Seriality and Standardization in the Production of “606”

Hist. Sci., xlviii (2010) SERIALITY AND STANDARDIZATION IN THE PRODUCTION OF “606” Axel C. Hüntelmann Bielefeld University The first major chemotherapeutic agent, the anti-syphilitic Salvarsan, is especially significant because its production in a network linking research laboratory, pharmaceutical industry and the clinic was the prototype for so much biomedical research in the twentieth century. Salvarsan, which originated in Paul Ehrlich’s laboratory as a compound numbered “606”, is also among the most famously serial objects in the history of science, technology and medicine. Ehrlich’s early biographers recounted its production as a planned, linear process. Every stable chemical preparation that exhibited a disinfectant effect against parasites or bacteria received its own number. So chemicals such as 306 (arcacetin) and 418 (arsenophenylglycine) were presented as mere waystations on the path to the production of 606 (arsphenamine). In these heroic tales about a scientific icon and benefactor of humanity, numerical growth correlates with progress and modernity, development and discovery, and illustrates Ehrlich’s dogged will to cure syphilis come what may.1 The story of Salvarsan has also been recounted as a chemist’s history of ingeniously combining and extracting derivatives, separating, purifying and recombining. At first, the numbers represented mere chemical combinations, but these came to embody progress as they grew.2 By contrast, this article will focus on the numbers themselves and the processes lurking behind them. I shall present the scientific object 606 as linked to countless other objects and subjects in a network of structures and procedures within which its status and relations continually changed. Chemical compounds were combined, rejected, purified, dissolved, diluted and their effects evaluated. Stable compounds were produced, dried, vacuum bottled, opened and used. The changes mark the trans- formation, in laboratory notebooks, medical journals, and the general press from a promising compound to a clinically tested and validated remedy sanctioned by the scientific community and the state. Only once 606 and then Salvarsan were recog- nized in this way could the tortuous process of development come to seem linear.3 In the course of the trials, 606 became the “Ehrlich-Hata-compound” — named also for the Japanese collaborator Sahachiro Hata — that was marketed as Salvarsan and celebrated in a major motion picture as “Dr Ehrlich’s Magic Bullet”. I draw on several publications by Ehrlich, his assistants and collaborators, as well as his personal papers and their notebooks. My interest is in neither the commercial scientist’s relations with the chemical industry and other allies,4 nor the intellectual history of the receptor concept. Both have been well described.5 Instead, I interpret research methods within his Institute for Experimental Therapy (IET) and the Georg Speyer House for chemotherapeutical research (GSH) in terms of standardization, 0073-2753/10/4803-0435/$10.00 © 2010 Science History Publications Ltd 436 · AXEL C. HÜNTELMANN organization, administration and rationalization. I wish to explore, for this iconic case, the role of serial practices in the standardization and industrialization of scientific methods.6 The first section of the essay introduces the two institutes, both headed by Ehrlich, and their links with industry. I then analyse a range of labour processes, commodity flows and production methods that were organized in extensive series, both temporally and spatially. I discuss the origins and significance of this kind of serial organization. Industrial modernity around 1900 has often been associated with the emergence of serial production systems and continuous throughput. Here the argument is extended from specialist forms of pharmaceutical expertise and the regulated division of labour to serial co-ordination through forms of accountancy and quality control. Seriality in this case was not solely a matter of accelerated production. For through complex links with standardization and surveillance on a genuinely vast scale, it also affected the career of the scientific product and the reputation it acquired. the iet, the Gsh, and their industrial links The interpenetration of science and industry, especially in the chemical and electrical industries of the second Industrial Revolution, meant mass production of science- based, technically complex products and the industrialization of scientific work. Large-scale screening necessitated more specialized training and more highly divided labour than was usual in academic laboratories.7 As research laboratories began to look more like industrial ones, larger experimental settings and arrangements became usual and were regulated according to national standards and norms. These developments led to the emergence of genuinely ‘big’ science.8 A fine example was the new production plant of the bacteriological department of Dyestuff Industries in Hoechst, officially inaugurated in November 1894. A few weeks later theMünchener medicinische Wochenschrift, Germany’s pre-eminent medical weekly, published an enthusiastic report about how serum was made there. The author, a physician who had visited the department a few days earlier, gave an overview of the architecture, spatial arrangement, production process, and work flow. The plant was equipped with the latest devices and designed for large-scale production of diphtheria serum — eighty horses produced serum that was bottled in thousands of phials. The author stressed the organizational aspects of the production and explained the “modern principle” of the division of labour: one worker filled the phials, another sealed them, a third labelled them, and a fourth assigned each phial a number before it was packed. Each step was registered in a database and assigned an operation number that made it possible to trace each phial back to the equine host and the specific day of bloodletting. Via the register, the operation number was linked to other journals for the serum hosts and the test animals, each serum host having its own journal documenting health, temperature, feeding, and bloodletting dates.9 After the state assumed control over diphtheria serum in the spring of 1895, the operation number became the organizational linkage between the local serum pro- ducer and the central state-run serum institute. Furthermore, the principle of operation numbers and the various administrative and production techniques became models SERIALITY AND STANDARDIZATION · 437 for the newly-founded state-run serum institute and for other serum producers as well.10 In 1896, Paul Ehrlich was appointed director of the Royal Prussian Institute for Serum Research and Serum Testing in Berlin. The institute’s principal task was serum inspection, but it also conducted basic research on serum therapy and the standardization of serum control. State approval was obligatory for every phial sold on the German market and producers paid a fee to cover the cost of materials and personnel. To promote more research, in 1899 the institute was reorganized, renamed the Royal Prussian Institute for Experimental Therapy, and moved to Frankfurt am Main. Alongside the original Serum Control Department, the institute was subdivided into a Hygiene Department doing bacteriological tests for the city, a so-called Experimental Biological Department conducting research, and a department for Cancer Research. Ehrlich now focused on experimental research, expanding and experimentally fortify- ing his side-chain theory to explain immunological processes and experimenting with dyestuffs and arsenic compounds.11 These experiments were very expensive; the costs for chemicals and test animals increased and the institute’s books recorded frequent deficits. Ehrlich therefore spent much time and energy exploiting his extensive network to acquire dyestuffs and other chemicals from colleagues and industry. Frequent requests for additional funding, including a full-time chemist, came to fruition when, in 1906, the GSH was founded as an independent research institute for chemotherapy. Funded by private donations, the institute was headed by Ehrlich and divided into a Chemical and a Biological Department. In the former, “countless” dyestuffs and arsenic substances were created and modified; in the latter the therapeutic effects of the compounds were systematically screened in animal experiments. The 606th compound created in the Chemical Department was arsphenamine.12 So 606 was developed at the intersection of several transformations: the most rapid phase of German industrialization, the constitution of the pharmaceutical industry, the standardization of different spheres of society, the differentiation of medical disciplines and an increase in biopolitical activities to improve public health in the national “struggle for survival”.13 This involved the foundation of public health insti- tutions, such as the Imperial Health Office, the Institute for Infectious Diseases, and the IET.14 The development, production, and regulation of such therapeutic agents faced problems similar to those in electrotechnics and precision engineering, and these similarly drove institutional innovation between the state, science, and industry. The IET may therefore be likened to the Imperial Physical-Technical Institute, which combined basic research in optics, electricity, and precision mechanics with the testing of devices, technical instruments and materials against national standards.15

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