Samuel Gershon: Lithium history
Janusz Rybakowski’s additional commentary
This year we observe the 70th anniversary of John Cade's paper which appeared in the Medical Journal of Australia (Cade 1949). A lot has been said about the circumstances of producing this article and its aftermath both in Sam's essay, the accompanying thoughtful comments and also in the Schioldann’s book (Schioldann 2009). However, the mere fact remains: the paper made a milestone in contemporary psychopharmacology. Some may even recognize it as the first paper of modern psychopharmacology since it preceded by three years the announcement of the first antipsychotic (neuroleptic) drug, chlorpromazine, by French psychiatrists (Delay, Deniker and Harl J-M 1952). By now, in the Scopus database, the paper has achieved well over 1,000 citations and is regarded as the most important paper of Australian psychiatry.
Having said this, it should be noted that the behavior of John Cade after the publication of the paper was a little bit strange and inconsistent. On the one hand, one year after the publication and as a possible reaction to the FDA ban on lithium, and also to death of Bill Brand, his first lithium patient, Cade prohibited the use of lithium in his hospital, stopped lithium studies and devoted himself mainly to didactic and organizational duties. On a scientific note, he made some research on the elements related to lithium such as rubidium, cesium and strontium. The latter he also tried on himself and claimed that he obtained with it some therapeutic results in patients with acute schizophrenia. He also further speculated on the biological causes of psychiatric disorders.
The other aspect of Cade’s behavior started in 1963 when he received a letter from Mogens Schou, the man who appeared as the greatest lithium researcher of the second half of the 20th century. In the letter Mogens informed him about his ill brother who obtained a total recovery with lithium. Following this, Cade realized that he could bear the great fruits of the paper he published in 1949. This started a chain of complementation between these two individuals. Schou complemented Cade for the introduction of lithium into psychiatry and Cade praised Schou for his investigations and advocacy of lithium therapy. In 1970 Cade visited Schou in his place in Risskov, Denmark, and in 1974 both became the awardees of the International Scientific Kitty Foundation Award for lithium research.
The beginning of the 21st century brought commemoration of John Cade’s discovery in theater and film. In 2003 the play Dr. Cade was staged in Sydney. Its scenario was written by Neil Cole, the former Justice Minister of Victoria state in Australia, who used lithium for therapeutic reasons in his own disorders. In 2004 a documentary film entitled Troubled Minds: The Lithium Revolution was released, based on interviews with John Cade’s sons, his patients and other people connected with him. The film won the main prize at the International Vega Awards for excellence in scientific broadcasting.
In the last years, two biographical books about John Cade appeared. The first, Finding Sanity: John Cade, Lithium and the Taming of Bipolar Disorder, was written by a Sydney psychiatrist, Greg de Moore, and Ann Westmore, a health sociologist from Melbourne. The authors describe Cade’s life beginning from childhood, into adulthood, military service, Japanese captivity, up through the discovery of lithium and its further fate. A considerable fragment of the book was dedicated to Bill Brown, Cade’s first patient, who died in 1950, probably due to the complications connected with lithium use. The second book, Lithium: A Doctor, a Drug, and a Breakthrough, was written by an American psychiatrist Walter Brown, working at the Brown University, Providence, RI. The author describes in detail the discovery of the therapeutic action of lithium by Cade and its world-wide consequences. He also recounts the further life of Cade and cannot reconcile the stopping by Cade, personally, the lithium studies and, after some time, passing them all over to Mogens Schou.
In conclusion, it can be speculated that be it serendipity or not, if it were not for Cade’s paper, 70 years ago, lithium could not have achieved the nowadays status of essential, although still underutilized, psychotropic drug.
Brown W. Lithium: A Doctor, a Drug, and a Breakthrough. Liveright, New York, 2019.
Cade JF. Lithium salts in the treatment of psychotic excitement. Med J Aust, 1949; 2(10):349-52.
Delay J, Deniker P, Harl J-M. Utilisation en thérapeutique psychiatrique d’une phénothiazine d’action centrale elective. Ann Méd-Psychol 1952; 110:112-31.
De Moore G, Westmore A, editors. Finding Sanity: John Cade, Lithium and the Taming of Bipolar Disorder. Allen & Unwin, Sydney, 2016.
Schioldann J. History of the Introduction of Lithium into Medicine and Psychiatry. Adelaide Academic Press, 2009.
April 2, 2020