The Nobel Prize And The Pancreas

How The Pancreas Was Directly Involved In 14 Nobel Prizes

Alfred Nobel, born in Stockholm in October 1833, was a chemist, engineer and prolific inventor. In his career, he became extremely wealthy from a total of 355 inventions. In 1894 he purchased the Bofors iron and steel mill, starting a period of inventions centered around high explosives and military armaments. He is best known for his inventions of ballistite and dynamite, earning the disparaging nickname "the merchant of death" during his own lifetime.

In 1895, in an effort to rehabilitate his image and leave a lasting legacy that did not involve death or destruction, he signed a will that would leave 94% of his assets (estimated at $200 million dollars in 2008) to form a foundation to award five prizes annually to honor those whose contributions had conferred the greatest benefit to humankind.  The first Nobel Prize was awarded in 1901 to Wilhelm Röntgen for his discovery of X-rays.

By 1900, the histology and general understanding of the function of the pancreas was in place. However, the details and in-depth understanding of the pancreatic molecular machinery placed the pancreas directly at the doorstep of the Nobel prize committee. These secrets also often revealed how the body functioned generally.

The first pancreas-related Nobel prize was awarded in 1904 to Ivan Pavlov "in recognition of his work on the physiology of digestion, through which knowledge on vital aspects of the subject has been transformed and enlarged." Pavlov developed the first modern physiology laboratory with multiple staff who worked together as a team. They showed that psychic stimulation or putting food in the stomach led to secretion from the pancreas, which was collected via a pancreatic fistula. 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.

The second Nobel prize that is related to the pancreas was awarded in 1907 to Emil Theodor Kocher, the brilliant Swiss surgeon. In 1903 "he described the surgical method that bears his name, also known as mobilization of the duodenum, which is used to reach the pancreas during operations on this organ." He designed many surgical instruments in use to this day and the prize itself was for "“his work on the physiology, pathology and surgery of the thyroid gland”.

The third Nobel prize for work about the pancreas is perhaps the most controversial, and we have covered this in detail in one of our prior Sweetbreads articles. This Nobel prize was awarded in 1923 for the discovery of insulin to Frederick Banting and John Macleod. Their work was groundbreaking, revolutionary and saved millions of lives. Their feud is legendary.

The next time the exocrine pancreas visited Stockholm was in 1946, when John H. Northrup shared the Nobel Prize in Chemistry for the discovery that enzymes were proteins and could be crystallized. Northrup, working at the Rockefeller Institute, initially crystallized pepsin from gastric juice. As part of a long and productive collaboration with Moses Kunitz, they crystallized trypsin and trypsinogen, discovered and crystallized chymotrypsinogen as a contaminant in trypsin, and Kunitz went on to crystallize ribonuclease, deoxyribonuclease, and the trypsin inhibitor from pancreas and soy beans.

Frederick Sanger won the Nobel prize in chemistry in 1958 for “his work on the structure of proteins, especially insulin”. In 1953 he had fully sequenced the amino acid structure of insulin. In 1960 he became interested in nucleic acids and in 1980 became the fourth person to received a second Nobel prize for his pioneering work in DNA sequencing, joining Marie Curie (physics in 1903 and chemistry in 1911), Linus Carl Pauling (chemistry in 1954 and peace in 1962) and John Bardeen (physics in 1956 and 1972). His method was the critical centerpiece of the Human Genome Project and he is regarded as one of the most important scientists of the 20th century.

Dorothy Hodgkin joined this boy's club of pancreas scientists and clinicians in 1964, receiving the Nobel prize for “her determinations of structures of important biochemical substances by X-ray crystallography”. She discovered the 3D structure of many substances such as insulin (1934), penicillin (1942, during World War II) and vitamin B12 (1948).

Although by this point in history the overall secretory pathways of the pancreas were well-known, the molecular machinery was not.  The new techniques of ultracentrifugation and electron microscopy allowed detailed understanding of cell function and this was applied to the pancreas and liver in earnest. Christian René de Duve, George E. Palade and Albert Claude's work at Rockefeller Institute in 1974 earned them the Nobel prize for “their discoveries regarding the structural and functional organization of the cell”. They broke apart the endoplasmic reticulum and characterized pancreatic zymogen granules in great detail. What they described as Palade particles ultimately were in fact ribosomes. During this period, not only was the work of the Rockefeller group pivotal in terms of technical development, but it also set high technical and conceptual standards in the field, with emphasis placed on the necessity to link structure and function. The lab was considered the most diversified and advanced in the country for research in biological electron microscopy, and their every discovery was closely followed through presentations at the American Association of Anatomists, the Histochemical Society, the Electron Microscope Society of America (before 1960), and the American Society of Cell Biology (after 1960).

Rosalyn Sussman Yalow, Roger Guillemin and Andrew Viktor Schally shared the Nobel prize in 1977 for their discoveries and development of a radioimmunoassay for peptide hormones, specifically, circulating insulin and somatostatin. Based on the development of this method, they could gradually determine the plasma concentration of different hormones and other substances that circulate in the blood in very small quantities.

The last Nobel Prize concerning the pancreas is somewhat tangential, but the experiments could not have been performed without it. Günter Blobel born in Eastern Germany, now Poland, joined the Palade group at Rockefeller as a postdoctoral fellow in 1967 after receiving his PhD at Wisconsin. His award, in 1999 was for “discovering that proteins have intrinsic signals that govern their transport and status in cells”. For his discoveries he used pancreatic acinar cells. In the 1970s he began to study the process by which proteins are transported through the membranes of different organelles in the canine pancreas. His works reveal the existence of a cellular coding system whereby each synthesized protein has established an organelle-specific direction that is recognized by receptors on the surface of the organelle. This seminal work has extended far beyond the pancreas, to the study of cystic fibrosis, Alzheimer's disease and AIDS.

As we have gained more knowledge about the pancreas, we have gained more knowledge about the human body as a whole. This has certainly deserved the noble/Nobel recognition of benefiting the whole of mankind.

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