Archives for: May 2009, 19

05/19/09

Permalinkby 03:29:15 am, Categories: Literature - Articles, 1584 words   English (UK)

Ribonucleotides and the revival of the "warm little pond" scenario

According to one commentator, the newly published research provides "one of the great advances in prebiotic chemistry". The media have captured the excitement with headlines like "Chemist Shows How RNA Can Be the Starting Point for Life" (New York Times), "Molecule of life emerges from laboratory slime" (New Scientist) and "How RNA got started" (Science News). These are strong statements and they deserve closer attention. What is going on in the field of OOL research?

RNA World graphic
Artistic portrayal of the 'RNA World' dream (Credit: Nicolle Rager Fuller & National Science Foundation, Source here)

The first point worth making is that new advances are often shown to be significant by referring to the lack of progress that had earlier characterised the field. This is often a surprise to the general public, who are typically fed a story that the problems are largely cracked and abiogenesis researchers are confident of tying up the loose ends in the near future. Wade's report refers to the solution of "a problem that for 20 years has thwarted researchers trying to understand the origin of life - how the building blocks of RNA, called nucleotides, could have spontaneously assembled themselves in the conditions of the primitive earth." Van Noorden explains the problem like this:

"An RNA polymer is a string of ribonucleotides, each made up of three distinct parts: a ribose sugar, a phosphate group and a base - either cytosine or uracil, known as pyrimidines, or the purines guanine or adenine. Imagining how such a polymer might have formed spontaneously, chemists had thought the subunits would probably assemble themselves first, then join to form a ribonucleotide. But even in the controlled atmosphere of a laboratory, efforts to connect ribose and base together have met with frustrating failure."

Abiogenesis researchers adopt either 'law' or 'chance' as causal explanations. They have rejected 'design' (not because it does not work, but because they insist on all causation being material). The new research is driven by a confidence in 'law'. The researchers are chemists. For them, the origin of life is a matter of chemistry. Thus, Sutherland, the lead author, is quoted as saying:

"My ultimate goal is to get a living system (RNA) emerging from a one-pot experiment. We can pull this off. We just need to know what the constraints on the conditions are first."
[and]
"My assumption is that we are here on this planet as a fundamental consequence of organic chemistry, so it must be chemistry that wants to work."

What, then, has been achieved? The researchers have synthesised both pyrimidine ribonucleotides (but not the purine ribonucleotides). As Van Noorden described it, they have "shown that it is possible to build one part of RNA from small molecules". They have not formed RNA molecules; they have not addressed the chirality problem, they have not generated any biological information and they have not made RNA do anything of biological significance, let alone become clothed with a membrane and undergo replication. Nevertheless, what they have done can be applauded as an elegant example of systems chemistry. A specific bond was needed between the Ribose and the Nucleobase, and a decade of research proved that the bond was not going to form directly. So what the researchers did was to create the bond and then turn the components on each side of the bond into the desired building blocks of the Ribonucleotide. Phosphate, which previously caused problems for OOL researchers, becomes a catalyst. Szostak's News and Views essay draws attention to the elegance of their approach:

"But in a remarkable example of 'systems chemistry', in which reactants from different stages of a pathway are allowed to interact, Powner et al. show that phosphate tames the combinatorial explosion, allowing oxygenous and nitrogenous reactants to interact fruitfully."
[. . .]
"The penultimate reaction of the sequence, in which the phosphate is attached to the nucleoside, is another beautiful example of the influence of systems chemistry in this set of interlinked reactions. The phosphorylation if facilitated by the presence of urea; the urea comes from the phosphate-catalysed hydrolysis of a by-product from an earlier reaction in the sequence."

It is good chemistry, but does it achieve a major advance in abiogenesis research? Questions can certainly be raised. The researchers argue that they are not starting with any unrealistic initial conditions: "We don't use any way-out scenarios - all the conditions are consistent with what we know about early Earth." However, this is disputed.

"The flaw with this kind of research is not in the chemistry. The flaw is in the logic - that this experimental control by researchers in a modern laboratory could have been available on the early Earth," says Robert Shapiro, a chemist at New York University.
[and]
Dr. Robert Shapiro [. . .] said the recipe "definitely does not meet my criteria for a plausible pathway to the RNA world." He said that cyano-acetylene, one of Dr. Sutherland's assumed starting materials, is quickly destroyed by other chemicals and its appearance in pure form on the early earth "could be considered a fantasy."
[and]
"But while this is a step forward, it's not the whole picture," [James] Ferris [of the Rensselaer Polytechnic Institute in Troy, N.Y.] points out. "It's not as simple as putting compounds in a beaker and mixing it up. It's a series of steps. You still have to stop and purify and then do the next step, and that probably didn't happen in the ancient world."

It can be argued that the chemical reactions documented actually yield products that are intelligently designed. The experimental conditions are engineered to selectively accumulate some reaction products (by fractional crystallisation) and selectively destroy others (by the influence of UV radiation). These conditions are considered more plausible in Darwin's hypothetical "little warm pond". Indeed, Wade's report says: "Dr. Sutherland's report supports Darwin". This is significant because the emphasis in abiogenesis research has shifted in recent years to other scenarios - notably at mid-ocean ridge locations. Those who find themselves impressed with the potential of this research would do well to reflect on the way the chemistry is engineered to achieve the outcomes and the associated fine tuning of environmental factors. These are not Darwinian emphases!

Of the other limitations mentioned above, the chirality problem is noted in Wade's report:

"A serious puzzle about the nature of life is that most of its molecules are right-handed or left-handed, whereas in nature mixtures of both forms exist. Dr. Joyce [an expert on the chemical origin of life at the Scripps Research Institute in La Jolla, Calif.] said he had hoped an explanation for the one-handedness of biological molecules would emerge from prebiotic chemistry, but Dr. Sutherland's reactions do not supply any such explanation."

For those of us more familiar with 'design' as a causal explanation, this work does not dent the arguments already in place to demonstrate the futility of explaining life without design. Notably, the idea that life is just a matter of chemistry simply fails to engage with the information necessary for a cell to function as a biological entity. We are impressed by the systems chemistry reported, but find it such a shame that the hype surrounding the research is driven by the quest to explain life without a designer. Sutherland has ambitions to make a compelling case for chemical evolution: "That is the goal of my career", he says. A more worthy goal, although probably with less hype, would be to apply his undoubted talents to address contemporary conundrums facing the human race.

Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions
Matthew W. Powner, Beatrice Gerland, John D. Sutherland
Nature 459, 239-242 (14 May 2009) | doi:10.1038/nature08013

At some stage in the origin of life, an informational polymer must have arisen by purely chemical means. According to one version of the 'RNA world' hypothesis this polymer was RNA, but attempts to provide experimental support for this have failed. In particular, although there has been some success demonstrating that 'activated' ribonucleotides can polymerize to form RNA, it is far from obvious how such ribonucleotides could have formed from their constituent parts (ribose and nucleobases). Ribose is difficult to form selectively, and the addition of nucleobases to ribose is inefficient in the case of purines and does not occur at all in the case of the canonical pyrimidines. Here we show that activated pyrimidine ribonucleotides can be formed in a short sequence that bypasses free ribose and the nucleobases, and instead proceeds through arabinose amino-oxazoline and anhydronucleoside intermediates. The starting materials for the synthesis - cyanamide, cyanoacetylene, glycolaldehyde, glyceraldehyde and inorganic phosphate - are plausible prebiotic feedstock molecules, and the conditions of the synthesis are consistent with potential early-Earth geochemical models. Although inorganic phosphate is only incorporated into the nucleotides at a late stage of the sequence, its presence from the start is essential as it controls three reactions in the earlier stages by acting as a general acid/base catalyst, a nucleophilic catalyst, a pH buffer and a chemical buffer. For prebiotic reaction sequences, our results highlight the importance of working with mixed chemical systems in which reactants for a particular reaction step can also control other steps.

See also:

Luskin, C. Scientists Say Intelligent Designer Needed for Origin of Life Chemistry, Evolution News & Views, 7 July 2009.

Szostak, J.W., Origins of life: Systems chemistry on early Earth, Nature 459, 171-172 (14 May 2009) | doi:10.1038/459171a

Van Noorden, R., RNA world easier to make, Nature News, 13 May 2009 | doi:10.1038/news.2009.471

Wade, N., Chemist Shows How RNA Can Be the Starting Point for Life, New York Times, 14 May 2009.

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