John Frederick Joseph Cade AO (18 January 1912 – 16 November 1980) was an Australian psychiatrist who in 1948 discovered the effects of lithium as a mood stabilizer in the treatment of bipolar disorder, then known as manic depression. At a time when the standard treatments for mania were electroconvulsive therapy and lobotomy, lithium had the distinction of being the first effective medication available to treat a mental illness. Cade's discovery in 1948 began a revolution in psychopharmacology.
Early life John Cade was born in Murtoa, in the Wimmera region of Victoria, Australia. John's father David was Murtoa's general practitioner. Ellen, John's mother, and younger brothers David and Frank completed the family. When John was a small boy, his father left for World War I and served in Gallipoli and France. On return from the war, his father suffered from 'war-weariness' and had difficulty in continuing in general practice. Therefore, his father sold the practice and accepted a position with the Mental Hygiene Department. Over the next 25 years, Dr Cade Sr became medical superintendent at several Victorian mental hospitals, namely Sunbury, Beechworth and Mont Park. John and his brothers spent many of their younger years living within the grounds of these institutions, which had a great bearing on John's later deep understanding of the needs of the mentally ill. John was educated at Scotch College, Melbourne, matriculating in 1928. He then studied medicine at the University of Melbourne, graduating at the age of 21 years with honours in all subjects. He became a House Officer at St Vincent's Hospital and then Royal Children's Hospital before becoming severely ill with bilateral pneumococcal pneumonia. While he was convalescing, John fell in love with one of his nurses, Jean. They married in 1937.
World War II Like his father before him, Cade left his young family to fight for Australia in the Armed Forces in World War II. Cade was appointed captain, Australian Army Medical Corps, A.I.F., on 1 July 1940 and posted to the 2nd/9th Field Ambulance. Although trained as a psychiatrist, Dr. Cade served as a surgeon and departed for Singapore in 1941 on RMS Queen Mary. He was promoted to major in September 1941. After the Fall of Singapore to Japan, he became a prisoner of war at Changi Prison from February 1942 to September 1945. During his imprisonment, he reportedly would observe some fellow inmates having strange, vacillating behaviour. He thought perhaps a toxin was affecting their brains and when it was eliminated through their urine, they lost their symptoms.
Discovery of the effect of lithium on mania
After the war, Cade recuperated very briefly in Heidelberg Hospital, then took up a position at Bundoora Repatriation Mental Hospital in Melbourne. It was at an unused pantry in Bundoora that he conducted crude experiments which led to the discovery of lithium as a treatment of bipolar disorder. Since he had no sophisticated analytical equipment these experiments mostly consisted of injecting urine from mentally ill patients into the abdomen of guinea pigs. His early experiments suggested to him that the urine from manic patients was more toxic. There are 2 toxic substances in urine: urea and uric acid. He found urea was the same in both ill and healthy people. He started to work on uric acid. In order to do that, he made artificial solutions of uric acid. To make up different strengths of uric acid he needed to convert it into a substance that he could more easily manipulate. On its own uric acid would not dissolve in water. Then, in an effort to increase the water solubility of uric acid, lithium was added to make a solution of lithium urate. Cade found that in the guinea pigs injected with lithium carbonate solution, as a control solution, the guinea pigs were more restful. His use of careful controls in his experiments revealed that the lithium-ion had a calming effect by itself, but even this finding may have been caused by the toxic effects of an excessive dose of lithium. After ingesting lithium himself to ensure its safety in humans, Cade began a small-scale trial of lithium citrate and/or lithium carbonate on some of his patients diagnosed with mania, dementia præcox or melancholia, with outstanding results. The calming effect was so robust that Cade speculated that mania was caused by a deficiency in lithium. He published these findings in the Medical Journal of Australia in a paper entitled 'Lithium salts in the treatment of psychotic excitement', published in 1949. While Cade's results appeared highly promising, the side effects of lithium in some cases led to non-compliance. The toxicity of lithium led to several deaths of patients undergoing lithium treatment. Of the first patients Cade treated with lithium, one died of lithium toxicity. Afterward, Cade stopped using lithium in his patients and stopped his research of the element. However, other scientists had already read his 1949 article and continued their research of the effect of lithium on mania. Among them, Mogens Schou and Poul Baastrup of Denmark conducted a new trial and published their results in 1954. Schou and Baastrup would later prove instrumental in picking up where Cade left off.
Cade continued researching mania, as well as the effect of other elements. He followed the developing research on lithium closely, but had abandoned its further research due to the initial patient death. After Cade's original hypothesis was proven correct by other scientists, Cade was recognized with a variety of awards and honors for the discovery of lithium's effect on mania and the prophylaxis of mania. There were several obstacles that hindered lithium's development. The problem of toxicity was greatly reduced when suitable tests were developed to measure the lithium level in the blood. The advent of the Beckman flame photometer allowed doctors to measure lithium levels more accurately to keep them within the tolerable range. Moreover, as a naturally occurring chemical, lithium salt could not be patented, meaning that its manufacturing and sales were not considered commercially viable. These factors prevented its widespread adoption in psychiatry for some years, particularly in the United States. Due to the efforts of Cade's colleagues in academia, lithium was finally approved by the US Food and Drug Administration in 1970.
Royal Park and RANZCP
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