Diabetes before the Concept of Organ Replacement

Next to the thyroid gland, the pancreas was the other organ that demonstrated the importance of organ replacement to doctors and scientists at the turn of the twentieth century. Before diabetes was associated with the pancreas, it was as much of a mystery as cretinism and myxedema had been. The disease entity of diabetes, however, was older and more clearly defined than the thyroid diseases. Its definition was based on the leading symptom, the presence of glucose in the urine (glycosuria), which gave the description of diabetes a continuity that can be traced back to antiquity. In the 1880s the general consensus was that diabetes was characterized by glycosuria, increased urination, thirst, progressive weight loss, and physical weakness. The definition thus followed the clinical picture and not the causal mechanism. In his 1877 lectures on diabetes, Claude Bernard summarized the state of the art on this mechanism: to date, neither clinical classification nor pathological anatomy had revealed the cause and pathogenesis of diabetes, and pathologists had not been able to associate the disease with any morphologically identifiable lesion of a particular organ. None of the numerous possible localizations of the disease (liver, kidneys, stomach, duodenum) seemed compelling. At the time, the pancreas was known to be an organ with an external secretion into the intestines. Since the 1870s, findings of pathological changes in the pancreases of diabetics had sporadically given rise to speculation about the contribution of that organ to the pathomechanism of the disease. These findings did not, however, lead to redefining diabetes as an organ disease; instead, this new definition was brought about by experimental research after 1889.

Performing experimental research on diabetes was not new at the time. Some of the earlier attempts at explaining diabetes had already been based on the findings of experimental physiology. In the 1840s and 1850s, Bernard showed that the liver produced and secreted glucose. Since diabetes was characterized by the presence of too much glucose in the blood, it seemed that it could be a liver disease. In addition, Bernard had observed in 1849 that glycosuria occurred in laboratory animals when they were pricked (piqûre diabétique) in a certain spot at the base of the fourth ventricle of the brain.