DISCOVERY OF THE FIRST WATER CHANNEL PROTEIN (LATER CALLED AQUAPORIN 1)

 

The outline presented below has been written by Gheorghe Benga in December 2013.

 

DISCOVERY BY GHEORGHE BENGA’S GROUP, IN CLUJ-NAPOCA, ROMANIA,

OF THE FIRST WATER CHANNEL PROTEIN (LATER CALLED AQUAPORIN 1)

A FEW YEARS BEFORE PETER AGRE (2003 NOBEL PRIZE IN CHEMISTRY)

 

Gheorghe Benga

1Chief, First Laboratory of Genetic Explorations, Cluj County Clinical Emergency Hospital, 2Professor, Department of Cell and Molecular Biology, “Vasile Goldis” Western University Arad, 3 Romanian Academy, Cluj-Napoca Branch, 4 Academy of Medical Sciences of Romania, Cluj-Napoca Branch,

5 President of The “Gheorghe Benga” Foundation and 6 President of The OUTNOBEL Foundation, 6 Pasteur St., 400349 Cluj-Napoca, Romania, Tel. 0040-264-594373; E-mail: gbgbenga@gmail.com

 

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, together with my coworkers I discovered the first water channel protein in the human (RBC) membrane; the discovery was reported in publications in 1986 in two landmark publications (18, 19). The presence and location of this water channel protein was detected among polypeptides migrating in the region of 35-60 kDa on the electrophoretogram of RBC membranes, labeled with 203Hg-p-chloromercuribenzene sulfonate (PCMBS) under conditions for the specific inhibition of water diffusion. In the first landmark publication (19) we have also indicated the way to further studies, by purification and reconstitution in lipid vesicles (liposomes). This work was extended (18) and reviewed by Benga in several articles published in 1988 – 1989 (2-5) including a chapter in a book published in a well known publishing house in 1989 in the USA (6).

In 1988, Peter Agre and coworkers, 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 kDa); in addition to the 28 kDa component, this protein had a 35-60 kDa glycosylated component, the one discovered in 1986 by 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” (25). Only in 1992, Agre’s group suggested that “it is likely that CHIP28 is a functional unit of membrane water channels” (31). In this report, they cited a paper of Benga and coworkers from 1983 (20), without mentioning their landmark 1986 studies (18, 19) or any of the reviews (2-6). In 1993 CHIP28 was renamed aquaporin 1 (the first water channel protein).

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 (7). The seminal contributions from 1986 of the Benga’s group, also mentioned in this review, were completely overlooked by the Nobel Prize Committee. No mention of the results of Benga and coworkers appeared in the historical description of the discovery of aquaporins that joined the prize announcement.

It is obvious and overwhelmingly documented from the facts presented above that the first water channel protein (aquaporin 1) was first discovered in by the Romanian scientist Gheorghe Benga and his group (18, 19), who 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.

As discussed by Benga (7) the landmark papers of his group in 1986 (18, 19) can be compared with the first detection of a child “in utero” by ultrasonography, or with the discovery of The New World of America; the first man who has “seen” a part of The New Land was Columbus; later, others, including Amerigo Vespucci (from whom the name derived), have better “seen” larger parts and the complexity of the Americas!

After the announcement of the 2003 Nobel Prize in Chemistry was released by Nobel Foundation I received a multitude of spontaneous messages (phone calls, E-mailed messages and faxed letters) from all over the world. The scientists who sent messages to Gheorghe Benga considered that in fact I and my group have first discovered the first water channel protein in the red blood cell membranes (the protein later called aquaporin 1). As a result I wrote a PETITION for the recognition of our priority, PETITION that is reproduced in this issue. The above mentioned claim and the PETITION was presented by me on October 18th at the 6th International Symposium of Molecular Medicine (Hersonissos, Crete, Greece) and immediately dozens of scientists from a lot of countries have signed in support of his PETITION.

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 (21-24, 26-27, 30, 34, 35,). Although in his Nobel Lecture (1) Agre mentioned twice Benga among “pioneers in water transport field”, Benga’s publications were not listed among the references.

Benga’s claim was presented on the web site of the Ad Astra Association (www.ad-astra.ro/benga) where a full story could be seen. The recognition of Gheorghe Benga as a discoverer of the first water channel protein from the human RBC membrane is growing. Thousands of science-related professionals from hundreds of academic and research units, as well as participants in several international scientific events, have signed as supporters of the priority of Benga’s group in the discovery of the first water channel on the web site of Ad Astra Association (www.ad-astra.ro/benga).

The above mentioned facts were also presented by Gheorghe Benga in 2003-2011 as invited lectures at over 50 international scientific events and in dozens of seminars at many European, American and Japanese universities, as well as at some World conferences (35, 36), steering favorable reactions. In recent years I published several invited reviews on the discovery of water channel proteins, as well as on their occurrence and physiological roles (7-17).

 

References

  1. Agre P. Aquaporin water channels (Nobel Lecture). Angew Chem Int Ed.2004, 43: 4278-4290

  2. Benga Gh. Water transport in human red blood cells. Prog. Biophys. Mol. Biol. 1988,51: 193-245

  3. Benga Gh. Water exchange through the erythrocyte membrane. Int. Rev. Cytol. 1989, 114: 273-316

  4. Benga Gh. Permeability through pores and holes. Current Opin. Cell Biol. 1989, 1: 771-774

  5. Benga Gh. Membrane proteins involved in the water permeability of human erythrocytes: binding of p-chloromercuribenzene sulfonate to membrane proteins correlated with nuclear magnetic resonance measurements; in Benga Gh. (ed) Water transport in biological membranes. CRC Press, Boca Raton 1989; vol. 2, pp 41-61

  6. Benga Gh. (ed):Water transport in biological membranes. CRC Press, Boca Raton 1989

  7. Benga Gh. Birth of water channel proteins – the aquaporins, Cell Biol. Int. 27, 701-709, 2003.

  8. Benga Gh. The discovery of the first water channel protein (later called aquaporin 1) in the human red blood cell membrane in 1985 in Cluj-Napoca, Romania, a few years before Peter Agre (2003 Nobel prize in chemistry) in “Metal Elements in Environment, Medicine and Biology”, Proc. 6th Int. Symp., Timişoara, Nov. 8-10, 2004, Gârban Z., Drăgan P., Gârban Gabriela (Eds), “Eurobit” Publishing House, Timişoara, vol. VI, pp. 61-74, 2004.

  9. Benga Gh. The first water channel protein (later called aquaporin 1) was first discovered in Cluj-Napoca, Romania, Rom. J. Physiol, 41, 3-20, 2004.

  10. Benga Gh. Water channel proteins: from their discovery in 1985 in Cluj-Napoca, Romania, to the 2003 Nobel Prize in Chemistry and their Medical Implications, The 9th World Multi-Conference on Systemics, Cybernetics and Informatics, Orlando, Fl. (USA), 10, 99-104, 2005.

  11. Benga Gh. Water channel proteins: from their discovery in Cluj-Napoca, Romania in 1985, to the Nobel Prize in chemistry and their implications in molecular medicine, The Keio J. Med., Tokyo, 55 (2), 64-69, 2006.

  12. Benga Gh. Water channels (aquaporins and relatives): twenty years after their discovery in Cluj-Napoca, Romania, Acta Endocrinologica, 2006, 2:323-335.

  13. Benga Gh. Water channel proteins: from their discovery in 1985 in Cluj-Napoca, Romania, to the 2003 Nobel Prize in Chemistry, Cell. Mol. Biol., 52, 10-19, 2006.

  14. Benga Gh. Water channel proteins of adipocytes, Biomedical Reviews, 17, 107-112, 2006.

  15. Benga Gh. Water channel proteins (later called aquaporins) and relatives: past, present and future, IUMB Life 61 (2), 112-133, (2009).

  16. Benga I., Benga Gh. Priorities in the discovery of the implications of water channels in epilepsy and Duchenne muscular distrophy, The 9th World Multi-Conference on Systemics, Cybernetics and Informatics, Orlando, Fl. (USA), 10, 111-115, 2005.

  17. Benga Gh., Kuchel P.W. Physiological significance of water channel proteins in the red blood cell membranes: analysis at the level of the cell- and of the whole-body systems, The 9th World Multi-Conference on Systemics, Cybernetics and Informatics, Orlando, Fl. (USA), 10, 105-110, 2005.

  18. Benga Gh. Popescu O., Pop V.I., Borza V Ana Mureşan, Ildiko Mocsy Water permeability of human erythrocytes. Identification of membrane proteins involved in water transport. Eur. J. Cell Biol. 1986, 41: 252-262

  19. Benga Gh., Popescu O., Pop V.I., Holmes R. p-(Chloromercuri)benzenesulfonate binding by membranes proteins and the inhibition of water transport in human erythrocytes. Biochemistry 1986, 25: 1535-1538

  20. Benga Gh., Popescu O., Pop V.I. Water exchange through erythrocyte membranes. V. Incubation with papain prevents the p-chlormercuribenzene-sulfonate inhibition of water diffusion. Cell. Biol. Int.Rep. 1983, 7: 807-818

  21. Blackman A: Leading lights in science prize-fight. Chemistry Matters, November 2003 and Otago Daily Times, 3 November 2003. Available at www.odt.co. nz/cgi-bin/search-display-story-online-new?date= 03Nov2003&object=NTL02J7657LS&type= html&WORDS=benga&DB= Editorial

  22. Bradley D: Chemical channels. Spotlight, October 2003. Available at www.psigate.ac.uk/spotlight/issue13b/ chemistry.html

  23. Bradley D: Nobel controversy, again and again. The Alchemist, 13 October 2003. Available at www. chemweb.com/alchem/articles/1063812326697.html

  24. Criticas envuelven la ceremonia del Nobel (DPA), El Universal (Mexico), December 11, 2003. Available at http://www.eluniversal.com.mx/pls/impreso/noticia.html?id_nota=32544&tabla=cultura

  25. Denker BM, Smith BL, Agre P et al: Identification, purification and partial characterization of a novel Mr 28,000 integral membrane protein from erythrocytes and renal tubules. J. Biol. Chem. 1988, 263:15634-15642.

  26. El sudafricano Coetzee ganó en literatura. Valoraron la lucha literaria contra el racismo. Protestas de cientificos por premios en medicina y química, La Capital (Argentina), December 11, 2003. Available at http://www.diariolacapital.com/2003/12/11/general/noticia_60281.shtml

  27. Kapoun J: Ohlédnutí za týdnem Nobelových cen (3): Chemie. 2003 Science WORLD. Available at www.scienceworld. cz/sw.nsf/ID/0BC262AFF133FFD0C1256DC1003018F3

  28. Kuchel P. W.,Benga Gh., Why is the transmembrane exchange of water in the red blood cell so fast? Bull. Mol. Med. Nos.15-16, 29-34, 2003.

  29. Kuchel PW, Benga Gh. Why does the mammalian red blood cell have aquaporins. Biosystems 82, 189-196, 2005.

  30. Nobel mystery. Newsletter of King’s College, January 2004

  31. Preston G.M, Carroll TP, Agre P. et al: Appearance of water channels in Xenopus oocytes expressing red blood cell CHIP28 protein. Science 1992, 256:385-387.

  32. Rognerud KK: Kemipriset vållar ny strid.Dagens Nyheter, 10 December 2003. Available at www.dn.se/DNet/jsp/ polopoly.jsp?d=597&a=212849& previousRenderType=6

  33. Strid kring medicinpriset….och kring kemipriset. Sydsvenska Dagbladet, December 11, 2003. Available at http://www.svd.se/dynamiskt/inrikes/did_6639108.asp

  34. Vandenberg J. I., Kuchel P. W.: Nobel Prize for magnetic resonance imaging and channel proteins. Med. J. Australia, 2003,179: 611-613.

  35. www.iiisci.org/sci2005

  36. www.cmbworldcongress2005

The outline presented above was written by Gheorghe Benga in December 2013.

ANY PUBLICATIONS CITED ON THIS SITE MAY BE OBTAINED FROM GHEORGHE BENGA. © Copyright The Gheorghe Benga Foundation