History of the Pancreas

by John M. Howard, M.D., Toledo, Ohio

1. The pancreas was apparently first discovered by Herophilus, a Greek anatomist and surgeon, who was born in 336 BC in Chalcedon on the Asiatic side of the Bosporus. Herophilus was one of the founders of the ancient school of Medicine in Alexandria, Egypt. He may have been the first to have performed dissections of human bodies before public audiences.

2. Four hundred years after Herophilus, Ruphos, in the 1st or 2nd Century AD, an anatomist – surgeon of Ephesus, also in Asia Minor, gave the name “pancreas”. Writing in Greek, the word meant “all flesh”.

3. Galen (Claudius Galenus 138-201 AD), born in Asia Minor, became “Physician to the Gladiators” of Rome, as well as to the Roman Emperor. Galen taught that the role of the pancreas was to serve as a cushion or pad to protect the large blood vessels lying immediately behind it. As the most famous physician in the World, Galen’s word was “law” – not to be challenged for well over a thousand years. Being wrong, he held back scientific investigation from the 2nd to the 18th Century.

4. The study of the pancreas began on March 2, 1642, when a German émigré, Johann Georg Wirsüng, discovered the pancreatic duct in the San Francisco Monastery in Padua, Italy. Wirsüng was murdered by a student the year after the discovery. Wirsüng never knew the function of the duct which he had discovered. “Is it an artery or a vein”, he asked; “I have never seen blood in it”. A colleague named it “The Duct of Wirsüng”.

5. Reignier de Graaf (1641-1673), a 22 year old student of Leiden, Netherlands used the hollow quill of a goose feather to cannulate the pancreatic duct of a dog in 1663. De Graaf thus introduced experimentation, rather than dogma, as a basis for medical knowledge. DeGraaf died of bubonic plague at age 32.

6. Anthony Van Leeuwenhoek (1632-1723) of Delft, a contemporary of de Graaf’s built 247 or more microscopes, in the period about 1673-1683. Although his models were gradually improved, none was apparently of research quality. Neither he nor his peers studied the pancreas but his discovery was later to open new horizons.

7. In his thesis of 1852, D. Moyse, a student in Paris, may have been the first to describe the histology of the pancreas. Crudely drawn, he apparently depicted the structure of the exocrine acini.

8. In his thesis of 1869, Paul Langerhans (“Junior”), a student in the famous Berlin Institute of Pathology, which was headed by the eminent Professor Rudolph Virchow, described the islets of the pancreas which were subsequently to be known as the “islets of Langerhans”, an endocrine system within the pancreas. Langerhans description was the first good histologic description of the pancreas.

9. Meanwhile, on March 30, 1842, Dr. Crawford W. Long (1815-1878), of Jefferson County, Georgia (USA) excised a tumor of the neck under ether anesthesia. General anesthesia, developed without thought of the pancreas, was to make possible new frontiers of surgery.

10. In 1871, Joseph Lister, a surgeon of Glasgow, later to be Lord Lister, introduced the practice of asepsis in surgery when he initiated the spraying of the operating room and the operative field with phenol. Essential to the safety of abdominal operations, the advance was again made with no thought of the pancreas but like the discovery of anesthesia was essential to the development of surgery.

11. On November 8, 1895, Wilhelm Conrad Röentgen (1845-1923), Professor of Physics at Würzburg, Germany, discovered the x-ray. For his discovery, he was to receive the Nobel Prize in Physics in 1901. It was not until 1927 that an abdominal x-ray study first proved diagnostic of pancreatic disease (pancreatic calculi). Radiologic imaging of the pancreas was to become an essential step in the diagnosis of pancreatic disease.

12. The problem, later to be known as diabetes, had been recognized at least 1500 years BC: (“Overabundant urine”, unquenchable thirst, a sweet-tasting urine, weight loss, death”.) Name of Diabetes was given by Aretaeus who lived in Asia Minor. (ca A.D. 81-150).

13. In 1889, Joseph F. von Mering (1849-1908) and Oskar Minkowski (1858-1931) of Strasbourg proved that total pancreatectomy in the dog resulted in diabetes.

14. In 1921, at the University of Toronto, Frederick Grant Banting (1891 – 1941) a young orthopedic surgeon, and Charles Herbert Best (1899-1978), a medical student, discovered insulin. First, they ligated the dog’s pancreatic duct. Next, they waited 8 – 10 weeks for the obstructed duct to cause the pancreatic acini to degenerate. They then excised the atrophic pancreas and extracted the insulin. Another dog had had his pancreas removed and was almost comatose from his resulting uncontrolled diabetes. They then injected intervenously the pancreatic extract into the second dog, which immediately recovered. Within 6 months Leonard Thompson who, at age 14, was dying of uncontrolled diabetes, was successfully treated with a refined extract. Within 18 months insulin was being marketed by multiple pharmaceutical companies. In 1923 Banting and J.J. R. MacLeod, Professor of Physiology at Toronto, received the Nobel Prize in Medicine and Physiology; Best was omitted. Banting, who was very upset by the omission split his prize money with his young colleague. The first islet cell hormone had been discovered – leading to the discovery of a new disease: an insulin producing tumor.

15. In 1958 Frederick Sanger (b. 1918) of England, was awarded the Nobel Prize in Chemistry for the determination of the molecular structure of insulin.

16. The digestive enzymes, (amylase, lipase, trypsin, etc), secreted by the pancreas into the intestine, were discovered in the mid to late 19th century. Demonstration of their effectiveness in breaking down fats, proteins and starches to smaller molecules which could be from the intestines was gradual. Discovery of this principle of digestive enzymes, as a primary function of the pancreas, included, among many other contributors, Johann Nepomuk Eberle (1798-1834); of Bavaria, Claude Bernard (1813-1878); of Paris, Alexander Danilevsky, of St. Petersburg (in 1862), and Willy Kuhne (1837-1900), of Amsterdam and Heidelberg.

17. In 1901 Karl Landsteiner, an Austrian- American, discovered human blood types – making possible blood transfusion and the development of blood banks. This was an essential step in the development of pancreatic surgery. For his discovery he was awarded the Nobel Prize in Physiology or Medicine in 1930.

18. In 1902, W.B. Bayliss and E.H. Starling, working in London, discovered secretin, and thereby introduced the hormone concept. Secretin, secreted by the duodenal and jejunal mucosa, stimulated the pancreas to secrete its juice into the intestine. In 1905, J.S. Edkins (1863-1940), also of London, was to discover “gastrin”, another hormone secreted by the stomach, which resulted in an outpouring of hydrochloric acid by the stomach. In 1955, Robert Zollinger and Edwin Ellison, of Columbus, Ohio, described the gastrinoma – a gastrin-producing tumor, often occurring within the pancreas. Another new disease: virulent gastro-intestinal ulcers, the “Zollinger- Ellison syndrome”, had been discovered.

19. In 1908, Julius Wohlgemuth, of Berlin, described a method for measuring the concentration of amylase (“diastase”) in the serum, thereby introducing the potential for diagnosing acute pancreatitis prior to laparotomy or autopsy.

20. Beginning in 1898, surgeons undertook resections of cancers of the ampulla of Vater and head of the pancreas: Codivilla (1898) and Halsted (1898), Kausch (1909), Hirschel (1913), Tenani (1918), and Whipple (1934-1940), culminating in the latter’s successful one-stage resection of a cancer of the head of the pancreas in New York City on March 6, 1940. To Allen O. Whipple (1881-1963), son of American missionaries in Persia, perhaps more than to any other individual, is due the recognition as being the “Father of Pancreatic Surgery”.

21. The discovery of Vitamin K, which corrected the blood-coagulation deficiency associated with obstructive jaundice, often a complication of pancreatic cancer, was made by Henrik Dam (1895-1976), of Denmark, in 1929, for which he shared with Edward Doisy (1893-1986), the Nobel prize in Physiology or Medicine in 1943.

22. The first human pancreatic transplant of the modern era was performed at the University of Minneapolis; the patient, a 28-year-old female with uncontrolled diabetes and renal failure. On December 17, 1966, a surgical team of Kelly, Lillehei, Merkel, Idezuki and Goetz, transplanted a cadaveric kidney and pancreas. The grafts function for almost two months.

23. In 1974, George Palade, a Romanian-American working at the Rockefeller Institute in New York, was awarded the Nobel Prize in Physiology or Medicine for his description in the exocrine pancreatic cell of the biochemical steps in protein synthesis, segregation, transport, storage and secretion, and the ultrastructural units related to each process.