RNAi pioneers Andy Fire and Craig Mello have won this year’s Nobel Prize in physiology for their discovery of RNAi, the Karolinska Institute announced this week.
Though most in the RNAi field had expected the two researchers would eventually receive the prize for their work, some were surprised that it had been awarded so quickly.
Despite this, and despite being the most important recognition of the gene-silencing technology, some stress that it is unlikely that the event will have much of an impact on the RNAi industry.
Although it can sometimes take decades before researchers are awarded the Nobel Prize for their work, Rockefeller University’s Tom Tuschl noted that the speed with which the Nobel Foundation recognized Fire and Mello speaks to the importance of their work.
RNAi “had a profound impact on publication status in journals; it has industry behind it, at least in mammalian systems, [producing] reagents that are used in pharmacologic research for target validation; it [led to] startup businesses that are developing drugs based on siRNAs,” he told RNAi News this week. “So I don’t know how long you have to wait to see an impact. I don’t know what else you need to make this a more visible field.”
Tuschl likened the discovery of RNAi to Kary Mullis’ development of PCR, after which “every laboratory [began] using it because there was no other way to amplify a gene in a fast period of time.” Mullis invented PCR in 1985 and was awarded the Nobel Prize eight years later in 1993.
In light of the impact RNAi has had, “the Nobel Prize is almost late,” Tuschl added.
RNA silencing had been observed as early as around 1990 by plant researchers, including Rich Jorgensen who, in a series of experiments attempting to intensify the purple color of petunias, found that sense constructs for genes responsible for pigmentation instead whitened the flower (see RNAi News, 2/6/2004).
However, it wasn’t until Fire and Mello began collaborating on the regulation of gene expression in C. elegans that the mystery was unraveled.At the Carnegie Institution, Fire and Mello found that while injecting into worms either mRNA or antisense RNA for a muscle protein had no effect, delivering sense and antisense RNA together led to abnormal movement similar to that observed in worms lacking a gene for the muscle protein.
Ultimately, they concluded that it was double-stranded RNA that triggered the gene-silencing effect that would be known as RNA interference. The findings were published in in Nature in 1998.
A little more than eight years later, Fire, now at Stanford University School of Medicine, and Mello, who is at the University of Massachusetts Medical School, were awarded the Nobel Prize for their work.
Some in the RNAi field have observed that, although Fire and Mello’s work is undoubtedly groundbreaking, by awarding them the Nobel Prize the Nobel Foundation may have passed over those plant researchers who laid the foundation for RNAi.
Jorgensen, who is now a researcher at the University of Arizona, said that although “it would have been nice” to see certain plant researchers included in Fire and Mello’s Nobel Prize win, the decision of Nobel Foundation was “perfectly appropriate.
“What they focused on was the impact of the discovery of double-stranded RNA, and that certainly was the thing that got everybody excited across genetics and soon across biology,” he told RNAi News.
Indeed, Tuschl observed, it was Fire and Mello who “provided a critical link … [about the] molecular details” that allowed the field to explode.
“Once you understood that double-stranded RNA are the trigger [for RNAi], everything made sense,” he said.
Although the awarding of the Nobel Prize to Fire and Mello marks the biggest recognition of the importance of RNAi to date, it appears unlikely that the event will have much of an impact on the industry.
“It’s a profound validation of this pathway,” Barry Polisky, senior vice president of research and CSO of Sirna Therapeutics, said. However, “for people in the field … no one is terribly surprised.
“This is already the method of choice for down regulating every gene conceivable in everybody’s laboratory, and big pharma and little pharma use it routinely for target validation,” he told RNAi News this week. “So it’s part of the landscape in terms of working scientists’ everyday tools. For people in the field, this is already a well-established everyday activity.”
Peter Barrett, a principal at venture capital firm Atlas Venture and board member of Alnylam Pharmaceuticals, agreed. RNAi is “one of the most pervasive technologies used in the pharmaceutical industry for drug discovery, and there is a lot of work going on in pharmaceutical companies [with it] in drug development,” he told RNAi News. “Certainly anybody in the industry knows about RNAi and most [people] deep into the technology are aware of Fire and Mello’s work.”
In light of the impact RNAi has had, “the Nobel Prize is almost late.”
Douglas Fambrough, a principal at VC firm Oxford Bioscience Partners and member of Sirna’s board, added that while Fire and Mello’s receipt of the Nobel Prize ”is very gratifying and a validation for the field,” its impact on the RNAi industry is likely to be small.
“For one thing, neither of the Nobel Prize winners … have a connection with one of the major public RNA interference companies,” he told RNAi News. “Secondly, the field has gotten quite a bit of press attention in the past; it has been trumpeted pretty loudly in the New York Times and Wall Street Journal, and it was breakthrough of the year in Science magazine” in 2002.
“I think there was already a recognition amongst many people that this is a very powerful technology,” Fambrough said. “While that is reinforced by the Nobel announcement, it isn’t anything new.”
Additionally, “if you weren’t already aware of RNA interference and you listened to the news [about the prize awards], you wouldn’t have connected it with” any of the companies in the field, he added. “The people who care already knew that this was a big deal.”
Sirna’s Polisky was a little more sanguine about the effects of the Nobel Prize, noting that it may “validate in the minds of investors this technology.” But he agreed that “people who follow this field already know the potential of this technology.”
In the end, the effect Fire and Mello’s Nobel Prize has on RNAi may mostly be seen among laypeople.
“The Science magazine award has a certain amount of impact, but nothing approaches the Nobel Prize in terms of the man on the street beginning to think about this as a validated technology,” Polisky said. “Being a breakthrough in Science — from a scientist’s point of view, that’s probably as good as it gets. But a Nobel Prize everybody understands. That’s a different realm.”