THE DISCOVERY OF UREA STIBAMINE AND THE BIRTH OF PHARMACEUTICALS IN INDIA

Dr. Aruna Muthumanickam

In his matchbox laboratory at the Campbell Medical School in Calcutta, UpendranathBrahmachari toiled tirelessly to create a finding a solution to combat Visceral Leishmaniasis. The disease, first emerging in the 1820s, had continued to fester and plague villages across what was then eastern Hindustan, wiping out entire villages in Assam and Bangladesh, by the 1870s. Until then, the only recorded chemical known to be lethal against Kala azar was Antimony Potassium Tartrate, a trivalent inorganic antimony compound, effective, but also very hazardous.

UN Brahmachari recognized the need for a safe and efficient drug that would help eradicate the disease. At a time when medicine in India was largely centered around ayurvedic practices and herbal remedies, Brahmachari sought to tap the properties of modern chemistry and to unlock a future where healthcare solutions are born in laboratories and not in the great outdoors. It was a revolutionary period for medicine in India; the first synthetic drug to be ever developed in the country and the second ever developed drug against an infectious disease, after Salvarsan for Syphilis.

The story of Brahmachari’s discovery is a lesson, not only in chemistry and history, but also, philosophy and human ambition, and the commitment a scientist must make to the furtherment of science. Brahmachari first synthesized newer inorganic antimonials, similar to Antimony Potassium Tartrate. These agents were colloidal metallic antimony and were effective by being taken up by the Reticuloendothelial system¹. However, he was not thoroughly satisfied with the result. There comes a moment in the birth of every new invention, where its creator must make a choice. To either stop while he is ahead and accept a certain degree of mediocrity, or to keep plowing forward until he crosses ordinary and extraordinary and reaches something astounding. This is precisely what Brahmachari sought to do. Finally, in 1919 Brahmachari prepared p-Stibanilic acid and its various salts. Over the next year he continued to perfect his formulae and produced urea stibamine, the first organic antimonial to achieve universal recognition as a treatment for leishmaniasis. With the use of the drug, the prevalence of leishmaniasis decreased from 95 percent to merely 7 percent², an unprecedented success rate of any other drug at that time. Not only was the drug exceedingly successful, but it was less hazardous than its former cousins, and less painful, by virtue of complexing with urea. It also won UN Brahmachari a nomination for the Nobel Prize in Physiology and Medicine in 1929. But most importantly, it initiated a domino effect in the then infantile pharmaceutical prospects in India. After that, there was only one way we were heading in the field of pharmaceuticals, and that was up. Today, the Indian pharmaceutical industry ranks third in the production per volume of allopathic medication. Over the years, we have witnessed, increased in-house investment of minds and money in R&D, expansion of public-private partnership and international collaboration, putting India on the map as one of the global leaders in high quality generics.

The drugs we use in routine practice need no introduction. But it would be a disservice to fail to mention the groundbreaking work that has transpired in the field of Pharma in the recent years. In April 2012, ‘Synriam’ became India’s first ever domestically produced antimalarial agent. Keeping with the latest Pl. falciparum patterns of the time, Synriam was a fixed-dose combination of arterolane and piperaquine. A simple OD treatment for 3 days for uncomplicated Falciparum malaria, capable of surviving resistance patterns for at least a couple of decades to come.
Until June 2013, it was widely agreed upon that no antilipid agent was capable of effectively reducing LDL and in parallel, increasing HDL, in diabetics. Until, Saroglitazar.
Lipaglyn, or Saroglitazar, (for you pharma geeks), introduced by Zydus Cadila became the world’s first glitazar to be approved for the treatment of dyslipidemia in Type 2 DM patients³.
In addition, it is also known to reduce fasting plasmaglucose and HbA1c as well.
Innovation has also been seen in the form of increased research and production in the field of Biosimilars. The greatest advantage has been in being able to replicate biologics with greater convenience and also being able to offset drug prices.

From a time when drug production was done in miniature beakers in laboratories with one vent and one door, to now being one of the largest producers and suppliers of medications worldwide, a lot has changed. But, at the root of all discovery, some principles remain firm and untarnished by time. Among these are an unfaltering commitment to the utilization of science for the alleviation of human suffering and the realization that vision and action cannot be mutually exclusive in the preparation for success.

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1. FatoHistórico, Marsden PD. The Discovery of urea stibamine. Revista da SociedadeBrasileira de Medicina Tropical 19: 115. Abr-Jun, 1986
2. https://yourstory.com/2017/12/indian-scientist-nobel-prize-medicine
3. Tanjore BalganeshTapas K. Kundu,TusharKanti Chakraborty and Siddhartha Roy, Drug Discovery Research in India: Current State and Future Prospects, 2014 Jul 10; 5(7): 724–726.