JOHN FREDERICK JOSEPH CADE

John Cade was born in 1912 in Murtora, Australia and received his M.D in 1933 from the University of Melbourne. He worked as House Officer at St. Vincent’s Hospital and trained in psychiatry before joining the Australian Armed Medical Corps, where he rose to major in 1941. After spending two years as prisoner of war, Cade retuned home and joined Bundoora Repatriation Hospital in Melbourne.

Influenced by Rolv Gjessing’s reports that altered metabolism with the production of mescaline-like substances was possibly responsible for a form of catatonia, and Albert Hofmann’s discovery that lysergic acid diethylamide, an ergot alkaloid, has psychomimetic effect in minute amounts, Cade began his research in the mid-1940s at Bundoora. He assumed that manic-depressive illness is analogous to thyrotoxicosis and myxedema, and hypothesized that mania is a state of intoxication by a normal product of the body in excess, and melancholia is a state of deficiency of the same substance. To test this hypothesis he compared the effects of intra-peritoneally injected manic urine with urine from normal subjects in guinea pigs and found the former more toxic in killing the animals than the latter.  Cade identified urea as the culprit that killed the animals; but when he administered lithium urate to establish uric acid’s toxicity enhancing effect on manic urine he found that instead of enhancing toxicity, it protected the animals from urea’s toxic effects. He attributed the protective effect of the substance to lithium and when trying to determine whether lithium salts alone have any discernable effect he found that after injecting them in large doses of aqueous solution into guinea pigs, the animals became lethargic and unresponsive. Since Cade’s investigations had commenced in an attempt to demonstrate the presence of a toxic substance excreted in the urine of manic patients, he compared the effect of lithium in 10 manic, 6 schizophrenic and 5 depressed patients, after taking the substance himself for about two-weeks to ascertain its safety, in the dose at which it was used before in gout, epilepsy, etc. He found that lithium was effective in controlling psychotic excitement especially in manic patients. The publication of his findings in 1949 in the Medical Journal of Australia, signals the rediscovery of lithium treatment in psychiatry.

Cade recognized that lithium exhibited remarkable specificity for mania, that it was not sedating to patients and that the treatment could be continued with a possible prophylactic benefit. Yet, concerned about its toxicity, after the death of one of his patients included in his first experiment he virtually stopped using lithium in his hospital and stopped experiments with the substance.

In 1953, Cade was appointed Medical Superintendent of Royal Park Hospital in Melbourne. In the years that followed he had done no further research with lithium but carried out investigations with protective foods in psychiatry and with high doses of thiamin in the prevention and treatment of memory disturbances in alcoholism. About fifteen years after the publication of his historical paper on lithium he reported high magnesium levels in schizophrenia and during the 1960s he studied the effects of manganese in mongolism.

Cade retired from his position at Royal Park in 1977, and died at age 68 in 1980.

Cade JF. Lithium salts in the treatment of psychotic excitement. Med J Aust 1949; 2: 349-52; Cade JF. A significant elevation of plasma magnesium levels in schizophreania. Med J Aust 1964; 1: 195-6; Cade JF. The story of lithium. In: Ayd FJ, Blackwell B, eds. Discoveries in Biological Psychiatry. Philadelphia: Lippincott; 1970, pp. 218 – 29.

Samuel Gershon
August 1, 2013