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If you have studied respiration, you know ATP as the cell's energy currency. Fewer students know that one of the scientists who first reported it in muscle was born in a village in Andhra Pradesh. Yellapragada Subbarow's work runs from basic biochemistry to some of the first cancer drugs. This post sets out what the papers and the peer-reviewed histories record about him, and ends with what a student can take from his way of working.
Who was Yellapragada Subbarow?
Peer-reviewed histories in Rheumatology (2022) and the Indian Journal of Dermatology, Venereology and Leprology (2017) record that he was born on 12 January 1895 in what is now Andhra Pradesh and studied at Madras Medical College. They note that he wore khadi in support of the non-cooperation movement and received the lesser Licentiate of Medicine and Surgery instead of an MBBS. He then taught anatomy and physiology at the Madras Ayurvedic College.
He went to the Harvard School of Tropical Medicine and, in 1924, joined Harvard Medical School, where he worked with the biochemist Cyrus Fiske. The Rheumatology article notes that he earned a PhD in 1929 but was not given a regular faculty position.
What did Fiske and Subbarow discover?
Their 1925 paper, The colorimetric determination of phosphorus84756-1) in the Journal of Biological Chemistry in 1925, described a way to measure phosphate in body fluids by the colour it produces in a chemical reaction. The Rheumatology history calls the Fiske-SubbaRow method one of the most cited works in the scientific literature.
Measuring phosphate accurately let them look closely at muscle. In 1927 they published a paper in Science on the nature of the "inorganic phosphate" in voluntary muscle, the work credited with identifying phosphocreatine. In 1929 came Phosphorus compounds of muscle and liver, the paper credited with reporting adenosine triphosphate (ATP) in muscle. The Rheumatology history describes both as discoveries worthy of Nobel consideration.
What did he do at Lederle Laboratories?
According to the Rheumatology article, he became director of research at Lederle Laboratories in Pearl River, New York, in 1940. His teams worked on vitamins, antibiotics and anti-parasite drugs.
Folic acid. In 1945 a Lederle team that included SubbaRow reported in Science the synthesis of a compound identical with the L. casei factor isolated from liver, that is, folic acid.
Antifolates. Compounds that block folic acid can slow fast-dividing cells. One of them, aminopterin, was tested by Sidney Farber's group, who reported in the New England Journal of Medicine in 1948 temporary remissions in acute leukaemia in children. The IJDVL article records that Farber acknowledged the Lederle team's contribution, and that SubbaRow's group went on to methotrexate, a less toxic antifolate still in wide use.
Antibiotics. SubbaRow recruited the mycologist Benjamin Duggar, who described aureomycin, the first tetracycline antibiotic, in 1948.
Filariasis. The IJDVL article also credits his laboratory with diethylcarbamazine, used to treat and prevent filariasis.
SubbaRow died on 9 August 1948, aged 53, only a couple of weeks after aureomycin was presented in New York, according to the IJDVL article.
How this connects to your syllabus
ATP and phosphate groups appear in Class 11 biology chapters on biomolecules and respiration. Our post on biomolecules in chemistry covers the structures, and the story of Alexander Fleming and penicillin gives another view of how antibiotics reached patients.
If a biochemistry idea such as why ATP releases energy on hydrolysis is unclear, the Fermi Concept Library has a lesson for each concept in biology and chemistry.
What can a student take from his way of working?
Build the measurement before the theory. His most cited work is a method. Being able to measure something precisely opened up the biology.
Keep going when the system is unfair. He was denied an MBBS and a Harvard faculty post, and still made a career of first-rate science.
Connect basic science to people. He moved from muscle chemistry to drugs for leukaemia, infections and filariasis.
Work in teams. Most of his results carry several names. Science at this scale is collaborative.
This week, read the abstract of Fiske and Subbarow's 1925 paper and write two lines on how a colour change can measure a concentration.
