juan de Lugo. In the 1660s, the use of Cinchona bark became known in England - and in Denmark by Thomas Bartholin. It was used for the treatment of malaria, but several debates on its value continued up to the 1730s. However, successful treatment of malaria was obtained by Thomas Sydenham, Robert Tabor and Francesco Torti. Sydenham emphasized a modern view that Cinchona bark was a unique specific drug for the treatment of malaria, and the treatment was fully accepted when Torti's Therapeutice specialis appeared. In the early 18th century, botanical expeditions were arranged in search of the most valuable Cinchona species for cultivation. The content of quinine was impor- tant, and determination of quinine was realized when Pierre Pelletier and Joseph Caventou isolated the alkaloid from the bark in 1820. Dutch plantations and quinine industry dominated the market, but the supply of quinine came to an end when the Japanese occupied Indonesia in 1942, cutting off the rest of the world from the main supplies of Cinchona. Synthetic antimalarials were developed and chloroquine became the drug of choice, but the intensive use of these drugs caused drug resistance. Chloroquine-resistant strains of P. falciparum are now treated with other drugs as artemisinin and artemether.

The controversial experiments on the intravenous administration of drugs (and air!) during the cholera epidemic of 1867 in Italy.

Cholera ravaged many American and European cities in the nineteenth century. Likewise, Italy was struck by six epidemics since the morbus first appeared in 1835-1837. After the International Sanitary Conferences held in Paris in 1851, there was a decrease of the cases due to consolidation of the city in terms of public and private health. Nevertheless, due to the lack of alternative and innovative remedies, the mortality remained unchanged, affecting more than 60 percent of patients. The city of Brescia in Northern Italy was severely hit by the epidemic of 1867. Not being able to implement effective therapeutic strategies, the administration of drugs like quinine and strychnine was proposed to be done intravenously. The results of intravenous injections were ominous, and all the patients died of "‘sudden death"’. Although the academic authorities forbade further experiments, some physicians carried on a long trial using test animals and mental patients as ‘"guinea pigs"’.

Science in the service of colonial agro-industrialism: the case of cinchona cultivation in the Dutch and British East Indies, 1852-1900.

The isolation of quinine from cinchona bark in 1820 opened new possibilities for the mass-production and consumption of a popular medicine that was suitable for the treatment of intermittent (malarial) fevers and other diseases. As the 19th century European empires expanded in Africa and Asia, control of tropical diseases such as malaria was seen as crucial. Consequently, quinine and cinchona became a pivotal tool of British, French, German and Dutch empire-builders. This comparative study shows how the interplay between science, industry and government resulted in different historical trajectories for cinchona and quinine in the Dutch and British Empires during the second half of the 19th century. We argue that in the Dutch case the vectors of assemblage that provided the institutional and physical framework for communication, exchange and control represent an early example of commodification of colonial science. Furthermore, both historical trajectories show how the employment of the laboratory as a new device materialised within the colonial context of agricultural and industrial production of raw materials (cinchona bark), semi-finished product (quinine sulphate) and plant-based medicines like quinine. Hence, illustrating the 19th century transition from 'colonial botany' and 'green imperialism' to what we conceptualise as 'colonial agro-industrialism'.

Building the world's supply of quinine: Dutch colonialism and the origins of a global pharmaceutical industry.

Quinine, a naturally occurring alkaloid from the Cinchona tree, was one of the first drugs produced and sold by a global pharmaceutical industry during the nineteenth century. Factories in Europe and North America dominated the manufacturing industry, and between 1890 and 1940, Cinchona plantations on Java supplied most of the bark for the quinine pharmaceutical business. At the end of the nineteenth century, the Dutch colonial state kept a hands-off approach to the Cinchona enterprises, in keeping with its liberal orientation. But the persistent low-price for bark, which led to the near ruin of the Cinchona planters, eventually pushed the colonial state to actively protect the Cinchona plantations. Colonial officials sought to stabilize the colonial Cinchona export-business by encouraging the integration of the quinine industry on a global scale. Most important was the colonial state's sponsorship in 1913 of the Quinine Agreement, establishing a set price for Cinchona bark, which created the world's first pharmaceutical cartel. In the interwar period, an alliance of Dutch government officials, planters, scientists, doctors and drug-makers, working in both the motherland and the colony, actively promoted the expansion of quinine consumption, as well as the merit of the Quinine Agreement, which they argued supplied guaranteed a steady supply of quinine, all for the wellbeing of global humanity.

Malaria and quinine resistance: a medical and scientific issue between Brazil and Germany (1907-19).

This article addresses the discussion about quinine-resistant malaria plasmodium in the early decades of the twentieth century. Observed by Arthur Neiva in Rio de Janeiro in 1907, the biological and social resistance of malaria sufferers to preventive and curative treatment with quinine was corroborated three years later by Oswaldo Cruz during the construction of the Madeira-Mamoré Railway in the Brazilian Amazon. Likewise in 1910, ailing German workers were transferred from Brazil to Hamburg's Institute for Maritime and Tropical Diseases, where quinine resistance was confirmed by Bernard Nocht and Heinrich Werner. When the First World War saw failures in treating and preventing malaria with quinine along with violent outbreaks of the disease on the Turkish and Balkan fronts, resistance to this alkaloid became the topic of the day within the field of experimental medicine in Germany. New attempts were made to account for the resistance, especially by the physician Ernst Rodenwaldt, who explored the topic by applying modern theories on heredity. The present article offers a preliminary survey and analysis of pronouncements about quinine resistance, shedding new light on the circulation of knowledge in the field of tropical medicine.

[History of malaria control in the French armed forces: from Algeria to the Macedonian front during the first World War]. / Histoire de la lutte contre le paludisme dans l'armée française : de l'Algérie à l'Armée d'Orient pendant la Première Guerre mondiale.

The French joint military health corps has long experience in malaria control. Many military physicians played an essential role in the 19th century: Maillot revolutionized malaria treatment by using quinine during the conquest of Algeria, and Laveran discovered the causal parasite (the genus Plasmodium) there. This experience continued under the direction of Laveran and the Sergent brothers on the eastern front in Greek Macedonia during World War I. The vast coordinated control plan established on this front from 1917 delivered the French infantrymen from malaria and led to victory over the Bulgarian forces, which capitulated in September 1918.

Clinical toxicology in Edinburgh, two centuries of progress.

The Scottish Poisons Information Bureau was established in Edinburgh in September 1963 and shortly afterwards one of the wards of the city's Royal Infirmary was designated a Regional Poisoning Treatment Centre. Both units were soon to be brought under one roof. To mark this 50th anniversary, we review how they built upon a history dating from the early 19th century and highlight their influence on current clinical toxicological practice and the delivery of poisons information. While many centres worldwide seek to improve the care of poisoned patients, the contribution of Edinburgh over the past 50 years has been notable.

The history of the Greek Anti-Malaria League and the influence of the Italian School of Malariology.

In 1905, a group of eminent Greek physicians led by Professor of Hygiene and Microbiology Constantinos Savvas and the pediatrician Dr. Ioannis Kardamatis founded the Greek Anti-Malaria League. The League assumed a role that the State would not, and for the next 25 years organized the country's anti-malaria campaign. During its first steps, the Greek Anti-Malaria League adopted the principles of Professor Angelo Celli's Italian Anti-Malaria League. The League's accomplishments include a decrease in malarial prevalence, due to mass treatment with quinine, new legislation ensuring the provision of quinine, State monopoly and the collection of epidemiologic data. However, defeat in the Greek-Turkish War (1922) and the massive influx of one million Greek refugees that ensued, led to a change in malarial epidemiology. In 1928, following a visit to Italy, the Greek League adopted the organization and knowledge of the Italian Malaria Schools in Rome and in Nettuno, and this experience served as the basis of their proposal to the State for the development of the anti-malaria services infrastructure. The State adopted many of Professor Savvas' proposals and modified his plan according to Greek needs. The League's experience, accumulated during its 25 years of struggle against malaria, was its legacy to the campaigns that eventually accomplished the eradication of malaria from Greece after World War II.

[Historical research on cinchona cultivation in Japan].

Cinchona is one of the most important medicinal plants as it contains quinine, a potent medicine for malaria. In this review, I reveal the history of cinchona introduction and cultivation in Japan. Cinchona was first introduced to Japan in 1876 from Java based on the proposal submitted by Takeaki Enomoto to the Meiji government. However, the cultivation attempt ended in failure. Later in 1922, Hoshi Pharmaceutical Co. succeeded for the first time in cultivating cinchona in Taiwan, which was then under Japanese colonial rule, and in manufacturing quinine from the cinchona tree in 1934. This was a historic feat in Japan, completing an entire process from cinchona cultivation to quinine manufacture all within the confines of the country. To commemorate this undertaking, the company dedicated a cinchona log harvested for the first time to the Imperial court. It was revealed that a log of unknown origin, which had been left untouched for years at Hoshi University, was the cinchona log from the time of commemoration. Yasusada Tashiro (1856-1928), who has made a great contribution to cinchona cultivation in Japan for over 50 years, led Hoshi Pharmaceutical Co. to success in cultivation.

[A history of malaria in modern Korea 1876-1945].

Although it is not certain when malaria began to appear in Korea, malaria is believed to have been an endemic disease from ancient times. It was Dr. H. N. Allen (1858-1932) who made the first description and diagnosis of malaria in terms of Western medicine. In his first year report (1885) of Korean Government Hospital he mentioned malaria as the most prevalent disease. Very effective anti-malarial drug quinine was imported and it made great contribution in treating malaria. After Japan had annexed Korea in 1910, policies for public health system were fundamentally revised. Japan assumed control of Korean medical institutions and built high-quality Western hospitals for the health care of Japanese residents. The infectious diseases which were under special surveillance were cholera, typhoid fever, dysentery, typhus, scarlet fever, smallpox, and paratyphoid fever. Among chronic infectious diseases tuberculosis and leprosy were those under special control. Malaria, however, was not one of these specially controlled infectious diseases although it was widely spread throughout the peninsula. But serious studies on malaria were carried out by Japanese medical scientists. In particular, a Japanese parasitologist Kobayasi Harujiro(1884-1969) carried out extensive studies on human parasites, including malaria, in Korea. According to his study, most of the malaria in Korea turned out to be tertian fever. In spite of its high prevalence, malaria did not draw much attention from the colonial authorities and no serious measure was taken since tertian fever is a mild form of malaria caused by Plasmodium vivax and is not so much fatal as tropical malaria caused by P. falciparum. And tertian malaria was easily controlled by taking quinine. Although the majority of malaria in Korea was tertian fever, other types were not absent. Quartan fever was not rarely reported in 1930s. The attitude of colonial authorities toward malaria in Korea was contrasted with that in Taiwan. After Japan had set out to colonize Taiwan as a result of Sino-Japanese war, malaria in Taiwan was a big obstacle to the colonization process. Therefore, a lot of medical scientists were asked to engage the malaria research in order to handle health problems in colonized countries caused by malaria. Unlike the situation in Taiwan, malaria in Korea did not cause a serious health problem as in Taiwan. However, its risk was not negligible. In 1933 there were almost 130,000 malaria patients in Korea and 1,800 patients among them died of malaria. The Japanese Government General took measures to control malaria especially during the 1930s and the number of patients decreased. However, as Japan engaged in the World War II, the general hygienic state of the society worsened and the number of malarial patients increased. The worsened situation remains the same after Liberation (1945) and during the Korean war (1950-53).

Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria.

Quinine remains an important anti-malarial drug almost 400 years after its effectiveness was first documented. However, its continued use is challenged by its poor tolerability, poor compliance with complex dosing regimens, and the availability of more efficacious anti-malarial drugs. This article reviews the historical role of quinine, considers its current usage and provides insight into its appropriate future use in the treatment of malaria. In light of recent research findings intravenous artesunate should be the first-line drug for severe malaria, with quinine as an alternative. The role of rectal quinine as pre-referral treatment for severe malaria has not been fully explored, but it remains a promising intervention. In pregnancy, quinine continues to play a critical role in the management of malaria, especially in the first trimester, and it will remain a mainstay of treatment until safer alternatives become available. For uncomplicated malaria, artemisinin-based combination therapy (ACT) offers a better option than quinine though the difficulty of maintaining a steady supply of ACT in resource-limited settings renders the rapid withdrawal of quinine for uncomplicated malaria cases risky. The best approach would be to identify solutions to ACT stock-outs, maintain quinine in case of ACT stock-outs, and evaluate strategies for improving quinine treatment outcomes by combining it with antibiotics. In HIV and TB infected populations, concerns about potential interactions between quinine and antiretroviral and anti-tuberculosis drugs exist, and these will need further research and pharmacovigilance.

A History of Malaria in Modern Korea 1876-1945 / 의사학

Although it is not certain when malaria began to appear in Korea, malaria is believed to have been an endemic disease from ancient times. It was Dr. H. N. Allen (1858-1932) who made the first description and diagnosis of malaria in terms of Western medicine. In his first year report (1885) of Korean Government Hospital he mentioned malaria as the most prevalent disease. Very effective anti-malarial drug quinine was imported and it made great contribution in treating malaria. After Japan had annexed Korea in 1910, policies for public health system were fundamentally revised. Japan assumed control of Korean medical institutions and built high-quality Western hospitals for the health care of Japanese residents. The infectious diseases which were under special surveillance were cholera, typhoid fever, dysentery, typhus, scarlet fever, smallpox, and paratyphoid fever. Among chronic infectious diseases tuberculosis and leprosy were those under special control. Malaria, however, was not one of these specially controlled infectious diseases although it was widely spread throughout the peninsula. But serious studies on malaria were carried out by Japanese medical scientists. In particular, a Japanese parasitologist Kobayasi Harujiro(1884-1969) carried out extensive studies on human parasites, including malaria, in Korea. According to his study, most of the malaria in Korea turned out to be tertian fever. In spite of its high prevalence, malaria did not draw much attention from the colonial authorities and no serious measure was taken since tertian fever is a mild form of malaria caused by Plasmodium vivax and is not so much fatal as tropical malaria caused by P. falciparum. And tertian malaria was easily controlled by taking quinine. Although the majority of malaria in Korea was tertian fever, other types were not absent. Quartan fever was not rarely reported in 1930s. The attitude of colonial authorities toward malaria in Korea was contrasted with that in Taiwan. After Japan had set out to colonize Taiwan as a result of Sino-Japanese war, malaria in Taiwan was a big obstacle to the colonization process. Therefore, a lot of medical scientists were asked to engage the malaria research in order to handle health problems in colonized countries caused by malaria. Unlike the situation in Taiwan, malaria in Korea did not cause a serious health problem as in Taiwan. However, its risk was not negligible. In 1933 there were almost 130,000 malaria patients in Korea and 1,800 patients among them died of malaria. The Japanese Government General took measures to control malaria especially during the 1930s and the number of patients decreased. However, as Japan engaged in the World War II, the general hygienic state of the society worsened and the number of malarial patients increased. The worsened situation remains the same after Liberation (1945) and during the Korean war (1950-53).