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Presentation speech by Professor Rickard Sandberg, Member of the Nobel Assembly at Karolinska Institutet, Member of the Nobel Committee for Physiology or Medicine, 10 December 2024.

Your Majesties, Your Royal Highnesses, Esteemed Nobel Prize Laureates, Ladies and Gentlemen,

For a moment, I invite you to look around this majestic hall. Imagine that we are not in a concert hall but inside a human cell. Look at the orchestra behind me, representing our genetic information, our DNA. Now, let each musician with their respective instrument correspond to a single gene. In a real cell, however, there are about twenty thousand such performing genes, each playing their tone and rhythm for different cellular traits and functions.

For an orchestra of this magnitude, effective conducting is naturally very important. For decades, it was known that proteins called transcription factors were conductors needed to guide the cellular symphony by amplifying or dampening the performing genes.

This year’s Nobel Prize in Physiology or Medicine is about the surprising discovery of a novel type of conductors, called microRNAs, that provide additional and crucial guidance over the cellular orchestra.

MicroRNAs are conductors with a special ability. Instead of passionately making gestures to either amplify or dampen music intensity, microRNAs tell musicians only when to quiet down or take a break. ‘You there, play softer! You, take a break!’

Victor Ambros and Gary Ruvkun, this year’s laureates, investigated how genes control organ development in a 1 mm long worm. More than a decade of persistent research led them to discover the first microRNAs, and to discover how microRNAs control gene activity. MicroRNAs bind to messenger RNA, the intermediate carrier of genetic information from the DNA to protein production, thereby reducing protein or messenger RNA levels.

Their groundbreaking discovery in a small worm had major implications for humans and all multicellular life. MicroRNA genes were soon found across animals and plants, and even in certain viruses. In fact, animal microRNAs arose around 600 million years ago, when cells organised themselves into more complex life forms, and microRNAs expanded in numbers in their genomes. The human genome contains around a thousand microRNAs, which control the activity of other genes throughout embryonic development and in adulthood: ‘You there, play softer! You, take a break!’

The laureates are excellent examples of how curiosity- driven basic research, exploring fundamental questions about cellular and organismal function, can advance our understanding of physiology and medicine in ways that couldn’t have been predicted. Basic research is the driver of biomedical knowledge!

Thanks to the groundbreaking research performed by Ambros and Ruvkun, a highly unexpected yet crucial layer of gene regulation was uncovered that is essential for complex multicellular life. The microRNAs regulate the activity of other genes to keep us alive and thriving. The laureates have revealed that sometimes the most beautiful cellular music comes not just from knowing when to play but knowing when to be quiet.

Dear Professors Ambros and Ruvkun, on behalf of the Nobel Assembly at Karolinska Institutet, it is my great honour to convey to you our warmest congratulations. I invite you now to step forward to receive the Nobel Prize from the hands of His Majesty the King.

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