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Gary Ruvkun: An out-of-the box thinker
More than three decades after their discovery of microRNA, Professor Gary Ruvkun received the “mythic call” from Stockholm to learn that he’d been awarded the Nobel Prize in Physiology or Medicine alongside his erstwhile colleague Victor Ambros.
Mere minutes after having received the call from the Nobel Assembly at Karolinska Institutet (KI) on October 7, Gary Ruvkun got another call. Adam Smith, chief scientific officer at the Nobel Prize Outreach, gave him a ring to capture his initial thoughts in a “First Reactions” interview. Ruvkun – who’s been described as good natured with a strong sense of humor by people who know him – joked that the call might have been a prank pulled on him by friends.
This year’s Nobel Prize in Physiology or Medicine is being awarded for the discovery of microRNA and its role in post-transcriptional gene regulation – a fundamental principle governing how gene activity is regulated. California-born Gary Ruvkun is now Professor of Genetics at Massachusetts General Hospital and Harvard Medical School. He has been working there since 1985, after receiving his PhD from Harvard University and then completing a postdoc at Massachusetts Institute of Technology (MIT) in the early half of the 1980s.
As young faculty members, Ruvkun and Ambros were investigating the lin-4 and lin-14 genes in their labs at Massachusetts General Hospital and Harvard Medical School, and Harvard University, respectively. The two researchers, who knew each other since their time as postdoctoral fellows at MIT, came together to compare their findings.
After conducting further experiments, they showed that lin-4 RNA turns off lin-14 mRNA by binding to the complementary sequences in its mRNA, blocking the production of lin-14 protein. They had discovered a new mechanism of gene regulation mediated by an unknown type of RNA, a tiny molecule called microRNA. When the results were first published in two articles in the journal Cell in 1993, the scientific community paid the discovery little attention, as the unusual gene-regulation mechanism was believed to be specific to the worm C. elegans, on which the research had been conducted.
This finding made the previously dormant microRNA explode.
“For a long time, microRNA was believed to be an oddity peculiar to C. elegans. This perception changed seven years later, in the year 2000, when Gary Ruvkun identified a second microRNA, produced by the let-7 gene in the worm. Unlike lin-4, let-7 was found to be highly preserved and present in humans and most of the animal kingdom,” Professor Olle Kämpe, member of KI’s Nobel Committee for Physiology or Medicine said at the press conference when the laureates were announced in Stockholm in October.
“This finding made the previously dormant microRNA explode. As it turned out, many microRNAs are highly conserved throughout evolution, over several hundred million years. In more complex organisms, a larger number of microRNAs have evolved, with humans having more than 1,000 distinct microRNAs. Today we understand that the majority of all genes are regulated by microRNAs,” Kämpe continued.
A surprise – yet not a surprise
When the Nobel Prize’s Adam Smith asked Gary Ruvkun if he had had any inkling at the time of discovering this new mechanism in the early 1990s, that it might be worthy of a Nobel Prize, he humbly responded: “No, at that moment, it was just a quirky thing that we were working on. We were young faculty members wanting to make sure that we were successful at the next stage of our careers. We weren’t thinking that this is going to win a Nobel Prize. We were thinking that this is really interesting.”
“You know, as the field exploded – which was just a joy to watch – then it was a sense that this is the sort of field, the sort of sea change that gets awards and things. But that took a long time, and it was an unbelievable pleasure to participate in,” Ruvkun said.
Already back then when I was at the Ruvkun lab, more than a decade ago, he was considered for the Nobel Prize.
When the announcement came, not everyone was surprised though. Christian Riedel, Principal Researcher at the Karolinska Institutet’s Department of Medicine worked at the Ruvkun Lab as a postdoctoral fellow for a five-year period up until 2012.
“I was definitely excited to hear that he got the Nobel Prize, at the same time it wasn’t super unexpected,” Riedel says to NLS. “Already back then when I was at the Ruvkun lab, more than a decade ago, he was considered for the Nobel Prize. There were a lot of discussions about whether he had a chance and whether he would get it. But there had recently been a Nobel Prize awarded to Andrew Fire and Craig Mello for their discovery of RNA interference (in 2006). This was a discovery in a similar field, so we were speculating that Gary’s research was too similar. In that regard it was funny that he got it in the end,” Riedel says.
Curiosity driven
Christian Riedel, who himself specializes in the regulation of aging and age-related diseases – which is also what he focused on at the Ruvkun lab – describes Gary Ruvkun as a creative scientist and an out-of-the box thinker.
He was always in a position to be well funded, and then you’re also not afraid to explore other areas.
“During my days there, there were more than 25 people in the lab. Gary’s actually been quite innovative in his research and his thinking, so he’s been innovating in many other areas as well – at the time they even had a branch looking at life on Mars,” Riedel says.
“He was never afraid to get into new research territories – wherever curiosity took him he would go there. He was in a great environment at Massachusetts General Hospital and Harvard Medical School, with good funding and a supportive environment. He was always in a position to be well funded, and then you’re also not afraid to explore other areas,” he says.
Despite being involved in so many other research areas, and despite the limited interest that his and Ambros’ findings first garnered from the scientific community upon publication in 1993, microRNAs always remained close to heart for Ruvkun.
What he enjoyed the most was to think of innovative explanations for problems in the field.
“When I was there in the lab from 2007 to 2012, Gary’s main passion out of all his subject areas was still in the small RNA biology. This was his most interesting area, so he always kept his main focus on this topic,” Riedel says.
“What he enjoyed the most was to think of innovative explanations for problems in the field. He was very curiosity driven and a creative thinker. Which probably helped him earlier in his career when they first encountered microRNA and didn’t quite know what it was, and then set out to understand microRNA,” Riedel concludes.
Updated: January 23, 2025, 10:32 am
Published: December 10, 2024
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