Friday, July 26, 2013

Birth Control for Bacteria.

On a cold December of 1935, Hildegard, the daughter of microbiologist, Gerhard Domagk, tripped and fell down the stairs of their family home in Wuppertal, Germany. She was holding a sewing needle, which punctured her hand, eyelet and then snapped off inside her. The needle was medically removed, but Hildegard came down with severe streptococcal infection in her arm. Death was the common outcome of such infections those days. Once the bacteria began multiplying, nothing could stop them. Coincidently, Domagk was working on a red industrial dye, which he had been secretly testing in his lab on mice. 3 years prior to Hildegard's fall, Domagk had injected a lethal dose of streptococcal bacteria on a litter of mice. 90 minutes later he injected the red dye, prontosil, on some of the littler. Four days later, every mouse which had received prontosil had survived, while the others died. Prontosil is a ringed organic molecule, with a sulphur atom. Although prontosil was lethal on bacteria in mice, it had no effect on the same bacteria in a test tube and no one knew why. Domagk was keeping a vigil on his deteriorating daughter, contemplating whether to try prontosil on her. When the doctor announced that Hildegard's arm had to be amputated, Domagk, sneaked in some prontosil and began injecting the red dye into her. At first, her fever worsened, and then it alternatively spiked and crashed. Then one day, Hildegard stabilized and she lived with both her arms intact. Domagk decided to publish his results and his employers I.G. Farbenindustire, who were selling prontosil as a dye, filed for a patent extension on prontosil as a medicine and forced Domagk to hold back, until the patent came through. Sales figure jumped for IGF by five fold in 1936 and another five fold the next year. Pasteur institute, in France, decided to investigate how prontosil worked. They soon realised that the mammal cells, split prontosil into two, one part was sulphonamide, which killed the bacteria. This explained instantly, why the bacteria in the testube did not die- The prontosil was not activated. Sulphonamide's sulphur atoms, disrupts the production of folic acid, which is used to replicate DNA. Mammals get folic acid in their diet, but bacteria have to produce their own stock. So Sulphonamide is bacteria birth control! Pasteur institute published its results, giving others an opportunity to circumvent the prontosil patent. IGF lost millions in product investment as competitors swept in and synthesised other "sulpha drugs."
Trivia: In prontosil, sulphur shares one electron with a benzene ring, one with a short nitrogen chain, and two each with two greedy oxygen atoms. A total of 6 bonds, with 12 electrons! Sulphur can pull off such a trick, because it's large enough to hold more than 8 electrons and small enough to let everything fit around it in 3D arrangement. Nature's magic!

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