Recognition at scientific events The priority of Gheorghe Benga in the discovery of the first water channel protein from the human red blood cell

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1 Recognition at scientific events The priority of Gheorghe Benga in the discovery of the first water channel protein from the human red blood cell membrane a few years before Peter Agre and the regrettable mistake of Gheorghe Benga's omission from the group of 2003 Nobel laureates in Chemistry was acknowledged at several scientific events: 1. The 8th World Congress on Advances in oncology and 6th International Symposium on Molecular Medicine, Hersonissos, Crete, Greece, October 16-18, 2003; 2. Days of the Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca (Cluj-Napoca, Romania, December 3-7, 2003); 3. The 9th Cluj-Napoca International Symposium of Molecular Medicine, Society and Public Health, Celebrating the 150th anniversary of the birth of Victor Babes, the 25th anniversary of the Department of Cell and Molecular Biology of the Iuliu Hatieganu University of Medicine and Pharmacy and of the Laboratory of Human Genetics of Cluj County Hospital and the 60th birthday of Professor Gheorghe Benga (Cluj-Napoca, Romania, April 23-25, 2004); 4. Ziua Medicamentului, Gr. T. Popa University of Medicine and Pharmacy Iassy (Iassy, Romania, April 29-30, 2004); 5. The 10th Cluj-Napoca International Symposium of Molecular Medicine, Society and Public Health, Celebrating Professor Claude Matasa (Cluj-Napoca, Romania, May 24, 2004); 6. The 3rd Congress of The Academy of Scientists from Romania (Constantza, Romania, June 1-4, 2004); 7. The 9th National Congress of The Romanian Society of Physiological Sciences (Timisoara, Romania, June 3-5, 2004); 8. The 5th Congress of The National Therapeutical Farmacology and Clinical Toxicology (Calimanesti-Caciulata, Romania, June 9-12, 2004); 9. Minisymposium: Discovery of aquapoprins, at The 22th Annual Scientific Session of The Romanian Society of Cell Biology (Sighisoara, Romania, June 10-13, 2004); 10. Days of Cluj Branch of Romanian Academy (Cluj-Napoca, Romania, May 24 June 12, 2004); 11. Symposium Celebrating the 150th anniversary of the birth of Victor Babes, Babes- Bolyai University Cluj-Napoca (Cluj-Napoca, Romania, June 25-26, 2004); 12. Bioinformatics and Genome Based Medicine (Cluj-Napoca, Romania, June 27 July 7, 2004); 13. The 12th Meeting of The Balkan Clinical Laboratory Federation (Neptun, Romania, September 15-17, 2004); eme Semaine de l'union Medicale Balkanique et 7eme Congres de l'entente Medicale Mediteranne (Oradea, Romania, September 16-19, 2004); 15. Advanced Spectroscopies on Biomedical and Nanostructured Systems, Cluj-Napoca, Romania, September 19-22, The 14th National Conference of Hematology (Bucharest, Romania, September 23-24, 2004); 17. 6th Symposium on Metal Elements in Environment, Medicine and Biology (Timisoara, Romania, November 8 10, 2004); 18. The 3rd National Congress of the Romanian Federation of Diabetes, Nutrition and Metabolic Diseases (Arad, Romania, November 10-12, 2004).

2 19. Symposium of the Romanian Society of Laboratory Medicine (Cluj -Napoca, Romania, November, 18 21, 2004). 20. Medicalis Students Scientific Conference in The Week of The Iuliu Haţieganu University of Medicine and Pharmacy Cluj-Napoca, Romania, December 6-10, The 1st OUTNOBEL SYMPOSIUM (Cluj-Napoca, Romania, December 10, 2004). 22. "Victor Babes Colloquium" (National and Kapodistrian University, Athens, Greece, December 17, 2004). 23. Acad. Nicolae Cajal Commemorative Symposium, Bucharest, March 29, Romanian Japanese Symposium on Science and Technology, Nagoya, May 31, 2005) 25. The 9th World Multi Conference on Systemics, Cybernetics and Informatics, Orlando, Florida, USA, July 10-13, st International Congress of Biochemistry and Molecular Biology, Tehran, Iran, September 11 15, th Romanian International Conference on Chemistry and Chemical Engineering, Bucharest, Romania, September 22-24, nd International Danubian Symposium of Laboratory Medicine, Arad, Romania, September 22 24, The 4th World Congress of Cellular and Molecular Biology, Poitiers, France, October 7 12, Medicalis 2005 International Congress of Medical Students and Young Physicians, Cluj-Napoca, Romania, November 2 4, 2005; 31. 9th International Symposium on Metal Ions in Biology and Medicine, Lisbon, Portugal, May 21 23, First International Congress of Medical Students, Novi Sad, Serbia, July 25= 27, International Conference in Gerontology, Arad, Romania, Sep , th Meeting of the European Association of Red Cell Research, Oxford, UK, March 16 18, The 3rd Int. Symposium Acad. Nicolae Cajal, Bucharest, Romania, March 29-30, The International Conference MEMODIC, Tg. Mures, Romania, April 12-14, The 25th Annual Session of the Romanian Society of Cell Biology, Bucharest, Romania, June 7-9, Conference of the Association of Medical Laboratories of Romania, Iassy, Romania, July 5-7, The 4th European Federation of Clinical Chemistry and Laboratory Laboratory Medicine (EFCC) Symposium for Balkan region, Belgrade, Serbia, June 17 21, EHRLICH II, The 2nd World Conference on Magic Bullets, Nürnberg, Germany, October 3-5, The XVIth Meeting of The Balkan Clinical Laboratory Federation (Athens, Greece, October 16-19, Second Joint Congress of the Global College of Neuroprotection & Neuroregeneration and of the Society for the Study of Neuroprotection and Neuroplasticity, Vienna, Austria, March 1-4, th International Symposium of The European Association for Red Cell Research,

3 Triuggio, Milano, Italy, April 23-27, Symposium on Genetic Disorders of Body Fluid Homeostasis, Euromedlab 2009 (18th EFCC European Congress of Clinical Chemistry and Laboratory Medicine), Innsbruck, Austria, June 4-6, th Meeting of Balkan Clinical Laboratory Federation, Ohrid, Macedonia, September 16 19, th Congress of the Romanian Society of Laboratory Medicine, Tg. Jiu, Romania, September 8-11, th Meeting of Balkan Clinical Laboratory Federation, Tirana, Albania, September 22-25, First Symposium of Medical Biochemistry and Molecular Medicine with International Participation, Iassy, Romania, October 7-9, Symposium Laboratory Management in Europe, Paris, France, April 8-9, rd Int. Congress of the Romanian Society of Cell Biology (Arad, Romania, and Szeged, Hungary, June 8-12, th Balkan Congress of Medical Genetics, Timişoara, Romania, September 15 17, th Meeting of the Balkan Clinical Laboratory Federation (BCLF 2011) Bucharest, Romania, September 21-23, Festschrift Symposium for Professor Philip Kuchel, Sydney, September 30, The First World Congress on Water Channel Proteins (Aquaporins and Relatives) Celebrating the 25th Anniversary of the Discovery of the First Water Channel Protein (Later Called Aquaporin 1), Cluj-Napoca, Romania, October 27-29, The MEMORANDUM signed at 9 TH CLUJ-NAPOCA INTERNATIONAL SYMPOSYUM OF MOLECULAR MEDICINE, SOCIETY AND PUBLIC HEALTH has also been signed at many of the above scientific events. MEMORANDUM OF THE 9 TH CLUJ-NAPOCA INTERNATIONAL SYMPOSYUM OF MOLECULAR MEDICINE, SOCIETY AND PUBLIC HEALTH REGARDING THE DISCOVERY OF THE FIRST WATER CHANNEL PROTEIN BY GHEORGHE BENGA IN ROMANIA, A FEW YEARS BEFORE PETER AGRE (2003 NOBEL PRIZE IN CHEMISTRY) In 1985, after a decade of systematic studies on water channels in human red blood cells (RBC) performed at Iuliu Hatieganu University of Medicine and Pharmacy in Cluj-Napoca, Romania, Gheorghe Benga and coworkers discovered the presence and location of the first water channel protein in the human (RBC) membrane among polypeptides migrating in the region of kda on the electroforetogram of RBC membranes (Benga Gh, Popescu O, Pop IV, Holmes R, Biochemistry, 25, , 1986). In this landmark publication Benga also indicated the way to further studies, by protein purification and reconstitution in lipid vesicles (liposomes). This work was extended (Benga Gh, Popescu O, Borza Victoria, Pop VI, Mureşan A, Mocsy I, Brain A, Wrigglesworth JM, Eur J Cell Biol 41: , 1986) and reviewed by Benga in several articles including a chapter in a book published in the USA (Benga Gh, (Ed) Water transport in biological membranes. CRC Press, Boca Raton). In

4 1988, Peter Agre and coworkers (Denker BM, Smith BL, Kuhaida FP, Agre P, J. Biol. Chem. 1988, 263: ), while working on the rhesus blood group antigen at Johns Hopkins University in Baltimore, USA, serendipitously isolated a new 28 kda membrane protein from human red blood cells, called, CHIP28 ( channel forming integral membrane protein of 28 kdaltons); in addition to the 28 kda component, this protein had a kda glycosylated component, the one detected in 1986 by the Benga s group. Agre and coworkers suggested that this new protein may play a role in linkage of the membrane skeleton to the lipid bilayer (Smith BL, Agre P., J. Biol. Chem. 1991, 266: ). Only in 1992, the Agre s group suggested that it is likely that CHIP28 is a functional unit of membrane water channels (Preston G.M, Carroll TP, Guggino WB, Agre P, Science, 1992, 256: ). In this paper, they cited a paper of Benga and coworkers from 1983 (Benga Gh, Popescu O, Pop VI. 1983, Cell Biol Int Rep, 7: ), without mentioning their landmark 1986 papers or any of the reviews. In 1993 CHIP28 was renamed aquaporin 1 (the first water channel protein). It is obvious and overwhelmingly documented from the facts presented above that the first water channel protein (aquaporin 1) was first discovered by the Romanian scientist Gheorghe Benga and his group in 1985 and reported in publications in They detected the glycosylated form of the protein (subsequently worked on by Agre s group), which they correctly identified as playing the key role in water transport across RBC membrane. In October 2003, Peter Agre was awarded the Nobel Prize in Chemistry, for the discovery of water channels. An invited review of the history of the discovery of water channels proteins was published by Benga in September 2003, one month before the Nobel Prize for Chemistry was awarded (Benga Gh, Cell Biol. Int. 2003, 27: ). The seminal contributions from 1986 of the Benga s group, also mentioned in this review, were completely overlooked by the Nobel Prize Committee. After the announcement of the 2003 Nobel Prize in Chemistry was released by Nobel Foundation Gheorghe Benga received a multitude of spontaneous messages (phone calls, ed messages and faxed letters) from all over the world. The scientists who sent messages to Gheorghe Benga considered that in fact he discovered the first water channel protein in the red blood cell membranes (the protein later called aquaporin1) several years before Peter Agre and the chemical definition of this channel protein by Peter Agre has no more value than the first demonstration and labeling of the site in the red blood cell membrane where the water channel protein is located. As a result Gheorghe Benga wrote a PETITION, presented on October 18 th at the 6 th International Symposium of Molecular Medicine (Hersonissos, Crete, Greece) that is now available at where a full background to the controversy can be seen.. The priority of Gheorghe Benga s group in the discovery of the first water channel protein has been mentioned in comments on the 2003 Nobel Prize in Chemistry (Bradley D. Spotlight, Bradley D., The Alchemist, 13 October 2003; Vandenberg IJ, Kuchel P., Medical Journal Australia, 179: , 2003; Rogerund K. Kemipriset vållar ny Nobelstrid, Dagens Nyheter, 10 Decembrie 2003; Strid kring medicinpriset...och kring kemipriset, Sydsvenska Dagbladet, December 11, 2003; Nobel mystery. Newsletter of King s College, January 2004). More than 2000 supporters form dozens of countries, including a Nobel Laureate, have signed at By now, many academic institutions, faculties, universities, scientific organizations and associations, research institutes, have recognized Gheorghe Benga as a discoverer of the first water channel protein before Peter Agre.

5 Considering the facts presented above, the participants in the 9 TH CLUJ-NAPOCA INTERNATIONAL SYMPOSYUM OF MOLECULAR MEDICINE, SOCIETY AND PUBLIC HEALTH (April, 23-24, 2004) agree to recognize Gheorghe Benga as a discoverer of the first water channel protein a few years before Peter Agre (2003 Nobel Prize in Chemistry). EXAMPLES OF WORLD CONGRESSES

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