Evaluation of whole-genome enrichment and sequencing of T. pallidum from FFPE samples after 75 years.

The recent developments in genomic sequencing have permitted the publication of many new complete genome sequences of Treponema pallidum pallidum, the bacterium responsible for syphilis, which has led to a new understanding of its phylogeny and diversity. However, few archived samples are available, because of the degradability of the bacterium and the difficulties in preservation. We present a complete genome obtained from a Formalin-Fixed Paraffin-Embedded (FFPE) organ sample from 1947, kept at the Strasbourg Faculty of Medicine. This is the preliminary, proof-of concept study of this collection/biobank of more than 1.5 million FFPE samples and the evaluation of the feasibility of genomic analyses. We demonstrate here that even degraded DNA from fragile bacteria can be recovered from 75-year-old FFPE samples and therefore propose that such collections as this one can function as sources of biological material for genetic studies of pathogens, cancer, or even the historical human population itself.

Reshaping the diagnostic borders: Historical analysis of the diagnostic changes following the introduction of the schizophrenia concept.

BACKGROUND: Although the concept of schizophrenia is still widely presented as having replaced that of dementia praecox, studies have shown that the former was broader than the latter, resulting in a more complex diagnostic redistribution. However, this is poorly documented by quantitative approaches. AIMS: We sought to test the hypothesis that the use of the concept of schizophrenia had caused a diagnostic redistribution and to quantify it. METHOD: A retrospective study, based on admission register archives of the Strasbourg University Clinic of Psychiatry was conducted. The frequency of diagnoses given to patients were examined at two key time periods: one before (TP1) and one after (TP2) the introduction of the schizophrenia concept (established between 1926 and 1928). Eight main diagnoses related to schizophrenia were considered. RESULTS: Patients diagnosed with schizophrenia at TP2 mainly received the diagnoses of dementia praecox but also depression, hebephrenia, manic depressive illness, hysteria, paraphrenia, catatonia and mania at TP1. Dementia praecox and hebephrenia were the most relayed by schizophrenia. Bayesian sensitivity analyses confirmed the robustness of our data against distinct scenarios challenging our hypothesis. CONCLUSIONS: Our results confirm the broadening of the concept of schizophrenia compared to that of dementia praecox but also qualify the different concepts supposed to have been impacted. They provide unique quantitative data that define the contours of the diagnostic redistribution thus provoked. They also give relevant input in the current context where the need to rethink the DSM/ICD concept of schizophrenia is still debated.

"A word from man to man". Interwar Venereal Disease Education Films for Military Audiences in France.

In the 1910s, in the wake of the glorious decade of syphilography (1900-1910), the early health education films lay the groundwork for a pragmatic approach to the containment of venereal diseases combining (early) diagnosis, treatment and prophylaxis. Realizing that WWI was turning into a durable military conflict, the French Army created a Cinematographic Section (SCA) in 1915 for the purposes of war propaganda and documentation. In 1916, secretary of war Justin Godard declared syphilis a "national public danger" and initiated information campaigns in military and civilian spheres. Conferences accompanied with film screenings were organized for all new military recruits, resulting in the production of a series sex hygiene films for military audiences characterized by a short, evocative and precise documentary style, contrasting with the romantic sex hygiene films aimed at the general public. This contribution examines the cinematographic origins of the instructional films for the military, as well as their evolution up to WWII and their influence on public sex hygiene films for civilians in the interwar period in France.

Packaging BCG: standardizing an anti-tuberculosis vaccine in interwar Europe.

Using the example of the anti-tuberculosis vaccine BCG during the 1920s and 1930s, this article asks how a labile laboratory-modified bacteria was transformed into a genuine standard vaccine packaged and commercialized as a pharmaceutical product. At the center of the analysis lies the notion of standardization inquiring why and how a local laboratory process with standard operating procedures (SOPs) reached its limits and was transformed when the product faced international distribution. Moving from Paul Ehrlich's initial technological notion of Wertbestimmung referring to a practice physiologically testing the effects of ill-defined antitoxins, the concept of standardization is extended to pharmaceutical and economical meanings implying quality control for biological therapeutic agents produced by a variety of industrial entrepreneurs. Following the request for product uniformity, two ways to maintain levels of compatibility and commonality are depicted opposing SOPs and end-product control. Furthermore, standardization is understood as a spiral, never ending process where progressive transformation of the vaccine in its production and medical uses periodically recreated the necessity of standardization. Developments analyzed are thus understood as a stabilization process aligning laboratory settings, products, and practices with medical theories and practices through technical, bureaucratic, and organizational systems. A paradox of the analysis is that standardization as a historical phenomenon and moment in the history of drug development was initially linked to a problem of under-determination of what was to be standardized and to a knowledge gap before it could become a central concept for quality control.

The 'experimental stable' of the BCG vaccine: safety, efficacy, proof, and standards, 1921-1933.

The anti-tuberculosis BCG (Bacille Calmette-Guérin) vaccine was conceived and developed between 1905 and 1921 at Pasteur Institutes in France. Between 1921 and A. Calmette's death in 1933, the vaccine went through a first period of national and international production and distribution for its use in humans. In France these activities were exclusively carried out by Calmette and his collaborators at the Pasteur Institute in Paris. Initially improvised production in a small room in the cellar gave way in 1931 to the construction of the spacious and magnificent 'New laboratories for research on tuberculosis and the preparation of the BCG' within the premises of the Pasteur Institute. Presentation and image-building of the vaccine in France insisted on the fact that the BCG was not a commercial specialty but distributed free of charge. The technical monopoly of its production nevertheless lay with the Paris Pasteur Institute and standardization of scientific proof of safety, efficacy and stability was dominated by that Institute in France. In contrast, the international production and distribution of the vaccine was entrusted and transferred, free of charge, to trustworthy laboratories outside France. Multiplication of producers and users led to an increased need for standardization. For this process the analysis distinguishes between the standardization of scientific proof concerning safety, efficacy and stability of the vaccine and standardization of its medical uses. Whereas standardization was rather successful in the inter-war period in France, the international efforts remained rather unsuccessful. Only after world war II under Scandinavian leadership and in the context of mass vaccination programs supported by the WHO and UNICEF was the international standardization effectively implemented and succeeded at least to some extend.

Experimental rage: the development of medical ethics and the genesis of scientific facts. Ludwik Fleck: an answer to the crisis of modern medicine in interwar Germany?

In 1930, the large-scale introduction of the BCG vaccination in the city of Lübeck in northern Germany led to a major scandal that focused public attention on medical experimentation with human beings as well as reviving criticism of the medical profession that had been voiced before. The trial following the catastrophe raised the first clearly identifiable public discussions on medical ethics in Europe, and led to the establishment of the first regulations for medical research on human beings in the western hemisphere; the German 'Richtlinien' of 1931. In 1935, Ludwik Fleck (1896-1961) published a now classic monograph entitled Genesis and Development of a Scientific Fact. The central hypothesis of this article is that, when Fleck published his book four years after the Lübeck trial, he was proposing answers to questions raised, at least partially, by the Lübeck case, although he never explicitly mentions it. Most interestingly, Fleck proposed a different approach to the fundamental dilemma of modern experimental medicine, the potential opposition between an individual's well-being, and the production and application of scientific knowledge in medicine. Where the standard answer to these questions has, since the 1930s, become moral reasoning and ethical regulation, known today as bioethics, Fleck portrays a different approach that could be characterized as the attempt to foster a deeper and more democratic understanding of science through an examination of its intimate functioning.