be sterilized by the authorities because of the rancid conditions after having been a refuge for countless homeless cats and dogs. Today no ethical committee would ever agree with Claude Bernard’s crude experiments which involved living animals being operated on without any anesthesia, which did not yet exist at the beginning of Claude Bernard’s career.
The Role of the Pancreas
In 1846 Claude Bernard began to focus his research on the study of metabolism and started his experiments to understand the function of the pancreas. In the 1816 edition of the textbook by his master, Magendie, it was still stated that the function of the pancreas was a mystery. In later years, the pancreas was considered to be an additional salivary gland. It was Claude Bernard who discovered that the secretion of the pancreas does not only help with digesting carbohydrates. Through a series of experiments, he was able to prove that the pancreatic juice could split fat into fatty acids and glycerine, and that proteins were dissolved by pancreatic juice after adding bile. Claude also noticed that the fetal pancreas had no effect on fat and found that the function of the pancreas on digestion begins only a very short time before birth. “Banting’s idea,” which indirectly resulted in the Noble prize for the treatment of diabetes with insulin, was based upon this finding. Bernard also tried pancreatectomy in dogs. Most attempts failed, except one – the dog survived but did not become diabetic. One can assume that, in this case, the pancreatectomy had not been complete. The discovery of pancreatic diabetes had to wait for the brilliant surgical skills of Minkowski and von Mering in 1889.
Understanding Glucose Metabolism
When Claude Bernard started to explore metabolism and diabetes, obscure theories and opinions about metabolism could be found in the textbooks. Magendie had published that animals were unable to synthetize glucose, protein, or fat. Apollinaire Bouchardat believed that diabetes was due to an increased absorption of glucose in the stomach (he changed his mind in later years following the findings of Bernard). Concerning glucose metabolism, in 1844 Mialhé (1807–1886) wrote that glucose was transported by the lymphatic system into the blood and “burned” there. Many assumed that the lungs were the place where this “burning” occurred. Claude encapsulated the level of knowledge in his little red notebook, which is still kept at the Collège de France: “The digestion of carbohydrates takes place in two steps: First: trans-formation of carbohydrates into glucose, second: glucose is burned in the lung. If this doesn’t happen, diabetes occurs.” Claude Bernard asked himself: “Is this true?”
Quoting Claude Bernard’s own words, let us explore the steps leading to his major discovery in August 1848: “To clarify this question, I had to find the sugar in the blood, and to look for the sugar from the vessel of the intestine where it is absorbed to finally the place where it is burned. To study this question I gave sweet milk soup to a dog and sacrificed the dog during digestion. I detected sugar in the vena hepatica. It was logic to conclude that all the glucose that I found in this vein resulted from the sugar the dog had eaten. More than one researcher would have stopped here and would have thought that any control experiment was useless. But I performed a control experiment because I am convinced that in physiology you should always doubt even if the doubt doesn’t seem to be permitted. Therefore, as a control experiment I chose a dog that was exclusively fed with meat. This animal was scarified during digestion and the glucose content of the vena hepatica was examined. I was very astonished noticing that the vena hepatica contained sugar even if the dog hadn’t eaten any carbohydrates.”
Fig. 3. Handwritten by Claude Bernard: “I baptize this substance glycogen” [2].
Following this observation, Claude Bernard wrote in his little notebook: “I don’t understand anything anymore!” (“C’est à n’y rien comprendre!”)
In his key publication De l’origine du sucre in October 1848, Claude Bernard summed up the results of his numerous experiments: “Normally in the blood and the liver there is always sugar. This sugar is produced by the liver. This is independent of the nutrition with sugar or carbohydrate. This synthesis of sugar starts already before birth and it is therefore totally independent of nutrition” [1]. This discovery was the beginning of modern metabolic research and, soon afterwards, Claude Bernard became famous all over the world.
When carrying out his experiments, martial law prevailed in Paris, which was only abolished on October 12,1848. A total of 5,000 rebellious workers had been killed by the army in Paris during the desperate June Revolution. While Claude was sacrificing dogs in his laboratory, 25,000 people went to prison after the failure of this first proletarian revolution in Europe. In December 1848, Louis Napoleon (Napoleon III) was elected as 1st President of the Republic of France with 74% of the vote. Claude’s fame would soon begin to shine like that of the last French Emperor. Politically, Bernard cannot be called an anti-royalist, it is known that he even made some critical comments against the liberal political ideas of Rudolf Virchow.
The Discovery of Glycogen
The next highlight in the career of Claude Bernard was his discovery of glycogen and its role in metabolism. On September 24, 1855, he reported to the medical academy in Paris: “Once having washed the liver with water 24 h later you can discover glucose in the vena hepatica. There must have been a production of new glucose. Where does it come from?” Finally, in February 1857, he isolated glycogen and wrote in his notebook: “I baptize this substance glycogen” (Fig. 3). The summary of the work was published in 1857 as “Nouvelles recherches expérimentales sur les phénomènes glycogéniques du foie” [3].
La Piqûre Diabétique
Another observation he became famous for during his lifetime was his “piqûre diabétique” (Fig. 4). On April 3, 1849, Claude Bernard punctured the fourth ventricle of a dog (and later in numerous other animals). Twenty minutes later glucosuria occurred, and 2 h later it was even more pronounced. He published this discovery, discussing the possibility of a central nervous origin of diabetes [4, 5]. The title of his exuberant first report to the biological society [4] was: “Chiens Rendus Diabétiques.” The use of the plural, however, was wrong. The experiment was positive in only 1 of the dogs, at least 3 others did not become diabetic. For decades, these experiments were an argument for a neuronal pathogenesis of diabetes even if his experiments were difficult to repeat. Some of the effects of Bernard’s “piqûre diabétique” may simply be explained by the terrible stress the tortured animals had been forced to endure.
Fig. 4. Drawing by Claude Bernard explaining the “piqûre diabétique” in a rabbit, from the archives of the Collège de France [9].
Honorem ei, qui meritur
After these discoveries, one honor followed the next. In 1849 the red ribbon of the Legion of Honour
