Yella

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In 1958 I started living in my MD Uncle's home at Vizagh. It was he who forged my signature on the Application Form for my admission into the coveted group of Dirty Dozen in the Physics Hons at AU since the last date was days away. And it was he of whom my GP, retired from BHEL here, said:

 "Oh, Yes! He is a Genius! He is brilliant!! He is God!!! We were all scared of him":

http://gpsastry.blogspot.in/2012/04/current-account-5.html

One afternoon when he returned from his duty at the King George Hospital there was this 'literature' (a colorful printed ad on thick glossy paper) from the Lederle Labs advertising Aureomycin lying on his centerpiece. He glanced at it and said:


"You know, our Yellapragada Subba Rao discovered it"


That was the first and the last time I heard of this crazy guy till a few days back when I found an entire page and more devoted to him in Sid Mukherjee's Cancer Tome.


You can wiki for his name and find more about him (Sid Mukherjee's book tops its list of references). I will only say that he failed twice in his Matriculation Exam from the Hindu High School, Madras, circa 1910. And, before I keyboard the passage from Sid Mukherjee's book, let me quote the last para of wiki about him:





http://en.wikipedia.org/wiki/Yellapragada_Subbarao

"...Subbarao's memory has been obscured by the achievements of others and his failure to promote his own interests. Part of the reason for his obscurity was that Subbarao did not market his work, or himself. A patent attorney was once astonished to find that he had not taken any of the steps that scientists everywhere consider routine for linking their name to their handiwork. He never granted interviews to the press; he never made the rounds of the academies which apportion accolades^{[citation needed]}; nor did he go on lecture tours^{[citation needed]}.

His 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 out of jealousy, did not let Subbarao's contributions see the light of the day."^[9]

A fungus was named Subbaromyces splendens in his honor by American Cyanamid. ^[10]

Writing in the April 1950 issue of Argosy, Doron K. Antrim observed,^[11] "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."^[12]"

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And here is Sid Mukherjee about him:

"Farber's supply of folic acid for his disastrous first trial had come from the laboratory of an old friend, a chemist, Yellapragada Subbarao --- or Yella, as most of his colleagues called him. Yella was a pioneer in many ways, a physician turned cellular physiologist, a chemist who had accidentally wandered into biology. His scientific meanderings had been presaged by more desperate and adventuresome physical meanderings. He had arrived in Boston in 1923, penniless and unprepared, having finished his medical training in India and secured a scholarship for a diploma at the School of Tropical Health at Harvard. The weather in Boston, Yella discovered, was far from tropical. Unable to find a medical job in the frigid, stormy winter (he had no license to practice medicine in the United States), he started as a night porter at the Brigham and Women's Hospital, opening doors, changing sheets, and cleaning urinals.

The proximity to medicine paid off. Subbarao made friends and connections at the hospital and switched to a day job as a researcher in the Division of Biochemistry. His initial project involved purifying molecules of living cells, dissecting them chemically to determine their compositions --- in essence, performing a biochemical "autopsy" on cells. The approach required more persistence than imagination, but it produced remarkable dividends. Subbarao purified a molecule called ATP, the source of energy in all living beings (ATP carries chemical "energy" in the cell), and another molecule called creatine, the energy carrier in muscle cells. 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 as Farber. In 1940, denied tenure and recognition, Yella huffed off to join Lederle Labs, a pharmaceutical laboratory in upstate New York, owned by the American Cyanamid Corporation, where he had been asked to run a group on chemical synthesis.

At Lederle, Yella Subbarao quickly reformulated his old strategy and focused on making synthetic versions of the natural chemicals that he had found within cells, hoping to use them as nutritional supplements. In the 1920s, another drug company, Eli Lily, had made a fortune selling a concentrated form of vitamin B12, the missing nutrient in pernicious anemia. Subbarao decided to focus his attention on the other anemia, the neglected anemia of folate deficiency. But in 1946, after many failed attempts to extract the chemical from pig's livers, he switched tactics and started to synthesize folic acid from scratch, with the help of a team of scientists including Harriet Kiltie, a young chemist at Lederle.

The chemical reactions to make folic acid brought a serendipitous bonus. Since the reactions had several intermediate steps, Subbarao and Kiltie could create variants of folic acid through slight alterations in the recipe. These variants of folic acid --- closely related molecular mimics --- possessed counterintuitive properties. Enzymes and receptors in cells typically work by recognizing molecules by using their chemical structure. But a "decoy" molecular structure --- one that nearly mimics the natural molecule --- can bind to the receptor or enzyme and block its action, like a false key jamming a lock. Some of Yella's molecular mimics could thus behave like antagonists to folic acid.

These were precisely the antivitamins that Farber had been fantasizing about. Farber wrote to Kiltie and Subbarao asking them if he could use their folate antagonists on patients with leukemia. Subbarao consented. In the late summer of 1947, the first package of antifolate left Lederle labs in New York and arrived in Farber's laboratory. 

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Postscript

Wiki:

"Despite his isolation of ATP, Subbarao was denied tenure at Harvard^[1] and remained without a green card throughout his life, though he would lead some of America's most important medical research during World War II...

Yella developed methotrexate for the treatment of cancer"

gps: That is part of the "chemotherapy" I routinely heard during my couple of hundred trips to the Cancer Centers here.

Wiki:

Chemotherapy

Methotrexate was originally developed and continues to be used for chemotherapy either alone or in combination with other agents. It is effective for the treatment of a number of cancers including: breast, head and neck, leukemia, lymphoma, lung, osteosarcoma, bladder, and trophoblastic neoplasms.^[1]

It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions.^[1] It acts by inhibiting the metabolism of folic acid. Methotrexate began to replace the more toxic antifolate aminopterin starting in the 1950s. 

The drug was developed by Yellapragada Subbarao.

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