Born To Be Remembered Sambhu Nath De The unsung Doctor Dr Sambhu Nath De pioneered a series of research that brought a breakthrough in medicine when he discovered the causal agent of the fatal disease, Cholera. Sambhu Nath De (popularly known as S N De) was born in Hooghly District, West Bengal, India. His father Mr Dasarathi De was a small businessman. Supported by his uncle Asutosh De, De completed the Matriculation examination with distinction that helped him to get the District scholarship as well as to pursue further education in Hooghly Mohsin College, which was then affiliated with the prestigious University of Calcutta. His higher education was supported by Kestodhan Seth, who identified De as an extraordinary student. De passed his M.B. examination in 1939 from Calcutta Medical College and completed a Diploma in Tropical Medicine (DTM) in 1942. Soon after graduation he joined Calcutta Medical College as a Demonstrator of Pathology and initiated his research under Professor B. P. Tribedi. In 1947, De joined as a Ph.D. student under Sir Roy Cameron at the Department of Morbid Anatomy, University College Hospital Medical School, London, and obtained his Ph.D. degree in Pathology in 1949. After his return, De worked on pathogenesis of cholera and started publishing his findings.In 1955, De became the Head of Pathology and Bacteriology Division of the Calcutta Medical College, which he continued until his retirement. De published more than 30 research papers and has written an excellent monograph on cholera and its pathogenesis. 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. Des 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 Des 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 Des 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 Des most-cited paper, cited 340 times until August 1986. Des 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, Des 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, Des 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 Des 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. De retired in 1973 from the Calcutta Medical College at the age of 58. After his retirement, he showed no interest in higher positions but continued his research at the Bose Institute, Calcutta. Des desire to purify the cholera toxin did not progress any further as the protein purification technology was not well established in his research settings. During his time of research, De worked with hypertoxin-producing classical strains of V. cholerae O1, which was abruptly replaced by El Tor biotype [producing less cholera toxin] in Calcutta from 1963. This new development was another reason why De could not continue his research on purification of cholera toxin. In 1978, the Nobel Foundation invited De to participate in the 43rd Nobel Symposium on Cholera and Related Diarrhoeas. De died on April 15, 1985 at the age of 70. His lifes ambition was to make the world a better place to live in through his dedicated selfless services in medical science.
Posted on: Sun, 02 Feb 2014 10:42:53 +0000