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Long trail from 1992 discovery to 2024 Nobel

Early work by Nobel laureate Gary Ruvkun revealed a new level of gene regulation in the C. elegans roundworm.

Harvard file photo

Science & Tech

Long trail from 1992 discovery to 2024 Nobel

Gary Ruvkun recounts years of research, which gradually drew interest, mostly fueled by NIH grants

4 min read

Gary Ruvkun and Victor Ambros were not known as superstars in their field back in 1992 when they discovered microRNA, a feat that would earn them the 2024 Nobel Prize in physiology or medicine.

“We were fine. We weren’t terrible,” said Ruvkun, a professor of genetics at Harvard Medical School. “But there was nothing about it that made it seem like, ‘Oh, these guys are walking on water!’”

Even after the former Harvard collaborators published their findings in the journal Cell in 1993, revealing a new level of gene regulation in the C. elegans roundworm, the evolutionary biology community was not overly impressed. It wasn’t clear that the genes Ruvkun and Ambros, now a professor at the University of Massachusetts Medical School, discovered mattered to other species, including humans.

Instead, their work, mostly funded by the National Institutes of Health, drew interest from a smaller group of RNA researchers and what Ruvkun calls the “worm community” — those interested in the same model organism.

Therapies based on microRNAs to treat heart disease, cancer, Crohn’s Disease, and Alzheimer’s are in clinical trials.

But the interest in the RNA field kept growing. Meetings that formerly would have drawn 100 attendees doubled in size within a few years. It became clear that the same tiny RNAs had the same role in plants and in worms, and scientists in all different fields were interested in the same questions.

Ruvkun started to realize, “This was some revolutionary stuff, and we were the only people thinking about tiny RNAs in the world.”

Decades of federally funded breakthroughs later, microRNAs are considered fundamental to how organisms develop, mature, and function — playing a key role in translating genes into proteins.

Studies have discovered that the human genome contains about 1,000 microRNAs that control most human protein-producing genes. Therapies based on microRNAs to treat heart disease, cancer, Crohn’s Disease, Alzheimer’s, and several other diseases are in clinical trials.

Ruvkun says about three-quarters of his lab research has been funded by the federal government for the past 40 years, at about $150,000 a year. The money provides enough support for about four people. “It’s not like I had a lab of 50,” he said.

He expresses puzzlement at calls to cut federal funding, emphasizing that spending on scientific work is far from wasteful. “The average pay of the people in my lab has always been about three times the minimum wage,” he said. “These are scientists, and they’re super educated. They have Ph.D.s or are getting Ph.D.s, but they’re paid a little better than working at Dunkin’ Donuts.”

Ruvkun is proud that basic research from his field has led to major pharmaceutical companies like Alnylam, which focuses on the discovery, development, and commercialization of RNA interference therapeutics for genetic diseases.

“It’s one of the 10 biggest companies in Massachusetts,” he said, “and it didn’t even exist 20 years ago.” He’s also glad that his research had enough of an impact that he can continue doing basic science while others worry about the business implications.

Of the top 500 companies in the country, Ruvkun emphasizes, well over half are driven by technology — much of the foundational research behind them driven by federal grants. He credits federal funding with turning the U.S. into a scientific and economic superpower during and after World War II.

He worries that a lack of investment could push members of his laboratory away from science research.

“I have all of these people who are 25, 30 years old, and they’re like, ‘What career do I have? What am I going to do?’” The answer, he said, might be the reverse of the post-war trend: They’ll leave the U.S. for more stable positions in Europe.

Ria.city






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