In the slim, synoptic history of twentieth-century psychiatry that he wrote after retiring as superintendent of Melbourne’s Royal Park hospital twenty-eight years ago, Dr John Cade devoted a short chapter to lithium: the ‘simple inorganic substance’ that to this day, and for reasons only dimly understood, is astoundingly effective in counteracting the horrendous affliction known as bipolar disorder.
Like the rest of Mending The Mind, the chapter is discursive, clear and elegant, with a few characteristic flourishes. Cade, a scourge of Freudians, permitted himself a dig at ‘the utter uselessness of psychotherapy based on psychopathological theories’; a devout Catholic, he digressed for a page and a half to muse on whether Pope Urban VI might have been a manic depressive. The chapter omits only one material fact: that he was lithium’s discoverer.
One of the most revolutionary papers in medical history, published fifty-six years ago, ran to only three pages under the unprepossessing title ‘Lithium Salts in the Treatment of Psychotic Excitement’. But when the Medical Journal of Australia surveyed the history of its contents six months ago, no contribution had been cited so often: 888 occasions. There have recently been other signs that Cade will receive belated due. In 2001, he was the subject of a bioplay, Doctor Cade, by Neil Cole, a former Victorian shadow attorney-general whose bipolar disorder was brought under control by lithium; an excellent documentary about lithium, Troubled Minds, directed by Dennis Smith, was aired on SBS in October 2004; medical historian Ann Westmore is planning a biography. But his significance is best conveyed by the title of his own book: Mending The Mind. When Cade became a psychiatrist, treatment of the mentally ill had barely changed since Hippocrates: patients were to be sequestered and subdued. Cade was among the first to conjecture that the mind could be ‘mended’; lithium prefigured a revolution in psychopharmacology that has made life more liveable for millions, and virtually emptied the institutions that once teemed with apparently intractable manias, depressions and anxieties. He did it, moreover, in circumstances so extraordinary that some have thought it simply a great mistake; in the context of his life, in fact, they make complete sense.
Cade was born in Murtoa, in Victoria’s Wimmera, on 18 January 1912. His father David, a general practitioner, served with the Army Medical Corps in France and won the Distinguished Service Order, but buckled beneath the strain of resuming practice amid the post-war flu pandemic, and accepted a less strenuous position as a medical officer in what was then called the Mental Hygiene Service – the very name attests the prevailing view of mental illness as a stain or contamination. The first mental patients that John Cade met were his father’s at the Beechworth and Sunbury Asylums, and the encounters impressed him forcefully; at twenty-four, he joined the service himself.
The old jest holds that those choosing psychiatry first wish to understand themselves. Cade doesn’t fit it. A slight figure with prematurely receding hair, seldom photographed without a tie, he was a man of pacific temper and quiet good humour, capable of disagreement without rancour and discipline without anger. Of modest means, he developed modest tastes to match. When he married a Royal Women’s Hospital nurse, Jean Charles, who had seen him through a severe bout of bilateral pneumococcal pneumonia, he could afford neither an engagement ring nor guests at their wedding.
Cade’s only disproportion was in his curiosity, insatiable and incurable. He was a close reader and a minute observer, who relished his garden and the bush. The Cades once took Mogens Schou – a Danish psychiatrist who Cade honoured as lithium’s ‘devoted foster father’ – on a picnic to Healesville Sanctuary on Melbourne’s outskirts. No sooner had they arrived than, without explanation, Cade picked up his sandwiches and disappeared into the woods. When Schou, embarrassed, finally asked if he had somehow offended his hosts, Jean reassured him: her husband was simply checking the animal droppings, which he was expert at distinguishing.
It was on his first posting to Beechworth that Cade emerged as a decidedly unorthodox clinician, startling colleagues by expressing an eagerness for ward rounds; he was thought stranger still when he began identifying, in the undifferentiated mass of the ‘mad’, patients whose problems were primarily medical rather than mental. Cade’s son Jack recalls: ‘He’d see some poor old duck with a rash and he’d say: “This woman has pellagra.” He’d see someone whose teeth were falling out and say: “This person has scurvy.” Or he’d find some freezing cold person wrapped up in a blanket and tell the staff: “Thyroid dysfunction.” Mixed with the patients were a lot of people who were totally curable. I think it was where my father developed his belief that good psychiatry should be founded on good medicine.’
War interrupted these insights, then perhaps deepened them. In 1940, Cade was commissioned in the 2/9th Field Ambulance, Eighth Division, and posted to Singapore. He proved to be an excellent officer, uncannily calm even amid the chaos of the fortress’s invasion. One night, in an ambulance in search of wounded, Cade and his driver found themselves flanked by columns of soldiers. ‘I don’t think we’ll make it tonight,’ Cade said at last. ‘Let’s head back to barracks.’ Later he asked the driver: ‘Did you notice anything about those soldiers?’ When the driver admitted he had not, Cade said: ‘They were Japanese.’
‘Why didn’t you tell me?’ the driver complained.
‘If I’d told you,’ Cade replied, ‘you might’ve panicked.’
During his three years in the infamous Changi prison camp, Cade did not merely continue his medical duties, but acted as the camp’s secret information officer: he was delegated to commit the nightly BBC broadcast on the camp’s hidden radio to memory for repetition to fellow POWs. Incarceration reduced Cade, like many others, to a ‘walking skeleton’ of 40kg; yet, the playwright Cole believes, it also crystallised his thoughts: ‘If ever there was a place where you would have thought depression was widespread and reactive, it was Changi. But it wasn’t the case. And it confirmed his own impression that there was depression “within” people irrespective of circumstance.’ When Cade returned to work at Bundoora Repatriation Mental Hospital, he indulged his curiosity in a series of experiments so speculative that they seem closer to alchemy than medicine.
John Cade’s bete noir was psychoanalysis. ‘Dad thought Freud had really set back the cause of psychiatry,’ says Jack Cade. ‘Not that the mind did not exist, but that, as a method of understanding mental illness, it was totally sterile. The brain was an organ. Like every organ, it was subject to injury; it was thus amenable to treatment.’ Cade’s objective was to find a chemical dimension to mental distress. In a wooden shed in the hospital grounds that he equipped as a laboratory, Cade began injecting fresh human urine into guinea pigs. The most toxic was the urine of patients with manic depression, the wild and debilitating fluctuation between euphoria and despair that afflicts about one per cent of the population, which Cade ascribed to concentrations of urea.
When he fortuitously used lithium urate to test how the concentration of uric acid affected the toxicity of urea, however, he was surprised to find that it seemed to have a protective effect; during a follow-up test using lithium carbonate, the animals lay contentedly on their backs for some hours before returning to normal. Was it safe? Cade answered that question, to his wife’s dismay, by trialling lithium carbonate on himself. When it had no ill effects, he selected nineteen patients for a clinical trial: ten with manic depression, six with schizophrenia, three with melancholia.
Jack Cade and his younger brother David were bemused eyewitnesses. With their father’s encouragement, they treated the hospital as a play area. ‘Of course, when we were growing up, our schoolfriends would say: “You live in the loony bin!”,’ recalls Jack. ‘But we learned such a lot about the patients: these lovely people whose brains had gone. At Bundoora, they were, of course, old diggers, including some from World War I. Lovely old guys, some a bit strange, some a lot strange, mostly completely lost; the hospital was their home.’ David Cade points out, however, that his father’s lithium brainstorm was decidedly out of the ordinary: ‘I find it astonishing that Dad at that time thought it likely there was something to be found which would lead to real treatment of psychiatrically-disturbed patients. Because there was no evidence to lead him to believe that. It was pure intuition.’ As David comments, his father’s audacity, by modern standards, was also breathtaking: ‘Even if he had been able to do that sort of work today, it would never have been accepted, because it wasn’t done under a conventional research protocol; nor would it have passed any test of the Therapeutic Goods Administration here or the Food and Drug Administration in the US.’
Cade’s research was essentially of his era, one in which the doctor omnipotent reigned; in mental health especially, clinicians enjoyed startling discretion. ‘As a medical superintendent in the 1940s,’ Westmore says, ‘you could basically give your patients what you wanted. There were no ethics committees, no-one looking over your shoulder. You were the boss. Unlike a big general hospital, psychiatric hospitals were isolated from the mainstream.’ Nonetheless, disciplines were no less binding for their self-imposition. Cade’s decision to submit himself to lithium before administering it to patients recalls the military nostrum that no commander should issue an order involving risk he would not take himself. ‘The military aspect of his [Cade’s] life was a strong one,’ agrees Westmore. ‘Cade himself had been in the Melbourne University Regiment before the war, which his father was very keen on. He didn’t love the army experience, but I think he did absorb some of its ethos.’
Cade’s case notes of his first subject, fifty-four-year-old William Brand, known universally as ‘Monkey’, are now in Melbourne University’s Medical History Museum. An itinerant labourer discharged from the Australian Light Horse due to ‘dementia’, Brand had been admitted by police almost five years earlier. Cade found him to be ‘so lacking even momentary attention that questions usually fail to interrupt his flight of ideas’; his manic energies were most conspicuously applied to frantic lawn mowing. Yet within days of his first doses of lithium citrate on 29 March 1948, Brand was clearly calmer.
‘Monkey’ was a favourite of the Cade boys, whom he favoured with humbugs. ‘We probably saw more of him than Dad,’ says Jack. David recalls his father’s questions: ‘When he started the treatments, because he knew that we were good friends with Monkey, Dad started asking us: “Have you seen Monkey recently? How is he?” And we told him we’d found him remarkably normal: the change was very noticeable.’ Within four weeks, Cade was noting in his small but tidy and legible hand: ‘He now appears to be quite normal. A diffident, pleasant, energetic little man.’ Eight weeks later, Brand was discharged, and returned to his old job. The results from the other nine bipolar patients were little less dramatic – the ‘garrulous, euphoric, restless, unkempt’ became the ‘quiet, tidy, rational’ – while as expected the others enjoyed no relief.
When Cade was almost finished writing up his researches, however, he received a demoralising shock. ‘Monkey’ was readmitted, wilder than ever. Cade was devastated: ‘It was the most bitter disappointment of my life.’ Then Brand’s brother confided that ‘Monkey’ had grown ‘blasé’ and ceased taking his medication; the relapse attested lithium’s efficacy rather than challenging it. Cade’s efforts to restabilise ‘Monkey’s condition were ultimately unsuccessful – Brand died in May 1950 – but lithium was by then in the public sphere.
Here the tales of Cade and his wonder drug part, their only similarity being that both had long periods to wait before recognition. Lithium had to surmount three obstacles. As Cade expected, his own obscurity told against the discovery: 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 US. Worse still, even as Cade’s paper appeared, there were American reports of fatalities from lithium toxicity following its reckless prescription as a salt substitute. It was precisely the worst time to be recommending lithium’s use for anything medicinal; not until October 1968 did the American Journal of Psychiatry publish details of clinical trials. Finally, there were economic realities. No-one can patent an element. Pharmaceutical companies, reliant on healthy margins to fund their research and development, scorned lithium until Pfizer and Rowell Laboratories made it available on a philanthropic basis from 1970. Then its results were immediate; it remains, in fact, an astoundingly powerful treatment, used in about a third of bipolar cases, alongside more recent drugs like carbamazepine and valproate.
Ten years ago, Science magazine estimated lithium’s value to the American economy alone as $US145 billion. But it has proven to be more than a drug. As the first psychotropic (mood-altering) medication – preceding by four years the discovery of the anti-psychotic neuroleptic drug chlorpromazine – it was the vanguard of a whole new approach to the treatment of mental illness. That is to say, it was an actual ‘treatment’ in which the patient ‘got better’, rather than remaining confined to preserve the greater ‘mental hygiene’.
Cade himself, meanwhile, all but abandoned lithium, content to leave its development to others better equipped, like Schou, who was spurred by the personal pain of a brother with bipolar disorder, and biochemist Edward Trautner, who in Man and Medicine, a 1955 publication by his Melbourne University, was even erroneously credited with its discovery.
Cade’s indifference surprised many; even, David Cade recalls, Jean: ‘Mum was disapproving that my father published his lithium research the way he did, after such a short time, and also that he didn’t follow it through, because he was the expert in the field. But my father felt three things: first, that it was obviously very effective, and that the sooner the news was released, the better for patients; second, that he had reached the limits of what he could do, for he had no real research facilities, and many people were better equipped to do the developmental work; and thirdly, he had other objects in mind already.’
For Cade had embarked on new, often idiosyncratic, adventures. One long-term project was mapping demographic patterns of mental illness across Victoria: he came to suspect, for instance, that the relative sanity of the Goulburn Valley’s inhabitants was associated with their consumption of stone fruits. Use of himself as a test tube also continued: he once said drolly that it ‘saved a lot of trouble with coroners’. Once, Cade even took strontium. ‘He nearly died,’ recalls David Cade. ‘For about a week, he looked shocking. Slate grey…Mum was terribly cross.’ He joked towards the end of his life of having eaten his way through the periodic table.
It is Cade’s cheerful amateurism that has led some to dismiss his discovery as chiefly accidental, yet lithium’s properties could only really have intrigued such a happy wanderer of research. If anything, Cade’s experimentation can be seen as conterminous with the main project in his life: his patients’ welfare. As superintendent of Royal Park Psychiatric Hospital between 1952 and 1977, he was endlessly solicitous of their needs, and never, despite administrative pressures, absolved himself of daily ward rounds. In his retirement speech, he reserved his most heartfelt thanks for those he had treated: ‘They taught me so much.’
As lithium came of age, Cade accepted recognition by his peers with characteristically little fuss: when he and Schou shared psychiatry’s prestigious Kittay Prize in April 1974, he left for New York with a briefcase that contained only a clean shirt and a toothbrush. A journalist who visited him at the time found him at Royal Park in ‘a rather Spartan little office, very public service décor, with green imitation leather chairs, drab carpets and grey metal filing cabinets’. Obeisance to departmental bureaucracy, in fact, never interested him; he lost himself only in cases. ‘He was always thinking,’ says David Cade. ‘He commonly saw things that others didn’t. It was a forte of his.’
Numerous stories concern Cade’s lateral approach to diagnosis. One morning, for example, he encountered in an isolation cell a noisy and incomprehensible man brought in the night before by police, and asked for the patient’s clothes. ‘This man isn’t sick,’ Cade announced. ‘Look at this paint. It hasn’t even dried. I suspect he’s a house painter, and that he was at work hours before he was arrested.’ When Cade asked the Health Department to send a senior public servant with a command of Greek, the reality emerged. The patient was a migrant fresh from the boat and working for the painter brother-in-law with whom he was staying; celebrating his first week of work at the pub, he had become disoriented, then angry that he could not remember where he lived. Cade himself drove the man around the streets of Brunswick, the Melbourne suburb with the greatest concentration of Greek migrants, until a familiar landmark guided them to the bosom of an anxious family.
Cade’s own family grew to four boys, all of them following him into medicine. Jack remains head of intensive care at Royal Melbourne Hospital, a role David filled at St Vincent’s; born after the war, Peter became a surgeon, Richard a laboratory technician. They speak of their father with an affection and respect that is deep rather than effusive – rather like the man himself. Only once is he recalled as being moved to tears; and, despite a life in which he was exposed to some of the ghastliest human torments and tortures, its cause was a simple domestic drama, when the family daschund broke into the woodshed ate some strynchine baits, and began to writhe in pain, wracked by grand mal epileptic fits of increasing severity. Calmly, practically, John Cade took his shotgun, and ended the animal’s agonies with a bullet in the back of the head. Then, to general surprise, he wept. For John Cade, this was perhaps the acutest suffering: a sense of being helpless to alleviate the suffering of others.