Dr. YellaPraga Subbarao, discoverer of methotrexate, was a colleague of George Herbert Hitchings, the Nobel Laureate. He was born on 12th January 1895 at Bhimavaram (West Godavari District) Andhra Pradesh State, India. He was a product of the Madras Medical College. The story goes that he was highly influenced by Mahatma Gandhi. On Bapu’s call to boycott British goods, he started wearing a hospital dress made of khadi. This act incurred the displeasure of M. C. Bradfield, his surgery professor, who denied Subbarao the MBBS degree despite good marks in all subjects and instead awarded him only an LMS certificate. A chance meeting with an American visiting India on a Rockefeller Scholarship and financial help from his father-in-law Subbarao set sail for Boston USA where he arrived on 26 October 1922. He earned a diploma from Harvard University. Later in 1930s, he discovered the role of phosphocreatine and adenosine triphosphate (ATP) in muscular activity, which earned him an entry into biochemistry textbooks. He completed his Ph.D. degree from Harvard in 1930. While at Harvard, together with Cyrus Fiske, he developed a method for the estimation of phosphorus in body fluids and tissues. The story is told that Cyrus Fiske tried to suppress Subbarao’s work at Harvard and that he was denied permanent position on the faculty. This led him to join Lederle Laboratories, a division of American Cyanamid (now a division of Wyeth which is owned by Pfizer), at Perl River, New York. Subbarao's colleague, George Hitchings, who shared the 1988 Nobel Prize in Physiology or Medicine with Gertrude Elion, said, "Some of the nucleotides isolated by Subbarao had to be rediscovered years later by other workers because Fiske apparently did not let Subbarao's contributions see the light of the day. Writing in the April 1950 issue of Argosy, Doron K. Antrim observed, "You've probably never heard of Dr.Yellapraga Subbarao. Yet because he lived you may be alive and are well today. Because he lived you may live longer." Among his major discoveries include diethylcarbamazine (‘heterazan’) and along with his student Benjamin Duggar made his discovery of the world's first tetracycline antibiotic, aureomycin in 1945. He is also credited with the discovery of adenosine triphosphate working with Lederle Drug Company at Pearl River, New York. American Cyanamid named a fungus Subbaromycessplendens in Subbarao’s honour. For immunologists and rheumatologists, Subbarao’s work on the isolation of folic acid from the liver and its role in the synthesis of nucleic acid has been of the greatest interest. Sydney Farber, working at Children’s Medical Center in Boston, encouraged him to synthesise folic acid analogues for disrupting cell cycle for therapeutic use. Subbarao came up with two compounds, namely aminopterin and amethopterin. In fact it was aminopterin that was the drug used for the first time by Sydney Farber for treating childhood leukemia and found to have remarkable efficacy [Farber S, Diamond LK, Mercer RD, et al. Temporary remissions in acute leukemiain children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid (aminopterin).N Engl J Med1948; 238:787–93.]. However, due to difficulties in its synthesis, aminopterin was later replaced by amethopterin that gained notoriety in the hands of Sydney Farber as one of the best for childhood leukaemia. Amethopterin was later named methotrexate and was routinely used in clinical practice for treating childhood leukemia. Soon after its synthesis by Subbarao, the credit for the use of several log orders less dose of methotrexate for treating rheumatoid arthritis goes to Gubner and colleagues in 1951 [Gubner R, August S, Ginsberg V. Therapeutic suppression of tissue reactivity. II. Effect of aminopterin in rheumatoid arthritis and psoriasis. Am J Med Sci1951;22:176–82.]. The rest, as they say, is history..

References

• Bhargava PM. Dr. YellapragadaSubbaRow (1895-1948) - He Transformed Science; Changed Lives. Indian Academy of Clinical Medicine 2001; 2(No. 1 and 2; January-June): 96-9.
• Wikipedia: http://en.wikipedia.org/wiki/Yellapragada_Subbarow

Acknowledgment:

This article is provided by Professor Anand N Malaviya