During a panel discussion last month at the University of California-Irvine, UCI biochemist Greg Weiss and I got to wrangling about the origin and stability of prebiotic RNA. I had mentioned the implausibility of prebiotic RNA and its relative fragility, as would have been the case on the early Earth, if RNA formed initially on (for instance) clay surfaces without the protection of a cell membrane.
Weiss disagreed, saying that I had overstated the fragility of RNA. Of course RNA breaks down readily now, he said. Surfaces in the current environment are swarming with ribonucleases (RNases), enzymes which snip RNA into pieces. But that wouldn't have been a problem in the RNA World, Weiss added, before such enzymes had evolved. RNA with no RNases to threaten it is quite stable.
I didn't have a chance to ask Weiss how he stored RNA in his own lab, but I remembered from conversations with friends who worked with the molecule that they used special buffers for their isolates. Back at my office, I dialed up the Ambion® webpage. Ambion, "The RNA Company," is a leading supplier of different types of RNA and related products, and offers technical advice about handling RNA. As Weiss had noted, at the top of the Ambion warning list were the ubiquitous RNases.
But further down on the tech sheet came advice about storing RNA after the RNases have already been dealt with:
Magnesium and other metals catalyze non-specific cleavages in RNA, and so should be chelated by the addition of EDTA if RNA is to be stored and retrieved intact.
EDTA: a handy molecule for binding metals, but, because it is anthropogenic, not likely to have been found in the RNA World. EDTA is not the only buffer ingredient for chelating metals that Ambion offers, however. The RNA Storage Solution® uses a different chelating agent, sodium citrate. This buffer "minimizes base hydrolysis by chelating free cations from solution with sodium citrate and by maintaining a low pH." As Ambion notes,
These solutions are prepared from the purest reagents available, under scrupulously monitored conditions in our state-of-the-art manufacturing facility. They are then subjected to rigorous quality control procedures to guarantee their purity and performance.
That's great to know if one is buying Ambion products; not so great, if one wishes to simulate a plausible RNA World on the early Earth, where interfering cross-reactions are very likely to have occurred (destructive metal cations, for instance, contaminating the environments where any RNA might have formed).
So Why Think RNA Arose Prebiotically?
The Israeli philosopher of science Iris Fry has noted that philosophy "goes to the core -- to the very 'right of existence'" of the field of abiogenesis research. If we see the prebiotic origin of RNA, a necessary step for any RNA World scenario, as a genuine problem to be solved by further research, then failure to solve that problem indicates only that we haven't tried hard enough, but nothing more. The philosophy that tells us, "Consider the natural or prebiotic origin of RNA a well-posed problem," does not allow us to abandon that problem in the face of failure.
Imagine giving a fourth-grader two large numbers to multiply. He makes an attempt, and shows you the product. It's wrong. So you ask him to try again. He does, but the answer is still wrong.
"There is no solution to this math problem," he complains.
Come on, you reply, of course there is. Try again. On his next attempt, he gets the product right.
But imagine now giving the same student, who remarkably turns into a math whiz a few years later, the problem of trisecting an angle using only a compass and straight edge. He immediately pushes the problem set back across the table at you with a smile. "No thanks," he says. "Impossible."
Mathematics and the empirical sciences are not the same, to be sure. Exact proof is possible in the first, but not in the second. Yet as endeavors of inquiry -- i.e., as problem-solving enterprises -- they share interesting parallels. We try to solve a problem only when we are persuaded that a solution is possible.
Why think that the prebiotic origin of RNA actually happened? That is, why regard the question "How did RNA arise in the absence of organisms?" as a genuine scientific puzzle that wants a solution?
Because that's what the best evidence indicates, one might reply: (a) the universality of RNA in terrestrial biochemistry, and (b) its fundamental roles in cell biology, both show that (c) RNA was very likely the primordial replicating entity, arising naturally in the absence of organisms.
OK -- but ask yourself if (a) and (b) could be true, and yet (c) false. Ask yourself further if the difficulty of demonstrating the prebiotic formation of RNA, and its (relative) fragility in the absence of organisms, should be taken not as problems to be solved, but rather as signs that a different view of RNA is needed: one in which RNA is not a primal cause of biological organization, but rather an essential constituent of larger, irreducibly complex systems -- systems whose origin requres design.
To fortify you as you wander off the materialist-reductionist ranch, here's a pair of papers on the origin of RNA.
Leslie E. Orgel, "Prebiotic Chemistry and the Origin of the RNA World," Critical Reviews in Biochemistry and Molecular Biology 39 (2004):99-123. [pdf freely available online]
Robert Shapiro, "Small Molecule Interactions Were Central to the Origin of Life," Quarterly Review of BIology 81 (2006):105-125.
This new paper by Shapiro gets my vote as the best theoretical biology publication of the first half of 2006.
