Contributions
De made significant contributions to our recent understanding of cholera and related diarrheal diseases and set a permanent milestone in the modern view of diseases caused by bacterial exotoxins. Followed by the discovery of Vibrio cholerae in 1884 by Robert Koch, many works have been carried out all over the world to answer many questions related with its pathogenesis and mode of transmission in causing outbreaks. The seminal works of De in Calcutta (now, Kolkata), during 1950-60 breached several qualms pertaining to the enteric toxin produced by bacteria including V. cholerae and Escherichia coli. Three of his works viz., ligated intestinal loop method (which was a reinvention of Violle and Crendiropoulo method in 1915, but De was unaware of this work and made an independent discovery) for studying cholera in rabbit model; ileal loop model to demonstrate the association of some strains of E. coli with diarrhea and lastly but most importantly is his discovery of cholera toxin in 1959 in the cell-free culture filtrate of V. cholerae that stimulated a specific cellular response.
Says Eugene Garfield, founder-editor of Current Contents and Science Citation Index and publisher of The Scientist, in his 1986 tribute to De: In 1959 De was the first to demonstrate that cholera bacteria secrete enterotoxin. This discovery eventually promoted research to find a treatment aimed directly at neutralizing the cholera enterotoxin. De’s paper “Enterotoxicity of bacteria-free culture-filtrate of Vibrio cholerae,” while initially unrecognized, today is considered a milestone in the history of cholera research. Biochemist W.E. van Heyningen, professor emeritus, University of Oxford, UK, and John R. Seal, former scientific director, National Institute of Allergy and Infectious Diseases, Bethesda, note that De’s paper “deserves to go down as a classic in the history of cholera, and, indeed, as later developments have shown, in the history of cellular physiology and biochemistry.” Thanks to De’s discovery of the cholera enterotoxin, research has been redirected to find a vaccine that will spark the immune system to fight the enterotoxin specifically, rather than the bacteria.
De and colleagues also published highly cited pioneering studies on V.cholerae action on the intestinal membrane.,, The 1953 paper “An experimental study of the mechanism of action of Vibrio cholerae on the intestinal mucous membrane” is De’s most-cited paper, cited 340 times until August 1986. De’s most-cited paper has been core to cholera research fronts for many years, especially research fronts on "E. coli and Vibrio cholerae enterotoxin: detection, characterization, and role of adherence" and "Characterization of cholera enterotoxin and other enterotoxins". As noted by John Craig, State University of New York Health Science Center at Brooklyn, De’s work was truly creative and novel, and it “forever altered our concepts surrounding the pathogenesis of secretory diarrhoea.”
These famous findings came out from the work he carried out at the Nilratan Sircar Medical College, Calcutta Medical College and Bose Institute, Kolkata in extremely modest laboratory settings. Using research methodology that was very simple, easy to perform and inexpensive, he set the highest standards of excellence in novel experimental design and execution.
In the words of Nobel Laureate Prof. Joshua Lederberg, “De’s clinical observations led him to the bold thought that dehydration was a sufficient cause of pathology of cholera, that the cholera toxin can kill ‘merely’ by stimulating the secretion of water into the bowel”. Thus, the oral rehydration therapy (ORT) for replenishing the massive fluid loss in cholera patients, has saved innumerable lives, should be considered as a direct outcome of De’s discovery of cholera toxin. His findings on exotoxins set the stage for the modern views of diseases caused by toxin producing bacteria, helped in the purification of cholera and heat-labile (LT) enterotoxins produced by V. cholerae and E. coli, respectively, and in the development of series of cholera and enterotoxigenic E. coli (in short ETEC strains) vaccines.
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