“There is no doubt that in mania patients’ improvement has closely paralleled [lithium] treatment. . .” ~ Dr. John Cade, September 3, 1949
A number of life-changing medications have been discovered by serendipity. Serendipity in medication discovery indicates finding a use for a drug for one thing while looking for something else. It’s happened for treatments as wide-ranging as the smallpox vaccine to penicillin. It happened in the case of lithium, and the life of people with bipolar disorder (or manic-depression, as it was known then) was never the same. Dr John Frederick Joseph Cade was an Australian psychiatrist who had just returned from fighting for Australia in World War II.
In 1948 Dr. Cade was working at Bundoora Repatriation Mental Hospital, and was perplexed by the confusing and out-of-control behaviors exhibited by some of the inmates. Along with many of his generation, Dr. Cade believed that mental illness, particularly manic-depression, was caused by a toxin in the body of the ill, which would be secreted in the patient’s urine. Ready to experiment on guinea pigs, he wanted to inject the patients’ urine into the animals, and observe if they reacted with symptoms of psychological distress.
Interestingly, the guinea pigs injected with the urine of the manic patients died more quickly and with less input than did the control group. Dr. Cade isolated the cause for toxicity: the urine of manic patients had higher concentrations of uric acid. Intrigued by his findings thus far, he then looked for something that could modify the toxic effect of the uric acid. But further study was blocked for the moment, as uric acid wasn’t soluble in water, and was thus difficult to inject into his guinea pigs. In a choice of pure serendipity, the doctor chose lithium, which, when combined with uric acid, creates a water-soluble solution. Dr. Cade injected the next set of guinea pigs with his new concoction, and the survival rate was much better.
Concluding that lithium protected against uric acid, he then hypothesized that lithium might have an impact on those with increased levels.
Back to the guinea pigs he went, this time with pure lithium carbonate. When injected with large doses of lithium, they become sedated and at times even lethargic. Dr. Cade was convinced enough of lithium’s anti-manic potential to take it himself to make sure it was safe. Soon he was experimenting with patients with a variety of diagnoses, but response for mania was so pronounced that the doctor theorized mania was in fact caused by a deficiency in lithium.
His results were strong enough to be published in the Medical Journal of Australia in 1949 under the title ”Lithium salts in the treatment of psychotic excitement” (see a copy of the original here), and, although it would be long years before the lithium was officially approved, the treatment of bipolar disorder, which until then had only been managed with electroconvulsive therapy or lobotomies, saw a new day dawning.
See:
Johnson G. Lithium-early development, toxicity, and renal function. Neuropsychopharmacology 1998; 19:200–205.
Mitchell PB, Hadzi-Pavlovic D. Lithium treatment for bipolar disorder. Bulletin of the World Health Organization 2000; 78(4):515-517.
About the author:
Rhona Finkel is a health writer and blogger with a special focus on mental illness, as you can see on Candida Abrahamson’s blog, which she co-authors, at http://candidaabrahamson.wordpress.com. You can follow Rhona at @abitofthisand on Twitter.
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