Categories
metabolism

Rapamycin

This is a cartoon I drew for a teaching session on metabolic control by a group of proteins called the mTOR complex. mTOR stands for ‘mechanistic Target Of Rapamycin’. Rapamycin is bit of a wonder drug and the story of its discovery is one of my favourite scientific tales of serendipity. Many antibiotics originally come from fungi or bacteria that produce them naturally for their own defence. There are probably thousands of useful compounds being churned out by microbes all over the planet right now that science has yet to discover. In the 1960s, researchers collected soil samples from the remote location of Easter Island. On the face of it, this was not the most promising place to look, it was widely believed to be ecologically barren but an airstrip was going to be built so this was a last chance to survey it in an undisturbed state. There was one intriguing reason to look for antibiotics in the soil: despite walking barefoot the local people rarely contracted tetanus even though it was prevalent. An antibiotic with promising antifungal properties was indeed isolated and named ‘rapamycin’ after Rapa Nui, the indigenous name for Easter Island.

The secret of Rapa Nui? Underground pharmacies!

Rapamycin also acted as an immunosuppressant and gained some interest from drug companies. What really catapulted it to wider attention was the efforts of one of the scientists investigating its function, Suren Sehgal, whose meticulous work in the 1970s revealed that it also had a potent anti-cancer effect. Deciphering how rapamycin actually worked took another two decades and led to the identification of the mTOR protein complex. This acts as a master regulator of metabolism in all cells from yeast to human. Despite its fundamental importance, it still only gets a brief mention in many medical textbooks. This is partly due to the time it takes (years!) for these to be updated with the latest advances and also because its physiological role still holds many mysteries. If you would like to read more about how mTOR functions in different organs and its relevance in many diseases, have at look at this excellent review by David Sabatini another scientist who played a major role in characterising mTOR.

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