Wednesday, February 20, 2013

Upendra Nath Brahmachari - A pioneer in Medicine


Upendra Nath Brahmachari

It was a shocking discovery - last medicine invented by an Indian was way back in 1929.

This article is about one of pineers in medicine in India Upendra Nath Brahmachari (December 19, 1873–February 6, 1946), who invented 'Urea Stibamine' for the treatment of Kala Azar (aka 'Visceral leishmaniasis'). He was nominated for Nobel Prize in 1939 for his contributions in the field of  Physiology and Medicine in the year 1929.

The article metioned below is a reproduction of Upendra Nath Brahmachari's story from an article in Vigyan Prasar, Department of Science and Technology (DST), Government of India, with permission.

Upendra Nath Brahmachari (December 19, 1873–February 6, 1946)

“As a matter of the most vital concern in nation-building, the problem of nutrition demands very careful consideration by statesmen and scientists alike, more so due to the fact, as has been recently observed, that a great part of the world’s population is not consuming the necessary food stuff. An eminent Swiss authority predicts the decay of civilization unless there is a fundamental revision of the people’s diet.

--- Upendra Nath Brahmachari in his General Presidential address to the Indian Science Congress (1936).

“Dr. Brahmachari has been the President of the Asiatic Society of Bengal for three times; has done extensive research in connection with tropical diseases such as malaria, blackwater fever etc., and as a research worker enjoys international reputation; recognized as a leading expert on Kala-azar in particular, in the treatment of which he has achieved remarkable success with his `Urea Stibanmine’ which he discovered; has earned a name in philanthropy; is one of the most eminent physicians in Calcutta and is held in esteem also by laymen of all communities.”

-- The then Viceroy of British India at Brahmachari’s Investure of Knighthood


Upendra Nath Brahmachari was a leading medical practitioner of India of his time. His monumental discovery of Urea Stibamine, an organic antimonial compound, played a crucial role in the treatment of and campaign against Kala-Azar. His “Treatise on Kala-azar” is a premier work on the subject. As a teacher and educationist his work was of a high order. He was associated with almost all the known scientific and literary organizations at Kolkata. He had an insatiable thirst for knowledge. He had large private collection of books, which included not only scientific works but also literary works. Brahmachari was a remarkable personality.

Upendra Nath Brahmachari was born in Jamalpore, in the Monghyr district of Bihar to Dr. Nilmony Brahmachari and Smt. Sourav Sundari Devi. His official date of birth was June 07, 1875. However it has been reported that Brahmachari, in his later life mentioned his actual date of birth 19 December, 1873. In those days Jamalpore was an important railway town of the then East Indian Railways. His father was a medical man and served the East India Railways at Jamalpore. As a physician he was very successful. Dr. Nilmony’s name was a household word at Jamalpore. He was a highly respected figure in both the European and Indian communities. After his retirement from the services of the railways Dr. Nilmony became a Municipal Commissioner and an Honorary Magistrate of Jamalpore.

The title Brhamachari has a little history. A person who lives a life of celibacy is called Brahmachari. It was Keshav Bharati who had initiated Sri Chaitanya Mahaprabhu into Sanyas. Keshav Baharati himself had taken Sanyas under the Bharati sect of Sri Shankaracharya. Thus he had no descendants of his own. Keshav’s elder brother Gopal had taken deeksha from him. Gopal renounced his family title of Mukhopadhyaya and became known as Gopal Bharati Brahmachari Thakur. Brahmachari’s ancestors were descendants of Gopal Bharati Brahmachari, he being in the ninth line of descent.

Brahmachari had his early education at the Eastern Railways Boys’ High School at Jamalpore. After passing his Entrance Examination from Jamalpore with credit, Brahmachari joined the Hooghly College, from where he passed his BA in 1893, with Honours in Mathematics and Chemistry. In those days it was possible for a student to appear in two honours subjects. Brahmachari stood first in order of merit in Mathematics in his BA examination and awarded the Thwyates Medal. Though Brahmachari loved Mathematics deeply and had shown great proficiency in the subject, he decided to join the Calcutta Medical College and the Presidency College at Kolkata (then Calcutta) for studying Medicine and Chemistry respectively. He passed his M.A. degree with First Class in Chemistry from the Presidency College in 1894.

He was taught chemistry by Sir Alexander Pedler and Acharya Prafulla Chandra Ray. Brahmachari was greatly influenced by Acharya Ray. Brahmachari also pursued his medical career with equal diligence. He obtained his L.M.S degree in 1899 and in the next year he took the MB degree. In his MB Examination Brahmachari stood First in Medicine and in Surgery and for which he was awarded Goodeve and McLeod Medals. In 1902 he obtained the MD degree of the Calcutta University. In those days it was a rare distinction. He also obtained Ph.D. degree of the Calcutta University for his researches in Physiology. His thesis was titled Studies in Haemolysis, a work, which even today is considered an important piece of work on physiological and physiochemical properties of the Red Blood Cells.

After a firm grounding in Mathematics, Chemistry, Physiology and modern Medicine, Brahmachari joined the Provincial Medical Service in September 1899. For a brief period he worked as the House Physician in the Ward of the First Physician Sir Gerald Bomford’s. Sir Bomford was highly impressed with young Brahmachari’s urge for carrying out research and his strong sense of duties. Bomford got Brahmachari appointed as Teacher of Physiology and Materia Medica and Physician in Dacca Medical School in November 1901. He spent about four years at Dacca. During this short period he had established himself as an excellent teacher, a medical practitioner and a consultant. He also did researches with Sir Neil Campbell, Superintendent of the Medical School.

After coming back to Kolkata in 1905, Brahmachari joined the Campbell Medical School (now renamed as Nil Ratan Sarkar Medical College and Hospital) as the Teacher of Medicine and First Physician. The most important part of his life was spent at the Campbell Medical School, where he spent 20 years. In 1923 Brahmachari joined the Medical College, Kolkata as Additional Physician. It may be noted here that Brahmachari and Lt. Col. K. K. Chatterjee were the first two Provincial Medical Service men outside Indian Medical service cadre, to get appointments in the Medical College. Lt. Col. Chatterjee had joined as Additional Surgeon. Brahmachari retired from the Government Service at the Medical College in 1927. After retirement from the Government service Brahmachari joined the Carmichael Medical College as Professor of Tropical Diseases. He also served the National Medical Institute as In-charge of its Tropical Disease Ward. He also became the Head of the Department of Biochemistry and Hony. Professor of Biochemistry at the University College of Science, Kolkata.

Brahmachari’s most outstanding research contribution was in the field of conquest of Kala-Azar (a Hindi term for black fever), a protozoal infection in both children and adults. The disease Kala-azar (Visceral leishmaniasis) was described by William Leishman and Charles Donovan in 1903. Kala-azar is also known as Leishman-Donovan infection. Kala-azar is an infectious disease of South Asian and Mediterranean countries. The protozoan parasite that causes the disease is called Leishmania donovani. The disease is transmitted by sand flies and it is characterised by an enlarged spleen and liver, irregular fever, anemia etc. Though various forms of treatment were in vogue but they did not help to reduce the death rate. In 1913, a Brazilian doctor named Vianna reported to have cured the South American form of Kala-azar by the intra-venous administration of tartar emetic (potassium salt of antimonyl tartrate). Then in 1915 Christina and Cortina of Sicily also recorded the successful use of tartrate emetic in infantile Kala-azar. Rogers in Calcutta also obtained favourable results in 1915, by the intra-venous use of tartar emetic. However, physicians soon found that there were serious disadvantages in the prolonged use of tartar emetic intravenously.

Brahmachari decided to improve the results over tartar emetic by using the sodium salt of antimonyl tartrate instead of the potassium salt. By doing this Brahmachari thought that he would avoid the depressant action of potassium and so he would get better results. He did get better results and used sodium antimonyl tartrate for years. It was found later that prolonged use of the sodium salt had also disadvantages. Brahmachari started using metallic antimony—first as fine powder and then as colloidal antimony. Both forms of antimony used by Brahmachari gave good results but they had the following disadvantages:

i. They were not readily available.
ii. As they could not be stored for a long time they had to be prepared afresh every time.
iii. The method of their preparation was tedious.
iv. The technique of their intravenous administration was quite complicated.

Seeing these disadvantages Brahmachari continued his search for a more efficient means of treatment of Kala-azar. Around this time Ehrlich was successful in treating sleeping sickness by using atoxyl or sodium salt of para-arsanilic acid. Brahmachari decided to replace arsenic of atoxyl by antimony and then use this compound for treatment of Kalaazar. Antimony was the causative agent and both arsenic and antimony belong to the same group of the Periodic Table. There were other people who were working on the similar idea. Towards the end of 1919 Brahmachari received a grant from the Indian Research Fund Association for conducting further research into the treatment of the disease. He carried out his research work in a small ill-equipped room in the Campbell Hospital. He did not have even simple facilities like a gas burner, a water tap or an electric bulb. Working under such adverse conditions Brahmachari discovered a potent agent against Kala-azar, which he named Urea Stibamine. It was the urea salt of para-amino-phenyl stibnic acid. Recalling the moment of his important discovery he later wrote: “I recall with joy that memorable night in the banished from India and other parts of the world where it occurs. That will be happiest and proudest day of my life if it falls to my lot to see it.”

Urea Stibamine was a great success in treating Kalaazar. In 1932, Col. H. E. Short, Director, Kala-azar Commission, appointed by the Government of India stated: “We found Urea Stibamine an eminently safe and reliable drug and in seven years we treated some thousands of cases of Kala-azar and saw thousands more treated in treatment centers. The acute fulminating type characteristic of the peak period of an epidemic responds to treatment extraordinarily promptly and with an almost dramatic cessation of fever, diminution in the size of spleen and return to normal condition of health.” Today the incidence of Kala-azar has drastically reduced in India and other parts of the world. There are occasional or sporadic cases here and there. Today Kalaazar persists only in very poor and remote areas.

Though mostly known for his brilliant work on Kala-azar, Brahmachari worked on other diseases like Malaria, Black- Water Fever, Cerebrospinal Meningitis, Diabetes, Filariasis, Influenza, Leprosy, and Syphilis. He published about 150 research papers. Brahmachari was the first to discover the presence of Qurtartan Fever in Kolkata and Dhaka. This disease was considered to be very rare. Crombie, the President of the Indian Medical Congress (1894) stated in his Presidential Address that he had met only one case in his whole experience in India. Brahmachari, after a most exhaustive and critical survey of the vast literature on the Old Burdwan Fever, concluded that the disease was a combination of two diseases namely malaria and Kala-azar. He published his conclusion in his paper, “On the nature of the epidemic fever in Lower Bengal commonly known as Burdwan Fever” published in the Indian Medical Gazette in 1911. Brahmachari had shown that in Black-water Fever the largest amount of haemolysis occurred in the liver during the active stage of the disease. He also prepared an antihaemolytic solution of quinine for treatment of cases of black-water fever whose blood showed the presence of malarial parasites.

In his Presidential Address to the Asiatic Society of Bengal in 1930 Brahmachari said: “When I recall to my mind that I had the privilege of teaching and examining many hundreds of medical students in Medicine, and remember the raw and restive youths to whom I lectured, and then look around and see the resulting product, I feel with Sir Ernest Rutherford that a transformation has occurred that is much more wonderful than the transformation of radium and must have involved much more energy in the process…India, the seat of earliest civilization of man, is regaining the healthy state that she must have enjoyed in the days of old. Diseases which for many centuries were considered incurable and destroyed millions of human lives in India, are now losing their terrors.”

Brahmachari was actively connected in various spheres in the University of Calcutta for nearly 40 years. He was Fellow of the Calcutta University since the beginning of the Universities Act 1904. He was a member of the Senate, the Calcutta Campbell Hospital at Sealdah where after a very hard day’s work I found at about 10 o’clock in a little room with a smoky dimly burning lantern that the results of my experiments were up to my expectations. But I did not know then that providence had put into my hands a wondrous thing and that this little thing would save the lives of millions of fellowmen.

I shall never forget that room where Urea Stibamine was discovered. The room where I had to labour for months without a gas point or a water tap and where I had to remain contented with an old kerosene lamp for my work at night. The room still remains but the signs of a laboratory in it have completely disappeared. To me it will ever remain a place of pilgrimage where the first light of Urea Stimamine dawned upon my mind.

To-day Urea Stibamine stands pre-eminent in the treatment of Kala-azar in India and as a powerful prophylactic against the disease. And it is a matter of supreme satisfaction to me that the treatment evolved out of my research has removed the terrors of this distressing disease. It may be hoped that before long the disease will be completely Syndicate and Boards of Studies of Medicine and of Science of the Calcutta University. He was also the Dean of the Faculty of the Medicine (1938) and Dean of Faculty of Science (1938-40). He was a Active Member in the Rules Revision Committee responsible for framing the University Regulations from the beginning of the Universities Act 1904.

Around 1924, Brahmachari had established a research institute in his own residence in Cornwallis Street, Kolkata. This institute was later converted into a Partnership concern with his sons Phanindra Nath and Nirmal Kumar. Under his guidance the Institute did remarkably well both in the fields of research and manufacture. Unfortunately the institute stopped functioning in 1963 and the nation lost a legacy of one of its great sons.

Brahmachari took keen interest in humanitarian and cultural activities. He played an important part in the formation of a Blood Bank at Calcutta. He was the Chairman of the Blood Transfusion Service of Bengal. He was the Vice President of the St. John Ambulance Association of the Bengal branch and also its President. He was the Chairman of the Managing Body of the Indian Red Cross Society of the Bengal Branch. In fact he happened to be its first Indian Chairman. He was a member of the Sanitary Board of Bengal. He was the Vice-Chairman of the Board of Trustees of the Indian Museum.

He was a charitable person. He made generous donations. Among the public institutions which received donations from Brahmachari are: The Indian Red Cross Society, The Blood Bank at Kolkata, the University of Calcutta, the Jadavpur Tuberculosis Sanatorium, the Central Glass and Ceramic Research Institute, the Physiological Society of India, Calcutta Medical College, the Indian Association for the Cultivation of Science, Indian Science Congress, Vicerroy’s Earthquake Relief Fund, Lady Jackson’s Darjeeling Victoria Hospital Fund, and Board of Industries of Bengal. There was hardly any hospital in India that did not get free gift of his Urea Stibamine. He sold urea stibamine to the government at his cost price. He had made provisions for several awards, scholarships and medals for the University of Calcutta. Many people do not know that the journal “Science and Culture” could be initiated because of a generous donation from Brahmachari. He generously contributed to the High School in Purbasthali near his ancestral home. The name of of the institution was later changed in the name of his father as Purbasthali Nilmoy Brahmachari Institution.

Among the various honours that he received included: the Griffith Memorial Prize of Calcutta University; the Minto Medal of the School of Tropical Medicine & Hygien; the Kaiser-I-Hind Gold Medal; the Sir William Jones Medal of the Asiatic Society of Bengal. He was felicitated and honoured by various medical and scientific bodies. He was: President, Indian Association of the cultivation of Science; Calcutta; President, society of Biological Chemists; President, Indian Committee of International Microbiological Congress, Paris; President, Physiological Society of India; President, Indian Science Congress; President, Asiatic Society of Bengal; President, Indian Science News Association, Calcutta; President, Indian Provincial Medical Service Association; Fellow, Royal Society of Medicine, London; Fellow, Royal Society of Tropical Medicine and Hygiene, London; Hony. Fellow International Faculty of Science, London; Fellow National Institute of Sciences of India (Later renamed Indian National Science Academy).

The then British Government recognized the importance of Brahmachari’s work. He was awarded the title of Rai Bahadur for his multifarious, humanitarian and other works. He was knighted in 1914.

He was a very good host. He used to love to entertain people. Lancet in its March 09, 1946 issue wrote: “In his large house in Calcutta, Brahmachari delighted to entertain his British and Indian friends. The fare was always good and the conversation even better. If all distinguished Indians, and for that matter all British officials, had shared his liberal outlook, many of the difficulties of India today would have been solved before they have time to develop.”

Brahmachari died on February 06, 1946.

Some Important works by Upendra Nath Brahamcarhy

1. Studies in Haemolysis, Calcutta University, 1909.
2. Kala-Azar : Its treatment, Butterworth & Co. Ltd. Calcutta 1917.
3. Kala-Azar in Doctor Carl Mense’s Handbuch der Tropenkranahaiten, vol. IV, 1926.
4. Treatise on Kala-Azar, John Bale, Son’s & Danielsson Ltd., London, 1928.
5. Campaign against Kala-Azar in India, Jubilee Publication on the 80th birthday of Dr. Prof. Bernhard Nocht, Hamburg, 1937.
6. Progress of Medical Research work in India during the last 25 years, an progress of Science in India, during the past 25 years, Indian Science Congress Association 1938.
7. Gleanings from my Researchers Vol. I, Calcutta University 1940
8. Gleanings from my Researchers Vol. II Calcutta University 1941
9. Infantile Biliary Cirrhosis in India in British Encyclopedia of Medical practice. Edited by Sir Humphrey Rolleston

Sajeev.

References

1. Upendra Nath Brahmachari - A Pioneer of Modern Medicine in india - Vigyan Prasar, Ministry of Science and Technology, GOI
2. Upendra Nath Brahmachari
3. Effect of ureastibamine on Leishmania donovani amastigote - NCBI
4. Gazette Issue 34056 published on the 1 June 1934 - London Gazatte
5. Primary and secondary education reform should be the top priority for india- Current News

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