The making of modern biotechnology: how ethidium bromide made fame

Abstract

Ethidium bromide is a household name in biology, and is arguably the most popular stain in molecular research. It was discovered as a consequence of the growth spurt in chemical synthesis towards the very end of 19th century and in the first half of the 20th century. The precursor compound phenanthridine aroused its potential as a drug, basically because of its quinoline ring, which is interestingly the basis of the medicinal properties of important drugs, such as quinine, known at the time. A medical breakthrough was made in 1938 when some derivatives of phenanthridine were experimented to effectively kill Trypanosoma congolense and T. vivax, the protozoan parasites causing trypanosomiasis (sleeping sickness) in cattle. In 1946, the most effective compound was identified, and with slight chemical modification, it was mass produced as a trypanocidal drug, dimidium bromide, or trypadine. It was the principal veterinary drug in Africa until another chemical modification in 1952 yielded a more potent and less toxic compound, the now-famed ethidium bromide. Manufactured by Boots Pure Drug Co., Ltd. as homidium (Ethidium®), it served as the drug of choice in cattle trypanosomiasis for three decades. Its pharmacological property lies on its ability to intercalate between base pairs in the nucleic acids. It was a serendipitous moment when Piet Borst and Cees Aaij, dismayed at their broken ultracentrifuge, began to use the compound for staining DNA in gel electrophoresis. And the rest, as they say, is history.

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