Edward Sharpey-Schafer (1850-1935)

Edward Schafer was one of the founders of the British school of physiology, which lagged far behind the Germans and French in the latter half of C19. He studied physiology at University College London and later came under the tutelage of William Sharpey. His reverence for his teacher was such that he changed his name to Sharpey-Schafer later in life as a token of respect. Another reason for the change was that two sons were killed in the First World War and he wished to anglicize his name. He obtained the Chair of Physiology in Edinburgh in 1899 and retained it until 1933. His most notable discovery was adrenaline, but he made many other contributions including the introduction of a standard procedure for resuscitation after drowning. Diabetologists remember him because he was one of several contemporaries who predicted the existence of insulin in advance of its discovery, and he was also the second person to propose the name of the new hormone.

Adrenaline

Edward A Sharpey-Schäfer
Edward A Sharpey-Schäfer
In 1893 a physician called George Oliver travelled from Harrogate to London. Physiological experimentation was his hobby, and he used his own family as a convenient source of experimental subjects. Having procured some material from the butcher he ground this up and injected it into his small son. It seemed to have an effect on the diameter of the radial artery. Reaching London, Oliver imposed himself upon Professor Schäfer at University College. Schäfer was busy measuring the blood pressure of a dog and was somewhat impatient at the interruption.

Failing to take the hint, Oliver produced the extract from his pocket and waited patiently until the experiment had ended. The exasperated Professor finally injected the mysterious substance, only to watch open-mouthed as the mercury column recording the dog’s blood pressure nearly blew its top off. Further experiments showed the extraordinary potency of the unknown material, which could produce striking changes after injection of less than one millionth of a gram per kilo of body weight. Their results were published in 1895[1]. The substance was purifed by John Abel at Johns Hopkins in 1899, although still contaminated by noradrenaline. It was Abel who opted to call it epinephrine, presumably to distinguish his own efforts from those of other investigators. This unfortunate misnomer has been perpetuated in the USA[2][3]. Abel was also the first person to crystallize insulin in 1926.

Takamine, a Japanese investigator, independently extracted a similar compound and sought (with Parke-Davis) to patent it under the name of Adrenalin (the final "e" was dropped to secure the patent). The claim was challenged on the grounds that you cannot patent a natural substance.

"Federal Judge Learned Hand listened to days of technical testimony and immersed himself in the chemical literature surrounding the rival claims. His cogent and chemically accurate summation contains one of the most famous lines in biotechnology patent history: “I cannot stop without calling attention to the extraordinary condition of the law which makes it possible for a man without a knowledge of even the rudiments of chemistry to pass upon such questions as these” (Circuit Court, S.D. New York, April 28, 1911, Federal Reporter 189:115). Judge Hand ruled in favor of Takamine"[4][5].

Insulin

Schäfer is best remembered by diabetologists for early use of the name "insuline", previously suggested by de Meyer in Belgium. Schäfer was probably unaware of Meyer's work, and was in any case the first to suggest the term "pro-insuline". Banting and Best initially preferred the name "isletin", but insulin soon became the popular choice.

Schäfer predicted the existence of a pancreatic secretion originating in the islets which controlled glucose metabolism as early as 1895[6], as many others were later to do. The term "hormone" was proposed by Starling, but Schäfer subsequently argued that the term should be reserved for stimulatory chemical messengers. He therefore proposed the term "autacoid" (roughly translated from the Greek as "self-remedy") for substances which could both stimulate and inhibit.[7]

He inferred the existence of insulin from the observation that duct ligature caused exocrine pancreatic destruction but not diabetes, whereas subsequent removal of the ligated remnant did produce diabetes. Furthermore, transplantation of this remnant to another site was sufficient to reverse diabetes. These experiments were supported by histological evidence of islet damage in some cases of diabetes. This led him to the following statement:

"The results of pancreas extirpation and and pancreas grafting can, as we have seen, be best explained by supposing that the islet tissue produces an autacoid which passes into the blood and affects carbohydrate metabolism and carbohydrate storage in such a manner that there is no undue accumulation of glucose in the blood. Provisionally, it will be convenient to refer to this hypothetical autacoid as insuline . It must however be stated that it has yet to be determined whether the active substance is present as such in the pancreas or whether it exists there as proinsuline which becomes elsewhere converted into the active autacoid". [8]

As to the nature of insulin, he suggested a number of theoretical possibilities:

  • It might be an enzyme whose role is to metabolize glucose
  • It might be a "kinase" which converted an inactive glycolytic enzyme into an active one
  • It might be an inhibitor of the breakdown of hepatic glycogen. In the absence of such an inhibitor the liver would no longer be able to store glucose, which would then spill into the circulation. This he considered the more likely alternative.

Sharpey-Schafer's response to the subsequent discovery of insulin does not seem to have been recorded.

References

  1. ^ Oliver G, Schafer EA. The physiological effects of extracts of the suprarenal capsules. J Physiol 1895; 18:230-76.

  2. ^ Abel JJ. On epinephrine, the active constituent of the suprarenal capsule and its compounds. J Physiol 1901; 27:237.

  3. ^ Aronson JK . ""Where name and image meet"—the argument for "adrenaline"". British Medical Journal 320 (2733): 506–509. doi:10.1136/bmj.320.7233.506

  4. ^ http://pubs.acs.org/subscribe/archive/mdd/v04/i12/html/12timeline.html

  5. ^ http://www.brainimmune.com/index.php/history-and-opinion/sections/history/159-the-discovery-of-adrenaline

  6. ^ Schafer EA. On internal secretion. BMJ 1895;2:341-

  7. ^ Rolleston HD. The endocrine organs in health and disease with an historical review. Oxford University Press, 1936

  8. ^ Schafer EA. The endocrine organs. An introduction to the study of internal secretion. Longmans Green, London, 1916.

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