This essay places some therapeutic vaccines, including particularly the diphtheria antitoxin, into their larger historical context of the late nineteenth century. As industrially produced drugs, these vaccines ought to be seen in connection with the structural changes in medicine and pharmacology at the time. Given the spread of industrial culture and technology into the field of medicine and pharmacology, therapeutic vaccines can be understood as boundary objects that required and facilitated communication between industrialists, medical researchers, public health officials, and clinicians. It was in particular in relation to evaluation and testing for efficacy in animal models that these medicines became a model for twentieth-century medicine. In addition, these medicines came into being as a parallel invention in two very distinct local cultures of research: the Institut Pasteur in Paris and the Institut für Infektionskrankheiten in Berlin. While their local cultural origins were plainly visible, the medicines played an important role in the alignment of the methods and objects that took place in bacteriology research in France and Germany in the 1890s. This article assesses the two locally specific regimes for control in France and in Imperial Germany. In France the Institut Pasteur, building on earlier successful vaccines, enjoyed freedom from scrutinizing control. The tight and elaborate system of control that evolved in Imperial Germany is portrayed as being reliant on experiences that were drawn from the dramatic events that surrounded the launching of a first example of so-called “bacteriological medicine,” tuberculin, in 1890.

The experimental development of a therapeutic serum against diphtheria between 1891 and 1894 was characterized by a scientific competition that pitted Emil Behring from the Institute for Infectious Diseases in Berlin against Émile Roux and Elie Metschnikoff from the Pasteur Institute in Paris. In general, their competition can be regarded as an extension of the fundamental differences that separated the research schools of Robert Koch and Louis Pasteur. However, to characterize the competition for a diphtheria-serum as “national rivalry” fails to account adequately for the mutual adoption of experimental practices by the Berlin and Parisian protagonists, whose contributions to the development of a therapeutic serum were intertwined in complex ways. Nor can it be characterized as “cooperation,” given their fierce public disputes over scientific concepts and the fact that these disputes also shaped the peculiarities of the experimental procedures in Berlin and Paris. A close analysis reveals a complex picture of the dynamic interaction between the conceptual and experimental activities of Behring, Roux, and Metschnikoff – interaction that defined as well as bridged the “French” and “Prussian” experimental systems of diphtheria-serum research.

Diphtheria serum production in France was dominated by the Pasteur Institute, which equipped a facility at Garches to produce the antitoxin on a large scale. This article treats the background to the founding of this facility, as well as its day-to-day functioning around 1900. The treatment integrates an examination of the practical undertaking of serum production by the Pasteur Institute with an analysis of the popular perception of the Institute and the mixed financing of the whole venture. We particularly emphasize the “industrial” features of this manufacturing process that involved living units of production, showing how bioassays influenced the destiny of the animals producing the serum. Finally, we argue that this monitoring of the horses, seen as serum-producing units, also provided information on the diseases the sera were intended to treat.

It is well known that the development of a diphtheria anti-toxin serum evolved in a competitive race between two groups of researchers, one affiliated with Emil Behring in Berlin and Marburg, and another affiliated with Émile Roux in Paris. Proceeding on the basis of different theoretical assumptions and experimental practices, the two groups developed a therapeutic serum almost simultaneously. But the standardized substance they developed took on very different forms in the two countries. In Germany the new serum was marketed in the private sphere and subjected to state regulations, becoming a kind of prototype of industrial medications. In France, however, the same substance was marketed as a gift of science to humanity and distributed through the communal health care system. This article demonstrates how a new medication emerged from the efforts to produce, market, regulate, distribute, and apply it in the two respective countries. It attributes the difference to the negotiations between the respective actors (scientists, industrialists, politicians, officers, and the public) and institutions (firms, academies, private and public institutes, legislative bodies, professional corporations). I develop this argument on three different levels: First, I stress the importance of the institutional foundations of serum production; second, I illustrate the decisive role played by existing “ways of regulating” in the rapid development of new legal statutes; and third, I describe the consequences that flowed from the respective administrative organization of marketing and dissemination. In sum, I explore how an experimental object was transformed into an object of the public health system and stabilized by administrative means.

The procedure of Wertbestimmung played a vital role in the implementation of serum therapy and the standardization of mass-produced pharmaceuticals. In fin-de-siècle Germany, a legal framework was put in place to guarantee serum quality and safety and to minimize any associated public health risks. Because the sera were biological remedies, it was difficult to produce them in uniform quality and the procedure of Wertbestimmung, i.e. determining the potency of the serum based on an objective and comparable value, was extremely complex. Various agents such as bacteria cultures, serum hosts, or test animals had to be regulated. In the years after 1895, numerous efforts to stabilize the procedures of Wertbestimmung were undertaken by serum producers and members of the state-run survey institute responsible for overseeing serum production. Despite efforts to stabilize the framework and to generate a reliable reference system, the framework's environment and agents were in constant flux: new producers entered the market and procedures were expanded to include other biologicals as well. The article describes the dynamics involved in the sustained efforts to maintain a stable framework in the face of constant alterations between 1895 and the 1920s.

When Pasteur and Chamberland hastily set up their small biological industry to meet the agricultural demand for the anthrax vaccine, their methods for preparation and production had not yet been stabilized. The process of learning how to standardize biological products was accelerated in 1882 when vaccination accidents required the revision of production norms as the first hypotheses on fixity, inalterability, and transportability of vaccines were invalidated and replaced by procedures for continuous monitoring of the calibration of vaccines and the renewal of vaccine strains. Initially, the incompleteness and ongoing development of production standards justified Pasteur's monopoly on the production of the anthrax vaccine under his immediate supervision. Later on, the Pasteur Institute maintained control of these standards in the framework of a commercial monopoly that it established on the veterinary vaccines first sent and then cultivated abroad by the Société de Vulgarisation du Vaccin Charbonneux Pasteur, founded in 1886.

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.