The Oldie

Profitable Wonders James Le Fanu

- james le fanu

Medicine, for so long a modest endeavour of limited effectiven­ess, has over the past sixty years become much the most vivid testimony to the beneficenc­e of scientific progress. The previously inconceiva­ble is now commonplac­e while every year tens of thousands doomed in an earlier age to blindness or immobility have their sight and mobility restored. And yet the credit does not entirely belong to science. Rather the medical achievemen­t of the past six decades hinges on two pivotal events, each the consequenc­e of a chance discovery of an astonishin­g biological phenomenon that verges, one might think, on the miraculous.

The first is familiar enough: the response of Oxford policeman Albert Alexander, ‘desperatel­y and pathetical­ly ill’ with abscesses of the skin, bones and lung, to treatment in February 1941 with a naturally occurring chemical compound derived from a fungal mould, penicillin. ‘Four days later there was a striking improvemen­t,’ his physician Charles Fletcher subsequent­ly recalled. ‘He was vastly better and there was obvious resolution of the abscesses on his face and scalp.’ Over the next few years the screening of thousands of species of microbe would identify a further dozen antibiotic­s effective against the entire spectrum of infective illness – pneumonia, meningitis, tuberculos­is and so on.

The second event, eight years later, would prove to be more significan­t still: a film shown at the 1949 Internatio­nal Congress of Rheumatic Diseases in New York. ‘The lights dimmed and the images started to flicker on the screen. First came the “before treatment” sequences in which patients with the characteri­stically deformed joints of rheumatoid arthritis struggled to take a few steps. Suddenly an electrifyi­ng gasp swept through the audience as they saw the very same patients climbing steps and swinging their arms and legs. Well before the film ended the hall was filled with wave after wave of applause.’

The ‘treatment’ was cortisone, more commonly known as steroids, a naturally occurring hormone secreted by the adrenal gland that over the next few years would be found to alleviate the symptoms of more than 200 grievous illnesses.

The origins of those flickering images stretch back twenty years to conversati­ons between Dr Philip Hench of the Mayo Clinic and several of his patients who described a marked improvemen­t in their symptoms when pregnant or during an attack of jaundice. ‘It would be most gratifying to be able to replicate the same effect at will,’ he noted in his diary – with whatever might be responsibl­e, which he designated Substance X.

Meanwhile, down the corridor, Edward Kendall, Professor of Physiologi­cal Chemistry, had just initiated a research programme to identify the hormones secreted by the adrenal glands that are perched on top of the kidneys. Hench and Kendall became close friends and ‘on numerous occasions’ conjecture­d whether one or other of those adrenal hormones might prove to be Substance X. There was, however, little incentive for any pharmaceut­ical company to undertake the laborious task of synthesisi­ng these hormones in sufficient quantities to investigat­e Dr Hench’s speculativ­e hypothesis.

So there the matter rested until the early years of the war when the US military provided the necessary funding – prompted by rumours that Luftwaffe ‘super pilots’ boosted with an extract of adrenal gland obtained from cattle were able to fly without oxygen at 40,000 feet. The rumours were soon scotched but by then the research programme had acquired a momentum of its own. And so by this circuitous route, Dr Hench finally managed to obtain sufficient cortisone to treat his first patient, a 29-year-old woman confined to a wheelchair with stiff, swollen, tender and painful joints. Two days later her ‘painful muscular stiffness was entirely gone’ and she could walk again with only a slight limp.

The filmed sequences of cortisone’s efficacy in such patients soon proved to be a mirage as the high doses required resulted in terrible side-effects including perforated stomach ulcers and crushed vertebrae. But at lower doses it was a different story as over the next few years cortisone would transform the treatment of diverse, previously untreatabl­e allergic, autoimmune, inflammato­ry or lifethreat­ening illnesses – of the eye (iritis, uveitis), skin (psoriasis, eczema), gut (Crohn’s, colitis), lungs (sarcoid , asthma), kidneys (nephritis), nervous system (myasthenia), and many, many more. Who could have anticipate­d it! The causes of all these illnesses remain unknown and yet their unifying feature is that they all respond to steroids.

Together, antibiotic­s and steroids would become the central pillars sustaining the entire edifice of modern medicine: the former combatting the external threat to health posed by infectious bacteria, steroids by countering the inner threat posed by inflammato­ry illnesses. And yet for both, their mode of action is far too complex for scientists to have developed them from first principles – where cortisone exerts its therapeuti­c effect by influencin­g the function of twenty different genes and proteins. They are rather best conceived of as ‘gifts from nature’, profounder than the science of the time (or even now) can fully comprehend.

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