Signal Transduction
Thus the extremely active substance formed in one part of the suprarenal gland, and known as adrenaline, was discovered.
Within a few months, Oliver and Schäfer had demonstrated that the primary effect of the extract is a profound arteriolar constriction with a resulting increase in the peripheral resistance.40,41 Their colleague Benjamin Moore reported that the activity could be transferred by dialysis through membranes of parchment paper, that it is insoluble in organic solvents but readily soluble in water, resistant to acids and to boiling, etc.42
Schäfer’s own account of his first meeting with George Oliver relates events that may have taken place on a another planet from Dale’s version:39
In the autumn of 1893 there called upon me in my laboratory in University College a gentleman who was personally unknown to me, but with whom I had a common bond of interest – seeing that we had both been pupils of Sharpey, whose chair at that time I had the honour to occupy. I found that my visitor was Dr George Oliver, already distinguished not only as a specialist in his particular branch of medical practice, but also for his clinical applications of physiological methods. Dr Oliver was desirous of discussing with me the results which he had been obtaining from the exhibition by mouth of extracts of certain tissues, and the effects which these had in his hands produced upon the blood vessels of man, as investigated by two instruments which he had devised – one of them, the haemodynamometer, intended to read variations in blood pressure, and the other, the arteriometer, for measuring with exactness the lumen of the radial or any other superficial artery. Dr Oliver had ascertained, or believed that he had ascertained, by the use of these instruments, that glycerin extracts of some organs produce diminution in calibre of the arteries, and increase of pulse tension, of others the reverse effect.
Hormones: a definition
These are blood-borne ‘first messengers’, usually secreted by one organ (or group of cells) in response to an environmental demand to signal a specific response from another. The first such messenger to be endowed with the title of hormone was secretin, later shown to be a peptide released into the blood stream from cells in the stomach lining, indicating the presence of food and alerting the pancreas. In the words of William Maddock Bayliss (co-discoverer with Ernest Henry Starling),
There are a large number of substances, acting powerfully in minute amount, which are of great importance in physiological processes. One class of these consists of the hormones which are produced in a particular organ, pass into the blood current and produce effects in distant organs. They provide, therefore, for a chemical coordination of the activities of the organism, working side by side with that through the nervous system. The
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Prologue: Signal Transduction, Origins and Ancestors
internal secretions, formed by ductless glands, as well as by other tissues, belong to the class of hormones.43
In fact, adrenaline, the signal for‘fright, fight, and flight’, is a much better candidate for the accolade of‘first hormone’.44 Together with noradrenaline it is secreted into the bloodstream in consequence of emotional shock, physical exercise, cold, or when the blood sugar concentration falls below the point tolerated by nerve cells. Extracts having the activity of adrenaline, enhancing the force and volume of the heart output had been reported 10 years before the discovery of secretin, almost simultaneously, by George Oliver and Edward
Schäfer in London,40,41 and by Napoleon Cybulski and Szymonowicz in Krakow.45
What’s in a name?
It has been customary in Europe to give the substance 4-[1-hydroxy-2- (methylamino)ethyl]-1,2-benzenediol, alternatively 3,4-dihydroxy- -[(meth ylamino)methyl]benzyl alcohol, the name adrenaline. In the USA the same substance is called epinephrine. Why have the Europeans preferred the Latin roots while the Americans go for the Greek? Behind this linguistic conundrum lie hints of scientific skulduggery.
John Jacob Abel, America’s first professor of pharmacology, initially at the University of Michigan at Ann Arbor and then at the new Johns Hopkins Medical School in Baltimore, is credited with the isolation of the ‘first hormone’ as a pure crystalline compound. As a part of his procedure, he treated the acidified and deproteinated extract of adrenal glands with alkaline benzoyl chloride. Then, and after further steps including hydrolysis, he obtained a crystalline material which he reported as being very active. Chemical analysis yielded an elementary formula of C17H15NO4. What is not so clear is whether the Japanese industrial chemist Jokichi Takamine, who had an arrangement with the Parke, Davis Company (Detroit, Michigan), gained some advantage from his visit to Abel’s laboratory sometime in 1899 or 1900. Certainly,
Abel appears to have been quite candid with his visitor, while Takamine, accustomed to the practices of commerce, never published reports of any sort until his preparation was well protected by patents and – importantly in this case – a trademark, with the name Adrenalin (no terminal ‘e’). What is clear is that Takamine used a simpler procedure for purifying the hormone, omitting the benzoylation step. T. B. Aldrich, also at the Parke, Davis Co. but recently
of the Department of Pharmacology at Johns Hopkins and therefore a late colleague of Abel’s, determined the correct elementary formula of Takamine’s preparation as C9H13NO3.
The Parke, Davis Co. lost little time in marketing the preparation, and continued to do so until 1975 when they replaced it with a synthetic product. It became evident that Abel’s failure to provide the correct formula was due
The European Pharmacopoeia now also indicates the use of the term epinephrine. We justify our preference for adrenaline not only on its historical primacy but for reasons of logic and common usage. Who ever heard of epinephric receptors? Who ever used the expression ‘that really gets my epinephrine up’? (It is said that George Bush père may have tried this on but the words actually used were ‘that really gets my cholesterol up’. Had he stuck with common usage, his meaning might have been clearer)
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