Lithium’s emergence as a viable treatment for bipolar disorder originated from a series of rudimentary experiments conducted in a repurposed pantry at the Bundoora Repatriation Mental Hospital in 1948. This discovery, made by an Australian psychiatrist using guinea pigs as subjects, fundamentally altered the trajectory of psychopharmacology and replaced invasive procedures like lobotomy for managing mania.
Early Influences and Medical Training
Born in 1912 in Murtoa, Victoria, John Cade was the son of a general practitioner. His exposure to the field of mental health began early as his father moved into positions within the Mental Hygiene Department, managing institutions in Sunbury, Beechworth, and Mont Park. Cade attended Scotch College before enrolling at the University of Melbourne. He completed his medical studies at twenty-one with honours, later serving as a House Officer at St Vincent's Hospital and the Royal Children's Hospital.
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In 1940, Cade joined the Australian Army Medical Corps as a captain. He was posted to the 2nd/9th Field Ambulance and traveled to Singapore in 1941, earning a promotion to major shortly thereafter. Following the fall of Singapore to Japanese forces in 1942, Cade spent three years as a prisoner of war at Changi Prison. During this incarceration, he observed erratic behaviours among his fellow captives, forming early hypotheses about the role of metabolic toxins in psychiatric illness.
The Lithium Experiments
Post-war, Cade worked at Bundoora Repatriation Mental Hospital. Lacking sophisticated laboratory resources, he injected urine from patients experiencing manic episodes into guinea pigs to test for toxicity. By using lithium carbonate to increase the solubility of uric acid, he observed an unexpected calming effect on the animals. After testing the substance on himself, he initiated trials with patients in 1949. While initial results showed promise for treating psychotic excitement, the narrow margin between therapeutic and toxic doses led to patient complications, causing him to temporarily cease his research.
Legacy and Clinical Leadership
In 1952, Cade became Superintendent and Dean of the clinical school at Royal Park Hospital. Following a tour of British psychiatric facilities, he modernized the hospital by promoting informal care and group therapy over authoritarian methods. Although he stopped his lithium research after witnessing toxicity-related deaths, his 1949 publication inspired researchers like Mogens Schou and Poul Baastrup. Due to the lack of patentability and initial toxicity concerns, the FDA did not approve lithium until 1970. In 1976, Cade received the Officer of the Order of Australia for his contributions.
Fast facts
- Born: 1912, Murtoa
- Died: 1980, Fitzroy
- Education: Scotch College, University of Melbourne
- Military service: Major, Australian Army Medical Corps
- POW location: Changi Prison, 1942–1945
- Breakthrough year: 1948
- Award: Officer of the Order of Australia, 1976
- Citizenship: Australia
Questions readers ask
Why did John Cade stop his research on lithium?
He halted his research after experiencing patient deaths linked to lithium toxicity.
What medical treatments did lithium replace for mania?
It provided an effective alternative to electroconvulsive therapy and lobotomy.
Achievements
- Officer of the Order of Australia — 1976
