Two U.S. scientists awarded Nobel Prize in Physiology or Medicine for genetic research

The 2024 Nobel Prize in Physiology or Medicine was awarded to American biologists Victor Ambros and Gary Ruvkun for the discovery of microRNA, molecules critical in regulating gene expression.

These findings help explain how countless cell types that make up a living organism, each with their own structure and function, result from a common set of genetic instructions found in that organism’s DNA, according to a press release from the Nobel Committee.

Ruvkun told Reuters that he and Ambros had been “joined at the hip,” as their discovery has garnered the pair multiple joint awards.

“Everyone thought the major problem in gene regulation had already been solved” prior to this work, said Olle Kӓmpe, vice chair of the Nobel Committee of Physiology or Medicine.

By the 1960s, scientists had discovered that proteins called transcription factors dictated which portions of DNA within a cell’s nucleus were transcribed into messenger RNA (mRNA), which carries instructions for building proteins out of the nucleus to the rest of the cell. Transcription factors allow different genes to be expressed at different times.

However, transcription factors alone could not explain the developmental mutations Ambros and Ruvkun studied during the late 1980s in a species of roundworm called C. elegans. These worms offer a streamlined model of gene expression because their simple cellular structures are analogous to organs in other animals, including humans.

Ambros, then a researcher at Harvard University, and Ruvkun, of Massachusetts General Hospital and Harvard Medical School, focused on two genes, lin-4 and lin-14, which have opposite effects on roundworm development.

Separately, the two researchers established that lin-4 counteracted lin-14 expression, but it did so without coding for any protein itself. Furthermore, lin-4 only affected lin-14 expression after the latter gene had already been transcribed into mRNA. The known pathways of gene regulation could not account for these results.

Ambros and Ruvkun decided to join forces, having met during their time as postdoctoral researchers with Robert Horvitz, who would go on to share the 2002 Nobel Prize in Physiology or Medicine for his research into programmed cell death. 

Through the pair’s collaborative research, they found that the small strand of RNA associated with the lin-4 gene binds to the mRNA transcribed from the lin-14 gene, blocking the protein production.

Published in Cell in 1993, these results illustrated how microRNA alters gene expression. Still, microRNA were considered a unique feature of C. elegans until 2000, when Ruvkun’s lab discovered let-7, a microRNA gene present across a broad array of species. 

Scientists now understand that microRNA regulates gene expression in all multicellular organisms as a “communication network among genes,” as Ambros told Reuters.

Researchers have since identified thousands of human genes that code for microRNA, and dysregulated microRNA is recognized as a factor in several health conditions as well as tumor development.

No existing medical treatments target microRNA, but clinical trials of microRNA therapies are ongoing, according to David Pendlebury, head of Research Analysis at Clarivate’s Institute for Scientific Information, told CNN.