The Nobel Pancreas: A Historical Perspective

Abstract

b i d c U a d o For everyone interested in the pancreas, it is truly a noble organ. Known to the ancient Greeks, its name n Greek “pan kreas” translates as “all flesh.” Aristotle elieved its function was to protect the great vessels and 4 enturies later Galen claimed it to be a cushion for the tomach.1 The Renaissance anatomists, beginning with esalius, defined its structure with its ducts, first shown y Johann Wirsung in 1642, to empty into the intestine. egnier de Graaf, of the Graafian follicle, was the first to tudy pancreatic secretion in 1664, using a goose quill nserted into the duct. In the 19th century, Claude Bernard n Paris, and others, showed the digestive capabilities of ancreatic juice for fat, carbohydrate, and protein.1,2 Paul Langerhans, a medical student in Berlin, described the eponymous islets in 1869 and in 1889, Miring and Minkowski described experimental diabetes in the dog after pancreatectomy.3 In addition to understanding the natomy and physiology of the exocrine pancreas, Hans hiari had described the autodigestion of the pancreas hat accompanies pancreatitis in 1896. By 1900, the hisology and general understanding of the function of the ancreas was in place. The 20th century was to be occupied rst with understanding the control of pancreatic secreion and then the understanding of specific cell types of he pancreas as molecular machines evolved to carry out pecific functions. A timeline for this increase in undertanding of the pancreas and its diseases is shown in igure 1. More detailed coverage of the last 160 years is hown in Figure 2. In 1896, the Swedish inventor Alfred Nobel died, and in is will he left much of his fortune— earned in the manfacture of explosives, including dynamite, which he inented—to establish prizes that bear his name in different reas of knowledge to be chosen by different academies in tockholm or Norway. One of these prizes in Physiology nd Medicine and another in Chemistry will be discussed ere. The first Nobel Prizes were awarded in 1901 and they ave been awarded annually since then to one to three ndividuals in a specific area. In this Commentary, I will eview the advances in scientific knowledge in which the ancreas led the way to the extent that it was recognized y the awarding of 5 Nobel Prizes for work that either elated directly to products of the pancreas or used the ancreas as a cellular source to understand fundamental hysiological and cell biological processes. I will also note ome omissions and controversies. The early years of the 20th century were marked by nderstanding of the neural and hormonal control of the ancreas. One of the early giants of modern physiology as Ivan Petrovich Pavlov who, before studying the conitioned reflexes for which he is best known, studied the eural control of gastric and pancreatic secretion. Pavlov, orking in St Petersburg, Russia, developed the first modrn physiology laboratory with multiple staff who worked ogether as a team. They showed that psychic stimulation r putting food in the stomach led to secretion from the ancreas, which was collected via a pancreatic fistula.4 Acid and fat were especially good stimulants and carbohydrate was not. His laboratory also identified enterokinase, the intestinal activator of trypsin, and described the cephalic phase of pancreatic secretion. Pavlov’s work was first summarized in a series of lectures and then in a book published first in Russian and then in English in 1902 entitled, The Work of the Digestive Glands.5 Pavlov’s contriution was recognized when he received the Nobel Prize n 1904 “in recognition of his work on the physiology of igestion.” Meanwhile, another famous experiment was arried out by William Bayliss and Ernest Starling at niversity College in London, in which they showed that n extract of the intestinal mucosa, when injected into a og with its pancreas completely denervated, led to copius secretion of pancreatic juice.6 This was, in fact, the first demonstration of a chemical messenger or “hormone,” a term coined by Starling in his Croonian Lecture of 1905 to the Royal College of Physicians. Thus was born the field of Endocrinology. Starling, probably the most