Cushny and Peebles, optical isomers and the birth of modern statistics

Arthur Cushny was born in Fochabers, Scotland, in 1866 and died in Edinburgh in 1926. He had a varied career that included periods in Switzerland, Alsace, America and England. Between 1893 and 1905, he was Professor of Materia Medica and Therapeutics at the University of Michigan and one of his last pieces of research in that post was to collaborate with Alvin Peebles (1884–1917), an instructor at Michigan who had probably been Cushny’s student. By the time the paper was published, Cushny had already taken up a chair at University College London. Arthur Cushny was very interested in optical isomerism, which he regarded as a key sign of living matter. He had previously carried out various researches in vitro and in vivo, using animals. The paper he co-authored with Alvin Peebles describes some of these experiments in dogs and frogs. These are reported concisely in terms of conclusions, but numerical details are largely absent. The paper ends, however, with a quite different sort of experiment, a clinical trial reported in sufficient numerical detail to have been awarded a special place in the history of statistics. The data reported by Cushny and Peebles were used by ‘Student’ in his famous paper, ‘The probable error of a mean’, and subsequently reported by Fisher in his book, Statistical Methods for Research Workers. These two works are classics of 20th-century statistics. However, as pointed out by Isidor Greenwald, a biochemist at Bellevue Hospital in New York, ‘Student’ had actually made a transcription error in the column labels he applied to the data, which Fisher went on to replicate. In this comedy of errors, the experiment was thus interpreted incorrectly by the statisticians Student and Fisher and correctly by the physiologists Cushny and Peebles. The trial reported by Cushny and Peebles was actually carried out at theMichigan Asylum for the Insane at Kalamazoo by two young doctors, Rudolph Light (1877–1961) and George Gill Richards (1883–1950), under the supervision of the superintendent, William Milan Edwards (1855–1905). Two isomers of hyoscine, the laevorotatory form and the racemate, were compared as hypnotics. Eleven patients in total were studied over several nights, with the hours of sleep they had being noted. Hyoscyamine was also studied, and there were nights without treatment to provide a ‘no treatment’ control. Thus, from a modern perspective, there were four ‘treatments’ (including absence of treatment). The study can be regarded either as an example of a cross-over trial or a collection of n-of-1 trials. However, randomisation was not employed and instead a scheme of systematic alternation was used. Some patterns such as the following seem to have been applied