Who Discovered Aquaporin for the First Time ?

Dear Professor Agre:


Professor Gheorghe Benga from the “Iuliu Hatieganu” University of Cluj, Romania, discovered in 1986 that binding of p-(chloromercuri)benzenesulfonate to the 4.5 band protein was correlated with the inhibition of water transport measured by a NMR technique. He concluded that his results indicate that band 4.5 protein is playing a role in water transport and could be associated with water channels(1). It turns out that band 4.5 protein is, actually, a glycosylated form of aquaporin. According to you, it is part of a tetrameric structure, but this glycosylated CHIP monomer behaves as an independent water pore(2) .

In 1988 you discovered CHIP, a 28,000 kDA protein with its HMW-28 kDa glycosylated component, that “bears a strong resemblance to protein 4.5, a group of membrane constituents most of which are poorly understood”(3) and in 1991 you re-discovered the glycosylated protein glyCHIP(4), both being described as band 4.5 by Benga in 1986, but you forgot to mention his name on both occasions. At the same time, Benga did not write to the editor and I would like to dissipate a confusion that is persisting in many minds even now.

In conclusion, Benga was the first to detect aquaporin in a glycosylated form and to realize its role in water transport, while you described its basic 28,000 kDa monomer, isolated it and described in detail its structure, related by Parker(5) to the water transport property, first mentioned by Benga.

My question is shaped this way:
--Why in your Nobel lecture(5) you saw Benga only as a pioneer in the water transport field ? Who is the first and real discoverer of the water channel protein called now aquaporin: Benga, who detected it “in situ” for the first time, or Peter Agre, who isolated it and described in detail its structure ?

Sincerely,

Mihai S. Jalba, M.D., Ph.D.
Postdoctoral research fellow
University of Medicine and Dentistry of New Jersey
Robert Wood Johnson Medical School


REFERENCES

1. Benga Gh, Popescu O, Pop VI, Holmes RP, 1986. p-(Chloromercuri)benzenesulfonate binding by membranes proteins and the inhibiton of water transport in human erythrocytes. Biochemistry 25: 1535-1538

2. P. Agre, G. M. Preston, B. L. Smith, J. S. Jung, S. Raina, C. Moon, W. B. Guggino, and S. Nielsen. Aquaporin CHIP: the archetypal molecular water channel. Am J Physiol Renal Physiol 265: F463-F476, 1993

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

4. Preston GM, Agre P. Isolation of the cDNA for erythrocyte integral membrane protein of 28 kilodaltons: member of an ancient channel family. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11110-4.

5. Agre P. Nobel lecture. As accessed on August 3, 2005 at http://nobelprize.org/chemistry/laureates/2003/agre-lecture.pdf

Word count: 298 (as measured at http://authors.nejm.org/letters/letter1.asp?type=ref)



Dear Editor:

I assisted to Professor Agre's presentation about the discovery of aquaporin at the 101th International Conference of the American Thoracic Society on May 23, 2005 where I tried to ask him a question, but, when I started to speak I found that the microphones were disconnected. I try to shape my question now.

The history of science is full of controversies concerning the priority over important discoveries. The Nobel prizes 2003 in Medicine and Chemistry are not an exception, with Damadian and Benga claiming priority.

I think that openness is a must in discussing controversial issues. Giving me an opportunity to obtain an answer to my question in your internationally renowned journal, which published a landmark paper in 1992 on the issue, may be a real benefit for the history of science.

For my biographical information, you may consult the volumes "Who's who in Medicine and HealthCare 2004-2005" and "Who's who in America 2005" and Pubmed. Thank you for giving me the opportunity to submit this letter to "Science" and I am looking forward to being published.

Sincerely,

Mihai Jalba, M.D., Ph.D.
Postdoctoral research fellow
University of Medicine and Dentistry of New Jersey
Robert Wood Johnson Medical School




Date: Wed, 10 Aug 2005 20:00:17 -0400
From: Science Editorial --science_editors@aaas.org--
Reply-To: Science Editorial --science_editors@aaas.org--
To: jalbams@umdnj.edu
Subject: Your Letter to Science
MS# 1118456

Dear Dr. Jalba,

Thank you for sending a Letter-to-the-Editor to Science. We have read over your contribution, but will not be able to publish it in the magazine. We are letting you know as a courtesy in case you wanted to seek another outlet for your letter.

Please do not reply to this email, as it will not be read by Science. Unfortunately the volume of submissions precludes specific discussions about individual submitted letters.

Sincerely,

The Editors
Science Magazine






From: Hill, Jayne [mailto:J.Hill@nature.com]
Sent: Friday, February 10, 2006 9:13 AM
To: 'jalbams@umdnj.edu'
Subject: Correspondence

Dear Dr Jalba

Thank you for your Correspondence submission, which we regret we are unable to publish. Pressure on our limited space is severe, so we can offer to publish only a few of the many submissions we receive.
Naturally, I am sorry to convey a negative response in this instance.
Yours sincerely

Jayne Hill
Correspondence
Nature

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ROMANIAN TRANSLATION FOLLOWS:

Stimate Domnule Profesor Agre,

Profesorul Gheorghe Benga, de la Universitatea “Iuliu Hatieganu” din Cluj, România, a descoperit în 1986, folosind o tehnică bazată pe NMR, că aditia para-cloromercurbenzensulfonatului la proteina din banda 4,5 s-a corelat cu inhibarea transportului de apă. El a concluzionat că rezultatele sale arată că proteina din banda 4,5 joacă un rol în transportul apei si ar putea fi asociată cu canalele de apă.(1). Se constată că proteina din banda 4,5 este de fapt o formă glicozilată de aquaporină. Potrivit Dvs, ea face parte dintr-o structură tetramerică, dar acest monomer CHIP se comportă ca un por independent pentru apă.

În 1988 ati descoperit CHIP, o proteină cu greutatea de 28.000 kDa, împreună cu componentul ei glicozilat HMW-28 kDa, care “arată o puternică asemănare cu proteina din banda 4,5, un grup de constituenti membranari, majoritatea având încă un rol putin cunoscut”(3) si în 1991 ati “descoperit” din nou proteina glicozilată glyCHIP, ambele descrise de Benga drept proteina din banda 4,5 în 1986, dar în ambele ocazii ati uitat să-i mentionati numele. În acelasi timp, Benga nu a scris o scrisoare către editor, asa încât eu as dori să împrăstii o confuzie care continuă să persiste în multe minti, chiar si acum.

În concluzie, Benga a fost primul care a detectat aquaporina în formă glicozilată si si-a dat seama de rolul ei în transportul apei, în timp ce Dvs. ati descris monomerul ei de bază cu greutatea de 28.000 kDa, l-ati izolat si ati descris în detaliu structura lui, legată de către Parker (5) de proprietatea transportului de apă, pentru prima oară mentionată de Benga.

Întrebarea mea este formulată în felul următor:
--De ce în lectura la Premiul Nobel (5) l-ati considerat pe Benga numai un pionier în domeniul transportului de apă ? Cine este primul si adevăratul descoperitor al proteinei canalului de apă denumită acum aquaporină: Benga, care a detectat-o “in situ” pentru prima oară, sau Peter Agre, care a izolat-o si i-a descris în detaliu structura ?

Cu sinceritate,

Mihai Sergiu Jalbă
Cercetător stiintific postdoctorat
Facultatea de Medicină “Robert Wood Johnson” a Universitătii de Medicină si Stomatologie a statului New Jersey




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