Origin of life # 3456: Okay, admit. We lost count.

Thanks for "clearing" that up. I knew that, of course, and was hoping to get a reply from the Nickster. Fat chance of that. Very nice illustration though. I will steal that sometime, somewhere, I'm sure. :-) tgpeeler

RNA nucleotides are not RNA, Nick. IOW Sutherland did not solve the problem of how to get RNA. sigh, shrug Joseph

1- There isn't any evidence that the nucleotides can string themselves together to form a strand of RNA 2- Stones are the building blocks of Stonehenge- by Nick's "logic" that means Stonehenge wasn't designed because we know mother nature can produce stones Joseph

Nick, The same would apply to Alzheimer's research or any other study if possible solutions were passed through baseless, fantastic assumptions and ideology. Alzheimer's research deals in reality with lives at stake, so they're more inclined to follow the traditional method of drawing conclusions from the evidence rather than forming half-baked conclusions based on their own imaginations and then looking for evidence to support it. That's why I trust science more when it's keeping airplanes in the air. OOL researchers get paid regardless of what science fiction they come up with. ScottAndrews

You could say the same for absolutely any unsolved question in science. We don't know the causes of Alzheimers, but we are making progress. But because of your pink flying unicorns argument, maybe Alzheimers is just unexplainable except by a miracle! Great argument. NickMatzke_UD

How do you know it's advancing without knowing where it's advancing to? You can't claim that it's advancing without already having the very knowledge you're looking for. If you don't start with the assumption that you're going to find what you think you're going to find, then the search doesn't look much like advancement at all. Example: I'm looking for a monkey that rides a flying pink unicorn. I'm sure it's out there. Today I found a pink feather - advancement. Today I saw a monkey - advancement. Today I saw a bat, proof that mammals can fly - advancement. And just yesterday you mocked me and said I'd never get anywhere. Who's laughing now? As you can see, my research into monkeys that ride pink flying unicorns is advancing steadily. Convincing, isn't it? ScottAndrews

"...classic case of an advancing, successful scientific research program." The modern equivalent of chanting among the priests. Upright BiPed

Sutherland's work solved a problem. In fact, it was a problem (how to get RNA when you have to synthesize the sugar and the base separately) that JonathanM and apparently many UD readers agreed was fatal just last week! It didn't solve all problems. But progressively solving problems = classic case of an advancing, successful scientific research program. NickMatzke_UD

"RNA has four different nucleotides, and so far Sutherland has only produced two of them. However, he says he is “closing in” on the other two. If he succeeds, it will show that the spontaneous formation of an RNA replicator is not so improbable after all, and that the first replicator was most likely made of RNA." Let's see. It takes Sutherland a lot of time, effort, and technology to intelligently and with purpose "produce" two RNA nucleotides and maybe all four and that is somehow proof that they could have spontaneously formed? What am I missing here???? tgpeeler

This was the dawn of evolution. Once the first self-replicating entities appeared, natural selection kicked in, favouring any offspring with variations that made them better at replicating themselves. Soon the first simple cells appeared. The rest is prehistory.

It's a nice story, but hardly believable. Yet people believe. Mung

Dream on uncle Nick. You are a real man of faith. This RNA enzyme stuff is marginally interesting ID resaerch but there is a US$1,000,000 prize for a testable origin of life theory that has not been claimed for the past 10 years. Richard Dawkins your great high priest says nobody has a clue how life started. You should inform him and claim the money. idnet.com.au

Way to leave out all the interesting stuff which indicates that RNA world is a hypothesis making progress in the traditional scientific way. Why, they even point out explicitly that the very problem that JonathanM raised the other day -- how to get the sugar, base, and phosphate to join together -- isn't a such a problem once you realize that Nature isn't obligated to use the subunits that we find convenient to classify in chemistry textbooks.

A big advance came earlier this year, when Philipp Holliger of the MRC Laboratory of Molecular Biology in Cambridge, UK, and colleagues unveiled an RNA enzyme called tC19Z. It reliably copies RNA sequences up to 95 letters long, almost half as long as itself (Science, vol 332, p 209). To do this, tC19Z clamps onto the end of an RNA, attaches the correct nucleotide, then moves forward a step and adds another. "It still blows my mind that you can do something so complex with such a simple molecule," Holliger says. So biologists are getting tantalisingly close to creating an RNA molecule, or perhaps a set of molecules, capable of replicating itself. That leaves another sticking point: where did the energy to drive this activity come from? There must have been some kind of metabolic process going on - but RNA does not look up to the job of running a full-blown metabolism. "There's been a nagging issue of whether RNA can do all the chemistry," says Adrian Ferré-D'Amaré of the National Heart, Lung and Blood Institute in Bethesda, Maryland. RNA has only a few chemically active "functional groups", which limit it to catalysing just a few types of chemical reaction. Functional groups are like tools - the more kinds you have, the more things you can do. Proteins have many more functional groups than RNAs. However, there is a way to make a single tool much more versatile: attach different bits to it, like those screwdrivers that come with interchangeable heads. The chemical equivalents are small helper molecules known as cofactors. Proteins use cofactors to extend even further the range of reactions they can control. Without cofactors, life as we know it couldn't exist, Ferré-D'Amaré says. And it turns out that RNA enzymes can use cofactors too. In 2003, Hiroaki Suga, now at the University of Tokyo, Japan, created an RNA enzyme that could oxidise alcohol, with help from a cofactor called NAD+ which is used by many protein enzymes (Nature Structural Biology, vol 10, p 713). Months later, Ronald Breaker of Yale University found that a natural RNA enzyme, called glmS, also uses a cofactor. Many bacteria use glmS, says Ferré-D'Amaré, so either it is ancient or RNA enzymes that use cofactors evolve easily. Either way, it looks as if RNA molecules would have been capable of carrying out the range of the reactions needed to produce energy. So the evidence that there was once an RNA world is growing ever more convincing. Only a few dissenters remain. "The naysayers about the RNA world have lost a lot of ground," says Donna Blackmond of the Scripps Research Institute in La Jolla, California. But there is still one huge and obvious problem: where did the RNA come from in the first place? RNA molecules are strings of nucleotides, which in turn are made of a sugar with a base and a phosphate attached. In living cells, numerous enzymes are involved in producing nucleotides and joining them together, but of course the primordial planet had no such enzymes. There was clay, though. In 1996, biochemist Leslie Orgel showed that when "activated" nucleotides - those with an extra bit tacked on to the phosphate - were added to a kind of volcanic clay, RNA molecules up to 55 nucleotides long formed (Nature, vol 381, p 59). With ordinary nucleotides the formation of large RNA molecules would be energetically unfavourable, but the activated ones provide the energy needed to drive the reaction. This suggests that if there were plenty of activated nucleotides on the early Earth, large RNA molecules would form spontaneously. What's more, experiments simulating conditions on the early Earth and on asteroids show that sugars, bases and phosphatesMovie Camera would arise naturally too. It's putting the nucleotides together that is the hard bit; there does not seem to be any way to join the components without specialised enzymes. Because of the shapes of the molecules, it is almost impossible for the sugar to join to a base, and even when it does happen, the combined molecule quickly breaks apart. This apparently insurmountable difficulty led many biologists to suspect to RNA was not the first replicator after all. Many began exploring the possibility that the RNA world was preceded by a TNA world, or a PNA world, or perhaps an ANA world. These are all molecules similar to RNA but whose basic units are thought to have been much more likely to form spontaneously. The big problem with this idea is that if life did begin this way, no evidence of it remains. "You don't see a smoking gun," says Gerald Joyce, also of the Scripps Research Institute. In the meantime John Sutherland, at the MRC Laboratory of Molecular Biology, has been doggedly trying to solve the nucleotide problem. He realised that researchers might have been going about it the wrong way. "In each nucleotide, you see a sugar, a base and a phosphate group," he says. "So you assume you need to make those building blocks first and then stick them together... and it doesn't work." Instead he wondered whether simpler molecules might assemble into a nucleotide without ever becoming sugars or bases. In 2009, he proved it was possible. He took half a sugar and half a base, and stuck them together - forming the crucial sugar-base link that everyone had struggled with. Then he bolted on the rest of the sugar and base. Sutherland stuck on the phosphate last, though he found that it needed to be present in the mixture for the earlier reactions to work (Nature, vol 459, p 239). Goldilocks chemistry Sutherland was being deliberately messy by including the phosphate from the start, but it gave the best results. That's encouraging: the primordial Earth was a messy place and it may have been ideal for making nucleotides. Sutherland now suspects there is a "Goldilocks chemistry"Movie Camera - not too simple, not too complex - that would produce many key compounds from the same melting pot. "Sutherland had a real breakthrough," Holliger says. "Everyone else was barking up the wrong tree." The issue isn't entirely solved yet. RNA has four different nucleotides, and so far Sutherland has only produced two of them. However, he says he is "closing in" on the other two. If he succeeds, it will show that the spontaneous formation of an RNA replicator is not so improbable after all, and that the first replicator was most likely made of RNA.

NickMatzke_UD