Unveiling Diabetes - Historical Milestones in Diabetology. Группа авторов
metabolism.
2nd. By proper methods this secretion may be extracted and still retain its activity.
Fig. 5. The “murdered manuscript” on Scott’s work, 1912 [15].
3rd. This secretion is easily destroyed by oxidation or by the action of the digestive enzymes of the pancreas.
4th. The secretion is insoluble or nearly so in strong alcohol but is readily soluble in acidulated water.
5th. The failure of previous workers to procure satisfactory results was due to their not preventing oxidation or the action of the digestive enzymes.
This formulation would have aroused interest in the scientific community. Today a journalist of the university would publish a press release adding that this research may soon provide a lifesaving treatment for diabetes – the paper would make the headline of The Times! In contrast Carlson’s summary was long-winded and dreary. Anyone who read this paper in the American Journal of Physiology may have thought: one more of these unsuccessful pancreatic extracts followed by some weird hypotheses – how boring! But judge for yourself, Carlson’s version ends as follows [15]:
Fig. 6. Summary of Scott’s experiments in his thesis [14].
Summary: Intravenous injections of the pancreas extract, prepared as above, into dogs rendered diabetic by complete pancreatectomy diminish temporarily the sugar secretion and lower the D/N ratio in the urine. It does not follow that these effects are due to the internal secretion of the pancreas in the extract. The injections are usually followed by a temporary rise of the body temperature, and this may be a factor in the lower sugar output. Physiologists are not agreed as to whether the internal secretion acts by diminishing or retarding the passage of sugar from the tissue into the blood, or by increasing the oxidation of the sugar in the tissues. The pancreas extract may decrease the output of sugar from the tissues by a toxic or depressor action of the pancreas secretion. If this is the case, we ought to get the same results by extract of other tissues.
The position in Kansas was unpleasant and eventually Scott went to Columbia University in 1912. Probably in 1913, Scott tried to raise the interest of Prof. J.J.R. Macleod, already an important figure in research on glucose metabolism. However, Macleod, who was still working in the USA at the time, did not hire the young man who might have helped him to get the Noble Prize a decade earlier. Scott became Professor of Physiology at Columbia University, retired in 1942, and died in 1966.
Following the introduction of the insulin treatment of diabetes Scott wrote a letter to JAMA, explaining his scientific priority concerning the method to produce insulin from pancreas tissue, which was published in 1923 [16]. He did not, however, oppose the US patents granted to the Torontonians.
In December 1922, Dr. Roberts from Cambridge criticized the early studies by Banting and Best and pointed out the priority of Scott’s work in a letter to the British Medical Journal [17]. A reply appeared a week later in the BMJ written by Prof. Dale, who was awarded the Noble Prize in 1936 together with Otto Loewi: “He [Roberts] did not know that the work he attacks was the first, unaided attempt at research by two young enthusiasts; that one spent half the war as a combatant, and the rest, after being seriously wounded, as a medical officer in England, while the other had not even yet completed his student course. He had no conception of the personal sacrifice and the heroic labor in which their enterprise involved them. Working thus on their own initiative, without the invaluable help and cooperation, given later by the head of the laboratory, who, happened to be in Europe, when the earlier work was done, they may have wandered along a wrong trail for a time, though this has yet to be proved. It may be that they made an unnecessary detour, before finding themselves at the point where E.L. Scott had stopped” [18]. The fact that Scott stopped is the truth, but Banting’s service in the British Army has nothing to do with the scientific priority. Otherwise, to be fair, Dale should have mentioned that Scott volunteered to serve in the US Army and returned home from the war in France with tuberculosis.
Fig. 7. Book about Paulescu by Prof. Pavel [21].
Scott formally denied the authorship of the 1912 “Carlson” paper in 1964. It is quite unusual to deny authorship half a century after a publication [14]. His second wife published his biography in 1972. In the notes to his book on the discovery of insulin, Michael Bliss mentions that her “extreme claims are undercut by the published papers and by unpublished letters” without providing details [13, p. 250]. Reading Aleita Scott’s book, one gets the impression that the Torontonians were sadly unable to share a bit of their glory with their unhappy precursor – Banting and Macleod were too busy arguing aggressively about the value of their own contributions to the discovery of insulin – a bit more modesty would have suited both of them. They should have considered what the famous author (and medical doctor) Friedrich Schiller stated at the end of his inaugural lecture as a professor of history at the University of Jena: “To each merit is opened a path to immortality, to true immortality I mean where the work lives and continues, even if the name of its author should be left behind” [19].
Nicolai Paulescu: A Misquoted Discovery and Embarrassing Political Activities
Nicolai Paulescu (Fig. 7) was born in Bucharest in Romania on October 30, 1869 – the same year as Paul Langerhans published his thesis discovering the islets in the pancreas. Paulescu was the eldest of four children, one brother became a general in the Romanian Army. His parents were part of the very wealthy bourgeoisie in Bucharest and Nicolai received an exceptional education. He was fluent in ancient Greek and Latin and his French was perfect [20]. Romania’s intelligensia was closely related to France and therefore Paulescu took up his medical studies in Paris in the autumn of 1888 – the same year Oskar Minkowski moved from Königsberg to Strasbourg. In 1891 he passed, with honors, the exam to become intern at the Hôtel Dieu hospital, a renowned center for diabetes research and care since the time of Apollinaire Bouchardat. His thesis on the spleen was considered to be excellent and he graduated at the Sorbonne in Biochemistry and Physiology. Paulescu graduated in 1897 as an MD and worked in Paris at the Hôpital Notre-Dame du Perpétuel-Secours headed by Prof. Etienne Lanceraux, one of the most famous French physicians at this time. Both became friends and together published a textbook of medicine with nearly 4,000 pages [21]. Lanceraux believed in the pancreatic origin of diabetes. In several publications, starting in 1877, he argued for the existence of two forms of diabetes, one of them being pancreatic diabetes [22, 23]. Paulescu’s research activities covered many areas resulting