From Decades to Minutes: Steps Toward the Structure of Strychnine 1910-1948 and the Application of Today's Technology.

Between 1910 and 1947, Robert Robinson (primarily), among others, published numerous proposed structures for strychnine. Robinson published 17 of his strychnine papers with his doctoral advisor William Henry Perkin, Jr., though all but two appeared after Robinson had taken his first permanent academic position. This Essay analyzes 20 key publications leading up to Robinson's (correct, then incorrect, then correct again though not definitively) proposal and Woodward's assignment of the actual structure of strychnine. We subjected the assignment of the strychnine structure to a modern computational quantum chemistry workflow. By computing, with density functional theory, 1 H and 13 C NMR chemical shifts for the literature-proposed strychnine structures, we were able to rule out most incorrect structures. 13 C NMR predictions were better at this, but 1 H NMR chemical shifts were helpful. A comparison is made between the consequences of publishing erroneous ideas in the first half of the 20th century and doing so in the 21st century.

The controversial experiments on the intravenous administration of drugs (and air!) during the cholera epidemic of 1867 in Italy.

Cholera ravaged many American and European cities in the nineteenth century. Likewise, Italy was struck by six epidemics since the morbus first appeared in 1835-1837. After the International Sanitary Conferences held in Paris in 1851, there was a decrease of the cases due to consolidation of the city in terms of public and private health. Nevertheless, due to the lack of alternative and innovative remedies, the mortality remained unchanged, affecting more than 60 percent of patients. The city of Brescia in Northern Italy was severely hit by the epidemic of 1867. Not being able to implement effective therapeutic strategies, the administration of drugs like quinine and strychnine was proposed to be done intravenously. The results of intravenous injections were ominous, and all the patients died of "‘sudden death"’. Although the academic authorities forbade further experiments, some physicians carried on a long trial using test animals and mental patients as ‘"guinea pigs"’.

Integrating mind and brain: Warren S. McCulloch, cerebral localization, and experimental epistemology.

Recently, historians have focused on Warren S. McCulloch's role in the cybernetics movement during the 1940s and 1950s, and his contributions to the development of computer science and communication theory. What has received less attention is McCulloch's early work in neurophysiology, and its relationship to his philosophical quest for an 'experimental epistemology' - a physiological theory of knowledge. McCulloch's early laboratory work during the 1930s addressed the problem of cerebral localization: localizing aspects of behaviour in the cerebral cortex of the brain. Most of this research was done with the Dutch neurophysiologist J.G. Dusser de Barenne at Yale University. The connection between McCulloch's philosophical interests and his experimental work can be expressed as a search for a physiological a priori, an integrated mechanism of sensation.

Payment deferred: strychnine poisoning in Nicaragua 65 years ago.

BACKGROUND: In 1933 in Leon, Nicaragua, a 22-year-old woman died after an acute convulsive illness in which she experienced trismus, opisthotonos, and hyperpyrexia. Three years later her husband, Oliverio Castaneda, was convicted of her murder and that of 2 other people in the same city. METHODS: We went to Nicaragua to investigate documents involved with that case and evaluate whether the verdict of murder by strychnine was substantiated by the data. We present the results of the investigation and provide information about the practice of medicine, pharmacy, and toxicology early in this century. RESULTS: The clinical picture in all 3 cases suggests strychnine poisoning. The clinical, toxicological, and circumstantial evidence is strong and implicates Castaneda as a murderer and strychnine as the weapon. CONCLUSION: We conclude that Oliverio Castaneda was the probable perpetrator of three 1933 strychnine murders in Leon and that he may have previously used strychnine to kill others in Nicaragua and neighboring countries.