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Sir Frederick Banting, victim of plane crush (February 20, 1941). News report on the accident in the Alliston Herald. Public domain
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Aims
The general objective has been the historiographical investigation of the organotherapy of diabetes mellitus between 1906 and 1923 in its scientific, social and political dimensions, with special emphasis on the most relevant contributions of researchers and institutions and on the controversies generated on the priority of the "discovery" of...
Citations
... In accordance with the premises of the call, the awarded researcher would give the "NC Paulescu Memorial Lecture" on August 27, 2003, as part of an academic act to be held at the Hôtel Dieu (Paris), where a commemorative plaque and sculptures of N.C. Paulescu and his mentor, E. Lancereaux, would be installed [20]. ...
Aims
Since the Nobel Prize in Physiology or Medicine was awarded in 1923 to FG Banting and JJR Macleod, many voices have been raised against this decision. The bitterest protest was that of the Romanian scientist Nicolae C. Paulescu. In 2002, The Romanian Academy of Sciences, the European Association for the Study of Diabetes (EASD) and the International Diabetes Federation (IDF) planned to hold a series of academic events the following year in Paris to acknowledge Paulescu's scientific merits in the discovery of the antidiabetic hormone. However, the initiative was cancelled in August 2003, when the European Center of the Simon Wiesenthal Foundation (SWC) accused Paulescu of being antisemitic. The authors of this manuscript have decided to approach "the Paulescu case" from its double aspect, scientific and sociopolitical, to analyze the circumstances surrounding the discovery of the antidiabetic hormone, and Paulescu's alleged antisemitic past in the historical context of the Romanian nation in the interwar period.
Methods
We contacted the SWC and people related to the 2003 events in Paris. We performed a comparative review of the documents published by the Toronto group and by Paulescu and analyzed the correspondence and articles generated by international experts from the scientific community interested in the controversy. We carried out an exhaustive bibliographic search through several online catalogs (INDEXCAT, NLM Gateway, EUREKA, MEDHIST). We travelled to Bucharest, where we visited Paulescu's house-museum, interviewed a former student of the Romanian professor, and a prominent medical historian who was knowledgeable about Paulescu's scientific and political biography. Dan Angelescu†, son of Dr. Constantin Angelescu (1904–1990), Paulescu's nephew and collaborator, provided us with a copy of all the available documentation from Paulescu's personal archive. It constitutes an essential source for understanding Paulescu's personal, political and academic biography. Archives consulted: Românǎ Academy (Bucharest). Personal Archive of Paulescu, House -Museum (Bucharest)*. Romanian Jewish Heritage (Bucharest). http://romanianjewish.org/ **. Simon Wiesenthal Center (Los Angeles, CA) http://www.wiesenthal.com **. Romanian Patent Office. Oficiul de Stat pentru Invenții şi Mǎrci (OSIM) (Bucharest)***. Nobel Archives (Stockholm) https://www.nobelprize.org . Internet Archive (San Francisco, CA) https://archive.org **. Wellcome Library (London) https://wellcomelibrary.org **. The European Library https://www.theeuropeanlibrary.org/ **. US National Library of Medicine, NLM historical collections http://www.nlm.nih.gov/hmd/index.html **. US. Holocaust Memorial Museum http://www.ushmm.org/ (*: archive consulted on site; **: material found in the online catalog of the archive; ***: archivists sent us digitized copies of archival material). Books consulted for information on the history of Romania and antisemitism: “Nationalist ideology and antisemitism. The case of Romanian intellectuals in the 1930s”, by Leon Volovici; “The mystique of ultranationalism: History of the Iron Guard, Romania, 1919–1941” by Francisco Vega; “Romania 1866–1947”, by Keith Hitchins; “History of Romania. Compendium”, by Ioan-Aurel Pop and Joan Bolovan; “The Holocaust in Romania. The destruction of Jews and Gypsies under the Antonescu regime, 1940–1944”, by Radu Ioanid; “The Jews of East Central Europe between the World Wars”, by Ezra Mendelson; “Cultural Politics in Greater Romania. Regionalism, Nation Building and Ethnic Struggle, 1918–1930”, by Irina Livezeanu, and “Judeophobia. How and when it is born, where and why it survives”, by Gustavo Daniel Perednik. Articles are referenced in the bibliography section at the end of the manuscript.
Results
A-Nicolae Paulescu developed an intense long-term research activity, which included complete pancreatectomy and preparation of a pancreatic extract (PE) containing the antidiabetic hormone he called pancreina. Parenteral administration of the PE achieved excellent results in the treatment of experimental diabetes in dogs and induction of hypoglycemia in the healthy animal. This work was initiated before 1916 and published at least eight months antedating the publication of the first article by Banting and Best (February 1922), who were acquainted with Paulescu's results, but misinterpreted them. The pancreatic extract of the two Canadian researchers, -iletin/insulin-, only achieved similar results to that of the Romanian scientist once they abandoned the use of the "degenerated pancreas" extract (ligation of the ductal system), replacing it with the pancreas of adult or fetal bovine. Pancreina and insulin were very similar. The award of the Nobel Prize in Physiology or Medicine to FG Banting and JJR Macleod in October 1923 honored the successful clinical use of insulin in patients with diabetes mellitus. Paulescu's achievements were ignored. B-Nicolae Paulescu publicly manifested his Judeophobic ideology on multiple occasions in academic and political interventions and in publications and participated with other figures from the Romanian intellectual sphere in the founding of the Uniunea Național Crestinǎ (UNC, National Christian Union) in 1922 and of the Liga Apǎrǎrii Național Cresține (LANC, League for Christian National Defense) in 1923, antisemitic far-right political parties, associated with an irrational Christian orthodoxy and hatred of Jews. Paulescu played a pivotal role in the spread of antisemitism.
Conclusions
A-The Romanian scientist NC Paulescu started an intense research program aimed at the isolation of the antidiabetic hormone before 1916, including an original procedure of pancreatectomy in the dog and the elaboration of a pancreatic extract that achieved excellent results in the treatment of experimental diabetes, demonstrating its beneficial effects on the metabolism of carbohydrates, proteins and fats and reducing both glycosuria and glycemia and the urinary excretion of ketone bodies of depancreatized dogs toward normality. The results of these investigations were published in 1920 and 1921, predating the first report published by FG Banting and CH Best in February 1922. It has been sufficiently demonstrated that Canadian researchers were aware of Paulescu's excellent results, mentioning them only in passing, albeit erroneously misrepresenting key results of the Romanian scientist's publication in the aforementioned seminal Canadian article. Expert historians and international scientists have recognized that the pancreatic extract that Paulescu called pancreina and that obtained by Banting and Best, insulin, were very similar. The October 1923 award of the Nobel Prize in Physiology or Medicine to FG Banting and JJR Macleod ignored Paulescu's scientific achievements in the treatment of experimental diabetes and rewarded the extraordinary advance of insulin treatment in human diabetes. B-At the end of August 2003, a few days before the date of the celebration at the Hôtel Dieu in Paris of the scheduled program of tribute to the scientific merits of NC Paulescu and his important contribution to the discovery of the antidiabetic hormone, convened by the Romanian Academy and the International Diabetes Federation, the Wiesenthal Foundation publicly accused the Romanian scientist of being an antisemite, an act that determined the cancellation of the announced events. The exhaustive investigation of the personal convictions and antisemitic behavior of Nicolae C. Paulescu has undoubtedly documented the Judeophobic ideology of the Romanian scientist, linked to his orthodox religious radicalism, manifested in multiple documents (mostly pamphlets) and interventions in collaboration with other relevant personalities of the Romanian intelligentsia of his time. Furthermore, Paulescu participated in the creation of political organizations of the most radical extreme right that played a fundamental role in the spread of antisemitism amongst the Romanian population and the university community.
... The treatment was associated with adverse side effects (1906)(1907)(1908) [27,28]. C. Zülzer obtained patents in Germany, Great Britain and USA for acomatol, his original formulation of pancreatic extract (1908-1912) [29]. D. Zülzer and Camille Reuter managed to minimize the toxicity of the pancreatic extract and increase its power to such an extent that it generated severe hypoglycemia (years 1913-1914) in the dog [30]. ...
... D. Zülzer and Camille Reuter managed to minimize the toxicity of the pancreatic extract and increase its power to such an extent that it generated severe hypoglycemia (years 1913-1914) in the dog [30]. The start of the First World War and the decision of Hoffmann La Roche to cancel the financial support precluded the continuation of the research project [28,29]. In 1923, Zülzer claimed the priority of the discovery of insulin in a document released by an international agency (Suppl. ...
... The Director of the Nobel Institute answered Milcu and Pavel's letter on December, 29,1969, stating that, according to the statutes of the Nobel Foundation, the Nobel Prize can only be awarded to shortlisted candidates, but Paulescu had not been nominated. Tiselius added that, in his opinion, Paulescu also deserved the prize [61]. ...
Aims:
To analyze the main contributions to the discovery of the antidiabetic hormone in the period between 1889, the year in which Oskar Minkowski demonstrated that complete pancreatectomy in dogs caused diabetes, and the year 1923, the date in which the clinical use of insulin was consolidated. A main objective has been to review the controversies that followed the Nobel Prize and to outline the role of the priority rule in Science.
Methods:
We have considered the priority rule defined by Robert Merton in 1957, which takes into account the date of acceptance of the report of a discovery in an accredited scientific journal and/or the granting of a patent, complemented by the criteria set out by Ronald Vale and Anthony Hyman (2016) regarding the transfer of information to the scientific community and its validation by it. The awarding of the Nobel Prize in Physiology or Medicine in October 1923 has represented a frame of reference. The claims and disputes regarding the prioritization of the contributions of the main researchers in the organotherapy of diabetes have been analyzed through the study of their scientific production and the debate generated in academic institutions.
Main results and conclusions:
(1) According to the criteria of Merton, Vale and Hyman, the priority of the discovery of the antidiabetic hormone corresponds to the investigations developed in Europe by E. Gley (1900), GL Zülzer (1908) and NC Paulescu (1920). (2) The active principle of the pancreatic extracts developed by Zülzer (acomatol), Paulescu (pancreina) and Banting and Best (insulin) was the same. (3) JB Collip succeeded in isolating the active ingredient from the pancreatic extract in January 1922, eliminating impurities to the point of enabling its use in the clinic. (4) In 1972, the Nobel Foundation modified the purpose of the 1923 Physiology or Medicine award to Banting and Macleod by introducing a new wording: "the credit for having produced the pancreatic hormone in a practical available form" (instead of "for the discovery of insulin").
The discovery of insulin was presented to the international medical community on May 3, 1922. Since then, insulin has become one of the most effective pharmacological agents used to treat type 1 and type 2 diabetes mellitus. However, the initiation and intensification of insulin therapy is often delayed in people living with type 2 diabetes due to numerous challenges associated with daily subcutaneous administration. Reducing the frequency of injections, using insulin pens instead of syringes and vials, simplifying treatment regimens, or administering insulin through alternative routes may help improve adherence to and persistence with insulin therapy among people living with diabetes. As the world commemorates the centennial of the commercialization of insulin, the aims of this article are to provide an overview of insulin therapy and to summarize clinically significant findings from phase 3 clinical trials evaluating less frequent dosing of insulin and the non-injectable administration of insulin.
