File:Ernest Henry Starling (1866-1927).jpg
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Ernest Henry Starling (1866-1927)
Sir Ernest Starling was the Jodrell Professor of Physiology at University College, London.
ABC Radio - Centenary of the word "hormone" (2005)
<html5media>File:Audio - centenary of hormone.mp3</html5media>
|Transcript - Centenary of the word "hormone"
|Robyn Williams: The word 'scientist' is quite a new one. It's been with us for about 170 years, since the master of Trinity College, Cambridge, the Reverend William Hewell, decided that natural philosopher was too broad a term, and science had grown to be extensive enough to deserve a separate label.
Well Jack Carmody is a scientist. I suspect he's also a natural philosopher as well, not to mention an opera critic and, no doubt, a theologian. He was until recently at the University of New South Wales, bravely facing medical students and teaching them neurophysiology and much else. But he's with us today to talk about one word, a scientific word that's having a birthday which he thinks you should help celebrate.
Jack Carmody: Some words give us the impression that they have been with us forever, and this is especially true if they let us feel, when we use them, that we really understand something very important or difficult. Both impressions can be deceptive. We may mis-use those words, and they may actually be far younger than we realise.
Take the word 'hormone'. Can we possibly imagine the 20th century without it? Would people feel impoverished if it did not exist? Yet it really is a rather young word. In fact, we know exactly when it entered the language, and it was on August 5th, 1905, a hundred years ago precisely.
It was in the famous English medical journal The Lancet, in an article by the great scientist Sir Ernest Starling, who was then Jodrell Professor of Physiology at University College, London. Starling's name has been known to generations of medical students, and it rightly still is, for the tremendously important work that he did on the functions of the heart and the blood capillaries. Ironically, he is scarcely remembered for his epoch-making (discovery) of the first definite hormone. Yet not only did he coin that word 'hormone', but, more importantly, by introducing it to the scientific lexicon, he really invented the very concept of endocrinology.
That is the extraordinary power of words: they not only meet an expressive need, they can also point our minds into previously unimagined directions.
So when in 1902 Starling and his brother-in-law William Bayliss discovered that first hormone, and interestingly, it was a product of the gut, called 'secretin', which activates the pancreas. This was by means of a rigorously conceived and brilliantly executed experiment which produced a result that seriously challenged the contemporary orthodoxy of medical science.
It was, indeed, a particularly exciting time in medicine. The intellectual leaders of the profession had learned from Andreas Vesalius, the great 16th century anatomist, and the brilliant 17th century physiologist, William Harvey, that medical science and practice must be based on careful and critically examined observation and experiment. Nevertheless, just like artists and poets, scholars are often inordinately proud of their discoveries and ideas and can resent being questioned. So for about 100 years before Bayliss and Starling's great intellectual challenge, really, ever since Volta and Galvani had discovered what they called 'animal electricity', physiologists had considered the brain as essentially an electrical device and supreme in the body's operations. It is true that, only a few years before the discovery of secretin, the great Spanish microscopist Ramon y Cajal had seriously challenged the fundamental electrical character of the nervous system when he argued that it is composed of individual cells (so how, then, did they communicate with one another?) but the supremacy of the brain seemed unassailable, notwithstanding the shenanigans of Professor Brown-Sequard who, some years previously, had championed the revitalising effects of injections of testicular extracts or, more seriously, Horsley's demonstration of the clinical utility of thyroid gland extracts.
Therefore the two men from University College had to challenge this long-established doctrine of neural omnipotence in a medical community which was reluctant to return to what was seen as mediaeval thinking about the bodily 'humours', as they were known. They also challenged the contemporary god of neurology, Ivan Pavlov. It is clear from reading Starling's research papers of that time that they took tremendous pains to counter the strong objections which came from the Pavlovian disciples. Those English experiments and their thoroughness are thrilling, even a hundred years later.
A few years earlier, Pavlov had shown that when acid or food material is instilled into the duodenum (the part of the gut that is just past the stomach), the pancreas pours additional digestive juices into the duodenum. Pavlov insisted that this was, exclusively, a nervous reflex. When Bayliss and Starling began to doubt this they had to produce something that was pretty powerful. First they did everything that they could to eliminate the intestinal nerves from the tissues that they were working with in their anaesthetised dogs: they knew that the Pavlovians would invoke the counter argument that there were some residual nerves (even some which had not yet been discovered!) to support the Pavlovian dogma. Bayliss and Starling honestly asked themselves that same question: What if we have left some functional nerves behind? Their response was to perform what they called the 'Crucial Experiment'. They cut out a piece of gut, mashed it up and injected the filtered product into the dog's vein; the pancreas secreted powerfully in response. And no nerves could have been involved with this effect. Even Pavlov had to acknowledge the significance of the English finding, though two years later he could not bring himself to so much as mention it in his Nobel Prize address in Stockholm. There is nothing so bitter for a scientist as making a discovery but not recognising what it really means.
By good fortune, the renowned scientist Charles Martin, who spent 12 important years at the Universities of Sydney and Melbourne, was visiting Bayliss and Starling on that January day in 1902 when they did their superb experiment: 'It was a great afternoon,' he later wrote. I'd call it a magical moment in medical science.
Some months after the Starling and Bayliss experiment, Wertheimer brilliantly proved their point in a different way: he exposed the lining of the small bowel to acid and collected some of the venous blood draining from it. He then injected that blood into another dog and observed a marked increase in pancreatic secretion. QED.
Though the existence of the new physiological agent was now confirmed, and named, Starling did not know what to call it so as to fit into a conceptual physiological scheme. In fact, for a few years he and his colleagues curiously referred to it as 'a body', until, with the help of a Cambridge classical scholar, Starling presented the new word, 'hormone', to the world a century ago. He then wrote, 'If a mutual control, and therefore co-ordination of the different functions of the body be largely determined by the production of definite chemical substances in the body, the discovery of the nature of these substances will enable us to interpose at any desired phase in these functions, and so acquire an absolute control over the workings of the human body.' He went on, in the vigorous language which was his characteristic, to refer to '...the chemical messengers which, speeding from cell to cell along the bloodstream, may co-ordinate the activities and growth of different parts of the body ... these chemical messengers or 'hormones' (from hormau, 'I excite or arouse') as we might call them, have to be carried from the organ where they are produced to the organ which they affect by means of the blood stream and the continually recurring physiological needs of the organism must determine their repeated production and circulation through the body.'
These words can still stand as a summary of endocrine activity but their effect on medical thinking was profound. While it is true that 10 years earlier, Sharpey-Schafer, Starling's professorial predecessor at University College, had published a lecture on 'the internal secretions' (what we would now call 'hormones'), it was Starling's work and thinking that caused this still-nascent intellectual seed to grow.
And grow it did, together with the recognition, in answer to Cajal's conceptual challenge, that nerve cells actually communicate with one another and with muscles by the secretion of chemicals, by local 'hormones', really. It is remarkable that a mere 16 years after Starling coined the word 'hormone', Otto Loewi first demonstrated this neurochemical link by studying the action of the Vagus Nerve on the heart. Loewi did this work in Graz, in Austria, but he had more than a conceptual link with Starling; he had worked in his London laboratory in that annus mirabilis of 1902.
And then in 1921, the very year of Loewi's discovery, Banting and Best, working in Canada, made the first successful extracts of insulin from the pancreas. They revolutionised the treatment of diabetes and opened the door to our understanding of its cause. About that same time, scientists were beginning to get an inkling of the functions of the adrenal gland and, therefore, the basis for Addison's Disease, while only a few years earlier, in the USA, Kendall had purified extracts of the thyroid gland and crystallised its principle hormone, thyroxine.
Thanks to Starling's impetus, endocrinology was on the march.
Soon enough, 'hormones' became a word of popular currency and became the facile explanation - as well as the exculpation - for a diversity of human behaviour. This implies the recognition that while our psychology may be dependent upon our acculturation and education, it is driven by our biology.
There could be no more spectacular or significant demonstration of this, and of the protean influence of medical science than the development of the contraceptive pill, synthetic hormones as that medication is. Perhaps the crucial discovery here, made in the 1930s, first by Knaus in Austria and then by Hartman and Rock in the USA, was that ovulation is a specifically-timed event, at the mid-point of the menstrual cycle. It was of great importance, too, that Kendall's biochemical studies had shifted to a class of molecules called 'steroids' and the adrenal, ovarian and testicular hormones are members of this class.
But purification of a complex compound is one thing; its successful synthesis is quite another, particularly on a commercial scale. In the early 1950s, in Mexico City, Djerassi and his team began to achieve that with ovarian steroids. So the way was then open, principally for Rock and Pincus, to begin extensive clinical trials of the efficacy and safety of these potential contraceptives.
Through all of this period, science and the Catholic church had conducted a kind of intellectual chess tournament, played to incompatible rules. In 1930, Pope Pius XI had condemned contraception in his encyclical, Casti connubi and Pius XII reiterated this in 1951 soon after his reinforcement of the Cult of the Virgin with the declaration of the dogma of the bodily Assumption of Mary. But the battle was lost. Millions of Catholic women ignored these males' injunctions and took control of their fertility in a decisive aspect of the feminist movement. This was a social analogue of the ancient Greek verb which had given Starling the word 'hormone' half a century earlier: 'I excite, I arouse, I call into action'. Thus endocrinology and its possibilities are arguably a definition of the 20th century. A word had become action.
Robyn Williams: Become action a hundred years ago. Dr Jack Carmody of the University of New South Wales.
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