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Whatsapp Dr John Cade with his wife Jean in the 1960s.

In the late 1940s, just outside Melbourne, an Australian psychiatrist called John Cade made a discovery that would improve the lives of millions with bipolar disorder, yet his name is virtually unknown. Now one Sydney psychiatrist is setting out to make sure Cade's work is recognised.

For most of his young life, John Cade lived alongside mental asylum patients.

Because he was a man of great honour ... he felt he couldn't inflict a new substance on a patient until he swallowed it himself.

Born in Horsham, Victoria, Cade was the son of a psychiatrist in the days where they lived on the grounds of asylums.

He would go onto be a psychiatrist himself, discovering one of the most important treatments of bipolar disorder to date, and this experience shaped his whole attitude to medicine and mental health.

'As a young boy, John Cade was taken from asylum to asylum and observed mentally ill patients every single day of his life,' says psychiatrist Greg DeMoore, author of Finding Sanity—John Cade, Lithium and the Taming of Bipolar Disorder.

'Instead of being objects of curiosity or people to fear he actually regarded them as friends from a very early age.'

In Cade's era, people with serious mental illness were living in a kind of netherworld, DeMoore says.

Then, it was almost romantically referred to as melancholia; now it would be considered severe clinical depression.

'The patient may remain frozen and locked in that depressive state for up to a year, until gradually the symptoms thawed and they returned to normalcy,' DeMoore says. 'That is, if they survived that year.'

Back then in the early 20th century there was really no effective treatment. Incarceration in asylums was really the only option.

Psychiatry in a war zone

During World War II, Cade was a prisoner of war in Changi for three and a half years. The only psychiatrist there, this turned out to be a key period of his life.

The Australians and British set up a hospital, inside of which Cade started a mental health unit.

Prior to the war it was a long-held belief that serious mental illness was caused by a poor upbringing.

But Cade's time in Changi observing patients who had similar symptoms to those he treated before the war led him to another explanation.

'What he observes is that serious mental illness can be caused by biological changes, changes to the chemistry of the brain,' DeMoore says.

When they did autopsies on these patients they found physical causes for the mental illness, for example, DeMoore says, a blood clot on the brain.

'He started to think illnesses like schizophrenia and manic depression, which we also call bipolar disorder, maybe there's an organic, a physical cause of it,' he says.

'That idea took root and incubated over the next three years before he came back to Australia.'

Urine leads to lithium discovery

After returning from the war, Cade started his experiments in earnest, starting with an obsession with urine.

'He has this idea that when you are manic, or high, there might be an excess of certain chemicals in your urine. And when you aren't there might be a deficit of it.'

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Whatsapp The kitchen at Bundoora Repatriation Mental Hospital where John Cade conducted some of his lithium experiments.

Cade was working at an asylum on the outskirts of Melbourne after the war, treating ex-diggers who were incarcerated with mental illness.

So he asked the nurses to collect their urine, which he then stored in his fridge at home.

He started to inject the urine from patients into guinea pigs, to observe the effects on them.

Cade's hypothesis was that there are two elements in urine which could be causing toxicity.

'If you add lithium to uric acid you get a thing called lithium urate,' DeMoore says.

'When he added lithium and injected the guinea pigs, something wonderful happened.

'I did a wonderful interview with his wife where she describes that moment in his shed, when John called her in and said "the guinea pigs are quiet, they are relaxed, I can turn them over."'

The next step from discovering that lithium calmed the guinea pigs was clear.

'Because he was a man of great honour, and he was a very religious man, he felt he couldn't inflict a new substance on a patient until he swallowed it himself,' DeMoore says.

'So he decides to test it on himself. He took it for several weeks.

'And he didn't die, he didn't curl up in a ball in the corner, didn't fit. So he decided it was safe to give the patients.'

Treating bipolar disorder with lithium

Once he decided it was safe, Cade knew who was going to be his first patient to try lithium.

Bill Brand had been psychotic for more than 30 years—a patient at an asylum in Bundoora for most of that time.

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Whatsapp Patients walk through the grounds of the Bundoora Repatriation Mental Hospital, c. 1940s.

'He'd fossick around the rubbish bins at the asylum. He was manic, he'd try to spend money, he'd abscond,' DeMoore says.

'Bill's life was the quintessential life of the seriously mentally ill patient. He cut off the tips of two fingers while working as a labourer.

'He was disowned and alienated from his own family and had been left in the asylum.'

In March 1948 John Cade decided to test lithium on Brand.

A man with a strong moral compass, Cade felt this was an ethical thing to do, DeMoore says.

'This man was almost going to die a miserable death alone—there was nothing too much to lose if you tried a new substance such as lithium,' he says.

'He was an experimentally minded individual, and he was a pragmatic individual.

'He thought "it's pointless testing things on guinea pigs, you've really got to take that next bold, courageous step". There were no ethics committees in 1948. He was only answerable to his conscience.'

Cade administered the lithium in liquid form, making up a special solution.

Slowly over the duration of three weeks, Brand started to look after himself. His speech slowed and he stopped fossicking in the rubbish bins.

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Whatsapp A typical ward in Bundoora Repatriation Mental Hospital, c. 1940s.

After about two months, the notorious patient walked out of the asylum that he'd called home for the best part of three decades.

"He walked out of the asylum back to his old job, perfectly sane,' DeMoore says.

'Nothing had been seen like it in mental health before.'

Determining the dose

Sadly, the lithium experiment didn't end well for Bill.

'In many ways Bill's story is the archetypal story of mental health. He returns to his old job, and decides he doesn't need the medication,' DeMoore says.

'He becomes very ill again with bipolar and gets hospitalised.'

If a patient takes too much lithium they become toxic, and in the late 1940s, the correct dosage wasn't known.

'When Bill returns John Cade pushes his lithium harder and harder in a desperate bid to get him back to a normal mental health state,' DeMoore says.

Because of this Brand became toxic with lithium and died in 1950.

The death rocked Cade, and made him uncertain about the future of lithium as a mental health treatment.

But over the course of the next two decades, the cause was championed by other psychiatrists, and ultimately it was successful.

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Today, DeMoore says, lithium is the gold standard treatment for severe bipolar disorder.

By the early 1960s Cade's discovery was heralded as something truly triumphant. But he never considered himself a brilliant man of medicine.

'[He] did something remarkable and kept it very quiet,' DeMoore says.

'He wrote a book about the history of psychiatry after he retired. There was a chapter on lithium and he didn't mention that he was the individual who discovered the miracle of lithium and how it can help people with bipolar disorder.

'He was a reluctant hero. He was truly a humble individual.'