who was interested in animal experiments, had previously succeeded where others had failed. He had managed to hepatectomize birds, such as geese, years before any others. Naunyn and Minkowski were also interested in determining the origins of bile pigments. In 1886, the hepatectomies allowed Minkowski to demonstrate the liver’s role in hemolytic jaundice [4].
Fig. 2. Prof. Adolph Kussmaul (Deutsches Archiv für klinische Medizin 73, Leipzig 1902).
In 1888 Bernhard Naunyn was appointed to the chair of Internal Medicine at the Kaiser Wilhelm University of Strasbourg. This new university was, at the time, the highest funded place for medical research in the German Empire, perhaps in the world – the German Emperor wanted to influence local opinion in favor of Germany. The university attracted a myriad of scientists who went on to achieve fame. Names such as Adolf Kussmaul, Friedrich Daniel von Recklinghausen, Hans Chiary, Wilhelm Konrad Röntgen, and Emil Fischer, to name but a few, were associated with this prestigious educational institution.
Bernard Naunyn was the successor of Adolf Kussmaul, known for his description of the “deep” respiration in diabetic ketoacidosis (Fig. 2). When he was a student, Kussmaul introduced, through poetic compositions, a character named “Biedermeier” – this name would later baptize a trend and style associated with the beginning of the 19th century. Naunyn knew that Kussmaul had not at all supported his nomination (like Hoppe-Seyler, the biochemist in Strasbourg) and therefore he avoided meeting Kussmaul when he moved to Strasbourg. Kussmaul left the stunning professor’s villa in Elisabethstrasse 7, adjacent to the hospital, in the morning of April 8, 1888. Naunyn turned up in the afternoon, once his predecessor had left (Fig. 3).
In 1888, Oskar Minkowski followed Naunyn to Strasbourg. It was here that he made his major discovery of pancreatic diabetes. This revelation began in April 1889 with a discussion between two researchers from different fields: the 31-year-young Dr. Oscar Minkowski, working in Naunyn’s Clinical Department who had arrived just a year beforehand, and the 40-year-old Prof. Extraordinarius Freiherr Josef von Mering, who was working in biochemistry and physiology and internal medicine. Von Mering was well established in Strasburg having been situated there since 1878. He had published numerous papers, including one on his discovery of the glucosuric effect of phlorizin in 1885 [5]. Their discussion took place in the library of Prof. Hoppe-Seyler’s institute of biochemistry (the first of its kind worldwide) and von Mering had the “home field advantage.”
Decades later there was some discussion concerning the contribution of the two researchers to the discovery of pancreatic diabetes. A student of von Mering wrote a letter to Minkowski, stating that von Mering’s contribution was not reported correctly. Therefore, Minkowski wrote a letter in 1926 describing the events surrounding the discovery and deposited it in the archives in Breslau (known today as Wrocław) in case “at some future time a student of the history of diabetes may be interested in the true facts.” Two professors, dismissed following the Nazi takeover in 1933, rescued the letter from the archives before leaving Germany. In the letter Minkowski wrote:
Fig. 3. Elisabethstrasse 7 in Strasbourg, home of Kussmaul and Naunyn (photo Dr. Jörgens).
In April 1889, I went to the biochemical institute to read some chemical publications, which were not available in our clinic, and I met von Mering in the library. He had recently recommended Lipantin, an oil preparation with 6% of free fatty acids as a replacement of cod-liver oil because he thought that the free fatty acids may be the most important substance acting in cod-liver oil.
Von Mering asked me, “Do you use Lipantin frequently in your clinic?” “Oh no,” I replied. “We give only good butter to our patients and not rancid oil.”
“Don’t laugh,” he said. “Healthy people must metabolize lipids and if the pancreas doesn’t work correctly, we have to give metabolized lipids to them.”
“Did you prove this in an experiment?” I asked him. This conversation was followed by a discussion on how to do the experiment and finally, Minkowski mentioned that this question should be studied in a dog following pancreatectomy.
“This is not so easy,” continued von Mering, “since the enzymes of the pancreas will still go into the intestines when you perform a ligation of the ductus pancreaticus.”
“What I mean is, we should take out the whole pancreas!”
“This operation is impossible,” von Mering replied.
Since I did not know about Claude Bernard’s publication stating that no animal would survive total pancreatectomy, and due to my young age, overestimating my capacities as a laboratory surgeon, I exclaimed, “There are no impossible operations. Give me a dog and I will take out his pancreas today.” Von Mehring replied, “Okay, I have a dog and you can try it.” The same day, I performed pancreatectomy in a dog in Naunyn’s laboratory with the assistance of von Mehring. The animal survived and initially seemed to be doing well. The day after the operation, von Mehring had to travel to Colmar because his father-in-law was suffering from severe pneumonia. He had to stay for one week. In the meantime the dog, which had been clean before, started to urinate more and more frequently in the laboratory. I reprimanded the laboratory assistant for not walking the dog frequently enough, but he replied, “I do walk him frequently but this animal is funny. As soon as it returns, it urinates again even immediately after having done it outside.” This observation led me to examine the urine of the dog [6].
Without this controversial discussion on lipids – which had no relation to the final discovery – the experiments would not have been carried out. Von Mering provided the dog and they performed the surgery together in Naunyn’s laboratory that same afternoon. Minkowski was legendary for his manual dexterity, and, as mentioned, had performed the world’s first successful hepatectomy upon a goose (successful in that the creature did not expire immediately). Sauerbruch, a giant in German surgery, called Minkowski “the greatest experimental physiologist of his time.” However, von Mering was also very well trained in experimental physiology – he had worked in the institute of Prof. Ludwig in Leipzig, one of the founders of modern physiology and had published a superlative study on glucose metabolism [7]. In the same institute some years later a young Scottish physician was trained in physiology and published his first paper (in German language), it was J.J.R. Macleod – honored with the Noble Prize for the discovery of insulin.
Fig. 4. The scientific laboratory of Naunyn’s hospital (archives of the Strasbourg University, provided by Prof. Brogard†, Strasbourg, unpubl.).
Minkowski and von Mering were a surgical “dream team” and succeeded, in contrast to Claude Bernard, in successfully performing a pancreatectomy. The operation was carried out in Naunyn’s laboratory which was located on Elisabethstrasse near Naunyn’s house.
Thanks to the historic research of Prof. Brogard in Strasbourg we know the floorplan of this laboratory (
