I had in many ways (but not all ways) a terrible childhood. My mother did not know what to do with me. In reality there was nothing so special about me, but for whatever reason I frustrated her and seemed to be a blot on her existence. She dealt with me as an infant by stowing me in a wind-up swing and when I got older by sometimes grabbing a clump of my hair and dragging me across the floor, a few times to the sink, where she washed out my mouth with soap, although I never swore. My mother herself was depressed and thus there’s a reasonable chance I learned depression from her, just as I learned from her the alphabet and how to ride a bike. That’s a theory – depression as something you acquire, even master, like an instrument with all sorts of strings. Another theory: that I was born with a broken brain and thus the blinding white dazzle that choked me the summer I was six or seven was simply the inevitable manifestation of an illness beginning, an illness I’d harboured if not since conception then soon after. There is some convincing evidence that depression, especially the bipolar sort that I have, is inherited via the genes, and there’s also speculation that mothers who are depressed during pregnancy may pass those dark dogs on to their offspring as the mother’s stress hormones, which accompany melancholy, seep into the body of her unborn baby and cause a second syndrome.
At the age of ten I started psychotherapy with a very tall woman named Dr Sugarman. This was because by year five I’d become so bereft and terrified that I skipped school most days. I lived with a horror of many things, most especially the supermarket with its clean, antiseptic aisles and bloody meats packaged in parts – here a thigh, there a breast. The chicken parts appeared to swim in anaemic-looking blood and the butcher waved a blade, his apron flecked with scarlet, his wares spread out in display cases on beds of crushed ice, long fillets of pale fish and, in a case of water, living lobsters with black blind eyes, their antennae wavering as they crawled over one another’s carapaces.
For me, ever since I was young (how young, and when, and why, I don’t know), the world has been a weird place, a surprisingly surreal stage on which little monkeys and handless men dance to jigs no one wants to hear. Chequerboard floors rolled out endlessly and sometimes my mother slapped me so hard her hand left an imprint on my face. Was this nature or nurture, the depression that came to claim me completely by the time I was thirteen and old enough to act out, which I did by using my mother’s razor to rend my skin, watching intently as blood bubbled up and astonished at how easy it was to do this?
By then Dr Sugarman was a thing of the past, but when the school saw my skin and the craziness of the cuts they persuaded my mother to find me a second psychiatrist. Dr Miriam Mazor was a psychiatrist in her mid-thirties who lived in the Orthodox Jewish section of Brookline, Massachusetts. I went to her office three times a week after school, transporting myself there by tram. I would drop my dime into the collection box and step down the stairs into a world where men wore what looked like black top hats and had coils of curls swinging at the sides of their faces, which were often buried in books they read even as they walked. Springs and summers the doors to the synagogues were often open and the haunting sound of Hebrew chanting often spilled into the street while I made my way to my doctor’s office. Behind the large plate glass windows of kosher delicatessens and shops, bakers kneaded their dough, stretching and softening it, shaping it, finally, into bundles they slathered with vegetable fat before sliding them into brick ovens.
I saw Dr Miriam Mazor from the time I was thirteen until I was in my mid-twenties, more than a decade of thrice-weekly appointments, and yet I cannot recall much of what we discussed. What mattered was not what I said or what she said. What mattered was that something was said, that conversation coursed between us like a river beneath whose currents ran a clear assumption: that whatever was wrong with me could be fixed by language, if only because it had been caused by language, or a lack thereof, words of love or affection never uttered in my household growing up. The idea of a chemical depression back then, in the mid-1970s, was almost unheard of among people with no special medical expertise. Nor was I in psychoanalysis. There was no leather divan on which I could fling myself down to free-associate. I sat upright in a chair and often looked at the pattern in her rug, seeing in it, on some days, friendly faces, and on other days sneers and stares.
While we rarely discussed the underlying assumptions of treatment, it became terrifically clear to both of us, as suggested by Dr Mazor, that I had repressed feelings, probably of anger, towards my less-than-nurturing mother, and that if I could just get in touch with these feelings and spit them out on to Dr Mazor’s rug or into her hands, I’d be cured of the dark mood, of my fear of the terrible white night-time snow and the monkey man, of the sensation of limblessness. Thus I spent a lot of time during my fifty-minute sessions trying in vain to locate certain feelings, trying to talk myself into rage, for instance, when all I felt was dead. Meanwhile, my symptoms kept getting worse and worse throughout my adolescence. The cutting continued, each slice a little closer to the tributaries of veins that forked at the rim of my wrist, and by the time I was eighteen I was swallowing promethazine and pseudoephedrine and afterwards having charcoal shoved down my throat in the A&E department as I retched into a blue bowl.
The 1970s passed; I went to university and acquired an eating disorder, bingeing and purging, the bones of my body now very visible. It was 1981, 1982, 1983 and I was vomiting into bin bags and then tossing the whole hot mess into skips at the fringes of the campus. I would force the food back up with my fingers or, when that failed to work, shove the handles of hairbrushes down my throat, scraping the tender lining of the oesophagus, until one day my throat started to swell with infection. My whole neck bulged. Swallowing was excruciating and it was hard to get my breath. I wound up in the campus infirmary, drinking the thick pink of liquid penicillin from a tiny cup four times a day. The medicine coated my blistered throat as my fever soared and I saw winged things and snowflakes, huge wheels of white lace falling all around me.
All through these years I had continued to cut, and to bleed out my arms even as my menstrual period dried up and went away. Three times a week I still saw Dr Mazor, who had witnessed my weight fall, my bones jut out, my throat collapse and then puff. When I was well enough to make my way from the infirmary back to her Brookline office, something shifted in the treatment. This was a time when electric typewriters were being replaced by primitive computers and daisy wheel printers that clattered as they worked. The World Wide Web was less than a decade away and some especially savvy people even knew how to email. Computer ‘memory’ could be stored on a chip. Humans, too, began to be viewed in machine-like terms. Our axons and dendrites were visible now on imaging devices, and the brain became a compendium of pieces and parts, of bleeps and flashes and chemicals we could replicate in test tubes.
This did not mean there was a quick fix for me, but I clearly recall the first session after my stint in the infirmary, a Friday afternoon. Dr Mazor watched me with an attentiveness – a thoughtfulness – that made me fidget in my seat. Now in her forties, she wore bifocals. Her eyes were large and luminous, a velvet brown rimmed with a fringe of thick black lashes. With her hands folded in a bundle on her lap, she sat at her desk and studied me for quite some time, the silence in the room growing denser by the moment, until at last she sighed and said, ‘I’ve been thinking you might respond well to drug treatment.’
It was a statement as banal as could possibly be today, when we chat about our chemical imbalances, our low serotonin, our site-specific drugs, all with the ease of people knocking back a few beers at the bar. But it wasn’t always this way. Even with the advances of chlorpromazine and lithium and other psychotropic drugs, during the decade I was in psychotherapy the prevailing belief among many psychiatrists was still that language and the insights it spawned could be profoundly curative. Psychiatric medication, to my mind and the minds of most of the general public, was for madmen and women locked up behind metal bars in stone-cold asyl
ums set high up on hills.
‘Imipramine,’ Dr Mazor continued. ‘I think you might respond well to it.’
‘Imipra what?’ I said, encircling my knobby wrist with my fingers and feeling the throb of my pulse patter away.
‘Imipramine,’ she repeated. ‘An antidepressant.’
It was 1982 and I had no idea what an antidepressant was. I also had a firm-as-fact notion that taking anything that might tamper with my brain seemed sacrilegious, seemed extreme beyond language. I resisted the argot itself, unable, literally, even to pronounce this drug’s name, while on a deeper level, I also resisted the idea that my problem was biological as opposed to psychological. For me it was rooted in deficiencies of nurture as opposed to nature. I believed, furthermore, that there was a deep division between psyche (the psychological) and brain (the biological), in which case cutting corners by taking drugs was tantamount to sin, a dangerous shortcut that eclipsed the insight of language and embraced quick chemistry in its stead. As I sat there, profoundly ashamed, thrashing this out in my nineteen-year-old mind, observing the rug as if it held the answer, my psychiatrist continued to study me as though I were a spectacle, her gaze sad, suggesting that we had come to the end of some road, that I had failed the calling of psychodynamic psychotherapy, in which I had placed all my faith and effort, arriving three times a week for half a dozen years so far and each session trying to fashion feelings my doctor would see as correct, obedient, cathartic.
At last, having no response from me, Dr Mazor picked up her pen and wrote me a prescription, which I took tentatively. I exited her office and walked out on to the street. It was mid-December and lights festooned the bushes and trees lining her lane. My breath was visible in the frosty air, each exhale a small ghost birthed from my body, floating by my face briefly before atomising into the wintry blue. There it was – my breath – unable to be captured. It was made of oxygen and carbon and could be described, even drawn in molecular terms, but that didn’t alter the fact that it drifted from my mouth and vaporised before I could catch it in my ready hands. When I was nineteen, all the ways that we did not, and could not, yield to science’s scalpel soothed me. I didn’t necessarily believe in ghosts or God, but I firmly believed the human mind was bigger than the brain that boxed it, that we would never be able to fully articulate that mass of corrugated matter because, in order to do so, we would need to rise above it with a keener, purer intelligence than we humans currently possessed. And that was as it should be. Human misery and mirth, I was convinced, had at least one limb in some heavenly sphere beyond language and touch.
Standing at the end of Dr Mazor’s street, several streets from the tram that would lead me to the train that would deposit me back on my university campus, I took the prescription from my coat pocket and tried to interpret the cryptic writing. I folded the piece of paper into the shape of a tiny plane and then put it on my palm and waited for the wind to take it. The wind did not come. When nothing happened I refolded the script into the shape of a swan – origami was something I was good at – and again placed it on my palm, an offering to the sky, but the bird would not fly. Snow began to fall, little icy flecks of it, almost like sleet. I opened up the bird and smoothed the paper flat, the creases still visible, then folded it into a small cube I put back into my pocket. Darkness was falling fast and the store windows glowed, huge orange squares of ambient light. The baker was making his Jewish bread known as challah, plaiting the dough with dusty expert hands.
The apothecary’s door jingled when I opened it. Down the end of a long aisle stood the pharmacist himself, in his white coat, counting tablets that seemed to glow preternaturally in the winter’s night. The shop must have been bright but in my memory the aisles are dim. Behind me, out the shop window, the snow had started in earnest, the tiny icy flecks having turned into fat flakes spinning lazily through the air and sticking to the streets, which were whitening fast.
‘Can I help you?’ the pharmacist asked and I said nothing, just reached for the cube in my pocket and tried to flatten it out on the counter between us. The pharmacist took the prescription and, glancing down through his bifocals, read it, then gave me a long look. I shrugged. ‘Give me ten minutes,’ he said, and that was that. In ten quick minutes I had sixty red tablets that were smaller than pick-and-mix sweeties, each of them with tiny indecipherable writing across their equators.
Back in my dorm room, right before bed, I took two, per the instructions on the bottle. I was unprepared for the effect. Sleep hit me like a wall of water. I didn’t merely go to bed. I fell into it, on to it, through it, under it, pounding away the hours in a deep slumber of densest black. When my alarm went off the next morning, I had to struggle up from unfathomable depths just to find the snooze button and then went down again, down and down to the bottom of some private sea.
Finding the Drug
It was March 1949 when 23-year-old Alan Broadhurst disembarked at a sagging train station in Rhodes, England, a small mill town outside Manchester that one imagines as a sooty place with crooked streets and a perpetual drizzle glazing everything with a dull gleam. The idealistic Broadhurst had come at the behest of the Swiss pharmaceutical firm Geigy, which had hired him to help establish its British branch. Broadhurst walked the town’s cobblestone pavements, looking for the company he had agreed to join, and finally found it, not in some impressive high-rise or esteemed brick structure with ivy lapping the sides, but in a tiny house with a film of filth over the windows and sunken stairs that increased his alarm with each step he took, until at last he stood before a door.
The interior of the Geigy office was cluttered. Broadhurst walked through tiny tilted rooms with cardboard boxes heaped everywhere and folders scattered on metal desks. In the laboratory, which was crammed into a back lavatory, test tubes lined the sink and the shower stall. It is difficult to imagine this abode as one that could give birth to the tricyclics in general and to imipramine in particular – and indeed the actual work of invention would be done back in Geigy’s Basel office – but it was here, with Broadhurst and other colleagues, that imipramine, a drug that psychiatry hails as its first antidepressant, and one that would help hundreds of thousands, perhaps millions, of people to overcome depression, got its notional start.
Broadhurst would certainly have known about the famous experiment performed by the German chemist Friedrich Wöhler, in 1828, in which Wöhler successfully demonstrated that urea, a substance found in mammalian urine, could be synthesised in a laboratory, the first evidence that the human body and its biological substrates could be made by man. In hindsight, according to David Healy, this was the first time we were confronted with the truth that there is ‘nothing intrinsically special about human life.’ Contrary to what many scientists had previously believed, the synthesising of urea revealed that ‘making life did not require a divine or other mysterious intervention.’ Had I known, at the age of nineteen, about Wöhler’s experiment, perhaps I would have been less ambivalent about seeing my disorder as biochemical. Whereas I, along with millions of others in both the nineteenth and twentieth centuries, saw human life as a transcendent, even spiritual phenomenon, firmly separated from test tubes and Bunsen burners, Broadhurst was prepared to use just this kind of equipment to make some new drug, in some new way.
But where to begin? For whom would this drug be intended? Broadhurst started by looking at the antihistamines. He and the executives at Geigy were aware of the exciting new developments at Rhône-Poulenc, particularly the phenothiazine nucleus that lay at the centre of the dye methylene blue. What would emerge in the end is imipramine, called a tricyclic because of its three-ringed molecular structure. Like its cousin chlorpromazine, this drug, the first antidepressant, was also developed from a dye, not methylene blue but summer blue, sometimes called sky blue. In the years before its psychiatric properties were understood, however, Geigy was hoping merely to discover another medication that could perhaps be employed in heart surgery, and as a sedative or analgesic, mu
ch as promazine (the precursor of chlorpromazine) initially had been. But they would have to do it without using the phenothiazine nucleus, which Rhône-Poulenc had been working from. Broadhurst wondered whether there might be more to mine from antihistamines, while at the same time he and Geigy wanted to avoid creating what the field calls a ‘me too’ concoction, a drug that is basically the same as its source with maybe a few side molecules tweaked. (An example would be valproate semisodium, the anticonvulsant that I discussed in the last chapter, which was the same as its predecessor, valproate, with the exception of a single ion.) Taking antihistamines and the desire to create a heterocyclic compound as their starting point, Broadhurst and his team wanted to create a truly unique drug.
In general, psychiatric drug development in the middle of the last century worked this way, and still to a considerable degree works this way today, with the drug preceding the knowledge of the exact disease it will treat. Drug research proceeds by serendipity, by hunches and building discoveries deductively, without a definite goal. Pieces of information drift in and are sifted and sorted, suggesting the next step, until at last a novel compound emerges, although what it might treat and whom it might help are questions to which the answers are still often unknown.
Remember, chlorpromazine started its life as an anaesthetic potentiator, lauded for its mood-altering properties, its ability to cool patients down, to slow the blood supply to the limbs and, in so doing, to make surgery easier to perform. Chlorpromazine as we know it was born not when chemists Paul Charpentier and Simone Courvoisier chlorinated the antihistamine promazine, but rather before that, when Henri Laborit observed the indifference in his surgery patients who were under the influence of promethazine, a similar antihistamine, and thus suggested it for psychiatric use. The drug came into being because someone saw it in a new way and dared to dream about uses that were not immediately obvious. In some senses all drug discovery, while clearly the work of scientists, is really done deep in dream, in vision, and proceeds more like the making of a novel than the compounding of chemicals for a clear purpose.
The Drugs That Changed Our Minds Page 13
