The Hidden History of a Famous Drug: Tracing the Medical and Public Acculturation of Peruvian Bark in Early Modern Western Europe (c. 1650-1720).

The history of the introduction of exotic therapeutic drugs in early modern Europe is usually rife with legend and obscurity and Peruvian bark is a case in point. The famous antimalarial drug entered the European medical market around 1640, yet it took decades before the bark was firmly established in pharmaceutical practice. This article argues that the history of Peruvian bark can only be understood as the interplay of its trajectories in science, commerce, and society. Modern research has mostly focused on the first of these, largely due to the abundance of medico-historical data. While appreciating these findings, this article proposes to integrate the medical trajectory in a richer narrative, by drawing particular attention to the acculturation of the bark in commerce and society. Although the evidence we have for these two trajectories is still sketchy and disproportionate, it can nevertheless help us to make sense of sources that have not yet been an obvious focus of research. Starting from an apparently isolated occurrence of the drug in a letter, this article focuses on Paris as the location where medical and public appreciation of the bark took shape, by exploring several contexts of knowledge circulation and medical practice there. These contexts provide a new window on the early circulation of knowledge of the bark, at a time when its eventual acceptance was by no means certain.

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.

Gene doping: an overview and current implications for athletes.

The possibility of gene doping, defined as the transfer of nucleic acid sequences and/or the use of normal or genetically modified cells to enhance sport performance, is a real concern in sports medicine. The abuse of knowledge and techniques gained in the area of gene therapy is a form of doping, and is prohibited for competitive athletes. As yet there is no conclusive evidence that that gene doping has been practiced in sport. However, given that gene therapy techniques improve continuously, the likelihood of abuse will increase. A literature search was conducted to identify the most relevant proteins based on their current gene doping potential using articles from Pubmed, Scopus and Embase published between 2006 and 2011. The final list of selected proteins were erythropoietin, insulin-like growth factor, growth hormone, myostatin, vascular endothelial growth factor, fibroblast growth factor, endorphin and enkephalin, α actinin 3, peroxisome proliferator-activated receptor-delta (PPARδ) and cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C). We discuss these proteins with respect to their potential benefits, existing gene therapy experience in humans, potential risks, and chances of detection in current and future anti-doping controls. We have identified PPARδ and PEPCK-C as having high potential for abuse. But we expect that for efficiency reasons, there will be a preference for inserting gene target combinations rather than single gene doping products. This will also further complicate detection.

Origin and spread of leprosy in Suriname. A historical and biomedical study.

The new world was considered free of leprosy before the arrival of Europeans. In Suriname, historical migration routes suggest that leprosy could have been introduced from West Africa by the slave trade, from Asia by indentured workers, from Europe by the colonizers, and more recently by Brazilian gold miners. Previous molecular studies on environmental and ancient samples suggested a high variability of the strains circulating in the country, possibly resulting from the various migration waves. However, a current overview of such diversity in humans still needs to be explored. The origin and spread of leprosy in Suriname are investigated from a historical point of view and by strain genotyping of Mycobacterium leprae from skin biopsies of 26 patients with multibacillary leprosy using PCR-genotyping and whole-genome sequencing. Moreover, molecular signs of resistance to the commonly used anti-leprosy drugs i.e. dapsone, rifampicin and ofloxacin, were investigated. Molecular detection was positive for M. leprae in 25 out of 26 patient samples, while M. lepromatosis was not found in any of the samples. The predominant M. leprae strain in our sample set is genotype 4P (n=8) followed by genotype 1D-2 (n=3), 4N (n=2), and 4O/P (n=1). Genotypes 4P, 4N, 4O/P are predominant in West Africa and Brazil, and could have been introduced in Suriname by the slave trade from West Africa, and more recently by gold miners from Brazil. The presence of the Asian strains 1D-2 probably reflects an introduction by contract workers from India, China and Indonesia during the late 19th and early 20th century after the abolition of slavery. There is currently no definite evidence for the occurrence of the European strain 3 in the 26 patients. Geoplotting reflects internal migration, and also shows that most patients live in and around Paramaribo. A biopsy of one patient harbored two M. leprae genotypes, 1D-2 and 4P, suggesting co-infection. A mutation in the dapsone resistance determining region of folP1 was detected in two out of 13 strains for which molecular drug susceptibility was obtained, suggesting the circulation of dapsone resistant strains.

Academic discourse on education during the early part of the pandemic.

As the global COVID-19 pandemic forced a sudden transition to emergency online education in early 2020, academic discourse quickly shifted to focus on the new situation and what could be learned from it. The present study gives an overview of the discourse on education during the pandemic in publications that appeared in the top-50 journals on the Clarivate Education list in the period April 2020-May 2021. Based on a final selection of 63 articles and 12 editorials, mostly on higher education, five main themes were identified: affect, teaching practice, teaching context, achievement and assessment, and equity. The academic discourse in these publications indicates that the emergency situation exacerbated previously existing issues: mental distress was observed to rise sharply for all stakeholders and gaps in access to education between different social groups widened. In response, teachers revisited the core values of education to guide them in approaching online teaching. Management focused less on procedures and communicated in a more human and empathic way. We argue that the acute interconnectedness experienced during the pandemic can be used to develop a pedagogy of care in which support is explicitly organized on both socio-emotional and academic levels.

Plandemic Revisited: A Product of Planned Disinformation Amplifying the COVID-19 "infodemic".

During the first few months of the COVID-19 pandemic, a 26-min documentary entitled Plandemic was released online and fanatically shared via Twitter and other major social media platforms. The producers of the documentary sought to spread misinformation and conspiracy theories and to discredit scientific experts using a sophisticated disinformation campaign. They set out to accomplish this by coaching citizens toward activism to maximize the speed at which the documentary propagated and decrease positive sentiments toward public health interventions. Applying techniques from social network analysis in conjunction with a formative content analysis of Twitter data, we examined the effectiveness of the Plandemic disinformation campaign as a case study of social engineering during the COVID-19 pandemic. By comparing the Twitter network's community structure and communication patterns before and after the release of the film, we demonstrate the Plandemic campaign to have been effective for two reasons. First, the campaign established a decentralized information sharing network on Twitter by coaching low-reach social media users to mass share the documentary, effectively subverting efforts to gatekeep its misinformation. Second, the campaign amplified negative sentiments regarding vaccination and containment measures among conspiracy theorists. These effects possibly have an indirect impact on the public's willingness to comply with public health measures. Our results show the necessity of further research about sophisticated social experiments such as the Plandemic disinformation campaign and provide important insights for policy-making to combat the spread of health misinformation during public health crises.

Lepra Bubalorum, a Potential Reservoir of Mycobacterium leprae.

In 1926, a mycobacterial skin disease was observed in water buffaloes by researchers in Indonesia. The disease was designated as skin tuberculosis, though it was hypothesized that it might be a form of leprosy or a leprosy-like disease. In a follow-up study (Ph.D. thesis Lobel, 1934, Utrecht University, Netherlands) a similar nodular skin disease was described in Indonesian water buffaloes and named "lepra bubalorum" or "nodular leprosy." Two decades later Kraneveld and Roza (1954) reported that, so far, the diagnosis lepra bubalorum had been made in 146 cases in Indonesia. After a final series of research reports by Indonesian veterinarians in 1961, no subsequent cases were published. Based on information from these reports, it can be concluded that, even though evidence of nerve involvement in buffaloes was not reported, similarities exist between lepra bubalorum and Hansen's disease (leprosy), i.e., nodular skin lesions with a chronic course and microscopically granulomatous reactions with AFB in globi in vacuoles. This raises the question as to whether these historical cases might indeed have been caused by Mycobacterium leprae, Mycobacterium lepromatosis or another representative of the M. leprae complex. The future use of state-of-the-art molecular techniques may answer this question and may also help to answer the question whether water buffaloes should be considered as a potential natural reservoir of the causative pathogen of Hansen's disease.

Toward a New Model of Understanding, Preventing, and Treating Adolescent Depression Focusing on Exhaustion and Stress.

OBJECTIVE: Adolescent depression is a heterogeneous disorder, with a wide variety of symptoms and inconsistent treatment response, and is not completely understood. A dysregulated stress system is a consistent finding, however, and exhaustion is a consistent trait in adolescent patients. The aim of this paper is to critically assess current hypotheses in adolescent depression research and reframe causes and treatment approaches. METHODS: A mixed-method approach involved a review based on publications from PubMed, Embase and PsycInfo, and two exemplary adolescent cases. RESULTS: Both cases show a spiral of stress and exhaustion, but with a different profile of symptoms and coping mechanisms. Reframing both cases from the perspective of coping behavior, searching for the sources of experienced stress and exhaustion, showed coping similarities. This proved essential in the successful personalized treatment and recovery process. In combination with recent evidence, both cases support the functional reframing of depression as the outcome of a stress- and exhaustion-related spiralling mechanism. CONCLUSIONS: We propose to open up a symptom-based, mood-centered view to a model in which adolescent depression is framed as a consecutive failure of stress coping mechanisms and chronic exhaustion. Addressing exhaustion and coping primarily as a treatment strategy in adolescents and young adults might work in synergy with existing treatments and improve overall outcomes. This perspective warrants further investigation.

Reservoirs and transmission routes of leprosy; A systematic review.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae) and the more recently discovered Mycobacterium lepromatosis (M. lepromatosis). The two leprosy bacilli cause similar pathologic conditions. They primarily target the skin and the peripheral nervous system. Currently it is considered a Neglected Tropical Disease, being endemic in specific locations within countries of the Americas, Asia, and Africa, while in Europe it is only rarely reported. The reason for a spatial inequality in the prevalence of leprosy in so-called endemic pockets within a country is still largely unexplained. A systematic review was conducted targeting leprosy transmission research data, using PubMed and Scopus as sources. Publications between January 1, 1945 and July 1, 2019 were included. The transmission pathways of M. leprae are not fully understood. Solid evidence exists of an increased risk for individuals living in close contact with leprosy patients, most likely through infectious aerosols, created by coughing and sneezing, but possibly also through direct contact. However, this systematic review underscores that human-to-human transmission is not the only way leprosy can be acquired. The transmission of this disease is probably much more complicated than was thought before. In the Americas, the nine-banded armadillo (Dasypus novemcinctus) has been established as another natural host and reservoir of M. leprae. Anthroponotic and zoonotic transmission have both been proposed as modes of contracting the disease, based on data showing identical M. leprae strains shared between humans and armadillos. More recently, in red squirrels (Sciurus vulgaris) with leprosy-like lesions in the British Isles M. leprae and M. lepromatosis DNA was detected. This finding was unexpected, because leprosy is considered a disease of humans (with the exception of the armadillo), and because it was thought that leprosy (and M. leprae) had disappeared from the United Kingdom. Furthermore, animals can be affected by other leprosy-like diseases, caused by pathogens phylogenetically closely related to M. leprae. These mycobacteria have been proposed to be grouped as a M. leprae-complex. We argue that insights from the transmission and reservoirs of members of the M. leprae-complex might be relevant for leprosy research. A better understanding of possible animal or environmental reservoirs is needed, because transmission from such reservoirs may partly explain the steady global incidence of leprosy despite effective and widespread multidrug therapy. A reduction in transmission cannot be expected to be accomplished by actions or interventions from the human healthcare domain alone, as the mechanisms involved are complex. Therefore, to increase our understanding of the intricate picture of leprosy transmission, we propose a One Health transdisciplinary research approach.

Lack of evidence for the presence of leprosy bacilli in red squirrels from North-West Europe.

Leprosy is a human infectious disease caused by Mycobacterium leprae or Mycobacterium lepromatosis that can also occur in animals and even manifest as zoonosis. Recently, both mycobacteria were detected in red squirrels (Sciurus vulgaris) from the British Isles. To further explore the presence of leprosy bacilli in North-West Europe, we screened Belgian and Dutch squirrels. Tissue samples from 115 animals tested by qPCR were negative for both pathogens. No molecular or pathological evidence was found of the presence of these zoonotic pathogens in North-West Europe.

Archival, paleopathological and aDNA-based techniques in leprosy research and the case of Father Petrus Donders at the Leprosarium 'Batavia', Suriname.

OBJECTIVE: We assessed whether Petrus Donders (died 1887), a Dutch priest who for 27 years cared for people with leprosy in the leprosarium Batavia, Suriname, had evidence of Mycobacterium (M.) leprae infection. A positive finding of M. leprae ancient (a)DNA would contribute to the origin of leprosy in Suriname. MATERIALS: Skeletal remains of Father Petrus Donders; two additional skeletons excavated from the Batavia cemetery were used as controls. METHODS: Archival research, paleopathological evaluation and aDNA-based testing of skeletal remains. RESULTS: Neither archives nor inspection of Donders skeletal remains revealed evidence of leprosy, and aDNA-based testing for M. leprae was negative. We detected M. leprae aDNA by RLEP PCR in one control skeleton, which also displayed pathological lesions compatible with leprosy. The M. leprae aDNA was genotyped by Sanger sequencing as SNP type 4; the skeleton displayed mitochondrial haplogroup L3. CONCLUSION: We found no evidence that Donders contracted leprosy despite years of intense leprosy contact, but we successfully isolated an archaeological M. leprae aDNA sample from a control skeleton from South America. SIGNIFICANCE: We successfully genotyped recovered aDNA to a M. leprae strain that likely originated in West Africa. The detected human mitochondrial haplogroup L3 is also associated with this geographical region. This suggests that slave trade contributed to leprosy in Suriname. LIMITATIONS: A limited number of skeletons was examined. SUGGESTIONS FOR FURTHER RESEARCH: Broader review of skeletal collections is advised to expand on diversity of the M. leprae aDNA database.

Detection of Mycobacterium leprae DNA in soil: multiple needles in the haystack.

Leprosy is an infectious disease caused by Mycobacterium leprae affecting the skin and nerves. Despite decades of availability of adequate treatment, transmission is unabated and transmission routes are not completely understood. Despite the general assumption that untreated M. leprae infected humans represent the major source of transmission, scarce reports indicate that environmental sources could also play a role as a reservoir. We investigated whether M. leprae DNA is present in soil of regions where leprosy is endemic or areas with possible animal reservoirs (armadillos and red squirrels). Soil samples (n = 73) were collected in Bangladesh, Suriname and the British Isles. Presence of M. leprae DNA was determined by RLEP PCR and genotypes were further identified by Sanger sequencing. M. leprae DNA was identified in 16.0% of soil from houses of leprosy patients (Bangladesh), in 10.7% from armadillos' holes (Suriname) and in 5% from the habitat of lepromatous red squirrels (British Isles). Genotype 1 was found in Bangladesh whilst in Suriname the genotype was 1 or 2. M. leprae DNA can be detected in soil near human and animal sources, suggesting that environmental sources represent (temporary) reservoirs for M. leprae.

From King Kong pills to mother's little helpers--career cycles of two families of psychotropic drugs: the barbiturates and benzodiazepines.

This article compares the careers of two families of 20th-century psychotropic drugs, the barbiturates and the benzodiazepines, in five different countries. Both families of drugs were used as so-called hypnotics and sedatives, and later as minor tranquillizers. In addition these drugs were extensively used as self-medication. The careers show a cyclical temporal course and generally encompass three phases: first, an expanding use of the drugs, accompanied by high expectations; then, rising criticism and disappointment; and finally contracting use and limited application. These phases need not have been sequential: they often overlapped. The cycle sometimes ended by the disappearance of the drug from mental health care, only to be replaced by new drugs with a profile of promise and hope. These cycles, which we term Seige cycles, are generally typical for the careers of psychotropic drugs. The analytical concept of the Seige cycle facilitates a comparative perspective on the commonalities as well as the differences between the various drug careers under consideration.

Addressing the challenge of high-priced prescription drugs in the era of precision medicine: A systematic review of drug life cycles, therapeutic drug markets and regulatory frameworks.

CONTEXT: Recent public outcry has highlighted the rising cost of prescription drugs worldwide, which in several disease areas outpaces other health care expenditures and results in a suboptimal global availability of essential medicines. METHOD: A systematic review of Pubmed, the Financial Times, the New York Times, the Wall Street Journal and the Guardian was performed to identify articles related to the pricing of medicines. FINDINGS: Changes in drug life cycles have dramatically affected patent medicine markets, which have long been considered a self-evident and self-sustainable source of income for highly profitable drug companies. Market failure in combination with high merger and acquisition activity in the sector have allowed price increases for even off-patent drugs. With market interventions and the introduction of QALY measures in health care, governments have tried to influence drug prices, but often encounter unintended consequences. Patent reform legislation, reference pricing, outcome-based pricing and incentivizing physicians and pharmacists to prescribe low-cost drugs are among the most promising short-term policy options. Due to the lack of systematic research on the effectiveness of policy measures, an increasing number of ad hoc decisions have been made with counterproductive effects on the availability of essential drugs. Future challenges demand new policies, for which recommendations are offered. CONCLUSION: A fertile ground for high-priced drugs has been created by changes in drug life-cycle dynamics, the unintended effects of patent legislation, government policy measures and orphan drug programs. There is an urgent need for regulatory reform to curtail prices and safeguard equitable access to innovative medicines.

Cancer health communication in the Netherlands 1910-1950: paternalistic control or popularization of knowledge?

From the First World War onwards anti-cancer organizations in Europe attempted to spread the message of "Do Not Delay": cancer is curable, if and when early diagnosed. This article reports on a systematic study of sources on cancer health education from the medical and public domains in the Netherlands between 1910 and 1950. Dutch cancer specialists were not at all enthusiastic about spreading too much knowledge about various aspects (genetic, environmental etc.) among laymen, fearing cancerophobia among the public, and preferred to channel information and guidelines through intermediate health professionals. Cancer health education campaigns, doing away with this paternalistic attitude, only started on a comparable scale to other countries in the 1950s, possibly because of the pressure of fund-raising. Before that time compliance of patients with public health policies was orchestrated by the intervention of intermediate civil bodies, such as home nursing services. Health policies in the Netherlands were characterized by indirect strategies involving different actors.

Systematic review of the mechanisms and evidence behind the hypocholesterolaemic effects of HPMC, pectin and chitosan in animal trials.

Dietary fibres have diverse mechanisms in reducing plasma cholesterol, which could be useful for treating high levels of low-density lipoprotein cholesterol (LDL-C). The objective of this review is to determine the state of the evidence for the cholesterol-lowering effects of three selected fibres and their mechanisms, using the most recent animal trials. Therefore, a systematic review was conducted for hydroxypropyl methylcellulose (HPMC), pectin and chitosan in Pubmed, Embase and the Cochrane Library. All fibres reviewed reduced total cholesterol, very low-density lipoprotein cholesterol (VLDL-C) and LDL-C. Pectin gave a small, and chitosan an impressive rise in high-density lipoprotein cholesterol (HDL-C). A limitation of this study is the variety of animal models, each with distinct cholesterol profiles. Possible publication bias was also detected. In conclusion, chitosan seems to be the most promising of the studied fibres. A dietary fibre could be designed that yields the best cholesterol-lowering effect, using experiences in tailoring physicochemical properties and primarily exploiting the biophysical mechanisms of action.

[Current thought on hereditary transmission and human genetics]. / Van degeneratie tot individuele gezondheidsopties. Het maatschappelijk gebruik van erfelijkheidsconcepten in de twintigste eeuw.

On the basis of a review of the historiography on thought about hereditary transmission and human genetics in the 20th century in Britain, the United States, Germany, Russia, Sweden, and the Netherlands, a new research perspective is formulated. Concepts of heredity and their use in society have been various and diverse. Definitions of heredity and of the influence of 'nature' and 'nurture' in shaping genetic material have significantly changed. In the new research perspective the focus is directed to the role of a broad range of concepts of heredity in framing debates and practices around health, disease, and behaviour, including but not exclusively the concepts of Mendelian genetics, neo-Lamarckism', and concepts prevalent in eugenic movements. A research programme is outlined that is directed at specific problem fields in health care (e.g. alcoholism), and uses various sources to examine the historical dynamics in medical and public spheres.

[Medical communication about the management of depression, anxiety and sleeplessness in the Dutch women's magazine 'Margriet' between 1950 and 1960]. / Margriet weet raad op nervositeit. Medische betekenistoekenning aan 'levensmoeilijkheden' in het vrouwenblad Margriet 1950 tot 1960.

The reporting of health and medicine in the media played an important role in the way people perceived, defined and coped with everyday health problems in the second half of the twentieth century. It was and still is predominantly a supply-market which is dominated by the medical approach; creating a medical aura of progress and the self-evidence of a cure. Although the medical approach figured also prominently in women's magazines, the reporting of illness and health is far more a product of supply and demand with a lively interaction between readers and the editorial office by the means of topic-related letter columns. As such women's magazines not only offer a gender-specific but also a more balanced source for acquiring a better understanding of how public definitions and perceptions of illness and health changed over time. In this article we will focus on the communication about the management of health problems related to depression, anxiety and sleeplessness in the prototypical Dutch women's magazine 'Margriet' between 1950 and 1960. Our guiding research question has been: how do notions about depression, anxiety and and about responsive health behaviour, of which psychotropic drug use is a part, change over time in the reporting of health problems in Margriet? This question is of particular interest to learn more about the historical dynamics of the culture- and gender-specific public interplay between patients and doctors in terms of conceptualising the aforementioned health problems and defining medical coping strategies. Among other things we show that although there was hardly any mention of any 'functional division of labour' between mind and body in 1950, the mind-body dichotomy started to play an important role in the way health problems were perceived in 1960.