Dr. Sambhu Nath Dey: The saviour who chased Cholera
When well-known scientists and medical practitioners attend college seminars in India on cholera, they often conclude their lectures with two questions addressed to the audience -- who discovered the causative agent of the disease cholera and the other question is, who discovered cholera toxin. Invariably there is an answer for question number 1 but rarely do participants know the answer to question 2. It is a matter of great shame indeed. How conveniently we have forgotten the seminal work of a great scientist, Dr Shambhu Nath Dey!
Dr. Sambhu Nath Dey’s most famous contribution to the field of medicine was his extensive studies on endotoxins of the cholera bacteria, which led to a great leap in our understanding and treatment of cholera and related diarrhoeal diseases. He designed several novel experimental methods to study the mechanism and mode of transmission of Vibrio cholerae, the pathogen responsible for causing cholera.
In a pioneering series of research spanning less than a decade starting from 1952 and culminating in the prestigious ‘Nature’ paper of 1959, Dr Dey worked relentlessly in search of the elusive toxin that caused the epidemic responsible for the killer disease.
Historically known as Asiatic cholera, cholera is a highly infectious disease, that is likely to have originated in India and caused at least three major epidemics in Bengal during the 19th century, before spreading across the world and killing millions. The terror of the scourge ensured that Ola Devi, the ‘anti-cholera goddess’, was devoutly worshiped by all Bengalis. John Snow’s 1855 discovery that the causative agent got transmitted via contaminated water revolutionized the field of epidemiology and public healthcare. A few decades later, Robert Koch, the iconic bacteriologist, conclusively identified the pathogenic bacteria: Vibrio cholerae.
Today, there has been a sea-change in our understanding of how a pathogen causes the disease. It is common knowledge that the actual mischief-maker is the cholera toxin (CTX), a complex of six proteins released by V. cholerae into the small intestine. When CTX enters the intestinal cells, it triggers a cascade of intracellular reactions. The final result is the opening of floodgates such that sodium, potassium, bicarbonate ions and water pour from these host cells into the intestinal lumen, causing intense diarrhoea (the feaces is typically rice-water-like in appearance) and a rapid loss of water and electrolytes from the body. Yet, Dr S.N. Dey, whose discoveries radically altered our understanding of the pathogenesis of cholera and also played a pivotal role in discovering CTX, is all but forgotten, even in his own country.
Dr. Sambhu Nath Dey’s most famous contribution to the field of medicine was his extensive studies on endotoxins of the cholera bacteria, which led to a great leap in our understanding and treatment of cholera and related diarrhoeal diseases.
In a pioneering series of research spanning less than a decade starting from 1952 and culminating in the prestigious ‘Nature’ paper of 1959, Dr Dey worked relentlessly in search of the elusive toxin that caused the epidemic responsible for the killer disease. Dey’s discovery of cholera toxin was almost three quarters of a century after Robert Koch first cultured Vibrio cholerae (known as comma bacillus at that time) in Calcutta and 105 years after the microscopic observation of the causative agent of cholera by an Italian anatomist, Filippo Pacini and the classic epidemiologic studies of John Snow, a British physician describing the waterborne nature of the disease. Prior to this, it was widely believed that the disease was caused by ‘miasma’ or unpleasant or unhealthy vapours emanating from sewers.
Dey’s method to understand the pathogenesis of cholera was distinctly different from all previous approaches. At that time, researchers believed that the pathogenesis of cholera was related to endotoxin and therefore used a multiplicity of methods and routes to replicate the disease which included introducing cholera stools into a variety of animals with little success. Following the course of the disease, Dey contented that the causative agent affects the permeability of the intestinal epithelium leading him to perform work at that interface using the now famous rabbit ileal loop model. Not only was Dey able to replicate the disease with the causative organism introduced in the ileal loops of the rabbit but was also able to replicate the disease with bacteria-free culture filtrate of V. cholerae clearly showing that the exotoxin nature of cholera toxin. He also went on to perform experiments which led to the birth of the concept of enterotoxin producing Escherichia coli which today is firmly entrenched as enterotoxigenic E. coli.
The discovery of exotoxin promoted a new paradigm in research on cholera into diverse areas and in finding a treatment aimed directly at neutralizing the cholera exotoxin. His discovery brought him international recognition and acclamation; although back home in India his work remained unsung and unnoticed. As noted by John Craig, State University of New York Health Science Centre at Brooklyn, Dey's work "forever altered our concepts surrounding the pathogenesis of secretory diarrhea." Nobel laureate Professor Joshua Lederberg stated that Dey's clinical observations concluded that dehydration is the lead cause of cholera pathogenesis, which is able to take the toll of a patient by massive secretion of water into the bowel. Therefore, replenishing the fluid loss by oral rehydration therapy (ORT) in cholera patients would save many lives. Success of ORT has been described as one of the 20th century's most important medical advances and this view is considered as a direct outcome of Dey's discovery of cholera toxin. Later, his findings led to purification of cholera (CT) and heat labile (LT) enterotoxins in the development of cholera and ETEC vaccines.
By 1963-64 the hyper toxin producing classical strains of V. cholerae O1, on which Dey worked, was abruptly replaced by El Tor biotype (producing less cholera toxin), which was prevalent in South-East Asia, but no epidemic and no cholera death has been reported in Calcutta in 1979. Dr Dey was forced to discontinue his work as there was no equipment for preserving the strains freeze dried and soon lost all interest in cholera. However, he continued to publish papers on cholera, the El Tor biotype and on other topics. Meanwhile, he visited England in 1960 with a Welcome Foundation Fellowship and again for the last time in 1962, to receive the D.Sc. degree in physiology of the London University. But, he was depressed due to lack of proper recognition of this work. A rude shock came with the death of Sir Roy Cameron in 1966, his constant source of inspiration and encouragement.
Dey retired from CMC at the age of 58 in 1973. He was offered two years’ extension as the Principal of the college but he declined. After retirement, he continued his research at the Bose Institute to purify the cholera toxin, which did not progress further because of the circumstances beyond his control. He was frustrated and established a clinical pathological laboratory in his residence to keep himself occupied. In 1978, the Nobel Foundation invited Dey to attend the 43rd Nobel Symposium on Cholera and related diarrheas and to deliver his views.
Dey breathed his last on 15 April, 1985 at the age of 70. His ambition was to create a better world to live in through his selfless services in the medical field. A few hours before his death, when he was in a state of coma, a letter arrived from the Editor, Indian Journal of technology, requesting him to contact with Eugene Garfield, Editor of Current Contents who was interested to know his professional contribution. But alas! Dey could not respond to his request. Garfield paid a tribute to Dr. Dey by publishing an article entitled "mapping of cholera and impact of Dr. Sambhu Nath Dey" in the ‘Current Contents’ issue of April 7, 1986. His pioneering work paved the way to more effective strategy for treatment and control of cholera. A special issue of the Journal of Current Science (Bengaluru), was published in 1990 in honor of Dr. Dey, to which several eminent scientist of national and international repute contributed.
