LONDON — A pair of scientists who discovered a type of RNA molecule that helps control the activity of genes — allowing our cells to perform their myriad functions in different tissues throughout the body — won the 2024 Nobel Prize in medicine or physiology on Monday.
The award went to Victor Ambros and Gary Ruvkun for their research into microRNA, which the Nobel committee described as a “groundbreaking discovery [that] revealed a completely new principle of gene regulation that turned out to be essential for multicellular organisms, including humans.”
Ambros, 70, conducted his prize-winning research at Harvard University and is now at UMass Chan Medical School. Ruvkun, 72, did his work at Massachusetts General Hospital and Harvard Medical School, where he remains a professor of genetics.
The pair will split the award of 11 million Swedish kronor, or just over $1 million. They join the ranks of medicine or physiology Nobel laureates that prior to this year had 227 people, including 13 women.
“The Nobel is in its own class with how much attention it gets,” Ruvkun said during a news conference Monday at Mass General. “I’ve won 10 to 20 awards in the last 20 years, but never had a press conference with cameras and nothing like this. It’s a completely different world.”
Ambros and Ruvkun’s discoveries helped pull back the curtain on how cells can take the relatively simple instruction manual that is our DNA and create something as complex as a human being.
The process starts with genes in our DNA getting transcribed to create strands of messenger RNA, which then get translated to produce proteins. These building blocks are responsible for just about everything, from our development as embryos to the absorption of nutrients that we eat, from fending off pathogens to the foundational acts of breathing and thinking.
But for all those different cell types performing all those different functions, the same roughly 20,000 genes appear in all our cells. How, then, do our bodies make the right proteins in the right place?
For years, dating back to the 1960s, researchers thought the main way gene expression was regulated was by proteins called transcription factors that bind to DNA, ensuring that only the correct genes would get “read” to produce the corresponding pieces of mRNA.
But as Olle Kämpe, the vice chair of the medicine Nobel committee, put it at a press conference in Stockholm Monday, “the mechanism would, however, turn out to be more complex.”
Ruvkun and Ambros’ discovery, published in 1993, elucidated another part of that mechanism, one that occurred later on in the process of making proteins.
Ruvkun and Ambros didn’t conduct their work in human cells, but rather with the trusty C. elegans, a roundworm that’s regularly used as a model organism in research. The worm only has 1,000 cells, but still forms many of the different tissues that humans do, including a nervous system, a gut, and muscles.
Ruvkun, who was born in Berkeley, Calif., and Ambros, originally from Hanover, N.H., had been postdoctoral fellows together in the 1980s in the Massachusetts Institute of Technology lab of Robert Horvitz, who himself would go on to win a Nobel in 2002. They were interested in studying genes that were involved in the worms’ development, ensuring that the right step happens in the right sequence to allow for the healthy growth of the animal.
Once they started their own labs, the two researchers began investigating the role of separate genes that were known to be crucial for the animal’s development. Ambros had already shown that one of the genes, called lin-4, could inhibit the activity of the other, lin-14, but it wasn’t clear how. (One of Ambros’ close collaborators was his wife, Rosalind Lee, who, along with a postdoctoral researcher named Rhonda Feinbaum, was able to clone lin-4 so that the scientists could study the gene in the lab and characterize its role.)
When the former colleagues started comparing what they were learning in their labs, they had their aha moment. They uncovered that a piece of RNA made by lin-4 — a strand that did not go on to be translated into a protein — could bind to the mRNA produced by lin-14, preventing it from being translated into a protein. The discovery of this microRNA was published in two papers in the journal Cell in 1993.
At first, the finding was treated as a scientific curiosity, an oddity contained to a gene found in the lowly C. elegans. But seven years later, Ruvkun and his colleagues showed that they had discovered another microRNA, and this one had been maintained across the animal kingdom.
The field exploded, with scientists uncovering more and more microRNAs that had been conserved as species evolved over hundreds of millions of years, underscoring the importance of these molecules.
It’s now known that humans have 1,000 microRNA genes. Researchers have also shown that microRNAs are involved in the development of cancers, with tumors disrupting microRNA networks so they can grow in uncontrolled ways.
“Today we understand that the majority of all genes are regulated by microRNAs,” Kämpe said. “Every microRNA regulates several mRNAs and each mRNA is often regulated by many distinct microRNAs, creating a robust system for gene regulation.”
Scientists are also now exploring the potential of microRNAs as a therapeutic approach. The idea is that the RNA strands could suppress or activate certain genes that either drive cancer formation or protect against that, or could inhibit the activity of mutant genes behind certain inherited diseases.
“The importance of Gary and Victor’s work has been clear for decades,” Harvard Medical School Dean George Daley said at the Mass General news conference. “MicroRNA biology is essential to numerous laboratories across the globe, including my own, where we have turned microRNA regulation and its understanding to a better insight into cancer, diabetes, metabolism, tissue regeneration.”
It was around the time of the now-Nobel winning research that Ambros was denied tenure at Harvard. He first went to Dartmouth Medical School, and then moved to UMass.
Notably, Ambros’ joint Nobel recognition comes a year after Katalin Karikó co-won the medicine prize, for foundational work that led to mRNA vaccines. Earlier in her career, Karikó had been demoted at the University of Pennsylvania as she pursued what was then seen as obscure research.
Their stories highlight how the value of basic research sometimes only comes to be recognized with time.
Harvard “lost a potential Nobel laureate because they simply didn’t see in him the potential that he had,” David Baltimore of the California Institute of Technology, himself a Nobel winner, told the Worcester Telegram & Gazette in 2008, when Ambros and Ruvkun were recognized with a Lasker Award. “It’s the nature of a seminal discovery that it’s seminal in retrospect. You can’t know ahead of time.”
Elizabeth Cooney and Anil Oza contributed reporting.
