Monkey glands and the science of renal hypertension

Quack medicine and technology contributed to the discovery of Renin in 1898

A 1928 advert exploiting the Monkey Gland craze.  Source

In 1889 the renowned scientist Brown-Sequard at the age of 72 publicly recounted how how he felt rejuvenated after injecting himself with extracts of animal testis.  This led to an extraordinary wave of quack medicine involving injections with all types of organ extracts (organotherapy), peaking most infamously with a fashion for transplantation of monkey testicles into rich men seeking rejuvenation. Surgeon Serge Voronoff working in France in the 1920s and 30s was the most prominent practitioner.  The only striking clinical success at the time was with thyroid extract injections for myxoedema in 1891, pioneered by young physician George Murray in Newcastle following his mentor Horsley, and based on substantial scientific background work.  Insulin and growth hormone came much later.

However the idea stimulated other serious scientific investigations.  Significantly it coincided with the realisation of the importance of blood pressure, and the development of the first practical devices for measuring blood pressure in humans.

Finnish physiologist Robert Tigerstedt picked up these strands while working at the Karolinska Institute. He probably recorded blood pressure with Poiseuille’s mercury manometer fitted with a float to link it to a kymograph, a modification introduced by Ludwig in 1847. In 1898 he described a substance in extracts of rabbit kidney that led to a rise in blood pressure.  It was very potent, and could be found in the renal cortex but not medulla, and in the renal vein but not the renal artery.  It was water-soluble but heat-labile, suggesting that it was a protein. It seemed to work by increasing peripheral vascular resistance without altering heart rate. They called it Renin.

Tigerstedt had other claims to fame; he wrote a very successful textbook of physiology, was asked to help draw up the principles for the Nobel Prize, and was a friend of the Russian physiologist Pavlov, who wrote the preface to his textbook.

The discovery of Renin was ahead of its time.  The word ‘hormone’ hadn’t been invented, indeed Renin was probably the first to be named.  The importance of the findings remained unproven for over 30 years, until Goldblatt published the first of a landmark series of experiments on renal ischaemia in 1934. He showed that renal artery constriction in dogs caused hypertension through release of a circulating substance.  Suddenly interest in Renin was rekindled.  In 1940 work simultaneously in Buenos Aires and Indiana defined how Renin seemed not to be active directly, but that its action led to generation of a mediator named hypertensin or angiotonin, in 1958 renamed angiotensin.

Interest in Renin seemed for many years to eclipse other possible mechanisms of renal hypertension. In fact salt handling is at least as important (and also affected by the downstream actions of renin, it turned out).

Authors of this post were Theodoros D Mountokalakis and Neil Turner.

Further info

Mountokalakis TD 1997.  The renal consequences of arterial hypertension.   Kidney Int  51 1639-53
Marks LS and MH Maxwell 1979. Tigerstedt and the discovery of Renin.  Hypertension 1:384-8
Sawin CT 2001. The invention of thyroid therapy in the late 19th century.  The Endocrinologist 11:1-3
Wikipedia on the history of hypertension is nice and concise

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