RNA Interference. 10 Kilodalton Penalty. First Down.

October 2, 2006 4:16 AM

[MediFilter] The 2006 Nobel Prize in Physiology or Medicine goes to the discoverers of RNA interference (RNAi) [Note: Links to original 1998 Nature paper .pdf]. The finding that cells have an intricate mechanism for blocking viral RNA replication quickly spawned a new technology for investigating the role of different genes by allowing scientists to quickly, (relatively) cheaply and easily "knock down" their expression and measure the effects. When Kerry Mullis won in 1993 for the discovery of the polymerase chain reaction (PCR), there was talk of whether or not the prize had gone to a technical advance and not a fundamental discovery. It will be interesting to see, in this case, which receives more focus: the discovery of a new technology or of a new cellular mechanism.
posted by scblackman (18 comments total)

Minor point: it's Kary Mullis.
posted by gene_machine at 4:17 AM on October 2, 2006

Sorry. Transcription error. Wasn't using the HiFi Taq. Har.
posted by scblackman at 4:24 AM on October 2, 2006

buy stock here.
posted by the painkiller at 4:53 AM on October 2, 2006

Read the Gold Bug Variations if you want to get a good handle on the whole RNA thing.
posted by bim at 5:06 AM on October 2, 2006

Really the only justification for this coming so soon is that it's a new cellular process. Applications for RNAi technology are here, but they don't approach even 5% of the broad usefulness of something like PCR, and probably won't for a while (or ever).
posted by rxrfrx at 5:25 AM on October 2, 2006

I second bim's recommendation. To quote from page 365, “The punched tape running along the inner seam of the double helix is much more than a repository of enzyme stencils. It packs itself with regulators, suppressors, promoters, case-statements, if-thens”.
posted by gene_machine at 6:36 AM on October 2, 2006

Is this the first time they've given the medicine prize to something RNA-related? PCR was in chemistry, as was the one for mRNA.

I'm trying to get an interview with a potential Nobel winner for work. "Potential" in that she was a leader on the HPV vaccine research.
posted by dw at 7:00 AM on October 2, 2006

Why does the Nobel for "medicine" need to go to a fundamental discovery, and not a new tech?
posted by delmoi at 7:15 AM on October 2, 2006

I think rxrfrx has missed the point here, it's not about "usefulness" of RNAi technology.

This research opened the door to the discovery and appreciation of a vast number of non-coding regulatory RNAs* that are important for normal cellular function, not just anti-viral–type activity. Possibly the most important of these new RNA species are microRNAs*, one of the largest classes of genes in the genome that we have recently come to realise regulate thousands of target genes during development. Plus, active research in the area is turning up new classes of small regulatory RNAs on almost a monthly basis. The discovery of RNAi opened the door to a huge and expanding field of research. You've heard tell of a primordial RNA World *? It turns out we're still living in it.

Having said that, the applications for this technology in basic research are already phenomenal. One of the best ways to work out what a given gene does is to take it away and see what process fails to work properly. RNAi technology has, in the past few years, made it possible to inactivate, one by one, every (known or predicted) gene in the genome and see what happens to a given process. It's hard to overestimate the power of this. RNAi (along with derivative technologies) has become an incredibly powerful technique for cellular and developmental biology.

I understand why people think things are only important if they are applicable to consumer electronics or treatments for disease, but from a basic science point of view the RNAi discovery has been the catalyst for huge advances in biology.
posted by nowonmai at 8:20 AM on October 2, 2006

RNAi is not binary, and signaling pathways are highly redundant. Knockdown != knockoff.
posted by Blazecock Pileon at 9:07 AM on October 2, 2006

This is certainly a fundamental discovery in a way PCR was not. Not that it matters.
posted by grouse at 9:27 AM on October 2, 2006

I haven't missed the point, because I specifically said that the award wasn't given for usefulness. It wasn't given for usefulness because RNAi isn't all that useful yet.

PCR isn't applicable to consumer electronics or any specific treatment for disease. It's a lot more useful for that, and based on its usefulness, I'd say it deserves a Nobel.

And you can do gene knockouts in quite a few animal species these days. This was well-established and in common use before RNAi. Being able to (more rapidly) knock expression down instead of just doing the knockout is not all that different. Sure, it saves time, but it's no huge thing.
posted by rxrfrx at 11:57 AM on October 2, 2006

I guess I missed your point in your earlier comment, as you were providing a direct answer to the question posed in the post, and I failed to read in the right context. Sorry about that, and yes I agree that it's the discovery of the cellular process that merits a Nobel prize, not any technological application (and had I remembered to place my bets before the prize announcement, this is where my money would have been).

On the other hand, if "RNAi isn't all that useful yet", how come thousands of biologists are using it every day? I am baffled.

Gene knockout techniques remain expensive and laborious, and are only appropriate once you have identified genes of interest; high-throughput whole-genome RNAi screening provides a complementary methodology to identify genes of interest for future study. Furthermore, RNAi and RNA-derived technologies can be used to knock down gene activity in species where knockout technology is not readily available. RNAi knockdowns are also more easily multiplexed. I think it's hard to challenge the usefulness of RNAi as a research tool, although as you and Blazecock Pileon point out, it's not a replacement for previous techniques and has limitations.
posted by nowonmai at 2:00 PM on October 2, 2006

Also, the New York Times writeup of of this is better than such things tend to be, and certainly better than I have read in other papers. (Guardian, you should be ashamed of yourself).
posted by nowonmai at 2:03 PM on October 2, 2006

Oh yeah, I wouldn't say it's not useful, but this was just in things-are-compared-to-PCR land. Working strictly with microbes myself, I suppose it's easier for me to ignore the timesavingness of knockdown vs. knockout.
posted by rxrfrx at 6:53 PM on October 2, 2006

My first reaction was that this would prove to be a particularly prescient decision. Admittedly, I can't speak to how PCR was received by the scientific community at its advent, but it feels like there's a palpable sense of excitement over RNAi, particularly about its possible research applications --- in a way, RNAi could conceivably do for large-scale proteomics what PCR did for, well, everything. Admittedly, it isn't the most widespread of research techniques right now, but then again, that's why I call it a prescient choice.
posted by Tiresias at 1:25 AM on October 3, 2006

It was still possible to replicate DNA before PCR. I know old hands who used to do so. They had three temperature baths that they had to cycle their samples between, adding polymerase every third step. It was tedious, time-consuming, expensive, and annoying. Just like previous knockout methods compared to RNAi.

So in a way, PCR just made something easier that was already possible. But that belies its true importance, and the revolution that occurred simply because something was made easier and cheaper.
posted by grouse at 2:34 AM on October 3, 2006

They had three temperature baths that they had to cycle their samples between

I would describe this process as PCR. I've heard the stories of "the bad old days" with three water baths and no thermostable polymerase... but isn't that just really rough PCR? I haven't read the patents so I don't know if it requires a polymerase that will survive the whole process, or what. But the concept of simple in vitro replication, whatever you call it, is the superuseful thing.
posted by rxrfrx at 4:29 AM on October 3, 2006