Volume 1

Contemporary classics in the life sciences / edited by James T. Barrett.

Date:: ©1986-

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Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: Contemporary classics in the life sciences / edited by James T. Barrett. Source: Wellcome Collection.

42/400 (page 20)

-This week's Citation Classic Majno G & Palade G E. Studies on inflammation. I. The effect of histamine and serotonin on vascular permeability: an electron microscopic study. J. Biophys. Biochem. Cytol. 11 :571-605, 1961. [Dept. Pathol., Harvard Med. Sch., Boston, MA and Rockefeller Inst., New York, NY] It was well known that histamine increased the permeability of small blood vessels; we found the mechanism: the cells that line the smallest veins become partially disconnect ed, so that fluid can escape between them. This is one of the key events in acute inflam mation. [The SC/® indicates that this paper has been cited over 625 times since 1961.] Guido Majno Department of Pathology University of Massachusetts Medical Center Worcester, MA 01605 June 26, 1981 Citation Classici Would I SI® care to open a new category of Refusal Classicsi Of all the scientific papers on which I was the senior author, only one was turned down: you know which one. This paper had been a labor of love. I had joined G.E. Palade's laboratory at the Rockefeller Institute in 1958, to be initiated in the new art of electron microscopy. We had carefully chosen a topic of common interest: Palade was an authority on blood vessels, and I was interested in any tissue as long as it was sick, so we settled for leaking blood vessels. Histamine was supposed to make capillaries leak, but nobody knew by what mechanism; so we in jected histamine into rats and began to look for leaking capillaries I remember spending days of frustration looking at capillaries that remained stubbornly normal —until we found out that the exciting events happened a little fur ther downstream, in the venules, which had become riddled with tiny leaks. In the process we also stumbled upon an extremely cheap and beautiful biologi cal trick: a drop of India ink injected in to the bloodstream causes leaking vessels to become elegantly 'tattooed' in black; an experimental technique now known as vascular labeling (the phenomenon itself had been published at least 12 times before, but with the wrong explanation). When I was advised that the result ing paper would be turned down by the Journal of Experimental Medicine, I was half shocked, half amused, but com pletely sure that the reason could not be scientific. Sure enough, the startling reason given by that grand old gentleman, Peyton Rous, was that the paper contained too much history ! Was I really supposed to chop out the historical roots of our work? 'Stick to your guns,' said Palade, lapsing into vernacular English (we used to speak French at that time). So we sent the paper to a new, competing journal, now called the journal of Cell Biology. (It took me another eight years to go one step further, and find that the leaks were caused by endothelial contrac tion.) 1 Looking back upon that work, pro duced under the wing of a great master, I can say with a touch of nostalgia that we were bound to pro duce a paper of more than passing value because we found out —just in time —that we had merely confirmed, with more refined methods, a paper that had appeared in Virchows Archiv in 1875. 2 Since 1961, a mountain of literature has been appearing on the endothelium. A review of this field was recently published in The Thrombotic Process in Atherogenesis 3 I believe that our work attracted at tention because it solved a long-stand ing functional riddle by very simple (and very aesthetic) morphologic obser vations. 1 Majno G, Sbe« S M A Leventhal M. Endothelial contraction induced by histamine-type mediators. J Cell Biol 42 :647-72, 1969. 2 Arnold J. Ueber das Verhalten der Wandungen der Blutgefässe bei der Emigration weisser Blutkörper. Virchows Arch 62 :487-503. 1875. 3 Ma|no G 6 lori» I. Endothelium 1977: a review. (Chandler A B, Eurenius K, McMillan G C, Nelson C B, Schwartz C J & Wessler S. eds.) The thrombotic process in atherogenesis New York: Plenum, 1978. p. 169-225; 481-526.