Gary Ruvkun has made a career out of imagining the unimaginable, and of surrounding himself with like-minded thinkers who let the wheels of thought spin until they catch on something hard, gain traction, and take off.
In the early 1990s, the thoughts of Ruvkun and colleague Victor Ambros caught on the idea of microRNA, tiny strips of genetic material that behave differently from how scientists believed RNA could. That development eventually transformed our understanding of how our body’s cells go about their business, of how they turn DNA on and off to create the proteins that do much of the body’s work.
Until then, scientists thought that proteins alone turned genes on and off and that RNA, a molecule related to DNA, carried out DNA’s genetic instructions.
Since then, science has come to understand that RNA, as well as proteins, can regulate DNA’s action and a new generation of scientists has turned to the study of microRNA.
Together with colleagues, the discovery netted Ruvkun, who is a genetics professor at Harvard Medical School (HMS) and an investigator at Massachusetts General Hospital’s (MGH) Department of Molecular Biology and Center for Computational and Integrative Biology, this year’s Warren Triennial Prize, MGH’s highest award for research, and the Albert Lasker Basic Medical Research Award.
Ruvkun attended to the University of California, Berkeley. He arrived in the fall of 1969, stepping onto campus during a time of freethinking and foment.
While many of Ruvkun’s peers protested their college years away, Ruvkun himself was too interested in his studies for that to happen. He marched, but also went to classes. He found himself drawn to study physics, enticed by the knottiness of its problems.
Ruvkun graduated in 1973 with a degree in biophysics and applied to medical school. Today he views the rejections that poured in — he didn’t get accepted anywhere — as a confirmation of the interviewers’ wisdom. He is certain they picked up on the fact that his heart wasn’t really in medicine.
Ruvkun went exploring, driving north into Oregon and working on a tree-planting co-op, whose members lived and worked communally in the mountains.
After leaving the co-op, Ruvkun headed south, with no other goal than to reach Tierra del Fuego. Ruvkun and a friend traveled by bus and train, not worrying about amenities or reservations.
He stopped one day at the Bolivian-American Friendship Club, picked up an issue of Scientific American and spent the day just sitting and reading. The grip in which the magazine held him made him realize that science was not just a passing fancy for him. If he was smart, he would make it part of his future.
When he got home, he applied to graduate school, getting accepted into Harvard’s biophysics program. He arrived in 1976, just two years after the publication of the first major paper describing recombinant DNA. Ruvkun said there was a growing sense that a scientific revolution was brewing.
He settled in the lab of Fred Ausubel, today a genetics professor at HMS and MGH who then was a young assistant professor nurturing a year-old lab. It was in Ausubel’s lab that Ruvkun learned all about DNA and how to manipulate it.
Worming into deep insights
After Ruvkun received his doctorate in 1982, he worked as a fellow with Walter Gilbert at Harvard and with Robert Horvitz at the Massachusetts Institute of Technology (MIT).
Horvitz introduced Ruvkun to the worm C. elegans, which Horvitz used as a model organism. Once in Horvitz’s lab, Ruvkun met Ambros, who was a postdoctoral fellow studying the worm’s passage through developmental phases from egg to adult.
The two worked on two genes called lin-4 and lin-14, which together controlled the pace at which the worms 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.