How does pharmacological and toxicological knowledge evolve? A case study on hydrogen cyanide in German pharmacology and toxicology textbooks from 1878 to 2020

Abstract

Little is known about how pharmacological and toxicological knowledge evolves. The aim of this study was to investigate the changes in the presentation of the poison hydrogen cyanide in sixteen German-language pharmacology and toxicology textbooks from 1878 to 2020. The categories of structure, molecular mechanism of action, occurrence, effects, resorption, areas of application, lethal dose, acute symptoms of intoxication, treatment of hydrogen cyanide poisoning, and recommended therapeutic preparations were evaluated. The knowledge on the structure, lethal dosage, and occurrence of hydrogen cyanide has remained constant. In contrast, knowledge on molecular mechanism of action and recommended preparations of the poison has changed dramatically. Until 1944, the binding of hydrogen cyanide to hemoglobin was considered the mechanism of action, whereas from 1951 onwards, the interaction of hydrogen cyanide with the Fe³⁺ of cytochrome oxidase was described. The number of preparations containing hydrogen cyanide decreased into obsolescence until 1951. The areas of application of hydrogen cyanide also show a change, as from 1919 onwards, mainly industrial areas of application of the poison are described instead of medical ones, and from 1951 onwards, criminalistic areas of application are also mentioned. Thus, pharmacological and toxicological knowledge develops non-linearly, molecular mechanism and uses being the most dynamic areas, whereas the knowledge about hydrogen cyanide's chemical structure, lethal dose, and occurrence remained constant. Older pharmacology and toxicology textbooks were better than newer ones at discussing changes in scientific concepts. Pharmacology and toxicology textbooks also mostly failed to discuss the misuse of hydrogen cyanide (Zyklon B) during the Nazi regime, missing an important opportunity to showcase the ethical responsibility of pharmacology and toxicology. Thus, future pharmacology and toxicology textbooks should improve on discussing the development of pharmacological and toxicological concepts and the ethical responsibility of the discipline.

Keywords: Content analysis; History of pharmacology and toxicology; Hydrogen cyanide; Poison; Textbook analysis.

Fig. 1

Methodological procedure for analyzing the data. For a detailed list of the encodings, see supplemental figures S1–S10

Fig. 2

Number of pages with content on hydrogen cyanide and its cyanides. The number of pages with content on hydrogen cyanide is based on the page references from the index, which are related to hydrogen cyanide or its cyanides and are listed in Table 1. If a page is listed in the index, but hydrogen cyanide or its cyanides are not explicitly discussed on the corresponding page, the page reference is not listed in the table and included in the analysis. Pages on which the content on hydrogen cyanide is continued from previous or neighboring specified pages are also listed as individual pages in the table and counted in the analysis. This also applies to pages that are labelled as subsequent pages in the index

Fig. 3

Total number of pages in the textbooks and relative share of poison pages in the total number of pages in the textbook

Fig. 4

Range of all categories. The calculation of a category’s range is based on the average range of all encodings within this category. The range of individual encodings results from the difference between the highest number of entries per textbook group and the lowest number. The number of possible entries and therefore the range of an encoding varies between 0 and 4. This is based on the number of textbooks per textbook group

Fig. 5

Information on the structure of hydrogen cyanide. The number of entries per encodings is given as a percentage of the total number of entries per textbook group

Fig. 6

Information on the molecular mechanism of action of hydrogen cyanide. The absolute number of mentions is shown

Fig. 7

Data on the occurrence of hydrogen cyanide. The absolute and relative number of mentions per textbook group is shown

Fig. 8

Information on the effects of hydrogen cyanide. The absolute number of mentions is shown

Fig. 9

Data on the resorption of hydrogen cyanide. The absolute number of mentions is shown

Fig. 10

Information on the areas of application of hydrogen cyanide. The absolute number of mentions is shown

Fig. 11

Information on the acute symptoms of hydrogen cyanide poisoning. The absolute number of mentions is shown

Fig. 12

Data on the lethal dose of hydrogen cyanide. The number of entries per encoding is given as a percentage of the total number of entries per textbook group

Fig. 13

Lethal dose of HCN and CN⁻ in mg. Only listed lethal doses for adults are included in the evaluation. If there are two different listed doses per textbook, only the higher dose is shown in the figure. If the specified dosage has a range, the mean value is calculated and shown in the figure. Lethal doses in the unit mg/kg body weight are offset against the average German adult weight in 2021 (77 kg) and indicated (Statistisches Bundesamt, , https://www.destatis.de/DE/Themen/Gesellschaft-Umwelt/Gesundheit/Gesundheitszustand-Relevantes-Verhalten/Tabellen/liste-koerpermasse.html)

Fig. 14

Information on the treatment of hydrogen cyanide poisoning. The absolute number of mentions is shown

Fig. 15

Information on recommended hydrogen cyanide preparations. The absolute number of entries is shown

Fig. 16

Discussion of incorrect content in pharmacological and toxicological textbooks. It was analyzed whether outdated and incorrect content is named and discussed as such in the textbooks. Only content that could be assigned to one of the ten analysis categories was included in the analysis. The proportion of textbooks in which incorrect content is discussed is given as a percentage of the total number of textbooks per textbook group