When Victor Ambros and Gary Ruvkun first met in the lab of Robert Horvitz at the Massachusetts Institute of Technology, none of them could have known that each would go on to earn a Nobel Prize. Horvitz's came first in 2002, for discovering the genes that instruct organs how to develop, and in 2024, Ambros and Ruvkun together earned the Prize for discovering microRNA—work that began in Horvitz's lab.
Both were fascinated with how a single cell, a fertilized egg, turns into the complex organisms that define the entire plant and animal kingdoms. Their discoveries came from the humble worm—specifically, a genetic aberration that prevented the worm from developing past a juvenile state. The culprit, they found, was an unusually small snippet of RNA, which they called microRNA (miRNA). These tiny pieces of RNA worked like a “knob to turn up or down to get more or less protein,” says Ambros. That’s similar but not identical to the mRNA that most people are familiar with from their role in the COVID-19 vaccines. miRNA, they found, works in parallel to mRNA as an additional layer of control that cells have over which genes are turned on or off, and at what levels.
At first, they thought miRNAs might be unique to the worm. But they found them throughout animal and plant species. It turns out that this system helps complex organisms create and refine specialized cells. “The idea is that by having various layers of control [over genes], you now have a much broader repertoire, like an orchestra,” Ruvkun says. MiRNAs mean “the difference between one instrument vs. the whole orchestra.”
The potential of their discovery is tremendous. With greater knowledge about how genes are controlled throughout development, researchers can start to think about modifying those instructions to address processes that go awry in disease, or even improve agricultural yield or address pests. Others have since discovered dozens of miRNAs in the worm, plants, and humans. “There was a chance that this little worm might have been doing something so weird,” says Ruvkun. “Fortunately for us, that wasn’t the case.”