CS Ramakrishnan, scientist

CSR’s publications in science
Cholera-like diseases were known in India in ancient times, but there is some dispute as to whether they were the same as the form noted in the 1600’s by the Portuguese (Barua & Greenough 1992). In modern times, there were six cholera pandemics between 1817 and 1923*. The sixth pandemic was followed by intensive work on cholera at the King Insitute, Madras. K. V. Venkatraman was engaged in this work starting in 1927.

The identification and classification of bacteria was based on surface antigens (Gardner & Venkatraman 1935, Journal of Hygiene 35:262). For proper identification, it was important to transport viable bacteria in stools samples to the laboratories at the King Institute.  An appropriate medium was needed for the transport of viable specimens. CSR assisted KVR in this painstaking work, which involved the testing of many chemicals, several of which were brightly coloured. Because of this, they called  their laboratory the ‘Rainbow Lab’ (CSR, pers. comm. 2007).  This work resulted in a publication:

Venkatraman KV, Ramakrishnan CS 1941. A preserving medium for the transmission of specimens for the isolation of Vibrio cholerae. Indian J Med Research 29: 681-684.

The “Venkatraman-Ramakrishnan” or “VR” fluid or medium still is used to transport stools (Barua & Greenough 1992). Citations of the paper in Web of Science, a reference database, are incomplete and given as Venkatraman KV Indian  J Med  Res, 1941. This suggests that users of the medium do not necessarily read the paper where it was originally published.
Barua D, Greenough WB. 1992. Cholera. Springer, 372 pages.
Microorganismos de los alimentos Volumen 1 Bibliography ISBN 842000908 

Vibrio cholerae was classified into cholera Vibrio (containing the ‘O1’ antigen**) and the non-cholera Vibrio (non-O1, also called El Tor, after the place in Egypt where it was identified).

The pathogenic form of the bacterium was found to secrete a toxin in the human intestinal system (De SN, 1959, Nature 183:1533-4. See historical note pdf).  The toxin causes a reversal of the normal action of the intestinal wall.  Instead of absorbing water and dissolved sugars and nutrients from the intestine and transporting it to the rest of the body, it drains the body of water and nutrients, which pass into the intestines. Effectively, the human intestine serves to amplify the bacterium in a nutrient rich medium (Daniel Dykhuizen, SBU, pers. comm. 2008). The toxin-producing Vibrio cholerae is believed to have evolved through the infection of an ancestral, non-toxic Vibrio cholerae by a bacterial virus (prophage) which then became incorporated into the bacterium (work by Waldor, 2001).
The non-O1 Vibrio was detected in lakes and rivers of India but was not associated with the disease:

Venkatraman KV, Krishnaswami AK, Ramakrishnan CS. 1941. Occurrence of Vibrio El Tor in natural sources of water in the absence of cholera. Indian J Med Research 29: 419-424.

(also Read WDB and Pandit SR, 1941, Ind J Med Res 29:403-315).
P Honig. 1945.  Science and Scientists in the Netherlands Indies. Board For The Netherlands Indies. 497 pgs.
Feachem R, Bradley D, Garelick H & Mara D. 1983. Sanitation and Disease: Health Aspects of Excreta and Wastewater Management. John Wiley & Sons. Chapter 17.
MS Islam, BS Drasar, RB Sack.1996. – Ecology of Vibrio Cholerae: role of aquatic fauna and flora. in Drasar, BD and Forrest BD, Cholera and the Ecology of Vibrio cholerae, Springer.
Cholera and the Ecology of Vibrio cholerae. Edited. by bs Drasar and bd Forrest. Pp. 355. London:. Chapman & Hall. ISBN 0 412 61220 8.
Apparently a prophage was transferred to the El Tor form, which became toxic and resulted in the pandemic that started in Indonesia in 1961.
Perhaps the modern form of Cholera, too, arose in some such fashion in the 1600’s or so (Daniel Dykhuizen, SBU, pers. comm. 2008).
*In 1854, the causative organism was found to be Vibrio cholerae (by Filippo Pacini, though traditionally ascribed to Robert Koch’s work in India).
**Currently about 206 ‘O’ serogroups of Vibrio cholerae are recognized (WHO – pdf).

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K.V. Venkatraman Centenary

The Hindu Apr 29, 2003

CHENNAI APRIL 28. The birth centenary of K.V. Venkatraman, one of the pioneers in cholera research in Asia, was observed today at the King Institute, Guindy here, where he had served for more than 20 years including as director.

Participating in the meeting, some of his junior associates recalled the doctor-scientist’s workaholic schedules and research ethics, and drew attention to his having opted for research rather than the more lucrative clinical profession.

C.S. Ramakrishnan, who was involved with the scientist in developing the pioneering an inexpensive Venkatraman-Ramakrishnan transport medium for choleraic stools, spoke about the former King Institute director’s insistence on perfection, his affable nature and the role he played in controlling the epidemic in India. Dr. Venkatraman began his career in the King Institute, and was later serologist and chemical examiner to the Indian Government and advisory member to the World Health Organisation on infectious diseases in India, the King Institute director, Lalitha C.Pillai, said. On the request of WHO, he was also deputed by India to set up the first vaccine laboratory in Kabul, Afghanistan.

Dr.Venkatraman’s son, K.V.Krishnan, announced a donation of Rs. 2 lakhs to the institute towards funds for a Dr.K.V.Venkatraman Endowment Memorial Lecture.

 

King Institute history

King Institute in need  [The Hindu]

A HUNDRED years old, little heard, less seen is an institution on the banks of the Adyar, between the two Mounts, that has an international reputation. In 1970, it was presented an award by UNESCO for the outstanding work it had done in the eradication of smallpox worldwide by producing the Freeze Dried Smallpox Vaccine. Today, it struggles to keep going due to inadequate funding, but does its best to continue with its vitally necessary activities in the field of preventive medicine.

Started as a depot for smallpox vaccine on November 7, 1899, it was named the King Institute for Preventive Medicine when it became the first organisation in the country to manufacture the lymph vaccine. It was named after Lt. Col. W.G. King, IMS, who was the Sanitary Commissioner of the Madras Presidency at the time of the founding. Today, the Institute has grown into a 16-department organisation that manufactures five different vaccines and offers a host of other medical services in the field of preventive medicine.

The King Institute’s main building in traditional red brick and lime with towers that was the architectural style for public buildings of the times, was inaugurated in March 1905, very likely to a Henry Irwin design. Over the years, other buildings have been added in the tree-rich campus where scientists work to the chirping of birds and a view of a spectrum of green. But these new buildings do not harmonise with the main block. In fact, closest to it in harmony is the old tiled `cottage’ in red that was the original vaccine depot and which remains a monument to the founding of The King.

It was in 1903 that the institute began expanding its activities, setting up the Bacteriology Department. The department undertook to carry out diagnostic tests on clinical samples sent to it from all over the Madras Presidency. It must have been a Herculean task in those days, given the size of the Presidency and the widespread prevalence of disease.

A Public Health Section was established in 1923 and has played an important role in water quality since 1947. The King began to live up to its full name during the 1920s when it started manufacturing other vaccines. Cholera and typhoid vaccines were the first to be produced. It was in 1927 that a young doctor, K. V. Venkatraman, joined the Institute and was put in charge of Cholera Enquiry. Over the next decade, he was to do pioneering research on cholera that was to be internationally recognised, and develop with Ramakrishnan the V-R fluid as a transport medium that preserved for more than six weeks the bacteria in cholera-affected samples, a contribution that proved invaluable in the study of the epidemiology of cholera outbreaks in remote areas.

In the 1960s, The King began producing tetanus toxoids and, a decade or so later when the World Health Organisation declared that smallpox had been eradicated, the institute switched to the production of anti-rabies vaccine.

The Serum Standardisation Laboratory was established in 1941 when it was decided three years earlier to manufacture prophylactic and therapeutic sera. The lab evolved as the Department of Antitoxins in 1943 and focussed on the production of anti-tetanus, anti-diphtheria, anti-gangrene sera. And in more recent years, moved on to making polyvalent anti-snake venom serum, one of the four production centres in the country.

Apart from the production and quality control departments, The King has several service departments, like the Diagnostic Department – going back almost to its first years – and the Department of Virology established in 1969. The latter, designated a National Polio Laboratory in 1993 and accredited to WHO shortly afterwards, played a major role in eradicating poliomyelitis by 2000, but now will have to play the role again as isolated cases have begun to be reported once more. AIDS is the new focus area of the institute.

Over the years, the institute has built up one of the finest libraries in the country on preventive medicine. Sections on microbiology, parasitology and related environmental sciences, including food and water analysis, are outstanding. The library, the institution’s work and the quality of its staff have led to it being recognised by the Madras and MGR Medical Universities for Ph.D. programmes.

But suffering from lack of funding, the institute is unable to modernise. Even maintaining its 200 horses and over a thousand guinea pigs is a strain on its resources. Yet work goes on quietly, patiently, fighting the war against disease and making people less threatened. And so there continues a proud record of service.