Sir U.N. Brahmachari and his battle against Kala-Azar

Abstract

Kala-azar or visceral leishmaniasis was at one time a scourge in the Bengal Presidency of British India comprising the present Indian states of Bengal, Bihar, Assam, and Odisha. The disease was rampant along the Ganga and Brahmaputra River adjoining areas. In the early 1900s, the treatment initiated was by the intravenous injection of tartar emetic, which had a narrow safety level and long-term use was marked with multiple side effects. In 1920, Upendranath Brahmachari discovered urea stibamine, which is the urea salt of para-amino phenyl stibnic acid and it revolutionized the treatment of Kala-azar with >90% cure rate and with minimal side effects. He is also credited with the description of post-kala-azar dermal leishmaniasis. He was conferred the knighthood of the British Empire as recognition of his important contribution. Although his name was twice nominated for Nobel Prize, unfortunately, he never received it.

INTRODUCTION

Kala-azar or visceral leishmaniasis was recognized by the British medical and administrative authorities as a public health problem in India. A lot of work was done to control this infection in the 19^th and early parts of the 20^th century by the authorities. The contribution of Upendranath Brahamachari remains mostly forgotten in this field. His discovery of pentavalent antimonial, urea stibamine saved millions of lives from this deadly protozoal disease transmitted by sandfly. Here, we present a brief life sketch of this doyen of biomedical research from India.

CHILDHOOD AND EDUCATION

Upendranath Brahamachari was born in Jamalpur, Bihar, in the erstwhile Bengal Presidency on December 19, 1873. His father Dr. Nilmoni Brahamachari was a doctor in the East Indian Railways at Jamalpur, while Mrs. Sourav Sundari Devi was his mother [Figure 1].

Figure 1.

Dr. U. N. Brahmachari (1873–1946) (Source: www.getbengal.com)

Young Upendranath completed his school education from Eastern Railways Boy's High School at Jamalpur, then joined Hooghly College (presently known as Hooghly Mohsin College) and obtained his BA degree with honors in Mathematics and Chemistry in 1893. He stood first in Mathematics and was awarded the Thwaytes Medal. Next year, he obtained his Masters in Chemistry from the Presidency College, Calcutta. Thereafter, he changed his discipline from Chemistry to medical sciences. He joined Calcutta Medical College and obtained Licentiate in Medicine and surgery in 1899 and MB degree in 1900. He stood first in Medicine and Surgery for which he was awarded the Goodeve and McLeod Medals, respectively. He obtained his Doctor of Medicine degree in 1902 and PhD in Physiology from the University of Calcutta in 1904. His work on “Studies in Haemolysis” earned him the PhD degree.[1]

PROFESSIONAL CAREER

After completion of medical studies, he was appointed as a teacher of Physiology and Materia Medica at Dacca Medical School under Sir Gerald Bomford and spent about 4 years there from 1901 to 1905. Bomford was impressed by Brahmachari's talent and encouraged him for research in the field of Medical Sciences. Dr. Brahamachari came back to Calcutta and joined as a Teacher of Medicine and First Physician at Campbell Medical School (presently known as Nil Ratan Sircar Medical College and Hospital) in 1905 and spent maximum part of his service life (about 20 years) here. Thereafter, he joined the Calcutta Medical College in 1923 and retired from there in 1927. After retirement, Dr. Brahamachari joined as a professor of Tropical Diseases at Carmichael Medical College, Calcutta. He also served as in charge of the Tropical Disease Ward of National Medical Institute and Head of the Department and Honorary Professor of Biochemistry in the University Colleges of Science, Calcutta. This eminent scientist breathed his last on February 6, 1946.

SCIENTIFIC ACHIEVEMENTS

With a strong background in chemistry, physiology, and modern medicine, Dr. Brahamachari made remarkable contributions in the field of biomedical sciences. One of his most outstanding work was the discovery of urea stibamine for the treatment of Kala-azar. The first epidemic of Kala-azar was reported from Assam in 1870 which spread to Bengal and Bihar along with the Brahmaputra and Gangetic planes. The disease claimed millions of lives, but the causal agent remained undiscovered till the end of the 18^th century. In 1903, William Leishman and Charles Donovan discovered the pathogen independently from the autopsy material of two soldiers from Calcutta and Madras, respectively. Sir Ronald Ross named the parasite as Leishmania donovani.[2] During 1913–1915, Kala-azar was treated with intravenous injection of tartar emetic (potassium salt of antimonyl tartrate). Several disadvantages were reported due to prolonged use of tartar emetic including cardiac and hepatic dysfunctions. Dr. Brahmachari attempted the use of sodium salt of antimonyl tartarate and showed better results than its potassium salt. Then, he started treating Kala-azar cases with powder and colloidal forms of metallic antimony, but it also had some disadvantages such as not readily available, could not be stored, a tedious method of preparation, and complicated administration technique.[3] Therefore, Dr. Brahmachari continued his research for better means of treatment of Kala-azar. During this time, Paul Ehrlich, a German physician and chemist, showed the effectiveness of atoxyl (sodium salt of para-amino arsenic acid) against sleeping sickness in 1905. Dr. Brahmachari took the inspiration from Ehrlich's work and paid his attention to replace the arsenic component of atoxyl by heavy metal antimony and used it for the treatment of Kala-azar patients. He continued his research in a small room with almost zero laboratory facilities at the Campbell Hospital and he was able to synthesize a new potent compound against Kala-azar named urea stibamine – the urea salt of para-amino phenyl stibnic acid in 1920.[4] Using urea stibamine, Kala-azar mortality rate could be brought down to 10% by 1925 and it had a cure rate of 95%. This drug was used for the treatment of Kala-azar not only in India but also in Greece, France, and China for many years.

Remembering the golden moment of his discovery he wrote “I recall with joy that memorable night in 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 a 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 Stibamine dawned upon my mind” [Figure 2].

Figure 2.

The room at the Campbell Hospital, Calcutta, where urea stibamine was discovered by U. N. Brahmachari (Source: A Treatise on Kala-azar by Upendranath Brahmachari)

Due to this remarkable discovery of Dr. Brahmachari, Sir John Kerr (then Governor of Assam) remarked that “The progress in the campaign against Kala azar in Assam has been phenomenally rapid. Dr. Brahmachari's research in the treatment of Kala azar were one of the most outstanding contributions in the tropical therapeutics, as a result of which three lakhs of human lives were saved in the Province of Assam alone during the course of 10 years.”

In 1932, the Chairman of the Indian Kala-azar Commission Col. H. E. Shortt stated that “We found Urea Stibamine an eminently safe and reliable drug and in 7 years we treated some thousands of cases of Kala-azar and saw thousands more treated in treatment centres. The acute fulminating type characteristics of the peak period of an epidemic respond 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.” Col. Shortt also remarked that “it was a dramatic success, overnight, a death rate of 90% was transformed into a cure rate of 90%.”

Another remarkable discovery of Dr. Brahmachari in the field of Kala-azar was the identification of cutaneous leishmaniasis among Kala-azar recovered patients. This cutaneous leishmaniasis was named as Brahmachari Leishmanoid[5] or the present name post-kala-azar dermal leishmaniasis.

Dr. Brahmachari was nominated for the Nobel Prize in Medicine in 1929 and 1942. Unfortunately, he did not receive the Nobel Prize.

Although Dr. Brahmachari is remembered for his work on Kala-azar, he also worked on many other diseases such as malaria, cerebrospinal meningitis, blackwater fever, leprosy, filariasis, influenza, syphilis, and diabetes. Dr. Brahmachari discovered the existence of quartan fever for the first time in Calcutta and Dhaka. He also established India's first blood bank at the Calcutta School of Tropical Medicine in 1935.

HONOURS AND AWARDS

Dr. Brahmachari held many prestigious positions and bagged many awards such as Rai Bahadur, Fellow-Royal Society of Medicine; Member of Central Malaria Committee, Bombay (1915); Griffith Memorial Prize, University of Calcutta; Minto Medal, Calcutta School of Tropical Medicine and Hygiene (1921); Vice President, Asiatic Society of Bengal (1922); Kaisar-i-Hind Gold Medal (1924); President, Asiatic Society of Bengal (1928–1929,1931); President of Society of Biological Chemists, India (1932, 1934–1935); Founder Fellow of the National Institute of Sciences of India (1935); President, Indian Science Congress Association; President, Indian Chemical Society (1936); Nomination for the Fellowship of the Royal Society London (1941–1942); and President, Indian Association for the Cultivation of Science (1942). At that time, British Government recognized Dr. Brahmachari by the title of “Rai Bahadur” and “Knighthood.”

CONCLUSION

Dr. Brahmachari was a very humble as well as influential man. He financially supported many institutions of Calcutta such as the journal “Science and Culture” (founded by Megh Nath Saha) and Indian Association of Cultivation of Science He set up a research institute in his residence in Calcutta named as “Brahmachari Research Institute.” Unfortunately, most of the Indians forget about the contribution of U. N. Brahmachari who almost conquered the deadly disease – Kala-azar.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.