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| image            = File:Yellapragada Subbarow 1995.jpg
| image            = File:Yellapragada Subbarow 1995.jpg
| image_size        =  
| image_size        =  
| caption          = Commemorative postage stamp celebrating the birth centenary of Dr. SubbaRow (anglicized version of Subba Rao)
| caption          = Commemorative postage stamp celebrating the birth centenary of Dr. SubbaRao
(anglicized version of Subba Rao)
| birth_date        = {{birth date|1895|01|12|df=y}}
| birth_date        = {{birth date|1895|01|12|df=y}}
| birth_place      = [[Bhimavaram]], [[Madras Presidency]], [[British Raj|British India]]<br/>(now in [[Andhra Pradesh]], India)
| birth_place      = [[bhimavaram ]], [[Madras Presidency]], [[British Raj|British India]]<br/>(now in [[Andhra Pradesh]], India)
| death_date        = {{death date and age|1948|08|08|1895|01|12|df=y}}
| death_date        = {{death date and age|1948|08|08|1895|01|12|df=y}}
| death_place      = [[New York City]], [[United States]]
| death_place      = [[New York City]], [[United States]]
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'''Yellapragada Subba Rao''' (12 January 1895&nbsp;– 8 August 1948) was a pioneering [[India]]n [[biochemist]] who discovered the function of [[adenosine triphosphate]] (ATP) as an energy source in the [[cell (biology)|cell]],<ref name="History of the discovery of ATP. Maruyama (1991) J Hist Biol">{{cite journal |last1=Maruyama |first1=Koscak |title=The discovery of adenosine triphosphate and the establishment of its structure |journal=Journal of the History of Biology |date=1 March 1991 |volume=24 |issue=1 |pages=145–154 |doi=10.1007/BF00130477 |url=https://link.springer.com/article/10.1007/BF00130477}}</ref> developed [[methotrexate]] for the treatment of [[cancer]] and led the department at Lederle laboratories in which [[Benjamin Minge Duggar]] discovered [[chlortetracycline]] (Aureomycin) in 1945.
'''Yellapragada Subba Rao''' (12 January 1895&nbsp;– 8 August 1948) was a pioneering [[India]]n [[biochemist]] who discovered the function of [[adenosine triphosphate]] (ATP) as an energy source in the [[cell (biology)|cell]],<ref name="History of the discovery of ATP. Maruyama (1991) J Hist Biol">{{cite journal |last1=Maruyama |first1=Koscak |title=The discovery of adenosine triphosphate and the establishment of its structure |journal=Journal of the History of Biology |date=1 March 1991 |volume=24 |issue=1 |pages=145–154 |doi=10.1007/BF00130477 |url=https://link.springer.com/article/10.1007/BF00130477}}</ref> developed [[methotrexate]] for the treatment of [[cancer]] and led the department at Lederle laboratories in which [[Benjamin Minge Duggar]] discovered [[chlortetracycline]] (Aureomycin) in 1945.


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, Subbarao did not gain tenure at [[Harvard University|Harvard]]<ref>{{cite book|last=Mukherjee|first=Siddhartha|author-link=Siddhartha Mukherjee|title=The Emperor of All Maladies: A Biography of Cancer|url=https://books.google.com/books?id=5rF_31RVTnMC|access-date=6 September 2011|date=2010|publisher=Simon and Schuster|isbn=978-1-4391-0795-9|page=31}} Quote: "Any one of these achievements should have been enough to guarantee him a professorship at Harvard. But Subbarao was a foreigner, a reclusive, nocturnal, heavily accented vegetarian who lived in a one-room apartment downtown, befriended only by other nocturnal recluses"</ref><ref name=IACM>{{cite journal |url=http://medind.nic.in/jac/t01/i1/jact01i1p96.pdf |author=Pushpa Mitra Bhargava |pages=96_100 |title=History of Medicine: Dr. Yellapragada Subba (1895–1948) – He Transformed Science; Changed Lives |journal=Journal of the Indian Academy of Clinical Medicine |volume=2 |issue=1,2 |year=2001}}</ref> 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. Subbarao died in the [[United States]] due to cardiac arrest.<ref>[http://www.ysubbarao.info/Archive/home.php Yellapragada SubbaRao Archives OnLine]. ysubbarao.info</ref><ref>Jadia, Varun (6 October 2016) [https://www.thebetterindia.com/70867/dr-yellapragada-subbarao-indian-scientist-medicine/ Dr. Yellapragada Subbarao Revolutionised the Field of Medicine]. ''The Better India''.</ref>
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 [[diethylcarbamazine]] (DEC), the only effective  drug for treating filariasis. Most of his career was spent in the United States. Despite his isolation of ATP, Subbarao did not gain tenure at [[Harvard University|Harvard]]<ref>{{cite book|last=Mukherjee|first=Siddhartha|author-link=Siddhartha Mukherjee|title=The Emperor of All Maladies: A Biography of Cancer|url=https://books.google.com/books?id=5rF_31RVTnMC|access-date=6 September 2011|date=2010|publisher=Simon and Schuster|isbn=978-1-4391-0795-9|page=31}} Quote: "Any one of these achievements should have been enough to guarantee him a professorship at Harvard. But Subbarao was a foreigner, a reclusive, nocturnal, heavily accented vegetarian who lived in a one-room apartment downtown, befriended only by other nocturnal recluses"</ref><ref name=IACM>{{cite journal |url=http://medind.nic.in/jac/t01/i1/jact01i1p96.pdf |author=Pushpa Mitra Bhargava |pages=96_100 |title=History of Medicine: Dr. Yellapragada Subba (1895–1948) – He Transformed Science; Changed Lives |journal=Journal of the Indian Academy of Clinical Medicine |volume=2 |issue=1,2 |year=2001}}</ref> 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. Subbarao died in the [[United States]] due to cardiac arrest.<ref>[http://www.ysubbarao.info/Archive/home.php Yellapragada SubbaRao Archives OnLine]. ysubbarao.info</ref><ref>Jadia, Varun (6 October 2016) [https://www.thebetterindia.com/70867/dr-yellapragada-subbarao-indian-scientist-medicine/ Dr. Yellapragada Subbarao Revolutionised the Field of Medicine]. ''The Better India''.</ref>


A contemporary of Subbarao, Cyrus H Fiske, suppressed and destroyed many of his important works out of envy. Subbarao'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."<ref>[https://web.archive.org/web/20140325205551/http://www.hindu.com/seta/2003/03/13/stories/2003031300140300.htm Discoverer of miracle medicines – Y. Subba Rao (1895–1948)]. ''The Hindu'' (2003-03-13)</ref> A [[fungus]] [[genus]] has been named ''[[Subbaromyces]]'' in his honor.<ref>{{citation |url=http://www.mycobank.org/BioloMICS.aspx?Table=Mycobank&Rec=57472&Fields=All |title=MycoBank |access-date=26 December 2015}}</ref><ref>{{citation |author=Hesseltine, C.W. |year=1953 |title=Study of Trickling Filter Fungi |journal=Bulletin of the Torrey Botanical Club |volume=80 |issue=6 |pages=507–514 |jstor=2481965 |doi=10.2307/2481965}} page 511</ref> Writing in the April 1950 issue of ''[[Argosy (magazine)|Argosy]]'', Doron K. Antrim observed,<ref>{{cite web |url=http://www.ysubbarao.info |access-date=10 March 2014 |title=Miracle man of miracle drugs: Dr Yellapragada SubbaRao}}</ref> "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."<ref>{{cite journal|title=Dr. Yellapragada SubbaRao (1895–1948): The man and the method |author=Kapur, S. & Gupta, S. P. K. |journal=Indian Journal of Experimental Biology|volume= 36|issue=11|pages=1087–92|pmid=10085777 |year=1998 }}</ref>
A contemporary of Subbarao, Cyrus H Fiske, suppressed and destroyed many of his important works out of envy. Subbarao'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."<ref>[https://web.archive.org/web/20140325205551/http://www.hindu.com/seta/2003/03/13/stories/2003031300140300.htm Discoverer of miracle medicines – Y. Subba Rao (1895–1948)]. ''The Hindu'' (2003-03-13)</ref> A [[fungus]] [[genus]] has been named ''[[Subbaromyces]]'' in his honor.<ref>{{citation |url=http://www.mycobank.org/BioloMICS.aspx?Table=Mycobank&Rec=57472&Fields=All |title=MycoBank |access-date=26 December 2015}}</ref><ref>{{citation |author=Hesseltine, C.W. |year=1953 |title=Study of Trickling Filter Fungi |journal=Bulletin of the Torrey Botanical Club |volume=80 |issue=6 |pages=507–514 |jstor=2481965 |doi=10.2307/2481965}} page 511</ref> Writing in the April 1950 issue of ''[[Argosy (magazine)|Argosy]]'', Doron K. Antrim observed,<ref>{{cite web |url=http://www.ysubbarao.info |access-date=10 March 2014 |title=Miracle man of miracle drugs: Dr Yellapragada SubbaRao}}</ref> "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."<ref>{{cite journal|title=Dr. Yellapragada SubbaRao (1895–1948): The man and the method |author=Kapur, S. & Gupta, S. P. K. |journal=Indian Journal of Experimental Biology|volume= 36|issue=11|pages=1087–92|pmid=10085777 |year=1998 }}</ref>


==Early life ==
==Early life==
===Youth===
He was born in [[Bhimavaram]], [[Madras Presidency]], now in [[West Godavari]] District, [[Andhra Pradesh]] in [[India]] to a [[Telugu language|Telugu-speaking family]].<ref>{{cite journal|last=Kamath|first=Priyanka|last2=Shenoy|first2=K. Ashok|date=2013|title=Yellapragada Subba Rao: The Unsung Hero|url=https://www.mjmsr.net/article.asp?issn=0975-9727;year=2013;volume=4;issue=2;spage=130;epage=132;aulast=Kamath|journal=Muller Journal of Medical Sciences and Research|volume=4|issue=2|pages=130–132}}</ref> 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.
He was born in [[Bhimavaram]], [[Madras Presidency]], now in [[West Godavari]] District, [[Andhra Pradesh]] in [[India]] to a [[Telugu language|Telugu-speaking family]].<ref>{{cite journal|last=Kamath|first=Priyanka|last2=Shenoy|first2=K. Ashok|date=2013|title=Yellapragada Subba Rao: The Unsung Hero|url=https://www.mjmsr.net/article.asp?issn=0975-9727;year=2013;volume=4;issue=2;spage=130;epage=132;aulast=Kamath|journal=Muller Journal of Medical Sciences and Research|volume=4|issue=2|pages=130–132}}</ref> 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.


===Education===
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 [[Licentiate in Medicine and Surgery|LMS]] certificate and not a full [[Bachelor of Medicine and Surgery|MBBS]] degree. Subbarao 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 [[Ayurveda|Ayurvedic]] medicines and began to engage in research to put Ayurveda on a modern footing. The promise of support from [[M.S.N. Charities|Malladi Satyalingam Naicker Charities]] in [[Kakinada]], and financial assistance raised by his father-in-law, enabled Subbarao to proceed to the U.S. He arrived in [[Boston]] on 26 October 1922.
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 [[Licentiate in Medicine and Surgery|LMS]] certificate and not a full [[Bachelor of Medicine and Surgery|MBBS]] degree. Subbarao 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 [[Ayurveda|Ayurvedic]] medicines and began to engage in research to put Ayurveda on a modern footing. The promise of support from [[M.S.N. Charities|Malladi Satyalingam Naicker Charities]] in [[Kakinada]], and financial assistance raised by his father-in-law, enabled Subbarao to proceed to the U.S. He arrived in [[Boston]] on 26 October 1922.


Line 33: Line 36:
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 called the Fiske-SubbaRow Method.<ref name="Fiske and SubbaRow (1925) J Biol Chem - Reference for Fiske-SubbaRow method">{{cite journal |last1=Fiske |first1=Cyrus H. |last2=Subbarow |first2=Yellapragada |title=THE COLORIMETRIC DETERMINATION OF PHOSPHORUS |journal=Journal of Biological Chemistry |date=December 1925 |volume=66 |issue=2 |pages=375–400 |doi=10.1016/S0021-9258(18)84756-1 |url=https://www.sciencedirect.com/science/article/pii/S0021925818847561|doi-access=free }}</ref> He also discovered the role of [[phosphocreatine]] and [[adenosine triphosphate]] (ATP) in muscular activity, which earned him an entry into biochemistry textbooks in the 1930s.<ref name="Fiske and SubbaRow (1929) Science - Discovery that ATP is the energy source for the cell">{{cite journal |last1=Fiske |first1=C. H. |last2=Subbarow |first2=Y. |title=PHOSPHORUS COMPOUNDS OF MUSCLE AND LIVER |journal=Science |date=18 October 1929 |volume=70 |issue=1816 |pages=381–382 |doi=10.1126/science.70.1816.381-a |url=https://science.sciencemag.org/content/70/1816/381.2.long}}</ref> He obtained his [[Doctor of Philosophy|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.
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 called the Fiske-SubbaRow Method.<ref name="Fiske and SubbaRow (1925) J Biol Chem - Reference for Fiske-SubbaRow method">{{cite journal |last1=Fiske |first1=Cyrus H. |last2=Subbarow |first2=Yellapragada |title=THE COLORIMETRIC DETERMINATION OF PHOSPHORUS |journal=Journal of Biological Chemistry |date=December 1925 |volume=66 |issue=2 |pages=375–400 |doi=10.1016/S0021-9258(18)84756-1 |url=https://www.sciencedirect.com/science/article/pii/S0021925818847561|doi-access=free }}</ref> He also discovered the role of [[phosphocreatine]] and [[adenosine triphosphate]] (ATP) in muscular activity, which earned him an entry into biochemistry textbooks in the 1930s.<ref name="Fiske and SubbaRow (1929) Science - Discovery that ATP is the energy source for the cell">{{cite journal |last1=Fiske |first1=C. H. |last2=Subbarow |first2=Y. |title=PHOSPHORUS COMPOUNDS OF MUSCLE AND LIVER |journal=Science |date=18 October 1929 |volume=70 |issue=1816 |pages=381–382 |doi=10.1126/science.70.1816.381-a |url=https://science.sciencemag.org/content/70/1816/381.2.long}}</ref> He obtained his [[Doctor of Philosophy|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 B<sub>9</sub>,<ref>{{cite journal | last1 = Farber | first1 = S | last2 = Cutler | first2 = EC | last3 = Hawkins | first3 = JW | last4 = Harrison | first4 = JH | last5 = Peirce Ec | first5 = 2nd | last6 = Lenz | first6 = GG | title = The Action of Pteroylglutamic Conjugates on Man | journal = Science | volume = 106 | issue = 2764 | pages = 619–21 | year = 1947 | pmid = 17831847 | doi = 10.1126/science.106.2764.619 }}</ref> 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 first cancer [[chemotherapy]] agents and still in widespread clinical use.<ref>Farber et al.'s article, published in the ''New England Journal of Medicine'' in 1946, noted Dr Subbarao'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.</ref><ref name="NEJM1948">{{cite journal| title =Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid (aminopterin)| journal =N. Engl. J. Med.| year =1948|author2=Diamond, LK |author3=Mercer, RD| volume =238| issue =23| pages =787–93| doi =10.1056/NEJM194806032382301| pmid =18860765| last1 =Farber| first1 =S|author4=Sylvester, RF, Jr.|author5=Wolff, JA}}</ref><ref>{{cite journal | last1 = Miller | first1 = DR | title = A tribute to Sidney Farber-- the father of modern chemotherapy | journal = British Journal of Haematology | volume = 134 | issue = 1 | pages = 20–6 | year = 2006 | pmid = 16803563 | doi = 10.1111/j.1365-2141.2006.06119.x | s2cid = 45434777 | doi-access = free }}</ref> Subbarao also discovered the basis for [[hetrazan]] which was used by the [[WHO|World health Organization]] against [[filariasis]].<ref>World Health Organization. (2002). [https://www.who.int/iris/handle/10665/67601 Report of the second meeting of the Global Alliance to Eliminate Lymphatic Filariasis]. Geneva</ref>
At Lederle, he developed a method to synthesize folic acid, Vitamin B<sub>9</sub>,<ref>{{cite journal | last1 = Farber | first1 = S | last2 = Cutler | first2 = EC | last3 = Hawkins | first3 = JW | last4 = Harrison | first4 = JH | last5 = Peirce Ec | first5 = 2nd | last6 = Lenz | first6 = GG | title = The Action of Pteroylglutamic Conjugates on Man | journal = Science | volume = 106 | issue = 2764 | pages = 619–21 | year = 1947 | pmid = 17831847 | doi = 10.1126/science.106.2764.619 }}</ref> 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 first cancer [[chemotherapy]] agents and still in widespread clinical use.<ref>Farber et al.'s article, published in the ''New England Journal of Medicine'' in 1946, noted Dr Subbarao'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.</ref><ref name="NEJM1948">{{cite journal| title =Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid (aminopterin)| journal =N. Engl. J. Med.| year =1948|author2=Diamond, LK |author3=Mercer, RD| volume =238| issue =23| pages =787–93| doi =10.1056/NEJM194806032382301| pmid =18860765| last1 =Farber| first1 =S|author4=Sylvester, RF, Jr.|author5=Wolff, JA}}</ref><ref>{{cite journal | last1 = Miller | first1 = DR | title = A tribute to Sidney Farber-- the father of modern chemotherapy | journal = British Journal of Haematology | volume = 134 | issue = 1 | pages = 20–6 | year = 2006 | pmid = 16803563 | doi = 10.1111/j.1365-2141.2006.06119.x | s2cid = 45434777 | doi-access = free }}</ref> Subbarao also discovered the basis for the anthelmintic [[diethylcarbamazine]] (Hetrazan), which was used by the [[WHO|World health Organization]] against [[filariasis]].<ref>World Health Organization. (2002). [https://www.who.int/iris/handle/10665/67601 Report of the second meeting of the Global Alliance to Eliminate Lymphatic Filariasis]. Geneva</ref>


Under Subbarao, [[Benjamin Duggar]] made his  discovery of the world's first [[tetracycline antibiotics|tetracycline]] [[antibiotic]], [[chlortetracycline]], in 1945.  Duggar identified the antibiotic as the product of an [[actinomycete]] he cultured from a soil sample collected from [[Sanborn Field]] at the [[University of Missouri]].<ref>Jukes, Thomas H. ''Some historical notes on chlortetracycline.'' Reviews of Infectious Diseases 7(5):702-707 (1985).</ref>
Under Subbarao, [[Benjamin Duggar]] made his  discovery of the world's first [[tetracycline antibiotics|tetracycline]] [[antibiotic]], [[chlortetracycline]], in 1945.  Duggar identified the antibiotic as the product of an [[actinomycete]] he cultured from a soil sample collected from [[Sanborn Field]] at the [[University of Missouri]].<ref>Jukes, Thomas H. ''Some historical notes on chlortetracycline.'' Reviews of Infectious Diseases 7(5):702-707 (1985).</ref>

Latest revision as of 01:05, 9 December 2021

Yellapragada Subba Rao
Commemorative postage stamp celebrating the birth centenary of Dr. SubbaRao (anglicized version of Subba Rao)
Born(1895-01-12)12 January 1895
bhimavaram , Madras Presidency, British India
(now in Andhra Pradesh, India)
Died8 August 1948(1948-08-08) (aged 53)
New York City, United States
NationalityIndian
Alma materHarvard Medical School
Madras Medical College
Known forDiscovering the role of phosphocreatine and adenosine triphosphate in muscular activity;
synthesis of folic acid;
synthesis of methotrexate;
discovery of diethylcarbamazine
Scientific career
FieldsBiochemistry
InstitutionsLederle Laboratories, a division of American Cyanamid (Acquired by Wyeth in 1994, now Pfizer)
InfluencedBenjamin Minge Duggar
George H. Hitchings

Yellapragada Subba Rao (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,[1] developed methotrexate for the treatment of cancer and led the department at Lederle laboratories in which Benjamin Minge Duggar discovered chlortetracycline (Aureomycin) in 1945.

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 diethylcarbamazine (DEC), the only effective drug for treating filariasis. Most of his career was spent in the United States. Despite his isolation of ATP, Subbarao did not gain tenure at Harvard[2][3] 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. Subbarao died in the United States due to cardiac arrest.[4][5]

A contemporary of Subbarao, Cyrus H Fiske, suppressed and destroyed many of his important works out of envy. Subbarao'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."[6] A fungus genus has been named Subbaromyces in his honor.[7][8] Writing in the April 1950 issue of Argosy, Doron K. Antrim observed,[9] "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."[10]

Early life[edit | edit source]

Youth[edit | edit source]

He was born in Bhimavaram, Madras Presidency, now in West Godavari District, Andhra Pradesh in India to a Telugu-speaking family.[11] 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.

Education[edit | edit source]

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. Subbarao 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 Subbarao to proceed to the U.S. He arrived in Boston on 26 October 1922.

Career in the United States[edit | edit source]

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 called the Fiske-SubbaRow Method.[12] He also discovered the role of phosphocreatine and adenosine triphosphate (ATP) in muscular activity, which earned him an entry into biochemistry textbooks in the 1930s.[13] 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,[14] 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 first cancer chemotherapy agents and still in widespread clinical use.[15][16][17] Subbarao also discovered the basis for the anthelmintic diethylcarbamazine (Hetrazan), which was used by the World health Organization against filariasis.[18]

Under Subbarao, Benjamin Duggar made his discovery of the world's first tetracycline antibiotic, chlortetracycline, in 1945. Duggar identified the antibiotic as the product of an actinomycete he cultured from a soil sample collected from Sanborn Field at the University of Missouri.[19]

References[edit | edit source]

  1. ↑ Maruyama, Koscak (1 March 1991). "The discovery of adenosine triphosphate and the establishment of its structure". Journal of the History of Biology. 24 (1): 145–154. doi:10.1007/BF00130477.
  2. ↑ 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 Subbarao was a foreigner, a reclusive, nocturnal, heavily accented vegetarian who lived in a one-room apartment downtown, befriended only by other nocturnal recluses"
  3. ↑ 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.
  4. ↑ Yellapragada SubbaRao Archives OnLine. ysubbarao.info
  5. ↑ Jadia, Varun (6 October 2016) Dr. Yellapragada Subbarao Revolutionised the Field of Medicine. The Better India.
  6. ↑ Discoverer of miracle medicines – Y. Subba Rao (1895–1948). The Hindu (2003-03-13)
  7. ↑ MycoBank, retrieved 26 December 2015
  8. ↑ 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
  9. ↑ "Miracle man of miracle drugs: Dr Yellapragada SubbaRao". Retrieved 10 March 2014.
  10. ↑ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ↑ Kamath, Priyanka; Shenoy, K. Ashok (2013). "Yellapragada Subba Rao: The Unsung Hero". Muller Journal of Medical Sciences and Research. 4 (2): 130–132.
  12. ↑ Fiske, Cyrus H.; Subbarow, Yellapragada (December 1925). "THE COLORIMETRIC DETERMINATION OF PHOSPHORUS". Journal of Biological Chemistry. 66 (2): 375–400. doi:10.1016/S0021-9258(18)84756-1.
  13. ↑ Fiske, C. H.; Subbarow, Y. (18 October 1929). "PHOSPHORUS COMPOUNDS OF MUSCLE AND LIVER". Science. 70 (1816): 381–382. doi:10.1126/science.70.1816.381-a.
  14. ↑ 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.{{cite journal}}: CS1 maint: numeric names: authors list (link)
  15. ↑ Farber et al.'s article, published in the New England Journal of Medicine in 1946, noted Dr Subbarao'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.
  16. ↑ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  17. ↑ 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. S2CID 45434777.
  18. ↑ World Health Organization. (2002). Report of the second meeting of the Global Alliance to Eliminate Lymphatic Filariasis. Geneva
  19. ↑ Jukes, Thomas H. Some historical notes on chlortetracycline. Reviews of Infectious Diseases 7(5):702-707 (1985).
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