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John Frederick Joseph Cade AO (18 January 1912 – 16 November 1980) was an Australian
psychiatrist A psychiatrist is a physician who specializes in psychiatry, the branch of medicine devoted to the diagnosis, prevention, study, and treatment of mental disorders. Psychiatrists are physicians and evaluate patients to determine whether their sy ...
who in 1948 discovered the effects of
lithium carbonate Lithium carbonate is an inorganic compound, the lithium salt of carbonate with the formula . This white salt is widely used in the processing of metal oxides. It is listed on the World Health Organization's List of Essential Medicines because it c ...
as a mood stabilizer in the treatment of
bipolar disorder Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of Depression (mood), depression and periods of abnormally elevated Mood (psychology), mood that last from days to weeks each. If the elevat ...
, then known as manic depression. At a time when the standard treatments for psychosis were
electroconvulsive therapy Electroconvulsive therapy (ECT) is a psychiatric treatment where a generalized seizure (without muscular convulsions) is electrically induced to manage refractory mental disorders.Rudorfer, MV, Henry, ME, Sackeim, HA (2003)"Electroconvulsive th ...
and
lobotomy A lobotomy, or leucotomy, is a form of neurosurgical treatment for psychiatric disorder or neurological disorder (e.g. epilepsy) that involves severing connections in the brain's prefrontal cortex. The surgery causes most of the connections t ...
, lithium had the distinction of being the first effective medication available to treat a mental illness.


Early life

John Cade was born in
Murtoa Murtoa is a wheat district town in Victoria, Australia, situated around Lake Marma on the Wimmera Highway, north-west of the state capital, Melbourne. The town is in the Shire of Yarriambiack local government area. At the , Murtoa had a popul ...
,Some authors state Cade was born in Horsham, one of the larger towns in the Wimmera area. However other authors, notably Cade's son Jack Cade, state John Cade was born in
Murtoa Murtoa is a wheat district town in Victoria, Australia, situated around Lake Marma on the Wimmera Highway, north-west of the state capital, Melbourne. The town is in the Shire of Yarriambiack local government area. At the , Murtoa had a popul ...
, a town NE of Horsham.
in the
Wimmera The Wimmera is a region of the Australian state of Victoria. The district is located within parts of the Loddon Mallee and the Grampians regions; and covers the dryland farming area south of the range of Mallee scrub, east of the South Aust ...
region of
Victoria, Australia Victoria is a state in southeastern Australia. It is the second-smallest state with a land area of , the second most populated state (after New South Wales) with a population of over 6.5 million, and the most densely populated state in ...
. John's father David was Murtoa's general practitioner. Ellen, John's mother, and younger brothers David and Frank completed the family. When John was a small boy, his father left for World War I and served in
Gallipoli The Gallipoli peninsula (; tr, Gelibolu Yarımadası; grc, Χερσόνησος της Καλλίπολης, ) is located in the southern part of East Thrace, the European part of Turkey, with the Aegean Sea to the west and the Dardanelles s ...
and
France France (), officially the French Republic ( ), is a country primarily located in Western Europe. It also comprises of Overseas France, overseas regions and territories in the Americas and the Atlantic Ocean, Atlantic, Pacific Ocean, Pac ...
. On return from the war, his father suffered from ' war-weariness' and had difficulty in continuing in general practice. Therefore, his father sold the practice and accepted a position with the Mental Hygiene Department. Over the next 25 years, Dr Cade Sr became medical superintendent at several Victorian mental hospitals, namely Sunbury, Beechworth and Mont Park. John and his brothers spent many of their younger years living within the grounds of these institutions, which had a great bearing on John's later deep understanding of the needs of the mentally ill. John was educated at
Scotch College, Melbourne (For God, for Country, and for Learning) , established = , type = Independent, day and boarding , gender = Boys , denomination = Presbyterian , slogan = , ...
, matriculating in 1928. He then studied medicine at the
University of Melbourne The University of Melbourne is a public research university located in Melbourne, Australia. Founded in 1853, it is Australia's second oldest university and the oldest in Victoria. Its main campus is located in Parkville, an inner suburb ...
, graduating at the age of 21 years with honours in all subjects. He became a House Officer at St Vincent's Hospital and then
Royal Children's Hospital The Royal Children's Hospital (RCH) is a major children's hospital in Melbourne, Australia. As a major specialist paediatric hospital in Victoria, the Royal Children's Hospital provides a full range of clinical services, tertiary care, as we ...
before becoming severely ill with bilateral
pneumococcal pneumonia Pneumococcal pneumonia is a type of bacterial pneumonia that is caused by Streptococcus pneumoniae (pneumococcus). It is the most common bacterial pneumonia found in adults, the most common type of community-acquired pneumonia, and one of the ...
. While he was convalescing, John fell in love with one of his nurses, Jean. They married in 1937.


World War II

Like his father before him, Cade left his young family to fight for Australia in the Armed Forces in World War II. Cade was appointed
captain Captain is a title, an appellative for the commanding officer of a military unit; the supreme leader of a navy ship, merchant ship, aeroplane, spacecraft, or other vessel; or the commander of a port, fire or police department, election precinct, e ...
, Australian Army Medical Corps, A.I.F., on 1 July 1940 and posted to the 2nd/9th Field Ambulance. Although trained as a psychiatrist, Dr. Cade served as a
surgeon In modern medicine, a surgeon is a medical professional who performs surgery. Although there are different traditions in different times and places, a modern surgeon usually is also a licensed physician or received the same medical training as ...
and departed for Singapore in 1941 on
RMS Queen Mary RMS ''Queen Mary'' is a retired British ocean liner that sailed primarily on the North Atlantic Ocean from 1936 to 1967 for the Cunard-White Star Line and was built by John Brown & Company in Clydebank, Scotland. ''Queen Mary'', along with ...
. He was promoted to
major Major ( commandant in certain jurisdictions) is a military rank of commissioned officer status, with corresponding ranks existing in many military forces throughout the world. When used unhyphenated and in conjunction with no other indicato ...
in September 1941. After the
Fall of Singapore The Fall of Singapore, also known as the Battle of Singapore,; ta, சிங்கப்பூரின் வீழ்ச்சி; ja, シンガポールの戦い took place in the South–East Asian theatre of the Pacific War. The Empire ...
to Japan, he became a
prisoner of war A prisoner of war (POW) is a person who is held captive by a belligerent power during or immediately after an armed conflict. The earliest recorded usage of the phrase "prisoner of war" dates back to 1610. Belligerents hold prisoners of ...
at
Changi Prison Changi Prison Complex, often known simply as Changi Prison, is a prison in Changi in the eastern part of Singapore. History First prison Before Changi Prison was constructed, the only penal facility in Singapore was at Pearl's Hill, beside ...
from February 1942 to September 1945. During his imprisonment, he reportedly would observe some fellow inmates having strange, vacillating behaviour. He thought perhaps a toxin was affecting their brains and when it was eliminated through their urine, they lost their symptoms.


Discovery of the effect of lithium on mania

After the war, Cade recuperated very briefly in Heidelberg Hospital, then took up a position at Bundoora Repatriation Mental Hospital in Melbourne. It was at an unused kitchen in Bundoora that he conducted crude experiments which led to the discovery of lithium as a treatment of bipolar disorder. Since he had no sophisticated analytical equipment these experiments mostly consisted of injecting urine from mentally ill patients into the abdomen of
guinea pig The guinea pig or domestic guinea pig (''Cavia porcellus''), also known as the cavy or domestic cavy (), is a species of rodent belonging to the genus '' Cavia'' in the family Caviidae. Breeders tend to use the word ''cavy'' to describe the ...
s. His early experiments suggested to him that the urine from manic patients was more toxic. There are 2 toxic substances in urine: urea and uric acid. He found urea was the same in both ill and healthy people. He started to work on uric acid. In order to do that, he made artificial solutions of uric acid. To make up different strengths of uric acid he needed to convert it into a substance that he could more easily manipulate. On its own uric acid would not dissolve in water. Then, in an effort to increase the water solubility of uric acid, lithium was added to make a solution of lithium urate. Cade found that in the guinea pigs injected with lithium carbonate solution, as a control solution, the guinea pigs were more restful. His use of careful controls in his experiments revealed that the lithium ion had a calming effect by itself, but even this finding may have been caused by the toxic effects of an excessive dose of lithium. After ingesting lithium himself to ensure its safety in humans, Cade began a small-scale trial of lithium citrate and/or lithium carbonate on some of his patients diagnosed with
mania Mania, also known as manic syndrome, is a mental and behavioral disorder defined as a state of abnormally elevated arousal, affect, and energy level, or "a state of heightened overall activation with enhanced affective expression together wi ...
, dementia præcox or
melancholia Melancholia or melancholy (from el, µέλαινα χολή ',Burton, Bk. I, p. 147 meaning black bile) is a concept found throughout ancient, medieval and premodern medicine in Europe that describes a condition characterized by markedly d ...
, with outstanding results. The calming effect was so robust that Cade speculated that mania was caused by a deficiency in lithium. He published these findings in the Medical Journal of Australia in a paper entitled 'Lithium salts in the treatment of psychotic excitement', published in 1949. While Cade's results appeared highly promising, side-effects of lithium in some cases led to non-compliance. The toxicity of lithium led to several deaths of patients undergoing lithium treatment. The problem of toxicity was greatly reduced when suitable tests were developed to measure the lithium level in the blood. Moreover, as a naturally occurring chemical, lithium salt could not be
patent A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an enabling disclosure of the invention."A ...
ed, meaning that its manufacturing and sales were not considered commercially viable. These factors prevented its widespread adoption in psychiatry for some years, particularly in the United States, where its use was banned until 1970.


Royal Park and RANZCP

In 1952 Cade was appointed Superintendent and Dean of the clinical school at
Royal Park Hospital Royal Park Psychiatric Hospital, commonly known as Royal Park is a former Receiving House and Psychiatric Hospital located in Parkville. Operating for over 90 years, Royal Park Hospital was the first psychiatric hospital established in Victo ...
. Two years later, at the request of the Mental Hygiene Authority which was planning to remodel Royal Park, he visited Britain for six months to inspect psychiatric institutions. On his return, he introduced modern facilities and replaced the rather authoritarian approach to patient care with a lot more personal and informal style that included
group therapy Group psychotherapy or group therapy is a form of psychotherapy in which one or more therapists treat a small group of clients together as a group. The term can legitimately refer to any form of psychotherapy when delivered in a group format, i ...
. Concerned at the number of alcohol-related cases, he supported voluntary admission to aid early detection and later proposed the use of large doses of
thiamine Thiamine, also known as thiamin and vitamin B1, is a vitamin, an essential micronutrient, that cannot be made in the body. It is found in food and commercially synthesized to be a dietary supplement or medication. Phosphorylated forms of thi ...
in the treatment of alcoholism. Cade served as the Superintendent at Royal Park until his retirement in 1977. He served as the federal president of the Royal Australian and New Zealand College of Psychiatrists in 1969–70, and also as the president for its
Victoria Victoria most commonly refers to: * Victoria (Australia), a state of the Commonwealth of Australia * Victoria, British Columbia, provincial capital of British Columbia, Canada * Victoria (mythology), Roman goddess of Victory * Victoria, Seychelle ...
branch from 1963 until his death in 1980. In the end, Dr. Cade's discovery did receive widespread acknowledgements and praise. For his contribution to psychiatry, he was awarded a Kittay International Award in 1974 (with
Mogens Schou Mogens Schou (24 November 1918 – 29 September 2005) was a Danish psychiatrist whose research into lithium led to its utilization as a treatment for bipolar disorder. Early years Schou was born in Copenhagen, Denmark, on 24 November 1918. ...
from Denmark), and he was invited to be a Distinguished Fellow of the
American College of Psychiatrists The American College of Psychiatrists is an American association of psychiatrists based in Chicago, Illinois (''City in a Garden''); I Will , image_map = , map_caption = Interactive Map of Chicago , coordinates ...
. In 1976, Cade was one of the first to be made an
Officer of the Order of Australia The Order of Australia is an honour that recognises Australian citizens and other persons for outstanding achievement and service. It was established on 14 February 1975 by Elizabeth II, Queen of Australia, on the advice of the Australian Go ...
. Dr. Cade remained humble about his chance discovery, describing himself as merely a gold prospector who happened to find a nugget. Finally, in July 2004, the Medical Journal of Australia reported that Cade's 1949 article, "Lithium salts in the treatment of psychotic excitement", was the number one most cited MJA article.


Legacy

John Cade died of oesophageal cancer at Fitzroy on 16 November 1980, and is buried at Yan Yean Cemetery in Whittlesea. Recognition of Cade's pioneering work continued after his death. The Adult Acute unit at Royal Park Hospital was named the "John Cade Unit" in recognition of Cade's long service to the hospital. After Royal Park's closure, the newly opened Adult Acute Psychiatric Unit at Royal Melbourne Hospital was named "John Cade Adult Acute Inpatient Unit". In 1980 the first John Cade memorial lecture was delivered by
Mogens Schou Mogens Schou (24 November 1918 – 29 September 2005) was a Danish psychiatrist whose research into lithium led to its utilization as a treatment for bipolar disorder. Early years Schou was born in Copenhagen, Denmark, on 24 November 1918. ...
at the congress in Jerusalem of the Collegian International Psychopharmacologium. In 2013 the
National Health and Medical Research Council The National Health and Medical Research Council (NHMRC) is the main statutory authority of the Australian Government responsible for medical research. It was the eighth largest research funding body in the world in 2016, and NHMRC-funded rese ...
(NHMRC) offered two $750 000 per annum fellowships for mental health research, entitled the "NHMRC John Cade Fellowship in Mental Health Research". The Fellowship recipients were Professor Helen Christensen of the
University of New South Wales The University of New South Wales (UNSW), also known as UNSW Sydney, is a public research university based in Sydney, New South Wales, Australia. It is one of the founding members of Group of Eight, a coalition of Australian research-intensiv ...
and Professor John McGrath of
The University of Queensland , mottoeng = By means of knowledge and hard work , established = , endowment = A$224.3 million , budget = A$2.1 billion , type = Public research university , chancellor = Peter Varghese , vice_chancellor = Deborah Terry , city = Br ...
. The RANZCP awards The John Cade Memorial Medal to a final year Victorian medical student following a special clinical examination at
Monash University Monash University () is a public research university based in Melbourne, Victoria, Australia. Named for prominent World War I general Sir John Monash, it was founded in 1958 and is the second oldest university in the state. The university has ...
or the
University of Melbourne The University of Melbourne is a public research university located in Melbourne, Australia. Founded in 1853, it is Australia's second oldest university and the oldest in Victoria. Its main campus is located in Parkville, an inner suburb ...
each year. The Faculty of Medicine at
University of Melbourne The University of Melbourne is a public research university located in Melbourne, Australia. Founded in 1853, it is Australia's second oldest university and the oldest in Victoria. Its main campus is located in Parkville, an inner suburb ...
also awards the John Cade Memorial Prize.


Troubled Minds

In 2004,
Film Australia Film Australia was a company established by the Government of Australia to produce films about Australia in 1973. Its predecessors were the Cinema and Photographic Branch (1913–38), the Australian National Film Board (1939–1955, under diff ...
and SBS screened the documentary ''Troubled Minds – The Lithium Revolution'', a 60-minute documentary portraying John Cade's discovery of the use of Lithium in mental illness. The documentary received international recognition, winning the main prize at the International Vega Awards for Excellence in Scientific Broadcasting. ''Troubled Minds'' was also recognised locally with writer/director Dennis K. Smith winning the AWGIE Award for Best Documentary.


See also

* Lithium pharmacology


Notes


References

* Mitchell PB, Hadzi-Pavlovic D. John Cade and the discovery of lithium treatment for manic depressive illness. Medical Journal of Australia, 1999, 171: 262–264. and Ref. No. 00-0612 Bulletin of the World Health Organization, 2000, 78 (4) * Mitchell PB. On the 50th anniversary {{DEFAULTSORT:Cade, John 1912 births 1980 deaths Australian psychiatrists Psychiatrists from Melbourne Officers of the Order of Australia World War II prisoners of war held by Japan Australian prisoners of war Bipolar disorder researchers People educated at Scotch College, Melbourne 20th-century Australian medical doctors