The Guinea Pigs of Lithium

How lithium came to be used as a treatment for bipolar disorder is quite an interesting story, which began at a Mental Hospital in Melbourne, Australia.

Dr John Cade (1912 –1980) was an Australian psychiatrist who served in the Armed Forces during World War II. Cade, however, became a prisoner of war at Changi Prison from 1942-1945.

Little was known about the causes of bipolar disorder back in the 1940s, but Cade had the idea that patients suffering from this condition may have had a metabolic disorder, which could be ascertained by the levels of urea in their urine. He believed that mania would cause an excess of uric acid in the urine and depression, he believed, would result in a deficit of uric acid.

So Cade began to conduct experiments which involved injecting urine from mentally ill patients into the abdomen of guinea pigs; only to find that the guinea pigs injected with the urine of the mentally ill patients died much faster than those that were injected with a healthy sample of urine. 

Acting on his hypothesis, that uric acid was present in the urine samples, provided by his mentally ill patients, Cade tried to increase the water solubility of uric acid and so he added lithium urate. 

After Cade added the lithium to the guinea pig injections, he found that the animals became very docile and quiet and they did not run about in their usual manic manner.  

Before testing lithium on his patients, Cade first tested the substance on himself for a few weeks and then, he began to give lithium to one of his patients, a man who was alienated from his family and who had been living in the asylum for 30 years, called Bill. 

With the lithium, Bill began to improve and his speech and self-care became better. After a while, Bill was able to return to his job. 

Unfortunately, Bill stopped taking lithium and his mental health deteriorated and he had to return to the asylum. 

Not knowing about the toxicity of lithium at high dosages, Cade gave Bill increased amounts of lithium, in an attempt to restore Bill's sanity. In 1950, Bill died from lithium toxicity. 

Over time, more research was conducted on lithium as a treatment for bipolar disorder to establish safe and effective dosages.

There are various ways proposed that may explain how lithium may work as a mood stabiliser, such as inhibition of protein kinase C and glycogen synthase kinase 3 and inositol-depletion.


Books To Read

The Marriage Plot, by American writer Jeffrey Eugenides. The story concerns three college friends from Brown University—Madeleine Hanna, Leonard Bankhead, and Mitchell Grammaticus—beginning in their senior year, 1982, and follows them during their first year post-graduation.