The Drugs That Changed Our Minds

by Lauren Slater

  Luckily for us, while the uric acid diathesis could and did die, taking lithium with it, the substance itself could never be completely extinguished. Of everything psychiatry has in its armamentarium, lithium is one of the only drugs that is not man-made. It is in and of Earth, or better yet the solar system, or better yet the universe, an element that pre-existed any human being and is therefore protected from propensities, from fashion. Gone was Buffalo Water, gone were the tablets from which one could concoct one’s own soothing, but lithium is ineradicable. Thus when we returned to it – or when one specific, unusual and modest man returned to it, in 1946 – it was waiting there for him, in all its blinding white abundance.

  A Beginning Down Under

  The story starts again in suburban Australia when a young and keenly curious Australian doctor named John Cade was released from a Japanese POW camp at the end of the Second World War and sent back home to his family to begin a new life, a life he’d have to create in good faith, despite the atrocities he’d witnessed as a prisoner of war. It involves a gaggle of guinea pigs, a Melbourne mental hospital and a single hypothesis Cade had developed and nursed all through his wartime imprisonment.

  Born in 1912 in a small country town in Victoria, Cade became a major in the 2nd/9th Field Ambulance, and was stationed in Singapore during the war. When the country fell to the Japanese, in February 1942, he was captured, shackled and blindfolded, with a bayonet pressed against his neck. Thereafter Cade was held as a prisoner of war for three and a half years, during which time he closely observed his fellow prisoners trying to cope with the brutality of their captors. The men at Changi camp were starved, a watery soup their only food, with vermin and filth everywhere.

  It was during these three and a half years that Cade began to develop his hypothesis of mental illness and mental health, watching men as they broke beneath the stress of frequent beatings and starvation, their minds going waywards and opening to voices and visions, to extreme excitability in some cases or abject despair in others. Cade stayed sane throughout all the horrors by turning his imprisonment into a psychological and anthropological study that had at its heart a single question: what caused a mental breakdown, and why did some succumb while others remained steady? As he toiled in the camps, as he spooned watery soup into his mouth, as he lay on his pallet of crushed leaves and moss and listened to the moaning of many men, Cade developed this idea: mania, he believed, must be caused by an excess of some normal metabolite the body produced, while depression must be caused by a dearth of the same metabolite. Interned, he had no way of testing his notion, but as soon as he was freed, he returned ‘mourning the wasted years and determined to pursue the ideas that had germinated in that interminable time’.

  After his release, Cade was at last reunited with his wife and two young sons, the older of whom had been only three when his father left for Singapore. He resumed psychiatric work on New Year’s Day in 1946, at the Bundoora Repatriation Mental Hospital, which had become Victoria’s chief mental hospital for war veterans. Haunted by the lost years in lock-up and spurred, as always, by his curiosity, Cade went to work trying to discover what this crucial metabolite that he had theorised might be. Right from the get-go, then, his emphasis was on aetiology. He was a man who sought the source of human suffering, which set him apart from his colleagues in other countries, such as Delay and Deniker at Sainte-Anne, who did not really reflect on the pathophysiology of their patients’ illnesses, and who, when presented with a drug to treat the delusions and hallucinations of schizophrenia, used it but appeared not to wonder why it worked, focusing instead on the purely empirical fact that it did. Cade, one might say, was a more ambitious scientist, seeking right from the start the biochemical substrates of mental pain, and willing to offer his own hypothesis based on nothing more than a hunch. He had his mental antennae tilted towards a world of molecular constellations, at the same time always observing the nuances of human gesture and language.

  Cade’s wife told a story from many years later of walking with him in the woods near Melbourne one time and happening upon some droppings still moist on the emerald leaves. Cade bent down to study them. After a moment, he straightened his spine, brushed off his knees and pronounced that an elephant had been there.

  ‘John,’ his wife said. ‘Have you gone mad? We’re in Australia.’

  The couple continued to walk. After some time, the woods gave way to a clearing, in which stood a circus, complete with elephants. Astonished, Cade’s wife turned to him and asked him how he had known. Cade explained that he remembered how the droppings looked from photographs he had taken of these massive mammals at the zoo.

  Now, with his psychiatric work resumed, he was ready to turn his highly absorbent brain towards the problems and possibilities of madness – the madness of deep despair, when all the world is stripped of contour and colour, and the madness of mania, with its high-flying colours and tossing trees and swirling skirts and screams. Where, however, to start? This metabolite, whether in excess or dearth, could be anywhere in the body or in the brain, which is itself crammed with billions of neurons. ‘Because I did not know what the substance might be,’ wrote Cade, as he stood on the threshold of this moment, ‘still less anything of the pharmacology for lower animals, the best plan seemed to be to spread the net as wide as possible and use the crudest form of biological test in a preliminary investigation.’

  Cade and Guinea Pigs: The First Experiment

  Cade and his wife by now had several children – three more were born after his return – and to the children the guinea pigs were pets. The family kept their guinea pigs caged in the back garden and they quickly became Cade’s first experimental subjects. Influenced by his predecessors, Cade opted to start his search for the metabolite with urine. The protocol: manic, depressed and schizophrenic patients on the wards of the Repatriation Hospital were to abstain from fluids for twelve to fourteen hours (overnight) before the following morning’s samples were collected, so long that the concentrated urine was swimming with sediment. Cade also took urine from controls, individuals not suffering from a mental illness.

  Once he had adequate samples, which one of Cade’s sons remembers his father storing in the family refrigerator, Cade set about injecting the urine – both the ‘clean’ urine and the urine from schizophrenic, manic and depressed patients – into the abdomens of his guinea pigs. What he found was that the urine ‘from the manic patients proved to be far more toxic than from the other groups, although all the samples led to deaths among the animals.’ As Cade acknowledged, though, ‘all that had been demonstrated so far was that any concentrated urine in sufficient quantity would kill a guinea pig, but that the urine from a manic subject often killed much more readily.’

  Thinking that the uric acid might be the element in the urine responsible for the deaths, Cade began to investigate the effects of uric acid on overall urea toxicity. Because uric acid is insoluble in water, Cade began adding lithium salts to his samples, in an effort to make the uric acid dissolve. He noted that the presence of lithium made the urea less toxic. That made him wonder how lithium used alone would affect the guinea pigs. He injected large doses of it into the abdomens of the animals.

  Cade was surprised, even stunned, by what happened next:

  After a latent period of about two hours, the animals, although fully conscious, became extremely lethargic and unresponsive to stimuli for one to two hours . . . Those who have experimented with guinea pigs know to what extent a ready startle reaction is part of their make-up. It was thus even more startling to the experimenter to find that after the injection of a solution of lithium carbonate they could be turned on their backs and that, instead of their usual frantic righting reflex behaviour, they merely lay there and gazed placidly back at him.

  Cade thought he was on to something here, and clearly he was. He had administered to usually timid, anxiety-prone animals a solution that eradicated these propensities and produced a quiet calm. For a psychiatrist at a l
arge asylum jam-packed with raving patients, it must have been mere moments before Cade wondered what effect this lithium would have on his charges. Before conducting that experiment, however, Cade tried the lithium solution on himself. We don’t know if he was scared or worried or confident, although surely he was curious. Surely he must have sat very still once he was done, waiting to feel whatever effects there might be. He must have been alert, and if the wind was in the trees, he must have heard it more keenly and wondered whether this was the drug or simply his heightened senses. Trying it several times over the course of a few weeks, Cade felt only mild ill effects: some transient nausea but nothing else. At that point, he surely must have smiled.

  After all, this might be very good news for an asylum crammed full of maniacal people with bent and broken ideas: men who believed spies lived in the white walls and whispered to them day and night. Women who careened down the corridors wearing lipstick so poorly applied that it made their mouths look brutal, pulped. Patients who could not sleep and so stayed up, dreamless and full of despair. People in such severe pain that even modest movement seemed too much of an effort – all purpose, all point, having been drained from lives lost years ago. Worst of all, though, were the ones who believed they were brilliant, whose chatter never ceased, words surging from their mouths in a stream of nonsensical sounds, their eyes bright with ideas that formed so fast they toppled one over the other like a house of cards continually coming down, unable to be soothed, clenched in a continual saga of operatic proportions that exhausted everyone around them, especially the nurses.

  Cade must have thought of them, and then thought of his guinea pigs resting easy on their backs, willing to be scratched, to be touched. Many hospital dispensaries had huge vats of lithium left over from the nineteenth century, so theoretically the drug would have been available to Cade. Even if the canister was furred with dust, as long as it was still sealed, the salt would be pure.

  A Night Drive

  I’ve never lived in a large asylum like the one over which Cade presided. The mental hospitals I’ve lived in have all been decidedly undramatic, single floors in general medical centres, the meal trolley wheeled off the lift three times per day, the forks and knives always plastic. As a thirteen-year-old girl, I used to watch Rosemary, a wisp of a woman, young and pretty, her eyes spilling a perpetual overflow of tears, until the liquid snaked slowly down her face, dangling at the edge of her chin and finally falling with a noise I swear I could hear, the quietest kind of crash. I used to listen to Gerry as he sprinted up and down the halls belting, ‘Some people sit on their butts, got the dream, yeah, but not the guts.’ While Rosemary was silent and still, Gerry was the opposite, a constant whir of motion and a continuous spew of sound, a carousel of Shakespeare and Ethel Merman and passages from huge tomes he’d drag into the dayroom to either stand on or read from. The Count of Monte Cristo was one of his favourites. Gerry had so much energy he hardly ever slept, not even after his nightly tablet, which was big and blue and which he’d only pretend to swallow, spitting it into his cupped palm once the night nurse turned her back, winking at me as he did so. ‘Kiddo,’ he called me. ‘Poet.’ He claimed he was a professor at Harvard, and who knows, maybe he once had been. But mania had got its teeth in him just as depression had seized hold of Rosemary, both of them pinioned in entirely opposite ways.

  As for me, I was just a mixed-up adolescent who modelled herself after Sylvia Plath. In the beginning at least, mental illness for me was some form of drama, of dangerous play, the razor so sharp it sliced the skin on my arms with barely any pain, blood rushing up and welling in the wounds I made, every one of which fascinated me. I flirted with mental illness when I was a teenager, but by the time I turned twenty the flirtation was over and I was seriously sick. Fluoxetine rescued me for decades when I was in my twenties, thirties and forties, enabling me to write several books and marry a man who was gentle and give birth to two babies. But even with all my abundance and all that extra serotonin, the sickness came back and back, morphing each time like a cruel chameleon, manifesting sometimes as obsessive-compulsive disorder and other times as generalised anxiety disorder, which is a name far too banal and clinical to adequately describe the terror of that condition, a terror so true and fanged that it can loosen your bowels as you crouch in some corner and cry.

  My last breakdown occurred seven years ago and involved, like lithium itself, stones. I became, at first, enamoured of stones; they were everywhere and each one was precious. No one knew this but me. I was living on a planet rife with precious heft, and I’d rush down the street collecting these gems, filling my pockets. Soon my study at home was piled high, and the heaps spilled into the hall and clattered down our steep stairs as my children and husband looked on in a kind of horror. I was gleeful, exuberant, because we were rich, we had stones, and it was just a matter of time before everyone else realised that when you held a simple rock you were clutching all of human history in your plain old palm, the rock millions, maybe billions of years old, its veins and pathways and sedimentary layers suggesting song and deep space and even the Big Bang itself. So excited was I by stones that I stopped sleeping and stayed up all night polishing my treasures with an electric grinder, and indeed I can say in sanity that there was something lovely about seeing a plain old stone with its grit gone, seeing its speckled or mottled hide, its blue hue or emerald artery. Yes, stones can be lovely, but in my manic state they were everything and I was on to something so special that sooner rather than later the whole world would go along with me.

  The major problem with mania is the inevitable depression that comes in its wake, and the more manic you are, the more depressed you will get, as if there is some law, or even some kind of divine punishment, for going up so high, because you will then go down proportionally so low and for the same period of time. True, there are the rare cases of people who have only mania; they somehow manage to be both blessed and cursed with only half of the bipolar diagnosis, and so we call them unipolar, a condition that many of them love, even as they irritate to pieces all the people around them and make terrible messes of their lives.

  But by far the most common conclusion to mania is the aftermath of depression, which for me did not come slowly or with subtlety. It was like having the turf pulled out from under me; a whisk and a whoa and all of a sudden, in a single and terrible second, I recognised that I was a forty-something female standing amidst stones that were scattered everywhere in her study and, worse, stored everywhere in her house, so that when you opened the cupboard, stones came tumbling out on to your toes. I had no energy, certainly not enough to clear away the stones, and besides that, I was embarrassed. I suddenly saw myself in a whole new light, or darkness may be the better word, a weird crazy old lady collecting pebbles and in some cases serious slabs that weighed as much as 4.5 or 9 kilograms (10 or 20 lb). What had come over me? And what was coming over me now, this dread, this fear, this gulf, this grief, this terrible understanding of time, which moved so slowly I could see it, that cruel second hand inching its way around the surface of an equally cruel clock with filigreed numbering on an otherwise blank white face, a huge moon face that mocked me from its place on the wall in the hall.

  I backed up. I backed away. I wanted to cry, and I remembered Rosemary, who’d had such unrestrained grief. Crying would have been a real release for me, and it would have also shown, to others, something of what I was now feeling inside; words could not do it justice but wetness would, or could. But I had no tears. My eyes were little scorched sockets, two holes in my head, that’s all. So I closed them and tried to go to sleep but I felt the heaviness of the house all around me, what with all these stones. I managed to call a contractor to come take them away. ‘What were you using them for?’ he asked me as he whisked the last batch out the door. ‘I had this idea,’ I said to him, but then I could not finish the sentence. There was no way to explain the ridiculousness of my collecting obsession, so instead I shoved money into his hand and turn
ed away.

  Now, without the mania, the nights were terrible. Sleep evaded me or, worse, came over me for only seconds at a time, the drift of a dream and the sudden snatch back into the blackness. I went driving then. I’d wake up and stuff my feet into dirty slippers and get into my car and drive the roads flanked with trees tremulous in the wind, the moon a sliver so small it threatened to disappear. I had a recurring thought: that one day the sun would never set. It would burn on and on, past five o’clock, past six o’clock, past nine and then ten o’clock, the sky stubbornly bright as our yellow star flared on and on, the heat high and the night-time driven down and out. A world in which there was no darkness, not even dusk, no crisp coolness, the lawns parched and everyone trapped in a white hysterical light.

  I dreaded the daylight because it provided too clear a contrast to the black ooze that was inside me. The nights, even though they rarely offered me the relief of sleep, were somewhat soothing, and so I cruised the empty roads, past darkened shopfronts and houses with every window snuffed. Sometimes I heard things: the yowl of a cat, the whir of wings, the coyotes as they exited the forest. I became confused as to what sounds were real and what were imaginary. Had I hallucinated a fox whisking over moss with a mouse in his mouth? I drove deep into the countryside, where there were no street lights, and yet still, somehow, I saw a black hat, like a magician’s hat, roll slowly across the road and disappear down an embankment.

  I stopped the car, stepped out. I wanted to catch that hat but it was gone. Even though the darkness was dense I had seen it specifically, perfectly, a tall black hat full of endless silver scarves, a hat I’d put on my head for an instantaneous cure. Above me circled a large hawk, and my eyes were suddenly so sharp I could see the rabbit clasped in its beak; I could see the blood on the rabbit’s hide, its paws pedalling the air in a frantic motion. Frightened, I stepped back into the car and resumed driving, fast, and it happened in just a shaving of a second, this shadow whipping across the road, the stick-thin legs of a little girl who carried, in each of her upturned palms, toads that glowed from within. I swerved but it was too late. I hit her anyway. When my car made contact, though, she did not go down. This ghost girl merely melted and the toads became winged things that went as high as the sky, until they too were gone.