Abstract
To the Editor
It was in his kitchen in Bundoora, Victoria, Australia that John Cade conducted the experiments that would convey his name to posterity. During the course of his experiments he found that guinea pigs ingesting urine concentrates obtained from manic patients showed toxic effects, whereas guinea pigs ingesting urine concentrates from normal individuals did not. He also found that urea ingested alone produced toxicity, but to a lesser degree. He hypothesized that uric acid is a possible contributor to this phenomenon. In order to test his hypothesis he increased the solubility of uric acid by adding lithium carbonate to urine. After administering lithium carbonate along with the urea and creatinine, Cade observed a significant reduction in toxicity (Cade, 1949).
Encouraged by these findings, he ventured to study the effects of lithium carbonate on humans. He ingested lithium himself to demonstrate its safety in humans. Cade then proceeded to conduct a small clinical trial. In 1949, he described lithium had a calming effect in manic patients. His trial had only 10 patients, one patient with schizo-affective disorder, six patients of episodic mania and three with chronic mania but all responded within days to the administration of lithium, with five patients showing sufficient improvement to be eventually discharged from hospital. However, lithium’s utility was soon restricted due to its side effect profile. Many viewed his findings sceptically and Cade lamented this initial scepticism years later remarking ‘a discovery made by an unknown psychiatrist with no research training, working in a small chronic hospital with primitive techniques and negligible equipment, was not likely to command attention’ (Malhi and Gershon, 2009; Walter, 1999).
Subsequently, Victor Wynn, Edward Trautner, Samuel Gershon and colleagues published a series of articles reporting methods to assay lithium, its safety and tolerability. These developments were milestones in the arrival of lithium as a mood stabilizer (Malhi and Gershon, 2009).
John Cade was born in Murtoa, Victoria, Australia on 18 January 1912. His father, who was a general practitioner, left for the First World War when Cade was just a boy. After returning from the war, his father was compelled to abandon his general practice as a result of ‘war weariness’ and took up a position with the Mental Hygiene Department. The young John and his brothers spent a lot of time at the several institutions where their father served over the next two decades. These experiences made a profound impression on Cade and fostered an understanding of the mentally ill and a deep sensitivity to their needs. Following in his father’s footsteps, Cade attended medical school in 1934 and then trained as a psychiatrist before going off to war like his father, in 1940. Upon returning home in 1946, he became superintendent of the Repatriation Mental Hospital in Bundoora, Victoria, Australia.
John Cade’s crucial experiments and his conclusions were vindicated with the conclusive demonstration of lithium’s efficacy by Schou and his colleagues in the 1950s (Schou et al., 1954). Many honours followed. Cade served as the president of the Royal Australian and New Zealand College of Psychiatrists in 1969–1970, and in 1970 – also the year in which lithium was approved for marketing in the USA by the Food and Drug Administration (FDA) – he was made a distinguished fellow of the American Psychiatric Association (Cade, 1999).
In 1985 it was estimated that Cade’s discovery saved the world US$17.5 billion and alleviated the suffering of millions (Rubinstein and Rubinstein, 1996). On the centenary anniversary of his birthday, we would do well to remember John Cade as one of the pioneering and most gifted researchers in the annals of modern psychiatry.