Unveiling Diabetes - Historical Milestones in Diabetology. Группа авторов
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Fig. 1. The house where Claude Bernard was born (photo Dr. V. Jörgens).
When he was 18 years old the family could no longer afford to keep their son at school. In January 1832, he found employment in a pharmacy in Lyon where the pharmacist sold a “remedy” containing up to 60 different drugs including opium. Claude was astounded when he noticed that the pharmacist took a lot of liberty with the formula of the drug which was considered to cure nearly everything. This experience must have awoken, for the first time, his objections against “empirical” medicine.
In Lyon, Claude frequently went to the Théatre des Célestines, where operettas and comedies were presented. He even composed a musical comedy himself entitled “La rose du Rhone” which, apparently, had some success – he earned 100 francs from it. Sadly this “Rose du Rhone” was never printed. Following this achievement, Claude embarked on a bigger project, a classical tragedy with the title “Anne de Bretagne.” He decided to leave the pharmacy in Lyon and travelled to Paris with dreams of a dazzling career as an author. As for the journey itself, it was sluggish, by horse-drawn carriage. Times were changing however, and just a decade later he would be able to take the train to his hometown.
A Failed Career as a Writer
In 1834, Claude Bernard arrived in Paris with his “Anne de Bretagne” and asked Saint Marc Girardin, writer and professor at the Sorbonne, for advice. Girardin told him, firmly, that he did not have any talent as a dramatist and that he should study something to support himself – why not medicine, since he already had acquired some knowledge in pharmacology? Claude Bernard nevertheless kept the manuscript “Anne de Bretagne” and gave it to a friend 1.5 years before his death, saying that he may publish it, but not until at least 5 years after Bernard’s death. A reprint of the piece is for sale in the Claude Bernard Museum in St. Julien, while the original can be found in the Bibliotheque Nationale in Paris. Fortunately, no theatre audience ever had to endure this tragedy. The widow of Claude Bernard opposed the posthumous publication of the piece. This minor act was possibly her only valuable contribution towards the reputation of her husband.
A Difficult Career Start
In autumn 1834, when he was 21 years old, Claude Bernard entered the Medical School in Paris. He was not a particularly outstanding student. Only the anatomy course unveiled his excellent manual talent. At this time there was no specific course on physiology. The leading researcher in this field in France was Prof. Magendie (1783–1855), who published a renowned textbook on physiology (Fig. 2). Magendie had the Chair of Physiology and a small laboratory at the Collège de France. At the same time Magendie headed a clinical department at Hôtel Dieu Hospital. When he was an intern at Hôtel Dieu, Claude noticed that Magendie was the only physician who was fighting against “bleeding” as the standard treatment of pneumonia. Magendie’s opinion was in contradiction with all textbooks, therefore the physicians in his department used to bleed the patients suffering from pneumonia once Magendie had left the ward.
Magendie was quite a boorish character. It took him some time to appoint Claude Bernard to his laboratory but, one day, while looking at Claude Bernard at the other end of a dissection table he shouted: “Hey, look here, I’ll take you as my préparateur at the Collège de France.”
Nevertheless, his salary as an assistant of Magendie was not sufficient for living and hence Bernard, together with a friend, opened a private laboratory where paying students could observe physiological experiments. This business model failed desperately. Everything seemed to be wrong. In 1844 he defended a thesis to become an agrégé – comparable to an assistant professor or the German Privatdozent – but he was unsuccessful. Another disappointment quickly followed in 1844 when his first application for membership in the Academy of Medicine was declined. At this point Claude Bernard felt like giving up his research career and returning home to practice medicine in his beloved Beaujolais region.
Fig. 2. “It is impossible to say what the role is of the liquid of the pancreas.” From the textbook on physiology by Magendie, 1817.
An “Arranged” Marriage
However, his friends found a solution for Claude Bernard’s chronic financial problems – a wife with a substantial dowry. In 1845 Bernard married Marie Françoise “Fanny” Martin, the daughter of a rich Parisian physician, for convenience. Her dowry served as an income for the young family and was even used to finance Claude’s research. In the marriage contract the bride’s dowry amounted to 60,000 francs, equivalent at the time to 180,000 L of wine! The couple had 4 children, 2 sons, both of whom died very young, and 2 daughters, who went on to join their mother in her political fight against “vivisection” led by catholic fundamentalists. The couple separated and finally divorced on August 22, 1870. His daughters continued their campaign against animal research and, after their deaths, their house had to 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