Thursday, October 05, 2006

What Fire and Mello's Nobel portends for law

Andrew Z. Fire   Medal   Craig C. Mello

RNA interference

It's old news by now that two young Americans, Andrew Z. Fire and Craig C. Mello, have won the 2006 Nobel Prize in Physiology or Medicine "for their discovery of RNA interference-gene silencing by double-stranded RNA." Although my BioLaw colleague Andrew Torrance has already posted some very intriguing observations on Fire and Mello's work, I'd like to add a few thoughts of my own.

C. elegansFire and Mello performed a new twist on what by 1998 had become an established trick: using RNA interference to manipulate gene expression in the nematode Caenorhabditis elegans, one of biology's favorite model organisms. (Aside to readers of the ongoing series, Genesis for the rest of us: the very existence of experiments using model organisms relies on the common descent of all organisms and the conservation of metabolic pathways, developmental pathways, and genetic material -- yes, bedrock principles of evolution.)

To the Fire-Mello team's surprise, double-stranded RNA was substantially more effective than single strands at genetic interference. The team reported this finding in a pathbreaking 1998 article, Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans, 391 Nature 806 (1998). Science blogger Jake Young describes the finding succinctly and vividly:
[I]f you insert double stranded RNA (dsRNA) into cells you get a generalized destruction of RNAs and cessation of protein synthesis. This is because dsRNA in cells is associated with viruses -- it shouldn't be there and the cell knows it.
It turns out that RNA interference is simply another biological strategy for fending off parasites.

Tobacco mosaic virus
The tobacco mosaic virus: All RNA, all the time
What strikes me as a nonscientist as even more interesting is the observation that RNA interference in bacteria appears to have evolved independently from RNA interference in eukaryotes such as C. elegans. (Yes, H. sapiens is a eukaryotic organism.) RNA interference might well have been the dominant antiparasitic strategy in a world without DNA. On evolution's treadmill of the gods, viruses developed an extraordinary counterdefense against RNA interference: DNA.

Using a quick but intriguing way of sampling patent filings, Andrew Torrance has concluded that "RNAi is on the march." It's worth noting other ways in which RNA interference will affect biological research (and, in due course, the legal systems that regulate such scientific work):
  1. RNAi provides an indispensable new experimental tool. RNAi allows researchers to suppress the production of any protein in a cell. Researchers can thus work with cells that lack a particular protein without regard to the limits on the transgenic engineering of such cells.

  2. RNAi exposes yawning new opportunities for research on the human genome. Introns, or regions of the genome that do not code for proteins, are not junk. Much of this DNA codes for RNAi.
(Again, a tip of the blogger's proverbial hat to Jake Young's Pure Pedantry.)

In other words, it's worth anticipating the applications underlying all those patents involving RNAi. Gregory J. Hannon and John J. Rossi, Unlocking the potential of the human genome with RNA interference, 431 Nature 371 (2004), have identified some leading therapeutic applications of RNAi technology:
  • Drug discovery using genome-wide RNAi screens
  • RNAi-based treatments for viral infections such as HIV and hepatitis
  • RNA-based treatments for cancer and genetic diseases
The bottom line is quite simple. Where biology leads, law will surely follow.

Editor's note: Cross-posted on BioLaw.


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