Lauder Brunton

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Biography

• Born on March 14, 1844 in Roxburgh, Scotland.
• In 1866, he graduated in Medicine at the University of Edinburgh where his research into pharmacology began. He was awarded a gold medal by the University for his thesis on digitalis
• In 1867 he became a house physician at The Royal Infirmary, Edinburgh.
• Upon graduating, he devoted three years to study in foreign laboratories in Vienna, Berlin, Amsterdam and Leipzig with Carl Ludwig (1816–1895). It was here much of his research on nitrites began.
• In 1871 he settled in London and was appointed lecturer in Materia Medica at St Bartholomew’s Hospital; it was during this period he began to write his ‘Experimental Investigation of Medicine’.
• In 1874, he was elected Fellow of Royal Society. The Fellowship of the Royal College of Physician was conferred upon him in 1876
• Brunton was knighted in 1900 by Queen Victoria at Osborne House and received a baronetcy in 1909
• Sir Thomas Lauder Brunton died on September 16, 1916 in London

There is a memorial in Bowden in the Scottish Borders, designed by Sir Robert Lorimer (1864-1929)

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Medical Eponyms

Nitrates in heart disease (1867)

1844 Antoine-Jérôme Balard (1802-1876), a French chemist best known for his discovery of bromine, originally synthesised amyl nitrite by directly heating purified alcohol with nitric acid.

1859 The chemical properties of amyl nitrite were first studied by Frederick Guthrie, a British chemist.

One of the most prominent of its properties is the singular effect of its vapour, when inhaled, upon the action of the heart. If a piece of bibulous paper, moistened with two drops of the nitrite of amyl, be held to the nostrils, through which the breath is exclusively drawn, after the lapse of about fifty seconds, a sudden throbbing of the arteries of the neck is felt, immediately followed by a flushing of the neck, temples and forehead, and an acceleration in the action of the heart.

It is probable that this body may find an application in medicine as a resuscitative, as in cases of suffocation, drowning or protracted fainting.

Guthrie 1859

1865 The first significant investigation into the possible medical applications of amyl nitrite was undertaken by Sir Benjamin Ward Richardson (1828-1896). He presented these findings at meetings of the British Association for the Advancement of Science between 1863-65.

Physiological Properties of Nitrite of Amyle. — Dr. B. W. Richardson read a paper on this subject before Sub-section D, of the British Association. He first described the mode of manufacture and the chemical properties of the nitrite, and then passed on to the physiological action. The first remarkable fact was that the nitrite when inhaled produced an immediate action on the heart, increasing the action of the organ more powerfully than any other known agent. As the action of the heart rises, the surface of the skin becomes red, and the face assumes a bright crimson colour. A little of the nitrite was here placed on a piece of bibulous paper, and passed round to show the effect on the face, and the effect was most remarkable, causing the faces of the persons who smelt the vapour to become instantaneously flushed. Carried to an excessive degree, the nitrite excites the breathing, and produces a breathlessness like that caused by sharp running or rowing. On animals, when the agent is given in large quantities, death is produced

The American journal of the medical sciences (1864)

When inhaled, produced an immediate action on the heart, increasing the action of the organ more powerfully than any other known agent.

The above investigations of Richardson were soon extended by Arthur Gamgee, a graduate of the University of Edinburgh three years Brunton’s senior, who “in an unpublished series of experiments, both with the sphygmograph and haemodynameter, has found that amyl nitrite greatly lessens the arterial tension, both in animals and man.

Article

1867 Brunton first published his report on the action of amyl nitrite. According to Brunton the phenomenon of angina pectoris was caused by an acute blood pressure elevation secondary to pronounced contraction of the peripheral arteries. He described dramatically how, with amyl nitrite, the patient immediately experienced facial flush as a sign of arteriolar dilation, and simultaneously the chest pain was relieved.

Brandy, ether, chloroform, ammonia, and other stimulants have hitherto been chiefly relied upon for the relief of angina pectoris; but the alleviation which they produce is but slight, and the duration of the attack is but little affected by them.

In now publishing a statement of the results which I have obtained in the treatment of angina pectoris by nitrite of amyl, I have to observe that the cases in which I employed this remarkable.

Brunton 1867

Note Brunton’s interpretation of the background of angina pectoris was later shown to be incorrect, and his famous discovery been called a ‘lucky shot’. It has long been accepted that angina pectoris is the result of a myocardial hypoxia, and that the pain is caused by imbalance between the oxygen demand of the myocardium and the actual supply.

1882 Writing to Gamgee, Brunton informed him “You seemed never to regard the sacrifice of your own time, nor heed the trouble it gave you to help me in some experiment which, but for you, would have failed…”

1885, the pioneering physiologist Henry Newell Martin, FRS (1848-1896) emphasised the significance of the steps that had led to the introduction of amyl nitrite into clinical practice

Interesting as is the history of strychnine and chloral, still more so is that of amyl nitrite, a drug not yet officinal, but now being born, if I may use such a metaphor. The chemist has discovered it ; the physiologist and pharmacologist have experimented with it ; and now the practicing physician is testing it clinically. Whatever his ultimate decision be as to its greater or less value, its story serves well to illustrate how a new remedy is discovered, and how many sciences cooperate to add to the physician’s armament.

Henry Newell Martin 1885

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Major Publications

• Brunton TL. On the use of nitrite of amyl in angina pectoris. Lancet 1867; 90(2291): 97-98
• Brunton TL. On digitalis: with some observations on the urine. 1868
• Brunton TL. Nitrite of AmyI in Angina Pectoris. 1870; Clinical Society’s reports, Vol. III
• Brunton TL. The Bible and science. 1881
• Brunton TL. A text-book of pharmacology, therapeutics and materia medica. 1887
• Brunton TL. Lectures on the action of medicines; being the course of lectures on pharmacology and therapeutics. Delivered at St. Bartholomew’s Hospital during the summer session of 1896
• Brunton TL. Collected papers on circulation and respiration. 1906
• Brunton TL. Therapeutics of the circulation. 1908

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References

Biography

• Shattuck FC. Sir Thomas Lauder Brunton (1844-1916). Proceedings of the American Academy of Arts and Sciences 1917; 52(13): 830-832

Nitrates in cardiovascular disease

• Balard AJ. Premier mémoire sur l’alcool amylique. Annales de chimique et de physique. 1844; 12: 294-335
• Guthrie F. Contributions to the knowledge of the amyl group. Chem Soc J 1859; 11: 245-252
• Martin HN: The study of the physiological action of drugs. Transactions of the Medical and Chirurgical Faculty of the State of Maryland. 1885: 79
• Fye WB. T. Lauder Brunton and amyl nitrite: a Victorian vasodilator. Circulation. 1986 Aug; 74(2): 222-9. 
• Berlin R. Historical aspects of nitrate therapy. Drugs. 1987; 33(4): 1-4.
• Divakaran S, Loscalzo J. The Role of Nitroglycerin and Other Nitrogen Oxides in Cardiovascular Therapeutics. J Am Coll Cardiol. 2017 Nov 7;70(19):2393-2410.
• Cheng D. Amyl Nitrites: A Review of History, Epidemiology, and Behavioural Usage. Journal of Student Research. 2013;2(1): 17-21.

Eponymous terms

• Tattersall R. Pancreatic organotherapy for diabetes, 1889-1921. Med Hist. 1995 Jul;39(3):288-316. 

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