Last week I mentioned how much I enjoyed watching Dudley Do-Right on Saturday mornings as a kid. I was also fond of Underdog. This canine parody of Superman battled criminals like Simon Bar Sinister and Riff Raff and came to the rescue of Sweet Polly Purebred. Whenever she cried out, "Oh where, oh where has my Underdog gone?" the humble shoeshine boy disappeared into a nearby phone booth, reemerging as Underdog.
When the origin-of-life community decried the problems with the RNA world hypothesis, one of the leading ideas for life's emergence, chemists from the University of Manchester in the U.K. arrived on the scene to seemingly rescue this idea from impending disaster. Applying "out-of-the-box" thinking and painstaking laboratory experiments, these researchers discovered a novel, straightforward chemical route to one of the hypothesis's key building block materials.
As I discussed last week, this work not only makes an evolutionary explanation for the beginning of life more plausible, it also opens up a new avenue of research for the origin-of-life community.
Validating the RNA World Hypothesis
In order to substantiate the RNA world scenario researchers need to establish the validity of several processes. These include:
- reasonable prebiotic chemical routes that will generate the building blocks (nucleobases, ribose, and phosphate) of RNA;
- reasonable prebiotic routes that will assemble these building blocks into ribonucleotides;
- a reaction scheme that will chemically activate the ribonucleotides;
- reasonable prebiotic routes that will assemble RNA from its building blocks into molecular chains long enough to form ribozymes.
Researchers have identified possible routes to make ribose and the nucleobases, but these pathways have questionable relevance for the origin of life. While the reactions work well in the laboratory, the conditions of early Earth would have frustrated these processes.
Traditionally, scientists divided possible prebiotic reactions into those that lead to sugars and those that yield nucleobases. Then they tried to find a way for the two products to eventually form ribonucleotides. But the Manchester chemists took a different tact. They looked for ways that the two prebiotic routes could intermingle.
Instead of thinking about sugar and nucleobase chemistries as separate, these researchers allowed the two chemistries to intermingle. This conceptual breakthrough allowed them to discover a very simple chemical route to produce activated ribonucleotides, which are chemically complex materials. In addition, the team allowed reactants from the final steps of the chemical pathway to intermingle with reactants in the early stages of the process. This, too, represents a conceptual advance in origin-of-life studies, and provides a reasonable way to "clean up" unwanted byproducts that otherwise would interfere with the generation of the ribonucleotides. The use of UV radiation to "purify" the final product, too, is reasonable. UV radiation would have impinged on early Earth.
Without question, these chemists have made an important contribution to the evolutionary paradigm. Their work paves the way for others to approach problems in prebiotic chemistry in an unconventional way that might lead to other key advances. Still, have they really rescued the RNA world hypothesis? In spite of the apparent success of this work, problems abound.
Problems for the Prebiotic Production of Ribonucleotides
No route exists to make two of the four ribonucleotides needed to make RNA molecules. In other words, the origin-of-life community is only part way to resolving problems concerning the source of activated ribonucleotides.
Plus, even though the researchers examined ways in which proposed prebiotic routes could intermingle, they still didn't take into account all of the possible byproducts that could hamper the reaction sequence they discovered. For example, the investigators ignored all the reactions that would competitively destroy cyanoacetylene and cyanoacetaldehyde, two key components in this pathway. They conducted their laboratory experiments using purified chemicals, carefully controlling the compounds added to the reactions. Such a level of control would never have been present on early Earth. This facet of their work raises concerns about the overall geochemical relevance of the study.
Additionally, the use of UV radiation to clean up unwanted byproducts of the reaction in the last step of the sequence poses issues. Exposure to UV radiation helps the last step of the reaction by selectively destroying contaminants; in the primordial world it would have indiscriminately destroyed all of the reactants in the earlier steps of the chemical route.
Another concern relates to the production of chemically activated ribonucleotides. If these compounds don't form, RNA chains can't assemble. But the compounds are highly reactive and would be consumed quickly by materials present on early Earth. Because of their high reactivity, it's not likely that these materials would exist at high enough levels to help the RNA world scenario. It's a no-win situation.
Perhaps the most significant problem has to do with this process' dependence on phosphate. The laboratory experiments required high levels of phosphate to allow the pathway to operate efficiently. Such levels simply would not have been present on early Earth. In fact, phosphate would not have been readily available at all. It interacts with calcium and magnesium to form insoluble salts that would have precipitated out of the water, removing phosphate from the early Earth's oceans.
Researchers have proposed several possible prebiotic chemical routes to polyphosphates. The most common include (1) the heating of apatite (a phosphate-containing mineral); (2) the high- temperature heating (from 392 to 1,112 °F, 200 to 600 °C) of dihydrogen phosphates; and (3) the phosphates' reaction with high-energy organic compounds.
Although several plausible routes to polyphosphates exist, scientists wonder if these chemical pathways pose any relevance to early Earth. For example, to produce polyphosphates from apatite and dihydrogen phosphate, water must be completely driven from the system—an impossibility for phosphate minerals confined to rocks. Furthermore, the high temperatures needed to form polyphosphates would in turn destroy any organic material.
The Case for Intelligent Design
The chemists from Manchester have done a masterful job of identifying a chemical route that could have generated two of the four ribonucleotides, in principle. They also went a long way toward ferreting out the chemical mechanisms that dictate the reaction sequence. But they failed to demonstrate that this chemical pathway possesses geochemical relevance. The conditions required to make the reaction sequence work would not have been present on early Earth.
In fact, these scientists have inadvertently provided direct, empirical evidence that apart from the work of an intelligent agent, this prebiotic chemistry cannot take place in a productive way. If it wasn't for chemists (1) carefully controlling the amounts and purity of the chemical components added to the reaction mixtures; (2) adjusting the reaction conditions, which includes adding the appropriate level of phosphate; and (3) selectively exposing the final reaction products to UV radiation as a way to get rid of unwanted byproducts, the generation of activated ribonucleotides would be impossible.
Commenting on this work, origin-of-life researcher Robert Shaprio said, "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."
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