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The merits of Thomas Addison

Dr Thomas Addison

By Kristian Løvås, PhD, MD
University of Bergen and Haukeland University Hospital, Norway

“The leading and characteristic features of the morbid state to which I would direct attention, are, anaemia, general languor and debility, remarkable feebleness of the heart’s action, irritability of the stomach, and a peculiar change of colour of the skin, occuring in connexion with a diseased condition of the supra-renal capsules”

These are the words of Thomas Addison in his famous monograph from 1855 entitled “ On the constitutional and local effects of disease of the supra-renal capsules”. Here he gives for the first time a precise description of the clinical syndrome, which we now call Addison’s disease or primary adrenal insufficiency.

This was, however, not his first contribution to the medical science. Six years earlier he read before the South London Medical Society a paper where he described a distinctive form of anaemia. As he recalls in the monograph from 1855: “For a long period I had from time to time met with a remarkable form of general anaemia, occurring without any discoverable cause whatever; cases in which there had been no previous loss of blood, no exhausting diarrhoea, no chlorosis, no purpura, no renal, splenic, miasmatic, glandular, strumous, or malignant cause”.

Thus, within six years he had described two clinical entities; Addison’s anaemia which we now know as pernicious anaemia – and Addison’s disease, which is the condition that brings us together here today.

Thomas Addison was born in 1793, in the village of Longbenton, now part of Newcastle-upon-Tyne. From 1812 to 1815 he was a student at the Edinburgh Medical School, and was conferred doctor of medicine with a thesis concerning Syphilis and Mercury. He then moved to London, where he remained in practice at Guy’s Hospital from 1817 un until he died in 1860.

It is difficult to get a real picture of his character. He appeared withdrawn and unapproachable, but those who knew him well ascribed this to excessive shyness and sensibility. He was a brilliant lecturer and diagnostician, who lived almost exclusively for his pupils and hospital work. Samuel Wilks, a pupil and close co-worker of Addison’s said that “every man during the 40 years of his teaching was a disciple of Addison, holding his name in the greatest reverence and regarding his authority as the best guide to the practice of the profession”. However, his severe, pompous manner, precisely chosen words and physically impressive appearance were renown, and said to struck fear into students. It is likely that his complex nature explains why he never acquired a large practice and a seemingly unpopularity with the medical establishment.

The contributions of Thomas Addison were not acknowledged in his lifetime. His monograph was not mentioned in the British Medical Journal, and only briefly in the Lancet. Only Trousseau eventually recognised the importance of Addison’s contributions and later named the syndrome Addison’s disease.

To really grasp how profound his discoveries were we need to have some idea of the state of the art in the middle of the 19 th century. Over a few centuries the great masters of natural science, Galilei, Descartes and Newton among many others, had opened disciplines of physics and chemistry to scientific inquiry. And although human biology leaped forward in the 17 th century with Vesalius’ description of anatomy and Harvey’s discovery of blood circulation, the sciences of biology and medicine lagged severely behind.

In Addison’s own words: It will hardly be disputed that at the present moment, the functions of the supra-renal capsules, and the influence they exercise in the general economy, are almost or altogether unknown. I am not aware that any modern authority has ventured to assign to them any special function or influence whatever.

We need also to keep in mind that at the time of Addison the ancient Greek sentiment still prevailed that phenomena in biology and medicine were driven by a natural or vital spirit, and therefore not subject to scientific investigation. This view was still fiercely defended by the Church, which likened this spirit to the Holy Spirit. Nevertheless, empiricists had begun to challenge this so-called vitalism; in Europe first and foremost by the great professor Magendie, whose student Claude Bernard is central to the history of endocrionolgy. Notably, Bernard first demonstrated the principle of interior secretion in 1850.

Thomas Addison and his fellows certainly had assimilated the empiricist and scientific thought, and systematically studied the relation between clinical diseases and pathological findings. Addison expresses this wonderfully in the opening words of 20.03.2009t physiology is to health, it appears reasonable to conclude, that in any given structure or organ, the laws of the former will be as fixed and significant as those of the latter; and that the peculiar characters of any structure or organ may be as certainly recognised in the phenomena of disease as in the phenomena of health”.

Over the years he became one of “the three Giants of Guy’s”- together with Richard Bright and Thomas Hodgkin. The merits of Addison and Hodgkin must certainly be shared with Bright, who organised the special clinical ward in close connection with post-mortem rooms, which became instrumental in their systematic studies of various diseases – which we today would simply call a clinical research facility.

In this way, a remarkable man gave us the definition of Addison’s disease 150 years ago, but he left a few questions to be answered. What is the function of the adrenals? What is the connection between adrenal disease and the clinical syndrome? What is its cause? How can it eventually be treated or prevented?

Interior secretion was not yet a mature concept, and the ductless glands like the adrenals were thought involved in cleansing or detoxification of the blood. It took several decades to establish that the adrenals produce hormones, and that Addison’s disease is a hormone deficiency syndrome. And a vivid discussion as to whether the adrenal medulla or the cortex is essential to life was not concluded until 1922. Not until adrenal lipid extracts were tried in the 1930s was any remedy available which could help these poor patients. Thanks to the eminent work of Reichstein and Kendall who eventually synthesised cortisone, certain death of these patients had been turned to prospects of normal life.

The intriguing question is still with us 150 years after Addison: what is the cause of this disease? Certainly, the last few decades have revolutionised the understanding of this as an autoimmune disease, but similarly impressive is the vast lack of knowledge of genetic and environmental causes. We are fortunate to experience the present surge in genetics and immunology, which is clearly embedded in the ambition of the Euradrenal project.

The first definitive description of the adrenals dates back to Eustachius in the 16 th century. After that the French Society for Science called for investigations into the function of the adrenals. None of the proposals were satisfactory, and the leader and great political scientist Montesquieu concluded: Maybe chance one day will reveal what all of this work was unable to do.

Truly, chance has its place in science, but the merits of Thomas Addison were not those of chance, but of a brilliant mind, hard work and ample resources. Inspired by his achievements let us hope the Euradrenal project will advance the science of Addison’s disease to unprecedented heights.