Yellapragada Subbarow

Yellapragada Subbarow (12 January 1895 – 8 August 1948) was a pioneering Indian biochemist who discovered the function of adenosine triphosphate (ATP) as an energy source in the cell, developed methotrexate for the treatment of cancer and discovered a broad spectrum of antibiotics including tetracycline and chlortetracycline. A student of Madras Medical College, his elder brother and younger brother both died due to tropical sprue in the span of 8 days. He subsequently discovered folic acid as a cure for tropical sprue. He discovered methotrexate, a chemotherapy drug still used today and also used for rheumatoid arthritis, and diethyl carbamazine (DEC), the only effective drug for treating filariasis. Most of his career was spent in the United States. Despite his isolation of ATP, Subbarow did not gain tenure at Harvard[1][2] though he would lead some of America's most important medical research during World War II. He is also credited with the first synthesis of the chemical compounds folic acid and methotrexate. Subbarow died in the United States due to cardiac arrest.[3][4]

Yellapragada Subbarow
Subbarow on a 1995 stamp of India
Born	(1895-01-12)12 January 1895 Bhimavaram, Madras Presidency, British India (now in Andhra Pradesh, India)
Died	8 August 1948(1948-08-08) (aged 53) New York City, United States
Nationality	Indian
Alma mater	Harvard Medical School Madras Medical College
Known for	Discovering the role of phosphocreatine and adenosine triphosphate in muscular activity; synthesis of folic acid; synthesis of methotrexate; discovery of diethylcarbamazine
Scientific career
Fields	Biochemistry
Institutions	Lederle Laboratories, a division of American Cyanamid (Acquired by Wyeth in 1994, now Pfizer)
Influenced	Benjamin Minge Duggar George H. Hitchings

A contemporary of Subbarow, Cyrus H Fiske, suppressed and destroyed many of his important works out of envy. Subbarow's colleague, George Hitchings admitted, "Some of the nucleotides isolated by Subbarao had to be rediscovered years later by other workers because Fiske, apparently out of jealousy, did not let Subbarao's contributions see the light of the day."[5] A fungus genus has been named Subbaromyces in his honor.[6][7] Writing in the April 1950 issue of Argosy, Doron K. Antrim observed,[8] "You've probably never heard of Dr. Yellapragada Subbarao. Yet because he lived, you may be alive and are well today. Because he lived, you may live longer."[9]

Early life

He was born in Bhimavaram, Madras Presidency, now in West Godavari District, Andhra Pradesh in India. He passed through a traumatic period in his schooling at Rajahmundry (due to the premature death of close relatives by disease) and eventually matriculated in his third attempt from the Hindu High School, Madras. He passed the Intermediate Examination from the Presidency College and entered the Madras Medical College where his education was supported by friends and Kasturi Suryanarayana Murthy, whose daughter he later married.

Following Gandhi's call to boycott British goods he started wearing khadi surgical dress; this incurred the displeasure of M. C. Bradfield, his surgery professor. Consequently, though he did well in his written papers, he was awarded the lesser LMS certificate and not a full MBBS degree. Subbarow tried to enter the Madras Medical Service without success. He then took up a job as Lecturer in Anatomy at Dr. Lakshmipathi's Ayurvedic College at Madras. He was fascinated by the healing powers of Ayurvedic medicines and began to engage in research to put Ayurveda on a modern footing. The promise of support from Malladi Satyalingam Naicker Charities in Kakinada, and financial assistance raised by his father-in-law, enabled Subbarow to proceed to the U.S. He arrived in Boston on 26 October 1922.

Career in the United States

After earning a diploma from the Harvard Medical School he joined Harvard as a junior faculty member. With Cyrus Fiske, he developed a method for the estimation of phosphorus in body fluids and tissues. He discovered the role of phosphocreatine and adenosine triphosphate (ATP) in muscular activity, which earned him an entry into biochemistry textbooks in the 1930s. He obtained his Ph.D. degree the same year. He joined Lederle Laboratories, a division of American Cyanamid (now a division of Wyeth which is owned by Pfizer), after he failed to gain a regular faculty position at Harvard. At Lederle, he developed a method to synthesize folic acid, Vitamin B₉,[10] based on work by Lucy Wills to isolate folic acid as a protective agent against anemia. After his work on folic acid and with considerable input from Dr. Sidney Farber, he developed the important anti-cancer drug methotrexate – one of the very first cancer chemotherapy agents and still in widespread clinical use.[11][12][12][13] Subbarow also discovered the basis for hetrazan which was used by the World health Organization against filariasis.[14] Under Subbarow, Benjamin Duggar made his discovery of the world's first tetracycline antibiotic, chlortetracycline, in 1945. This discovery was made as a result of the largest distributed scientific experiment ever performed to that date, when American soldiers who had fought all over the world were instructed at the end of WWII to collect soil samples from wherever they were, and bring the samples back for screening at Lederle Laboratories for possible anti-bacterial agents produced by natural soil fungi.[2]

References

1. Mukherjee, Siddhartha (2010). The Emperor of All Maladies: A Biography of Cancer. Simon and Schuster. p. 31. ISBN 978-1-4391-0795-9. Retrieved 6 September 2011. Quote: "Any one of these achievements should have been enough to guarantee him a professorship at Harvard. But Subbarow was a foreigner, a reclusive, nocturnal, heavily accented vegetarian who lived in a one-room apartment downtown, befriended only by other nocturnal recluses"
2. Pushpa Mitra Bhargava (2001). "History of Medicine: Dr. Yellapragada Subba (1895–1948) – He Transformed Science; Changed Lives" (PDF). Journal of the Indian Academy of Clinical Medicine. 2 (1, 2): 96_100.
3. Yellapragada SubbaRao Archives OnLine. ysubbarao.info
4. Jadia, Varun (6 October 2016) Dr. Yellapragada Subbarao Revolutionised the Field of Medicine. The Better India.
5. Discoverer of miracle medicines – Y. Subba Rao (1895–1948). The Hindu (2003-03-13)
6. MycoBank, retrieved 26 December 2015
7. Hesseltine, C.W. (1953), "Study of Trickling Filter Fungi", Bulletin of the Torrey Botanical Club, 80 (6): 507–514, doi:10.2307/2481965, JSTOR 2481965 page 511
8. "Miracle man of miracle drugs: Dr Yellapragada SubbaRow". Retrieved 10 March 2014.
9. Kapur, S. & Gupta, S. P. K. (1998). "Dr. Yellapragada SubbaRao (1895–1948): The man and the method". Indian Journal of Experimental Biology. 36 (11): 1087–92. PMID 10085777.CS1 maint: multiple names: authors list (link)
10. Farber, S; Cutler, EC; Hawkins, JW; Harrison, JH; Peirce Ec, 2nd; Lenz, GG (1947). "The Action of Pteroylglutamic Conjugates on Man". Science. 106 (2764): 619–21. doi:10.1126/science.106.2764.619. PMID 17831847.
11. Farber et al.'s article, published in the New England Journal of Medicine in 1946, noted Dr Subbarow's work as a foundation for this landmark paper. The paper remains one of the earliest top-cited research articles and is a classic in the field of medicine.
12. Farber, S; Diamond, LK; Mercer, RD; Sylvester, RF, Jr.; Wolff, JA (1948). "Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid (aminopterin)". N. Engl. J. Med. 238 (23): 787–93. doi:10.1056/NEJM194806032382301. PMID 18860765.CS1 maint: multiple names: authors list (link)
13. Miller, DR (2006). "A tribute to Sidney Farber-- the father of modern chemotherapy". British Journal of Haematology. 134 (1): 20–6. doi:10.1111/j.1365-2141.2006.06119.x. PMID 16803563.
14. World Health Organization. (2002). Report of the second meeting of the Global Alliance to Eliminate Lymphatic Filariasis. Geneva