Methotrexate is one of the best US FDA-approved drugs for dermatologists. Most clinicians in India have also prescribed methotrexate, without realising who conceptualised it. Dr Yellapragada SubbaRow, an Indian-American biochemist, discovered the molecule.
He also made some of the greatest contributions in pharmacology, microbiology, oncology, and nutritional science as well, which are applied to numerous relevant experiments even today. SubbaRaow’s article, ‘The colorimetric determination of phosphorus’, has been frequently cited across the globe.
Dr SubbaRow was born on January 12, 1895, in the West Godavari district of Andhra Pradesh, and studied at Madras Medical College. He later went to Harvard School of Tropical Medicine, Boston, for post-graduation. After earning a diploma at Harvard in 1924, he managed to join Harvard Medical School, where he worked under Dr Cyrus Fiske, who had been assigned the task for accurate measurement of phosphorus in cell, nerve, and bone tissue.
SubbaRow began working in his laboratory, where they developed the Fiske-SubbaRow method for the estimation of phosphorus in body fluids and tissues. His discovery of the role of phosphocreatine and adenosine triphosphate (ATP) in muscular activity, earned him an entry into biochemistry textbooks. His journey towards liver extract fractionation and isolation of factors, which can cure pernicious anaemia started in 1927.
Pharma companies desperately looking for top scientists to work in vitamin research, approached SubbaRow, who gladly consented. Along with Fiske, he was able to isolate the anti-pernicious anaemia factor (vitamin B12), niacin and its therapeutic effects in pellagra, pantothenic acid (vitamin B5) and biotin. With the help of other researchers, SubbaRow developed a method to isolate and synthesise folic acid (vitamin B9) on an industrial scale.
After the 1941 attack on Pearl Harbour, when the US Army got involved in the Pacific Theatre, SubbaRow initiated a new project to protect soldiers by including ‘parasiticides’ in his research agenda. His work was directed towards development of an orally administrable non-metallic drug, which led to the discovery of diethylcarbamazine, a piperazine compound, which has been recognised by the WHO as a principal element for prophylaxis and treatment of filariasis.
After SubbaRow presented evidence of success of methotrexate in leukemia, Dr Richard Gubner of New York College of Medicine, along with physicians from the Kings County Hospital, carried out a clinical trial of aminopterin in psoriasis, proving it to be a potent inhibitor of connective tissue proliferation and effective in psoriasis. SubbaRow passed away in 1948.