Harvard scientist awarded Nobel Prize

Gary Ruvkun, professor of genetics at Harvard Medical School and an investigator at Massachusetts General Hospital, is a recipient of the 2024 Nobel Prize in physiology or medicine for the discovery of microRNA, a class of tiny RNA molecules that regulate the activities of thousands of genes in plants and animals, including humans. He shares the award with Victor Ambros, Silverman Professor of Natural Science at the University of Massachusetts Medical School. Ambros was a professor at Harvard starting in 1984 until moving to Dartmouth in 1992.

Ruvkun was sleeping when the call came in from the secretary of the Nobel committee.

“The phone rang and we don’t get middle-of-the-night phone calls,” Ruvkun said in an interview shortly after receiving the prize. “We answered it and it was the secretary of the Nobel committee and it sounded real We’ve received awards for this and it’s always been wonderful. It was great. It’s a big deal.”

The scientists received the award for the “discovery of microRNA and its role in post-transcriptional gene regulation.” The discovery revealed a completely new principle of gene regulation that turned out to be essential for multicellular organisms. It is now known that the human genome codes for over 1,000 microRNAs. The discovery by Ruvkun and Ambros revealed an entirely new dimension to gene regulation. MicroRNAs are proving to be fundamentally important for how organisms develop and function.

In a Gazette story published in 2008, Ruvkun recalled meeting Ambros in the early 1980s, when both were postdoctoral fellows in an MIT lab. The two worked on two genes called lin-4 and lin-14, which together controlled the pace at which the worm c. elegans developed.

By the mid-1980s, both Ruvkun and Ambros had moved on. Ruvkun was at MGH, while Ambros was first an assistant professor and then associate professor at Harvard.

They continued to work on the problem. Ruvkun’s lab figured out that lin-14 was the master gene, producing proteins that spurred early development and then were shut off, allowing later development to proceed. Ambros figured out that it was the product created by the other gene, lin-4, that stopped lin-14 when early development was complete.

Ambros’ lab tried to isolate whatever it was that stopped lin-14 from producing protein, expecting it to be another protein.

In June 1992, Ambros called Ruvkun and said he didn’t think it was a protein, but it might be a tiny piece of RNA. If it was, the two realized, it could block lin-14 from working by binding to the messenger RNA that carried instructions to the cell’s protein-making machinery.

Given that Ambros had the sequence of the blocking molecule and Ruvkun had the sequence of lin-14, the two labs exchanged data. All the two had to do to confirm it was indeed a new kind of RNA would be to see if the bases matched. They did.

“The response of both of us was, ‘This is just too pretty to be wrong,’” Ruvkun said.

Ruvkun was born in Berkeley, California, in 1952. He received his Ph.D. from Harvard University in 1982. He became a principal investigator at Massachusetts General Hospital and Harvard Medical School in 1985.

Material from a Nobel press release and previous Gazette stories was used in this report.