Abstract
Fifty years ago, on 3 September 1949, the Medical Journal of Australia published a short report detailing a case series of 10 manic patients who had responded dramatically to one of the Cinderella compounds of the pharmacopoeia — lithium. The author was John Cade, a 37-year-old psychiatrist from Melbourne working in a repatriation (Veterans Affairs) hospital for patients with chronic psychiatric illnesses.
An intellectually curious and self-effacing man, his research was undertaken in a converted laboratory in a humble wooden shed in the hospital grounds; hardly an auspicious start for a medication that was to spark the ‘psychopharmacology revolution’ referred to, in this volume, by Goodwin and Ghaemi.
The unlikely origins of such a major discovery are well articulated in two quotes in the article by Johnson and Gershon:
That the attempt was made by an unknown psychiatrist, working alone in a small chronic hospital with no research training, primitive techniques and negligible equipment was hardly likely to be compellingly persuasive, especially in the United States. (John Cade, 1970)
and
…the modest proclamation of its use for mania and other excitement states [was] in a journal of limited circulation in a remote country that passed almost unnoted. (Nathan Kline, 1968)
The dramatic effects of lithium were in stark contrast to the treatments available for mania prior to that time, which are evocatively described in the article by John Cawte.
This special supplement of the Australian and New Zealand Journal of Psychiatry celebrates the 50th anniversary of that momentous discovery. It is issued in conjunction with a scientific meeting — ‘50 years of treatments for bipolar disorder: A celebration of John Cade's discovery’ — to be held in Sydney on 4–5 December 1999 to commemorate this event.
Cade's discovery was not only a major event in the history of Australian medical research but it represented one of the landmark discoveries of biomedical research worldwide [1], with a 1994 article in Science estimating that it had saved the USA economy alone US$145 billion since its introduction in 1970 [2].
Despite the historic impact of Cade's report, little has been documented about the man and his work. It is hoped that this volume, and in particular the articles by Burrows and Tiller, Chiu and Hegarty and Davies will go some way towards rectifying this deficiency.
Johnson and Gershon refer to the ‘virus of lithium’ that spread around the world. The ‘virus’ soon spread to Scandinavia where the work of the Danish researchers Mogens Schou and Poul Baastrup finally confirmed the efficacy of lithium. Schou provides a masterly overview in his foreword, and then reviews the early European studies from the perspective of his central involvement in that work. The spread of the ‘virus’ to North America is chronicled by Johnson and Gershon. Sam Gershon, originally a Melbourne psychiatric trainee, first undertook lithium research in that city, in association with the physiologist Trautner who had published his research on lithium with the clinician Noack in 1951. Gershon moved to the USA in 1959 and very quickly disseminated the ‘virus’, initiating some of the earliest USA studies. Gordon Johnson joined him in the 1960s, eventually returning to re-introduce the ‘virus’ to Sydney. Schweitzer and colleagues describe the subsequent Melbourne research and clinical interest in lithium.
The impact of lithium on psychiatric thought and practice worldwide is reviewed in a statesmanlike fashion by Goodwin and Ghaemi. (Goodwin himself undertook much of the critical lithium and bipolar disorder research during his career.) Indeed, the discovery of lithium's efficacy as a mood-stabilising agent not only revolutionised the treatment of patients with bipolar disorder but sparked a revolution that has reshaped both medical and scientific as well as popular concepts of severe mental illnesses.
What has transpired in our understanding of the aetiology and treatment of bipolar disorder in the 50 years since Cade's report? While the mechanism of action of lithium is not yet clearly understood, advances in understanding its pharmacological effects have advanced dramatically, as detailed by Manji et al. One cannot but compare with awe the technology described by Manji et al. with the basic facilities and technologies utilised by Cade in his shed at Bundoora. Recent advances in the development of new mood stabilisers are reviewed by Mitchell, while Potter and Ozcan outline the approaches necessary to develop novel compounds for this terrible condition.
Enough of science! What of the consumers of lithium and other mood stabilisers? We were delighted when five capable creative Australians (Neil Cole, parliamentarian/playwright; Diana Dennison, journalist/photographer; Margo Orum, journalist/PhD student; Penelope Rowe, novelist; and Meg Smith, academic psychologist) who have been public about their experience of bipolar disorder took up our challenge to reflect on their own experience of bipolar disorder and creativity. We hope that the reader of this volume will enjoy their accounts as much as we have.
This volume represents a coalescence of the Australasian research and the professional organisations, RANZCP and ASPR, an appropriate reflection of Cade's role as the flexible clinician researcher.
Finally, our gratitude to those who have assisted us along the path to publication: Bozena Zembrzuski of Novartis for the generous sponsorship of this publication; Mrs Jean Cade for the photographs of her late husband; Edmond Chiu for Cade's case notes; Kate Murray of Blackwell Science Asia for guidance through the publishing process; Sidney Bloch, Editor of the Journal, for kind but clear direction about the task of producing a supplement to his journal; Georgina Barratt-See for secretarial skills and time commitment above and beyond the call of duty, and Kerrie Eyers for commenting on and checking the final drafts.