of the city.
Oskar Minkowski was born here on 13 January 1858. In 1872 anti-Semitic measures adopted by the tsarist government forced the Minkowski family to emigrate to the nearby Königsberg in Prussia. Max, Minkowski’s older brother, later took over the family business and became prosperous here as a middleman, trading in grain. Hermann, his younger brother, become a world-famous professor of mathematics and found a place in history – all students of mathematics know his name. His contributions to the geometry of numbers were essential and his book Space and Time was a precursor to the discoveries of Einstein, who attended his lectures. It is highly probable that Hermann would have shared the Noble Prize with Einstein had he not died on January 12, 1909 from appendicitis.
In Königsberg (now Kaliningrad) the family lived in the city center, in Knochenstrasse 31–32, near the river Pregel. This was a street lined with the buildings of merchants, akin to the streets of Lübeck as depicted in Thomas Mann’s literary masterpiece Buddenbrooks. His father’s business was flourishing and two of his sons went to the University of Königsberg, which dates back to 1544. This place of learning was the proud alma mater of such imminent names as Immanuel Kant and the physician and physicist Prof. Hermann von Helmholtz, who invented the ophthalmoscope in Königsberg in 1851 – a discovery which became vital for people with diabetes.
Oskar Minkowski studied medicine in Freiburg and Strasbourg and completed his medical studies in Königsberg. His medical thesis was accepted in 1881. The supervisor of his thesis was Prof. Bernhard Naunyn (1839–1925; Fig. 1), who was the head of the Medical University Clinic in Königsberg from 1872 to 1888. Before Königsberg, Naunyn had worked in Berlin, Dorpat, and Bern.
In his autobiography, Bernhard Naunyn describes his favorite pupil, Oscar Minkowski: “I found a first-class employee in Oskar Minkowski. He was of substantial benefit to me. Minkowski is a man of outstanding intelligence. His independent and clear way of thinking and his mental mobility based on very speedy and precise perceptions gave him a perfect basis for scientific research” [2].
Fig. 1. Prof. Bernhard Naunyn, from Naunyn [2].
Minkowski’s dissertation was a study of the relationship between electrical stimulation of the brain and blood circulation. His abilities won him an assistantship in Naunyn’s clinic. Ernst Stadelmann, Minkowski’s predecessor, had been analyzing diabetic urine and had isolated an unknown acid as one of its components. In 1884 Minkowski identified this substance as β-hydroxybutyrate [3]. Further research enabled Minkowski to confirm the importance of acidosis in diabetic coma. Naunyn was also investigating the role of the liver in metabolism. In 1885, Naunyn proposed observing the effects of hepatectomy on a dove and asked Minkowski to attempt this delicate operation. Minkowski, 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.”