I have had my fair share of psychiatric difficulties, and at times, in depressions too deep for words, I have seen my world drained of colour, the trees flat and stark, a strange black hat rolling across a midnight road. This is as close as I have ever come to madness, too close for comfort but not nearly close enough to really comprehend. Thus, meandering around that old asylum which was emptied during deinstitutionalisation, I look for clues. I touch the suckers that were once attached to scalps to deliver current straight through the cranium, causing the patient’s brain to seize again, and then again. I riffle through dusty tomes in a library where stacks of books are home to beetles and other bugs. I watch a spider spin her lair in a patient’s long-abandoned room, and remember the experiment in which spiders were dosed with hallucinogens and, under their influence, made ever more complex and wild webs, each one a work of silk and art, impermanent and impossible to replicate. I put my hand on the flat pillows on each of the dusty beds and try to conjure the hurting heads that each night rested here, with their squalls mixed up in the sweaty sheets, the blue dreams that might lie ahead as yet unknown.
In room number 332, on the second floor, the glass in the window is crazed with cracks, and the last light is leaving now, the sun visible only as an orange seam at the very edge of a summertime sky. Below me on the street walk people in sandals and skirts, oblivious to the huge history this asylum holds. I lift up the pillow on the bed and beneath it find a scrap of paper so thin and soft my touch almost turns it to talc. Written on the paper, a single word: HELP. Is it the delusion of a patient who believed an alien was lifting him up towards a cruel and cryptic planet? Or a simple statement made once chlorpromazine finally cleared a confused mind, emptying its screams and shards? Impossible to know. HELP. A sign of illness or recovery? HELP. Something every one of us wants to have, in whatever fashion it arrives. I think about bringing the scrap back home with me, but it seems wrong to remove it from its intended place beneath the pillow, and so I put it back and cover it up, as it was, and will continue to be, until the wrecking ball brings this edifice down. In the place where this building now stands – what will come? I imagine a field of flowers, a pretty park, a deep pond in which fish float like lamps beneath the clear surface. A wishing pond that collects the pennies of those who close their eyes and toss.
If I had one wish to make, it might be for a perfect preparation, an ultimate drug that works according to the precise needs of its imbiber, eradicating depression, turning mania into happiness, schizophrenia into simple creativity. I’d wish for a blue concoction that could give birth to something like serenity for everyone who wants it – and who would not? I’d wish for a drug with no side effects except supreme mental health, a robust brain packed with well-proportioned neurons all speaking smoothly to one another and, under the influence of this ultimate recipe, a world brimming with good, with great intentions and a happily-ever-after kind of ending. But that is not what we have here. We have, instead, a single word –HELP – which signals something ambiguous at best. Was the juggler helped for his whole lifetime? Or did side effects make the medication impossible for him? What happened to the barber from Lyon? For how long was he helped before the strange and scary motor movements came to claim him? Would we ever have an antipsychotic that removes symptoms without causing crippling side effects? Chlorpromazine brought psychiatry very far, but in the end, not far enough, not nearly.
2
Lithium
A Salted Stone
An Ancient Element
Unlike other drugs, lithium is older than we are, born in the big blast that gave our universe its considerable kick start. An element found in meteors and stars and space, lithium appeared within twenty minutes of our universe’s initial explosion. The element is so light that it atomises on contact with air, bursting into crimson flames. It was first discovered on Earth more than two centuries ago, in 1800, by Brazilian geologist José Bonifácio de Andrada e Silva, who was working in an iron ore mine on Utö, a rocky island off the coast of Sweden rich in minerals, including a new one that Andrada called petalite. If you were to travel to Utö today, chances are fair that you, too, might come across petalite – crenellated and raspy to the touch. Scientists in the nineteenth century who later studied petalite found that it contained not only silica, alumina, manganese and water – elements embedded in other rocks as well – but also a small amount of an odd salt no one had ever seen before. Curious, investigators passed an electric current through the salt, which melted with a red flash and a crackle. The salt came to be called lithion, after the Greek word for ‘stone’.
The Uric Acid Diathesis
The lightest of all the metals, grand and timeless, an ingredient in sun and stars, meteors and comets, lithium came to be used for mere mankind. Though an unstable element itself, it has the ability, perhaps ironically, to confer on its users a kind of quiet calm. But in the nineteenth century, long before the drug was commonly applied for psychiatric purposes, lithium came to be prized for its ability to alkalinise excessively acidic urine. According to the doctors of yesteryear, uric acid was responsible for all manner of serious problems, not only gout, which in fact does arise from too much uric acid in the joints, but also bladder stones and renal stones, feelings of faintness, migraine headaches, instability of mood, low tone, lack of appetite, swathes of sadness, surpluses of delight, irritable excitement, epileptic fits, tumours and tics and flus and fevers of every sort. Many doctors further believed that lithium, this strange white salt, could eliminate uric acid, meaning that lithium was therefore seen as a salve for practically every illness.
But because the vast majority of diseases and disorders are not, in fact, caused by or even in any way related to high uric acid or to gout, it stands to reason that most patients treated with lithium in the nineteenth century and beyond did not get well. It is true that lithium salts make urine more alkaline, but that’s irrelevant if one is suffering from, say, diabetes, a disorder rooted in insulin resistance, and one that would therefore not have responded to a change in urine metabolism in any way. And yet treatment with lithium salts for all kinds of physical and mental complaints continued well into the twentieth century, and did not disappear from texts like The Merck Index and The Pharmacopoeia until as late as 1940. In other words, a treatment that we now know to have had no effect on almost all patient complaints, a treatment that failed time and time again, nevertheless lived a long and healthy life. Why, when the diabetic remained diabetic even after lithium administration, or when the migraine sufferer still had hammers in his head, did these mounting failures not put an end to what seems, in our day and age, to be an overly simplistic if not outright foolish notion, the linking of complex and varied diseases to a simple stream of urine and the acid found within it?
There is one possible explanation for the long and vital life of what has come to be called the uric acid diathesis: the treatment – administration of lithium salts – made patients feel good. Even if their bodies were still suffering, the patients’ minds were nevertheless soothed by what we now know is a potent psychoactive drug. Researchers, for instance, have measured the amount of naturally occurring lithium in tap water in twenty-seven counties in Texas and found a negative association between lithium levels in the water and suicide rates, meaning the higher the level of lithium in the water, the lower the suicide rate. Similar studies have been carried out elsewhere, such as in Japan, where researchers studied the tap water of eighteen districts of the Oita Prefecture and noted that even very low levels of lithium in the water supply may be protective against suicide, and by extension against depression as well. Until 1948, the lemon–lime flavoured soft drink 7UP, popular in the United States, contained lithium citrate, a little boost contained in a drink. F. Neil Johnson, the author of a history of lithium therapy, published a letter he received from an unnamed correspondent whose mother, a depressive, was prescribed lithium for something unrelated, and who recalled its effect on her:
I was born
in 1917 and soon afterwards my mother . . . suffered a depressive illness for which she was admitted to [the hospital] . . . When I was quite a young child she suffered from ‘gravel’ for which she was prescribed lithium citrate and this she took for almost all the rest of her life . . . Aged 73 she began to be incontinent . . . and at operation the urologist removed a pear-sized stone from her bladder . . . Post-operatively she discontinued the lithium citrate as there seemed no need for it. Six months later . . . she suddenly broke down with agitated depression from which she suffered for seven and a half years until her death.
The medicinal use of lithium was first discovered by Alexander Ure, a Scottish surgeon, who gave a talk in 1843 about how lithium, ‘a substance of which no therapeutic action has been heretofore made’, could dissolve bladder stones. Ure went on to show his audience an actual stone that had significantly shrunk after immersion in a lithium bath. Sir Alfred Garrod, at one point Queen Victoria’s doctor, repeated Ure’s experiment but this time on gout deposits rather than bladder stones. Garrod reasoned, correctly, that gout was caused by excess uric acid in the body, and it was he who went on to promulgate the theory that many other diseases could also stem from this excess, thereby conceiving of the uric acid diathesis.
Lithium Spas
Lithium was usually administered to patients in a carbonate solution until, in the mid-nineteenth century, spas and springs became popular. Various regions in England and continental Europe boasted natural mineral springs said to contain high concentrates of lithium, and doctors would ‘prescribe’ a dip in these springs to their ailing patients, who were usually well-to-do and willing to travel, sometimes hundreds of miles. Entrepreneurs took note. By the late nineteenth century, hydropathic establishments were proliferating. At the same time, companies selling potable lithium water in bottles made of clear green glass, with pop-off tin tops, flourished both in the United States and abroad as well-known doctors endorsed lithium, making public statements about the benefits one could derive from the spas and springs and drinks. The list of ailments that the waters could putatively cure included prostate enlargements, gonorrhoea, cystitis, portal vein congestion, jaundice, hepatic diabetes, obesity and atonic dyspepsia, to name just a few. So many famous doctors chimed in that a powerful consensus formed about how potent these waters really were, with medical journals publishing report after report of hydro successes.
But as the coffers of the spa resorts and the bottled-lithium makers rapidly filled, some scientists began to question just what these waters were made of. The first sceptical report, published in 1889, came from a chemist who announced that the lithium content of commercially available spring water was in fact much lower than the label advertised. Similar reports followed, including an 1896 claim that an analysis of three of the most widely consumed brands of lithium waters had found absolutely no lithium in two of them. It took a while, but by 1914 a lawsuit again Buffalo Lithia Water finally reached the Supreme Court of the District of Columbia, which rendered this unequivocal opinion: ‘For a person to obtain a therapeutic dose of lithium by drinking Buffalo Lithia Water he would have to drink from one hundred and fifty thousand to two hundred and twenty-five thousand gallons of water per day . . . Potomac River water contains five times as much lithium per gallon as the water in controversy.’
Unsurprisingly, the happy hydro industry went south, and by the early 1920s bottled lithium water was no longer widely available. With it, one might surmise, went the uric acid diathesis. Instead, although the credibility of the hydropathic establishment went to waste, the uric acid diathesis stayed as strong as ever. In place of bottled water, lithium tablets were brought to market, which allowed any sufferer to make his or her own liquid concoction and control the concentration at the same time.
Lithium for Depression
While, in the nineteenth century, lithium was used primarily to treat a variety of illnesses beyond the brain, some doctors of the time did note the drug’s efficacy in reversing states of depression or despair, as had happened with the dye methylene blue. In 1888, British doctor Alexander Haig, following a series of experiments on both himself and others, suggested that high uric acid was correlated with certain sorts of depression, and that any drug that lowered uric acid levels, as lithium did, would be a beneficial psychiatric treatment. Two years later Carl Lange, a Danish internist familiar with Haig’s work, published a description of what he called ‘periodical depression’, a psychological state that many of his patients seemed to suffer from. This sort of depression wafted like the wind; it came and then it went, but it always came back again. Lange was the first to use lithium prophylactically – and for a psychiatric condition. Around the same time, John Aulde, a Philadelphia doctor, also began to give it to his patients prior to their plunges and advised them to take it continually, in this way warding off ‘the old trouble coming back’.
The prophylactic use of lithium in the treatment of depression would emerge again in the mid-to late twentieth century as a major and contentious issue, but at the time of the article in which Lange described his treatment protocol, no one took much notice, except perhaps his brother Fritz, who oversaw the Danish asylum at Middelfart. Fritz Lange followed his brother’s lead by giving lithium to several hundred patients suffering from depression, in doses similar to what we would prescribe today. In 1894 Fritz published a book stating that the benefits of lithium treatment for depressives appeared just a few days after commencing the drug. Not as quickly as chlorpromazine would eventually act on psychotic patients, but swifter and more effective than any other medication then available.
The Collapse of the Uric Acid Diathesis
Given the prevalence of lithium and the iron grip of the theoretical rationale that underscored its use, how and why did the uric acid diathesis ever die out? Thomas Kuhn, writing about paradigm shifts in science in the twentieth century, describes how one set of beliefs gives way to another, seemingly more relevant set, and thus the scientific field progresses in fits and starts. But when it came to lithium and the uric acid diathesis, there was no single paradigm that displaced what was by all accounts a deep belief. Instead there was a series of pivotal discoveries – antibiotics, anaesthesia and the resultant advancement of surgery among them – that one might say eventually, and incrementally, stole the show.
The 1930s, for instance, saw the introduction of sulphonamides, a group of bacteria-inhibiting drugs, followed a decade later by the mass production of penicillin, which made its entry into medicine with a dramatic flourish. In 1942, in Boston, Massachusetts, a packed nightclub called the Cocoanut Grove caught fire, with people trapped in the flames and unable to escape. Nearly five hundred died, and hundreds more suffered burns over much of their bodies, their skin crisped and blackened. Ambulance after ambulance rushed the charred survivors to area hospitals. Inevitably, infection started to set in. Antibiotics were still in trial and thus not available, but Massachusetts General Hospital made a special plea to the pharmaceutical company Merck, located in New Jersey, to release some of the product to its doctors as soon as possible. Merck responded by sending 32 litres (7 gallons) of antibiotic ampules packed in ice, carried in a car flanked by policemen on motorcycles, the whole caravan making its way across one state and into another in a grand and solemn procession. Once the yet-to-be-tested antibiotic arrived at the hospital, the doctors broke open the ampules and delivered this new medicine to their burn victims, whose wounds by now were suppurating, festering with pus. Within hours these wounds began to clear up, and within days, when the bandages were unwrapped, newborn skin, as pink as the inner lip, was visible, the burns healing rather than rotting. The new drug, penicillin, a breakthrough miracle, was celebrated in print, on the radio and in conversations across the country.
But penicillin wasn’t the one thing that eradicated the uric acid diathesis. The theory had been steadily fading for years, diminished by the arrival of antibiotics, along with the emergence of advanced anaesthetics, the development of steroi
ds and diuretics, and anti-hypertensives and hypoglycaemic agents, many of which were mass-produced as chemical companies turned into pharmaceutical houses with corporate capitalistic agendas that shifted the emphasis away from the dinosaur days when urine ruled the roost.
Eventually the uric acid diathesis fell out of fashion, like cargo trousers and lace curtains. In an era that witnessed the first successful heart transplant, the notion that the whole of human pain could be explained by your urine had been rendered quaint. Into the vacuum created by this theory’s exit rushed all manner of new inventions and discoveries, not only in medicine but also in astrophysics, in genetics, in biology. The world widened. The moon moved closer as NASA developed rocket fuel and dreamed of the travel that would one day come. We learned that stars have life cycles, that they begin as disorganised gasses and end as black holes, fathomless infinite pits of emptiness that are enough to make human depression look like a playdate in the park. Can it really be a surprise, then, that the diathesis slipped away, trampled by technology which was, every day, exceeding even itself in its range and reach?
The twentieth century left behind the diathesis and its sidekick, lithium, a little old salt from an old wives’ tale that we once believed might help us, even heal us. Lithium slipped into the sea of old ideas, washed up on a beach littered with rocks and other discards. By the 1940s you couldn’t get your hands on a lithium tablet if you tried. The drug was gone, long gone, except here and there, in preparations no one had ever heard of and certainly had never used.
The Drugs That Changed Our Minds Page 7
