Gary Ruvkun’s speech at the Nobel Prize banquet, 10 December 2024.

Your Majesties,
Your Royal Highnesses,
Your Excellencies,
fellow Laureates,
Ladies and Gentlemen,

Victor Ambros and I gratefully celebrate the Nobel Foundation for its century of magnificent awards.

Our discovery of a surprising world of tiny RNAs only 22 nucleotides long – dramatically smaller than any RNAs known at that time – began in 1993 with the discovery of the first microRNA lin-4 in a nematode by the Ambros lab, and its role in translational control of its target lin-14 messenger RNA by the Ruvkun lab. This world of tiny RNAs grew to include almost a billion years of animal evolution with the discovery in 2000 by the Ruvkun lab of the second microRNA, let- 7, that is perfectly conserved in animals, including humans. When similar 22 nt siRNAs were discovered to mediate RNA interference in plants in 1999 by the Baulcombe lab, a complex universe of tiny RNAs in all animals, plants, and fungi was revealed. Today thousands of miRNAs have been identified from thousands of animal and plant species. These miRNAs mediate key transitions in animal development, in the flowering of plants, in cancer.

Much of the tiny RNA revolution emerged from genetic and genomic analysis in the worm and plants, in small budget labs with a dozen researchers. Large genome sequencing centers over the past 30 years have produced genome sequences of 30,000 diverse animal, plants, and fungal species — many named by Linnaeus. Our tiny RNA labs have explored the patterns of miRNA gene pathway retention and loss in these thousands of genomes, which has been crucial for understanding miRNAs.

Poised at this intersection of genetics and comparative genomics, the tiny RNA field attracted visionary students and postdocs, drawn by the ambition, exuberance, and collaborative reflexes of the worm community. Thousands of us now study this worm C. elegans, a genetic discovery powerhouse. The tribes of our labs, our childhood and our education have been inspiring and seriously fun. And our home tribes are a joy: Natasha Staller and Victoria for me, and Candy, Matt, Andy, and Greg for Victor.

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