On June 10, 2003, I had the opportunity to hear three well-known researchers speak at UC San Diego on the "origins of life:" Jeffrey Bada, Leslie Orgel, and Gerald Joyce. The talks were given in honor of the 50th anniversary of Stanley Miller's famous experiment, which was published in Science in May of 1953. The experiment was reviewed by Bada in a recent issue of Science ("Prebiotic Soup-Revisiting the Miller Experiment," by Jeffrey Bada and Antonio Lazcano, vol 300, pg 745-746, May 2, 2003). Dr. Miller was present at the events and talks of the day.
These were two of the most informative talks I've heard on the subject in a long time, and I personally learned a lot. Given that in the past couple of years, both Bada and Joyce have reviewed two of the leading origins-of-life paradigms for Nature and Science, they are truly leaders in this field. Two reports follow.
The first will be a report of Jeffrey Bada's talk entitled, ''Revisiting the Miller Experiment 50 years later." The second will report on Gerald Joyce's talk entitled, "The Antiquity of RNA-Based Evolution."
Introduction by Leslie Orgel:
The opening remarks were made by Leslie Orgel. He noted that every society is "puzzled" by the origin of life, and have recognized two problems: The first is that humans and higher animals have methods of reproduction where they come from one another. Because "life comes from life" this has spawned, according to him, the many creation myths that are found in ever culture. The second problem is how each new generation arises--he referred to Aristotle who believed that frogs emerged from the slime at the bottom of the Nile.
He noted that in the 17th century, Radi (sp?) said that if you prevent flies from laying their eggs on rotting food, then there is no larva, and began to disprove spontaneous generation. But that idea, he said, really died in the 1860's with Pasteur, who took a sample of broth, pumped out the air, added heat, and got no life. Orgel said this effectively disproved spontaneous generation for the masses of scientists. He noted that for 90 years, nobody thought about spontaneous generation until Stanley Miller in 1953. Then Jeff Bada spoke.
Report of Jeffrey Bada's talk, ''Revisiting the Miller Experiment 50 years later":
Bada is the director of the NASA Specialized Center of Research and Training (NSCORT) in Exobiology at Scripps Institution for Oceanography at the University of California at San Diego. He has worked with Stanley Miller for over 30 years on the origins of life and is the recent co-author, with Christopher Wills, of ''The Spark of Life: Darwin and the Primeval Soup.'' There is a sense that Bada is highly respected as a researcher because of his willingness to question exobiology findings from other labs that would otherwise excite many in exobiology. On various occasions he has tested claims of exobiology findings from other labs and found them to be false. If my memory serves me correct, this includes the famous ALH001 meteorite which fell in Antarctica in the mid-90's, which contained organic material, but which he determined had been contaminated after NASA got excited about organic material from outer space. He's done a lot of interesting stuff. Edward Peltzer, a pro-ID chemist who works at Monterey Bay Aquarium Research Institute, did his Ph.D. under both Stanley Miller and Jeffrey Bada in the late 70's.
>From what I could gather of Bada's account of himself, he came to UCSD in the early 1970's and had studied under Linus Pauling at some point. He met Miller and they have now been friends for 30 years. Bada showed Miller's original Science article from May 15, 1953 and told the story of the printing of Miller's paper. Some of this is in Bada's recent review of Miller's experiment from Science. Miller's paper was unique because it was published very quickly and he Miller did it at the age of 23!
It in 1952 started when Harold C. Urey wrote a paper entitled, "On early chemical history of the earth and origin of life" (PNAS, 38:351- 363, 1952). Urey spoke at the University of Chicago in 1951 and said that conditions on the early earth were different than today--he said the early atmosphere was Hydrogen, Methane, and Ammonia. Bada said Urey had spoken of someone named "Calvin" who did an experiment that made formic acid and said new ideas were needed. It seemed that Urey basically conceded that pre-Miller, there was no firm paradigm for the origins of life and that much work was needed.
Here is a table Bada gave of organic molecules that had been synthesized from inorganic "building blocks" prior to 1953:
1825: Wohler synthesized Urea 1850: Strecker synthesized Alanine 1900: Someone synthesized Glycine
Then in 1924, Oparin, Haldane, Lipmann, and Harvey proposed the idea that the earliest life was heterotrophic, meaning that it was not photosynthetic but rather went around eating a see of primordial soup molecules. The first life, they said, literally ate the soup.
Miller approached Urey desiring to do the experiment when Miller was a young grad-student. Apparently Urey was hesitant to let Miller do the experiment, but allowed it. In the end, Miller actually did three simulations:
1) An "ocean simulation" where he spark the gasses methane, ammonia, and hydrogen w/ a weak spark and simulate the organics being formed in an ocean-like environment
2) A "volcano simulation" where he sparked the gasses methane, ammonia, and hydrogen with a weak spark and simulated the organics being formed in a volcanic environment
3) A final simulation where he spark the gasses methane, ammonia, and hydrogen through a "silent discharge" using sulfuric acid and a HUGE spark.
Miller would analyze with paper chromatography. Bada said he was impressed because he found that when the experiments were repeated today and analyzed using a mass-spectrometer, it turns out that Miller found almost everything through paper chromatography that was present in the resulting chemical mixture.
Bada continued that experiment 1 is the famous one we hear about. It produced various amino acids. Experiment 2 is lesser known, but apparently it had the same results as experiment 1. Experiment 3 did NOT produce significant amino acids of interest to the origins of life.
Apparently after Urey saw the results, he told Miller, "put it in Science." Bada acclaimed Urey because Urey didn't even ask to have his name put on the paper, but yet was instrumental in getting it published. Urey and Miller submitted the paper to Science in early February, 1953. Apparently, Urey wanted a rush publication. Only 2 1/2 weeks after submitting the paper, Urey wrote Science and asked why he hadn't yet received back any communication about when it would be published nor proofs of the to-be-published version! Urey asked this only 2 1/2 weeks after submitting the paper! Wow, he expected it to go pretty quick. Why was Urey so anxious to get it published? Bada thinks he had a clue.
On March 8th, 1953 a New York Times article cited someone named Dr. Wollman MacNevin was written up performing an experiment that sounded similar to that of Miller. Bada speculated that Urey got nervous that someone would beat them to the publication of these results, and subsequently wrote a very sharp letter to the editor of Science demanding that Miller's paper be published immediately or he would take it to some other journal!
Science responded back by writing back to Miller (not Urey, as Miller had authored the paper) and told Miller that his paper would be published soon. Interestingly, in the letter, the Science editor disclosed to Miller the name of the senior reviewer of Miller's paper. That would be quite unorthodox today, and in that day as well. It seemed like this was a big paper and Miller had all the cards and bargaining power in what happened to it.
In any case, Miller's paper was published on May 15th, 1953, reporting that he had produced amino acids by sparking methane and ammonia and hydrogen gas, attempting to simulate what he thought was the earth's early environment.
Bada mentioned another paper from that time (I did not catch the reference) which found that if the gasses used were not reducing, then the chemistry did not take place and amino acids did not form. Miller and Urey realized that it was primarily the "Strecker Reaction" (note Strecker's findings in 1850 above) that was taking place. They found that if ammonia was present then you got amino acids, but if no ammonia was present, then you got no amino acids. One paper he cited that revisited the Miller Experiment was Ring, Wolman, Friedmann, and Miller (PNAS 69:765-768, 1972).
Bada continued with his timeline saying that in 1953 Miller did his expeirment, in 1961 Oro made Adenine, connecting amino acids chemistry to nucleobase chemistry, and then subsequently the RNA world hypothesis arose. But Miller got a lot more than just amino acids, which was somewhat problematic. Furthermore, Bada noted that the paradigm required that all these little monomers had to form polymers, and according to Bada, "from this Gammish of polymers something arose which was the origin of life." Sounds easy enough? Well first the good news, and now the bad news.
Bada noted that people immediately began to question Miller's results. It is widely known that Miller assumed that amino acids were important in early life and more or less tailored his experiments to produce them. Two references I had on this point include:
"It is assumed that amino acids more complex than glycene were required for the origin of life, then these results indicate a need for CH4 (methane) in the atmosphere." (Stanley Miller and Gordon Schlesinger. Prebiotic Synthesis in Atmospheres Containing CH4, CO, and CO2. Journal of Molecular Evolution 19:376-382 (1983))
"We believe that there must have been a period when the earth's atmosphere was reducing, because the synthesis of compounds of biological interest takes place only under reducing conditions." (Miller, S.L., and Orgel, L.E., The Origins of Life on the Earth, Englewood Cliffs, Prentice Halt, p. 33 (1974))
Bada explained that the formation of the moon blew off the early primary atmosphere on earth, and then degassing formed the atmosphere- he said that Miller's experiment used H2 [hydrogen gas], CH4 [methane], and NH3 [ammonia]. However, on the early earth, H2 would quickly have been lost to space, and methane and ammonia would have quickly photo- decomposed due to UV light. Thus, he said that all that would remain in the early atmosphere is CO2 (carbon dioxide) and N2 (nitrogen gas) which does not produce any amino acids in Miller-type experiments.
Thus, Bada essentially conceded that Miller's experiment was not relevant to earth chemistry because the atmosphere was not what Miller used. So, as Bada explained, people began to turn their hopes for the origin of amino acids to material arriving from space.
Bada mentioned the 1969 Murchison Meteorite in which they found amino acids (Nature 228:923-928). They found that there was a racemic mixture, meaning that there were both right and left-handed amino acids in the meteorite, indicating that it had not been contaminated by earth amino acids (life on earth uses only left-handed amino acids). Bada also noted how the Murchison metoerite had very similar proportions of amino acids to what was found in Miller's experiment-telling them that Strecker chemistry was going on. So, Bada said that although Miller's experiment did not necessarily apply to what was happening on earth, it could apply to what was happening in space.
Bada noted that the next problem is how you get the material to earth. According to Bada, In Basick and Douda (Planetary Space Science 47:577- 584, 1999), it was found that most meteorites would simply get too hot and would destroy most amino acids and organic material during entry to the earth's atmosphere. In this paper, the only possible way to get significant organic material to earth was through interplanetary dust particles (IDPs).
Bada himself later heated IDP's and found that during entry they can easily heat up to 1200 C, easily hot enough to destroy most organic material. Apparently the only amino acid that ever remained during Bada's simulations was glycine. Bada called this "bad news." Thus, IDP's don't help you either and from what I could tell, this officially leaves origins of life researchers with no way to safely get organic material from space to earth.
Bada's hypothesis to save the day was to look towards "localized synthesis" where instead of an earth-wide primordial soup with Miller- chemistry happening everywhere, you have specific places where Miller chemistry is possible and organic material was forming. Bada's favoriate place was volcanic island arcs where there is lots of volcanism and also a lot of associated lightning-up to 10 times the normal amount of lightning on earth. Bada referred back to Miller's "volcano" experiment that produced amino acids.
At this point, my question was why should volcanic arcs help us any? We already know that you can spark the heck out of a mixture of common volcanic gasses-CO2 and N2-and not get anything! I wasn't clear on exactly why Bada felt that because there was more lightning at volcanic island arcs that somehow he could somehow get organic material. The atmosphere is the same everywhere, and there is no where on earth that I know of that methane and ammonia are naturally prevalent, perhaps apart from inside the intestines of a cow. What good is island arc-lightning going to do you if the gasses in the atmosphere are not the right ones for Miller- Chemistry. Bada already conceded that the atmosphere on earth wouldn't work for Miller's experiment, so I am at a loss as to how "localized synthesis" saves the day. Another problem I noticed was that the "primordial soup" hypothesis had been attractive because it carried with it the idea of a vast sea of chemicals where anything was bound to happen. Though questionable such thinking may be, the concept of "localized synthesis" would surely place even more severe limits the number of opportunities and locations where the origins of life could have taken take place. The odds just seemed to be getting worse and worse for the theory.
It was a good talk, full of historical and scientific insight, but my feeling was that Bada didn't want to end the talk on a low-note, so he put forth a plausible-sounding theory which, according to what he said during the rest of his talk, seemed to me to be absolutely impossible. The bottom line is that by the end, Bada seemed to have conceded 2 key points:
1. The atmosphere on earth is totally improper for Miller-experiment chemistry, and the best evidence says it always has been that way.
2. There is no way to get significant organic material to earth from space, even if Miller-experiment chemistry was happening in space on meteorites.
So, Bada single-handedly seemed to implicitly concede that the Miller- paradigm of the origins of life is dead. From what I've read, many others agree with Bada. In 1990, the Space Studies Board of the National Research Council, referring to the Miller-paradigm, recommended a: "reexamination of biological monomer synthesis under primitive Earthlike environments, as revealed in current models of the early Earth" (The Search for Life's Origins. National Research Council Space Studies Board, National Academy Press: Washington D.C., 1990, pg. 66, 67, 126)
The government's top scientists basically think this model is dead. It's too bad that others don't. I like these guys-Miller, Bada, Urey- they were and are imaginative scientists who persistently, honorably, and objectively promoted their paradigm despite its strengths and weaknesses. Unfortunately I'm not sure how often they took time to reflect upon the philosophical implications of their work, or how much they let it affect them. In any case, the Miller-paradigm of amino- acid synthesis is effectively dead, as far as I could tell from this talk.
To conclude, one telling point that Bada made was that he stumbled upon a video made by Miller in the late 1960's where apparently Miller was discussing his work and had essentially the exact same paradigm he had today. The only difference, according to Bada, was the theory about how the moon originated. This led me to the feeling that that in 50 years since Miller's experiment, the only progress that has been made in the origins of life is to determine that Miller's work is moot with regards to the naturalistic origins of life.
Report on Gerald Joyce's talk, "The Antiquity of RNA-Based Evolution":
Joyce's talk followed Bada. Apparently Joyce went to the University of Chicago (as an undergrad?) and worked near the building where Stanley Miller first did his experiment there in 1953. In 1978-79, Joyce was in the M.D.-Ph.D. program at the UCSD medical school, and wanted to use Darwinian principles as a method of computation. This was in the days before calculators and PC's, so Joyce thought it might be a practical method for computation. In any case, Joyce got started in the field after he took a class taught by Stanley Miller, who by then was at UCSD. Miller saw Joyce's interest, and Miller contacted Orgel, and Orgel took on Joyce as a grad student, and Joyce switched from a doctor to a lab experimenter.
Joyce's talk was primarily about how we could form the first replicating RNA molecule / system. Joyce didn't seem to care so much about the Miller-paradigm of amino-acid synthesis. He seemed to feel that if we could just get a self-replicating molecule using nucleotides, rather than using amino-acids, then we wouldn't need Miller's hypothesis anymore. I'm not sure how to get those nucleotides, etc., but at least he has another idea to replace the dead Miller-paradigm. I wondered if this talk was strategically placed after Bada's talk because Bada basically conceded that Miller's work wasn't helping things much anymore. Without Joyce, origins of life researchers might have left the day feeling quite hopeless!
Joyce gave a very fast, and thorough presentation on the "RNA World" hypothesis of the origins of life. Get ready, because this is heavy, and I hope that deficiencies in my vocabulary of biochemistry do not muck this report up too badly. My apologies if it does.
Joyce defines life as a self-sustained chemical system capable of undergoing Darwinian evolution. In other words, once you get a self- replicating system that undergoes mutation, then you can have life.
Darwinian evolution, according to him, is 3 step process:
1) Amplification (make stuff-create a phenotype) 2) Diversification (mutation) 3) Selection process.
In biology today, Joyce noted that we go from DNA -> RNA -> protein. Joyc's idea is that before there was RNA <- -> RNA, where RNA essentially was capable of creating itself, and RNA molecules did all the work. He envisions the RNA world as a host of self-replicating RNA molecules capable of replicating an entire metabolism. At least that's what it became. From what I could tell, he's looking for a self- replicating RNA molecule akin to a polymerase as the big kick-start to the RNA world.
Basically, for him, RNA was the genetic AND the phenotypic molecule. He admitted firsthand that this is a "just-so story" or a "fairy tale" parts of which he didn't even necessarily believe. But this is his paradigm, and he then proceeded to give an account of it.
4.6 Ga: Solar system is an interstellar dust cloud. 4.5 Ga: Early earth forms 4.2 Ga: Somewhat more hospitable planet with a hydrosphere 4.1 Ga: Prebiotic Chemistry (he doesn't care about Strecker chemistry & amino-acid research, but is concerned with how we can get nucleotides and then create polymers that can replicate. Joyce basically says that we can easily create the bases and sugars needed through pre-biotic chemistry.) 3.9 Ga: RNA World: consists of RNA that can translate and replicate itself into another a molecule of RNA. Essentially, he just wants a self-replicating RNA molecule. 3.6 Ga: DNA and protein-based life emerge.
Joyce then said that "we must look at every aspect and question its strengths and weaknesses." He was frank about some of the weaknesses, but in my view it seemed like he focused mainly on the strengths and didn't really tell us much about the weaknesses.
He first asked if RNA could arise under natural conditions. He said he'd love to do a Miller experiment for the RNA world, where he mixes up some gas and ends up with RNA, but he said you just can't do that (because, I assume, it is too complex)! But he said it is easy to imagine the building blocks of RNA arising under primitive conditions. Here is how he imagined it:
1. Aldehydes combine to make ribose through the formose reaction. But this reaction gives both the D and L form of ribose plus a whole huge host of other types of sugars.
2. Then you string together the sugars, and use the sugars to make a backbone.
3. Then you make the purine bases (adenine and guanine) which can be made by UV light. (along with this comes a host of other purine molecules). 4. Then you make the pyrimidines (cytozine and uracil) through similar reactions, but these also create a host of other pyrimidines.
Apparently this enough to convince Joyce of the plausibility of forming an RNA molecule naturally. Why all these molecules would join up to form RNA is a question I can't answer, and my guess is neither could Joyce.
Also, during the pre-RNA-pre-biotic chemistry, Joyce made it clear a very large host of other molecules are created, which happens to contain, among many many other molecules, the proper forms of ribose, adenine, guanine, cytozine, and uracil necessary for RNA. Joyce called all the molecules the "Pre-biotic clutter." It is out of this "clutter" that Joyce hopes you'll get RNA. Joyce pointed us to his review article on the RNA world from Nature ("The Antiquity of RNA-Based Evolution," Nature 418:214-221, July 11, 2002). With that, Joyce said he would "come clean" about what we know and do not know about whether or not his paradigm can work.
Joyce started off by showing a panspermia website, "panspermia.org", where he found the following quote: "Life comes from space because life comes from life." These panspermia proponents were obviously critical of origins of life hypotheses because they want us to be space- babies, but Joyce noted (and I would agree) that there is some very shaky logic in their statement. Interestingly, however, he compared these panspermia proponents to "creationists" and even went as far as to call it at one point "a creationist website." Joyce also said that the panspermia website is "creationism meets Star Trek." Interesting comparison-apparently all skeptics of Darwin's theory are lumped into the creationist category.
However, this panspermia website went on to say that Joyce in his Nature review (cited above), presents the RNA world fairly. Joyce said he appreciated this comment, and retorted that he only wished that creationist would return the favor (implying that they do not treat issues fairly). And thus the token-jab at creationists drew a laugh from the audience, as it invariably does at all of the many talks like this I have attended in my life at UCSD
Joyce didn't take himself too seriously, which was good and appropriate. He noted that the panspermia website did a word analysis of Joyce's Nature review of the RNA-world hypothesis and found that out of 7 pages and 6332 words, there were something like 39 "maybe's" 15 "perhaps's" and counted off dozens of mushy and soft qualifying words that Joyce used (also including many "we can imagine's" and "it could possibly be's.") Joyce found this very amusing and seemed to admit that the word-count showed that Joyce's paper was pretty soft in hard facts, and pretty strong in weak speculation.
Joyce then asked if life began with RNA? He answered, "No" because it is too complex to form from the "cluttered" mix of prebiotic chemicals he envisioned. He suggests that life began with some simpler molecule with a backbone and nucleic acids. He sought some kind of a precursor to RNA. He made 3 suggestions:
1. "GNA" (glycerol nucleic acid) which is simpler than RNA. Apparently the bonds glucose bonds in GNA are too "floppy" and so this molecule clearly won't work as an RNA precursor.
2. "PNA" or Peptide-nucleic acid (from Nielson et. al., Science, 1991) which looked like a candidate but apparently also has problems (he did not elaborate).
3. "TNA" or Threose-nucleic acid (from Schoning et. al., Science, 2000). This was his favorite because apparently it didn't have all of the other known problems of the other molecules which used to be the favorites until their problems were discovered. Given previous trends, however, perhaps in a couple of years TNA will be out of favor. It was only 1999 that a talk I attended by Stanley Miller reported that PNA was the likely candidate. But of course now that TNA is around they readily admit problems with PNA, which I don't believe I was told about in 1999 before TNA was around. Such is how things typically go. However, he did note that it has not yet been experimentally shown that this molecule has any auto-catalytic capabilities.
Joyce did not discuss how any of these could transform into RNA, how they would arise in the first place or why any of that would happen.
Joyce asked if TNA could transform directly to DNA, thus circumventing the need for an RNA world. He thinks this isn't possible because there must have been an RNA world. How did he know this? Well, he cites modern day examples to show what he think is the smoking gun of the possibility of an RNA world. Here are some examples:
-Apparently there are RNA-based genomes (not RNA-based life, but just genomes in certain viruses) that use RNA and some RNA enzymes.
-He said that DNA can be synthesized from RNA through some metabolic pathways, and says that this suggests there was a pathway from RNA to DNA. This seems ridiculous to me, because this pathway is totally biosynthetic and requires a precisely specified set of enzymes to perform the transformation. The presence of a metabolic pathway is a lot different from the possibility of an evolutionary transformation (this reminds me why the post-natal transformation of marsupial jawbones into earbones does not prove that the transformation could have happened in an evolutionary process.)
-He just thinks that RNA and DNA are similar enough that it isn't too implausible to say one turned into the other.
-He cited that ribosomes use RNA to create proteins. He thought that the fact that RNA is used to create the peptide bonds in the protiens in ribosomes is the best evidence of an RNA world.
Interestingly, as an aside, Joyce noted that he thinks that the rest of the non-protein-coding genome that most people call "junk-DNA" is really an RNA-based metabolism behind the cell that is a "secret society" that is "not-so-secret" anymore because we are beginning to discover it in the past 3 years. But he says these are all remnants of the RNA world. Joyce is definitely a believer that junk-DNA is NOT really just junk! He sees a whole suite of functions including the sustenance of an RNA-based metabolism. Very interesting!
Joyce still is apparently yet to determine if RNA has the catalytic abilities necessary for Darwinian evolution. Naturally occurring RNA enzymes exist but there are only about 4 present examples today-not enough to produce the RNA-metabolism of RNA-based life he expected. So, Joyce basically turns to "test-tube-evolution" to select for RNA strands the exact type of RNA functions he desires to get the right molecules. He says that over 100 RNA enzymes have been made through this process, and you can do much different types of chemistry through RNA enzymes.
However, it should be noted here that when he says "test-tube- evolution" what he really means is basically "intelligent design." Joyce knows the exact sorts of RNA molecules that he needs for his RNA world of an RNA-based metabolism to function. He uses "test-tube- evolution" as a method of selecting for RNA strands that do the job he wants. However, he already knows the desired job and so he specifies the selection pressure beforehand and essentially intelligently designs the molecules such that they come out the way he wants. A Darwinian process might be involved in its creation, but this is front- loaded design if there ever was such a thing.
How does he do it? String random RNA letters and try to selectively amplify the functional molecules with extreme selection pressure. They have produced a number of RNA enzyme analogues to enzymes of the DNA world:
-an RNA ligase can help reproduce one more unit of RNA.
-an RNA polymerase-not just an RNA ligase but a polymerase. He says this is good progress, however it can only string 14 successive nucleotide pairs with 98% accuracy. I have to admit that I was impressed that they have constructed such a molecule out of RNA, but then again, how impressive is it? Joyce and his fellow RNA researchers essentially create these designer
-RNA molecules through extreme selective pressures of this "test-tube evolution." There is no reason for these RNA molecules to ever arise in nature. In my view, together, perhaps, they might be able to create an RNA-based metabolism one day in the lab, but then that would still just be a giant irreducibly complex RNA-based system! You can design such a system, but it is intelligently designed and way too complex to arise randomly. Given that they are just artificially selecting for a molecule they want, there is no reason to expect that this highly complex suite of RNA-based molecules would arise naturally--it would be far too improbable. If they were to create such a system in the lab, its only strong point for their theory would to show that an RNA world could exist. But there is no reason to think that an RNA world could come into existence in the first place, or come from TNA, or that a TNA world could come into existence or exist, or that an RNA world could transform to a DNA world. The chances of such an RNA- based metabolism arising naturally are like the chances of our DNA- based metabolism arising naturally-extremely small. It seems likely that even a TNA-based metabolism would be too complex. The bottom line is that the complexity of life is too much for chemistry to bring it into existence. In any case, they aren't anywhere near creating this RNA suite of interacting RNA metabolic molecules. They've only created isolated RNA-analogues to the DNA world and never tested them all together.
Here are some other interesting points:
The RNA polymerase can only polymerize 14 base pairs, but it itself is 200 base pairs long. Thus, Joyce said that he is only 14/200 of the way to getting a totally autocatalytic self-reproducing RNA molecule. Furthermore, it only has 98% accuracy during reproduction. That is equivalent to 1 mutation in 50 base pairs. Joyce noted that for life to survive, it needs at least a 99.5% accuracy. That to me also seems lower than what it should be -I'd say that if your mutation rate is as high as 1 in 500, you're still in trouble. But regardless, Joyce is apparently not anywhere near creating the molecule that he wants-a totally self-replicating RNA polymerase. He thinks that it can be done, but it sure seems like faith to me!
But, Joyce told a just-so story of how this could all happen in nature:
1) The ribosyme strung aldehydes together to make ribose (he says no one has done this but it is feasible). The result he said would be ribose--the building blocks of RNA.
2) Then all you have to do is add a phosphate, but there is apparently no known way to turn inorganic phosphate into organic phosphate.
3) Then you must activate the phosphate
4) Then you take piece of RNA and extend it one letter at a time through a polymerization process (but he can only do this 14 times with his RNA polymerase)
If you can do all this, then you have the RNA world: RNA's that go around reproducing and creating new RNAs.
He also said that RNA protein synthesis could take place as evidenced by the ribosome. He hasn't had much success with this because he's only been able to connect 2 amino acids through RNAs they have created. That's a pretty short peptide.
He thinks that one day they'll be able to make an RNA world in the lab, but my gut feeling about this whole RNA world is that there are so many other little parts needed to sustain an RNA based metabolism that this is way too complex to arise naturally. It's just like any irreducible complexity problem: why would the needed parts come into existence?
A couple of the questioners asked questions to which Joyce conceded that there were other parts needed to this system that hadn't been created yet. This made me suspect that there may be many more necessary parts to this RNA world than Joyce made apparent in his talk. The RNA world would have been a complex world indeed.
Interestingly, as the day ended, an elderly gentleman sitting in front of me asked the last question of the day-it was a great question and he seemed somewhat skeptical of the whole story. It turned out to be Duane Gish who was sitting almost directly in front of me. Dr. Gish agreed that though impressive these designer-made RNA enzymes may be, these systems representing RNA-based life are still very complex and far too complex to even remotely approach what could arise naturaly. Even if a full RNA-based metabolism could one day be constructed in the laboratory (a feat towards which Joyce made it sound like some progress has been made, but a great many key hurdles remain to be overcome), there is no evidence that such a system could arise naturally nor that it could or would want to turn into DNA/Protein system.
If you want more information on either Joyce or Bada's, I highly recommend reading Joyce's review in Nature ("The Antiquity of RNA-Based Evolution," Nature 418:214-221, July 11, 2002) or Bada's recent paper in Science (Prebiotic Soup-Revisiting the Miller Experiment," by Jeffrey Bada and Antonio Lazcano, vol 300, pg 745-746, May 2, 2003).
File Date: 06.20.03