Dr Snow killed a bird: The genesis of pharmacokinetics and pharmacodynamics in anaesthesia.

This essay presents a pharmacologist's perspective of what would be now called 'preclinical research' and 'uncontrolled clinical trials' surrounding the first public demonstration by William Thomas Green Morton of painless surgery achieved by the inhalation of ether in a patient at the Massachusetts General Hospital on 16 October 1846. Of the many people who made history in those earliest days of surgical anaesthesia in both the United States and Great Britain, John Snow stands out for his personal research that spanned basic science and clinical medicine. Primarily, Snow used the relationship between the vapour pressure of a volatile liquid and temperature to design a vaporiser. This allowed control of the inspired concentration of the volatile liquid epitomised by diethyl ether, and thus the time-course and depth of anaesthesia. In an era when developments in anaesthesia were almost exclusively based on empirical modifications to apparatus and technique, Snow, and to a lesser extent his contemporary Andrew Buchanan, stood out from all others in advancing the quantitative basis of anaesthesia. Both described the physiological basis of control over gas uptake whereby they related that gas moved across concentration gradients in the body: alveolar to arterial to tissue to venous gas tensions, and Snow devised a progressional semi-quantitative scale of five 'stages' of ether anaesthesia. They thereby introduced the elements of what would be referred to 'pharmacokinetics' and 'pharmacodynamics', a century later. This essay attempts to place them and their scientific insights into context with contemporaneous principal personae and knowledge.