Add caption:-》Crosstalk: How Two Modest Heroes Won the Battle Against Childhood Leukaemia BY SUNIL LAXMAN ON 20/03/2016•

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Crosstalk: How Two Modest Heroes Won the Battle Against Childhood Leukaemia

BY SUNIL LAXMAN ON 20/03/2016 •

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While experimenting with several agents, he became aware of the importance of the vitamin folic acid, present in the blood. In the slave-like textile mills in distant Bombay, many workers – especially women – were affected with anaemia due to poor nutrition. When these workers were given marmite (yeast extracts), they would recover. It was later found that the active agent in marmite was folic acid. Farber figured that treating leukaemia-afflicted cells with the acid would cure them, but to his horror, he found that the compound made the cells grow even faster.

Today, we know that this is because folic acid helps cells make more DNA and RNA, molecules needed for growth. At that time, Farber quickly reasoned that if he could do the reverse and stop folic acid being used by using an ‘anti-vitamin’, perhaps he could cure leukaemia. But where could he get an anti-vitamin that could do this? He then remembered Yella, his old friend at Harvard, who he knew was at Lederle Labs and, most importantly, whom he recognised as the grandmaster of making such compounds.

In the late 1940s, Farber wrote to Subbarow, who immediately and generously sent Farber a range of folic-acid-like compounds that he and his team had painstakingly synthesised for the first time. These were remarkable feats in chemical synthesis, never accomplished before that. Remarkably, Farber’s hunch proved to be right and some of these molecules stopped leukaemia dead in its tracks. Farber had a patient then, a child suffering from the disease. In an era before countless consent forms, approvals and clinical trials, Farber decided to directly treat the child with the compounds Subbarow had sent him. The child was very sick and on the verge of death. Miraculously, once injected with the compound, his white blood cells count started dropping to normal and days later he could walk.

Methotrexate, one of the folate antagonists that Subbarow made in the 1940s, went on to become the first choice drug against leukaemia, saving thousands of lives. It remains widely used to this day. In addition to these enormous contributions, Subbarow and his team also made compounds that treated filariasis, apart from developing other antibiotics. His immense contributions are much better appreciated today, decades after his death in 1948. And somehow this unassuming scientist with a fascination for biochemistry and a relentless quest for discovery helped transform cancer research.

Farber’s and Subbarow’s stories are beautifully described in Siddhartha Mukerjee’s Pulitzer-Prize-winning book The Emperor of All Maladies (2010).

Sunil Laxman is a scientist at the Institute for Stem Cell Biology and Regenerative Medicine, where his research group studies how cells function and communicate with each other. He has a keen interest in the history and process of science, and how science influences society.

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