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Simon Flexner and Hideyo Noguchi’s work discusses venom research from the perspective of immunology. They could draw on a much broader pool of resources than Mitchell had available—conceptual, methodological, and material. The mechanism of venom poisoning served as a model for the immune reaction and as a convenient tool for its investigation. Drawing heavily on Paul Ehrlich’s conception of the immune response, Flexner and Noguchi examined the activity of various components of snake venoms. They aimed to establish the existence and agency of substances that were not directly observable, while stabilizing very complex experimental environments. These methodological challenges linked their work with contemporaneous medical and biological experimentation in bacteriology and in seemingly remote fields, such as experimental embryology. The chapter illustrates how venom researchers and other experimenters in the life sciences addressed the problems of validating hypotheses about invisible entities and how they relied on standard units and thresholds to control the variability of experimental conditions, organisms, and biological specimen. The chapter also charts the emerging discussions about how to write scientifically. One of the main motivations for the turn to so-called deductive composition was the notion that “composing deductively” could facilitate the researcher’s understanding of a paper's main points.

The physician and literary writer Silas Weir Mitchell had a long-standing interest in venom research, spanning the second half of the nineteenth century. Mitchell’s work showcases the dynamics of medical and methodological thought during a key period in the history of the biomedical sciences, just like Mead’s Mechanical Account of Poisons did for the eighteenth century. Venom research was situated at the intersection of several areas of biomedical investigation—including toxicology, physiology, medical chemistry, and therapeutics. The chapter shows how Mitchell appropriated experimental approaches from various fields to characterize both the cause and the effects of the disease caused by snake venom. The chapter also highlights the shift of emphasis in the methodology of experiments from variations of experimental procedures to comparative tests and checks. At that time, comparative experimentation was explicitly discussed both in the life sciences and in the emerging philosophy of science. However, the scientists’ discussions were driven by pragmatic concerns and thus differed significantly from systematic accounts of comparative experimentation such as Herschel’s and Mill’s philosophies of science.

In the early twentieth century, venom research migrated into the domain of protein and enzyme studies. Venom researchers consciously drew on new analytic techniques and approaches from research on enzymes, proteins, and hormones to understand the composition and biological action of venom. The methodological worries and discussions of venom researchers were fueled by the concerns about complexity—not only by the complex organization of biological substances but also by the intricacy and opacity of instruments and techniques for the investigation of ever more remote things. Early twentieth-century researchers responded to the problem of how to investigate subvisible mechanisms and things by pursuing multiple lines of research, using multiple techniques. Complexity was still the main concern of scientific authors as well. Instruction manuals for scientific writing addressed questions of how to prepare and organize scientific and technical papers and reports and how to handle definitions, descriptions of procedures and machines, and explanations of processes. The modular structure became the recommended format for scientific articles.

In the 1880s, venom served as a means to explore specific body functions, and the changes thus produced were recorded with novel kinds of recording devices. Venom was tested systematically with a battery of common chemical testing procedures. Venom was also being scrutinized for any microorganisms that it might contain, and these microorganisms were studied with the help of novel culturing techniques. There were dramatic changes in the preferred kinds of protocols. The chapter draws attention to the appearance of the concept of control in biomedical experimentation and compares scientists’ notions of control with Mill’s analysis of experimental methods. In the 1880s, increased efforts to control unwieldy experiments were the flipside of the encounters with variations, instability, and complexity. At the same time, there were complaints and expressions of concern about confusing and rambling medical writing. Medical men commenting on scientific writing called, above all, for brevity, conciseness, and telling titles. In the late nineteenth century, the ideal of quick access to information had trumped the late eighteenth-century notion that the narration of journeys of discovery could inspire the reader with confidence.

Fontana’s renewed engagement with the subject of viper venom resulted in a massive study of more than 600 pages. Book II of the Treatise on the Venom of the Viper produced a new interpretation of the working of viper venom and turned to the exploration of the “hidden causes” of the observable effects of venom poisoning. The new book is again permeated by methods discourse. Fontana’s methodological statements became much more pointed and elaborate, and he drew them together in a methodological essay. Most early modern texts contained quite detailed and often vivid narratives of concrete experiments. Fontana’s commitment to variations turned the attention from single events to series of experiments and from the uniformity of outcomes to differences. This opened up new questions, both questions of experimental design and related questions of conceptualization, interpretation, and, ultimately, reporting: What are the factors need to be varied? What do the differences between different experiments tell us? How much of this work should be reported? And how should the report be organized? The chapter argues that Fontana’s sprawling account was meant to demonstrate the discoverability of empirical findings.

In the mid-seventeenth century, experiments on snake venom were conducted within the larger contexts of discussions about body functions and the nature of disease; about blood, its role in the body, and its circulation; about nerve function and the theory of animal spirits; about chemical and mechanical philosophy; about iatrochemistry; and about the analogy between the actions of poisons and the actions of specific medicines. Francesco Redi’s extended studies of viper venom showed that a substance was responsible for the adverse effects of the bite—namely, the “yellow liquor” that was discharged from the viper’s teeth. Taken by mouth, this substance was innocent. Put in wounds, it was fatal to humans and animals. Moyse Charas, his French adversary, turned against Redi and argued that the rage of the viper was responsible for the fatal effects. These writings on venom exemplify how more concrete methodological views and conceptions of experimentation were integrated in experimental reports to establish proper procedure. Two experimental strategies stand out: comparisons and repetitions. The chapter argues that repetitions, not comparisons, were the new feature in Redi’s experimental project.

Felice Fontana’s Treatise on the Venom of the Viper; on the American Poisons; and on the Cherry Laurel, and some other Vegetable Poisons is considered a milestone in venom research. Throughout the nineteenth and early twentieth centuries, his research served as a starting point for investigations of snake venom, and his experimental methods were praised as exemplary. Fontana’s methods discourse was both as a creative appropriation of a long tradition and as a product of the challenges he encountered in his own endeavors. Fontana performed countless experiments to explore the effects of viper venom on the animal body, initially to confirm Redi’s (and Mead’s) view that the yellow liquor flowing from the viper’s protruding teeth was the substance that contained the poison. Like Redi and Mead, Fontana was a committed experimentalist. Unlike his predecessors, Fontana offered very detailed discussions of experimental strategies, emphasizing the significance of variations in experimental practice. The treatise describes numerous experiments on the nature and action of venom. As an integral part of the account, it offers detailed comments on proper procedure, describing countless variations and drawing attention to the circumstances of each trial.

Richard Mead’s Mechanical Account of Poisons includes a study of viper venom as well as a critical commentary on Redi and Charas. The several editions of Mead’s Mechanical Account showcase the state and dynamics of medical thought in the first half of the eighteenth century and its effect on research into poisons, and they illuminate conventions for writing, expectations for medical scholarship, and the different ways in which methods discourse could be integrated in a treatise about experimental research. For the history of methods discourse, Mead’s Mechanical Account of Poisons serves as a proof of concept. The chapter presents Mead’s work an experimentalist treatise, which contains almost no discussion of research techniques, experimental strategies, and criteria for proper procedure.

The continuation of the dispute between Redi and Charas brought methodological issues to the fore. The chapter shows that while both investigators were experimentalists, they had quite different understandings of certain methodological concepts, particularly of the concept of repetition and of the significance of accidents and contingencies. The dispute about snake venom remained unresolved.