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10 - ‘There is a Frog in South America / Whose Venom is a Cure’: Poison Alkaloids and Drug Discovery

from Part III - The Making of Contested Biologics

Klaus Angerer
Affiliation:
Humboldt-University in Berlin
Alexander von Schwerin
Affiliation:
Technical University Braunschweig
Heiko Stoff
Affiliation:
Technical University Braunschweig
Bettina Wahrig
Affiliation:
Technical University Braunschweig
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Summary

Whereas there are many known cases of bioactive compounds obtained from medicinal plants and used in drug discovery, substances isolated from animal sources are less frequently utilized in pharmaceutical research and rarely the subject of historiographical analysis. The present essay focuses on the trajectory of epibatidine, an alkaloid isolated from poison frog skin secretions that turned out to be a decisive contribution to research on analgesic substances binding to nicotinic receptors and, thus, ‘a possible first step toward producing a long-sought drug: a powerful non-sedating, non-opioid painkiller’.

In the 1970s, the National Institutes of Health (NIH) chemist and pharmacologist John Daly and his colleagues undertook several field trips to Ecuador and collected a large number of skins taken from tiny poison frogs belonging to Epipedobates anthonyi, a species endemic to southern Ecuador and a small part of northern Peru. Back in their laboratories at the NIH, they investigated the properties of the frog skin extracts and, among many other alkaloids hitherto unknown to science, also managed to isolate a small sample of a highly toxic alkaloid that, much later, was named ‘epibatidine’. Quite soon they realized the alkaloid's enormous potential for analgesic drug discovery, but only in the 1990s, after many delays, dead ends and confusing results were they finally able to determine its molecular structure and mechanism of action, thus rendering it suitable for further research and development.

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Publisher: Pickering & Chatto
First published in: 2014

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