The Rise and Fall of Modern Medicine (12 page)

In 1950 the drug company Rhône-Poulenc, alerted to the possibility that promethazine might be useful in the treatment of psychiatric disorders, initiated a major research programme. The group of drugs to which promethazine belongs are known as the phenothiazines, and Paul Charpentier, the company's chief chemist, set out to synthesise as many variations of its molecular structure as possible in the hope of finding one that had the same, or greater, ability to create a sense of ‘euphoric quietude'. The compounds he synthesised were then tested on rats that had learned to climb a rope to avoid an electric shock signalled by the ringing of a bell. One compound in particular, chlorpromazine, left the rats unmoved when the bell was rung.
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Hearing of this, Jean Delay and Pierre Deniker, two leading Parisian psychiatrists, were the first to treat a schizophrenic patient, a 57-year-old labourer, Giovanni A., who had been admitted to hospital for ‘making improvised speeches in cafés, becoming involved in fights with strangers, and walking around the street with a pot of flowers on his head proclaiming his love
of liberty'. After nine days on chlorpromazine he was able to have a normal conversation and after three weeks he was ready to be discharged. This was much better, much quicker, much safer than any response that had been obtained by the physical therapies such as ECT and insulin coma.
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The news then spread to Britain, where Joel Elkes at Birmingham's Winson Green Hospital – as already described – started to give chlorpromazine to the ‘burned-out' cases on the long-stay wards on whom at the time no treatment availed.

Chlorpromazine was the first swallow, and in rapid succession over the next few years four other major groups of drugs applicable to the whole spectrum of psychiatric illness – depression, mania and anxiety states – were introduced in exactly the same way, through a combination of chance, shrewd observation and the screening of chemical compounds. Nor indeed could it have been otherwise, for at the time there was simply no perception of how the brain functioned, nor even an inkling of what abnormalities lay behind mental illness and consequently no idea of how these drugs – which appeared to work so well – worked at all.
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Thus in 1955 the Parisian psychiatrists Delay and Deniker, when summarising their experience of treating 1,000 patients, clearly had not the slightest idea of its mode of action. They suggested variously that it might stimulate the sympathetic nervous system, or reduce oxygen metabolism in the brain, or alter the pattern of the brain waves in the same way that occurs during sleep.
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It was not until 1963 – eleven years after Giovanni A. had first been given chlorpromazine – that it was shown to interfere with the action of the neurotransmitter dopamine. It was thus only natural to infer that the underlying problem in patients with schizophrenia was a neurochemical one. Perhaps their brain contained too much dopamine, or
dopamine in the wrong place, or the receptors to dopamine in the brain were oversensitive. But this obvious explanation turned out to be incorrect. Neither autopsy studies nor sophisticated scanning techniques have been able to identify or demonstrate any single abnormality of dopamine biochemistry in the brain of schizophrenics (or indeed that of any of the other neurotransmitters).

The history of psychiatry in the post-war years exemplifies, in a very dramatic form, how the growth of the possibilities of treating illness could occur in the absence of any substantial understanding of the nature of the problem being treated, or indeed why the treatment worked.
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Human intelligence – such as Henri Laborit's acute perception of the euphoric quietude induced by promethazine – played a role. So of course does ‘science', in particular neurochemistry and pharmacology. Nonetheless we are dealing with the triumph of empiricism, where everything else is a mystery. Why should a compound that blocks histamine in the tissues of the body also interfere with an entirely different chemical – dopamine – in the brain in a way that alleviates symptoms of schizophrenia? What is schizophrenia? What is its cause? The map of mental illness, like that of Africa before the arrival of the Victorian explorers, remains a blank.

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An account of the many other important therapeutic innovations in the treatment of psychiatric illness can be found in Appendix II.

T
here are many reasons why people may end up on an intensivecare unit, most frequently following major operations, but also after head injury, septicaemia or respiratory failure from paralysis of the chest muscles. At any one time a patient can be hitched up to a dozen or more pieces of equipment: heart monitor, machines to measure the concentration of gases in the blood and the blood pressure, a pacemaker, a dialysis machine. It all looks, and is, so impressive that it can be difficult to appreciate that central to all this technological wizardry is just one piece of equipment, the ventilator blowing oxygen into the lungs. Oxygen alone ensures the heart carries on beating, ‘buying time' for tissues to heal and the complications of impaired body function to be attended to. The indispensable role of oxygen in human physiology has been known for the best part of 200 years, but the appreciation of its central role in the survival of the critically ill starts abruptly with the Copenhagen polio epidemic of 1952
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Anyone wandering on to Ward 19 of Copenhagen's Blegdams Hospital in the autumn of 1952 would have been confronted by
an extraordinary sight. In each of the seventy beds arranged in two straight lines lay a child paralysed with polio with a hollow plastic tube inserted into the trachea through a cut in the neck – a tracheostomy – to which was attached another long piece of tubing, at the end of which was a rubber bag. Next to each bed sat a young medical student who, every few seconds, would squeeze the bag, blowing oxygen through the tubing into the child's lungs and then letting go, repeating this action for six hours at a stretch. Four times a day the shift changed and another group of students would arrive on the ward to take over, a routine that continued day in, day out for more than six months. Many quit after a few weeks, suffering from emotional and physical exhaustion, yet according to Ann Isberg, one of the children, ‘it was not a sad time', rather ‘like [during the] war there was a spirit of resistance – everybody was doing their best'. By the time the polio epidemic was over, 1,500 medical students had ‘done their best', squeezing the bag for more than 165,000 hours, as a result of which the mortality rate among the polio victims had fallen from over 90 per cent to 25 per cent. There is really nothing remarkable about this type of treatment – other than its scale. The technique of ventilation by ‘bagging' through a tube had been common practice in operating theatres for many years. Nonetheless, it required a major shift in thinking, precipitated by the catastrophic polio epidemic in Copenhagen in 1952, for ‘assisted ventilation' to become the central feature of the care of the seriously ill.
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The polio virus is ingested in contaminated food or water and absorbed through the gut wall, from where it spreads to paralyse the nerves in the spinal cord that control muscular movement. Most cases arose in the summer, hence its description as ‘the summer plague'. Periodically it flared up to cause a major epidemic whose fearful impact is not difficult to imagine.
One day a child was happy and healthy, the next day he was in bed with a temperature and the day after he would wake up unable to move a limb. With luck the paralysis progressed no further and the child was left with a weak, flaccid and useless limb, but when the virus travelled up the spinal cord to involve the nerves controlling the muscles of respiration, the consequences were dreadful.

In 1931 the Harvard physician Philip Drinker came up with a solution of sorts – the ‘iron lung' that permitted some polio
victims to be kept alive long enough for their nerves to recover and the power of the respiratory muscles to be restored. Within the iron lung a series of valves created a negative pressure that pulled the chest wall outwards, forcing air into the lungs. The pressure in the iron lung then promptly returned to normal and the natural elasticity of the lungs forced air out again.
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There was, however, one group of polio patients for whom not even the iron lung could offer the hope of salvation. In these the virus travelled even further up the spinal cord to involve not just the muscles of respiration but also the muscles at the back of the throat involving swallowing. Their lungs had no protection against the secretions from the mouth; they literally drowned in their own saliva.

In September 1951 the University of Copenhagen hosted the Second International Poliomyelitis Conference. The atmosphere was one of well-justified optimism, as it was attended by both men involved in the development of the soon-to-be-released polio vaccine, Jonas Salk and Albert Sabin. Nonetheless the presence of so many doctors and scientists involved in the treatment of polio meant that almost inevitably some would have been ‘silent' carriers of the polio virus, so they were almost certainly the source of the catastrophic epidemic that engulfed Copenhagen the following year.
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When the epidemic began, Blegdams Hospital was poorly prepared, possessing only one iron-lung-type ventilator and six smaller ones that fitted over the chest. Over the previous decade about ten patients a year had been admitted with polio sufficiently severe to require ventilatory treatment (seventy-six in all), but of these only fifteen had survived – a mortality rate of 80 per cent. But this time the hospital was literally overwhelmed. By the middle of August it was admitting new polio cases at the rate of fifty a day. ‘We were soon faced with the
intolerable dilemma of having to choose which patients to treat with the few respirators at hand and whom not to treat,' recalled Dr H. C. A. Lassen, the hospital's chief physician. Clearly the acquisition of more respirators was not the solution, as even those lucky enough to be treated on the few that were available still died. As Lassen observed, ‘We were forced to seek new ways of ventilating our patients, the need for improvisation became imperative.' Dr Mogens Bjorneboe, another physician at the hospital, suggested they seek the advice of an anaesthetist, Dr Bjorn Ibsen, but Lassen was sceptical, reflecting a prejudice very prevalent at the time that anaesthetists were not really ‘proper doctors' but technicians whose competence did not stretch beyond the operating theatre.
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There were, however, no other suggestions forthcoming, so Ibsen was duly summoned. He was indeed a competent technician but also a profoundly thoughtful man, as the revolutionary solution he proposed required him first to challenge the fundamental tenets of contemporary medical understanding of the precise cause of death in polio.

The final stage of the illness was signalled by a rise in blood pressure, fever and clammy skin, following which death came quite suddenly. This sequence of events had always been attributed to the disease process itself, in which it was believed that the virus had attacked the brain centres involving control of temperature and circulation. Ibsen, after observing patients on the ward, talking to the doctors and visiting the autopsy room, realised this explanation was incorrect. He was struck by the fact that even the children treated with the iron lung ventilator still had such a high mortality rate. These children, he suggested, were dying not from the polio virus's effect on the brain but from inadequate ventilation, and their terminal symptoms – the rise in blood pressure, fever and clammy skin – were caused by
insufficient oxygenation of the brain. His solution was extreme. The iron lung respirators should be dispensed with, and to ensure adequate ventilation all the polio patients should have a tracheostomy, after which they should be ventilated by hand, the only certain way of getting sufficient oxygen into their lungs. This requires some clarification. The iron lung simulated the normal action of the lungs by creating a negative pressure, which expanded the lungs and in doing so drew air down into them. Ibsen's technique, by contrast, involved placing a tube down into the airways through an incision in the trachea, through which it was possible not only to aspirate the secretions that might be blocking the airways but also to blow oxygen into the lungs. The essence of Ibsen's solution, then, was to replace one relatively ineffective method of ventilation with a much more effective one.