THE STORY OF THE DISCOVERY OF AQUAPORINS: CONVERGENT EVOLUTION OF IDEAS - BUT WHO GOT THERE FIRST?

A critical analysis of the discovery of the first water channel protein (later called aquaporin 1) has been performed. In 1986 Benga's group in Cluj-Napoca, Romania, published in Biochemistry, a US-based journal, the results of experiments that provided the first visual and tangible evidence that the very rapid water exchange that occurs through the membranes of the human red blood cell (RBC) is mediated by a particular protein or small group of proteins. Benga and co-workers did see bands in a gel that corresponded to water transporters, and were the first to do so. In 1988 Peter Agre and co-workers in Baltimore, USA, while working on the rhesus blood group antigens, purified a "new" membrane protein that they called CHIP 28 (channel integral membrane protein of molecular weight 28k). At the time they had no idea of its function. In 1992 came the definitive experiment, that was done, according to Peter Agre in his Nobel Lecture, after much discussion with colleagues about the likely candidate function of their 'orphan' protein. In a paper published in 1992 in Science Agre and his group describe how CHIP28 has the properties of a water channel protein. In 1993 the name of the protein was changed from CHIP28 to aquaporin 1. It became obvious that one of the labelled bands observed by Benga's group (the one in the region of molecular weight similar to 35,000 to similar to 60,000) corresponds to glycosylated CHIP28 (aquaporin 1). So Benga and co-workers did first see bands in a gel that corresponded to water transporters, and were the first to do so. The "mercury labelling" experiments were confirmed and extended in Cluj-Napoca by Benga's group and the results were published in 1986 in the European Journal of Cell Biology, another international journal. The work was reviewed by Benga in subsequent years in international series and even as a chapter in a book on water transport edited for a well-known US-based publisher. Agre's group did include a reference to Benga's work in their Science paper; but this reference was only to a 1983 paper on protease resistance of "water channels" (which was relevant) and not the pertinent 1986 Biochemistry paper, or even the subsequent publications. The report of the recent exciting finding of possible involvement of aquaporins in epilepsy, published in 2005 in Proc Natl Acd Sci USA by a group including Agre failed to cite Benga and Morariu's novel and startling report in Nature in 1977.