OOL on the Rocks 02/15/2007
An important survey of the origin-of-life (OOL) field has been published in Scientific American. Robert Shapiro, a senior prize-winning chemist, cancer researcher, emeritus professor and author of books in the field, debunks the Miller experiment, the RNA World and other popular experiments as unrealistic dead ends. Describing the wishful thinking of some researchers, he said, “In a form of molecular vitalism, some scientists have presumed that nature has an innate tendency to produce life’s building blocks preferentially, rather than the hordes of other molecules that can also be derived from the rules of organic chemistry.”
Shapiro had been explaining that millions of organic molecules can form that are not RNA nucleotides. These are not only useless to life, they get in the way and clog up the beneficial reactions. He went on to describe how extrapolation from the Miller Experiment produced an unearned sense of euphoria among researchers: “By extrapolation of these results, some writers have presumed that all of life’s building could be formed with ease in Miller-type experiments and were present in meteorites and other extraterrestrial bodies. This is not the case,” he warned in a section entitled, “The Soup Kettle Is Empty.” He said that no experiment has produced amino acids with more than three carbons (life uses some with six), and no Miller-type experiment has ever produced nucleotides or nucleosides, essential for DNA and RNA.
Shapiro described in some detail the difficult steps that organic chemists employ to synthesize the building blocks of RNA, using conditions highly unrealistic on the primitive earth. “The point was the demonstration that humans could produce, however inefficiently, substances found in nature,” he said. “Unfortunately, neither chemists nor laboratories were present on the early Earth to produce RNA.” Here, for instance, is how scientists had to work to create cytosine, one of the DNA bases:
"I will cite one example of prebiotic synthesis, published in 1995 by Nature and featured in the New York Times. The RNA base cytosine was prepared in high yield by heating two purified chemicals in a sealed glass tube at 100 degrees Celsius for about a day. One of the reagents, cyanoacetaldehyde, is a reactive substance capable of combining with a number of common chemicals that may have been present on the early Earth. These competitors were excluded. An extremely high concentration was needed to coax the other participant, urea, to react at a sufficient rate for the reaction to succeed. The product, cytosine, can self-destruct by simple reaction with water. When the urea concentration was lowered, or the reaction allowed to continue too long, any cytosine that was produced was subsequently destroyed. This destructive reaction had been discovered in my laboratory, as part of my continuing research on environmental damage to DNA. Our own cells deal with it by maintaining a suite of enzymes that specialize in DNA repair."
There seems to be a stark difference between the Real World and the imaginary RNA World. Despite this disconnect, Shapiro describes some of the hype the RNA World scenario generated when Gilbert first suggested it in 1986. “The hypothesis that life began with RNA was presented as a likely reality, rather than a speculation, in journals, textbooks and the media,” he said. He also described the intellectual hoops researchers have envisioned to get the scenario to work: freezing oceans, drying lagoons, dry deserts and other unlikely environments in specific sequences to keep the molecules from destroying themselves. This amounts to attributing wish-fulfillment and goal-directed behavior to inanimate objects, as Shapiro makes clear with this colorful analogy:
"The analogy that comes to mind is that of a golfer, who having played a golf ball through an 18-hole course, then assumed that the ball could also play itself around the course in his absence. He had demonstrated the possibility of the event; it was only necessary to presume that some combination of natural forces (earthquakes, winds, tornadoes and floods, for example) could produce the same result, given enough time. No physical law need be broken for spontaneous RNA formation to happen, but the chances against it are so immense, that the suggestion implies that the non-living world had an innate desire to generate RNA. The majority of origin-of-life scientists who still support the RNA-first theory either accept this concept (implicitly, if not explicitly) or feel that the immensely unfavorable odds were simply overcome by good luck."
Realistically, unfavorable molecules are just as likely to form. These would act like terminators for any hopeful molecules, he says. Shapiro uses another analogy. He pictures a gorilla pounding on a huge keyboard containing not only the English alphabet, but every letter of every language and all the symbol sets in a typical computer. “The chances for the spontaneous assembly of a replicator in the pool I described above can be compared to those of the gorilla composing, in English, a coherent recipe for the preparation of chili con carne.” That’s why Gerald Joyce, Mr. RNA-World himself, and Leslie Orgel, a veteran OOL researcher with Stanley Miller, concluded that the spontaneous appearance of chains of RNA on the early earth “would have been a near miracle.”
Boy, and all this bad news is only halfway through the article. Does he have any good news? Not yet; we must first agree with a ground rule stated by Nobel laureate Christian de Duve, who called for “a rejection of improbabilities so incommensurably high that they can only be called miracles, phenomena that fall outside the scope of scientific inquiry.” That rules out starting with complex molecules like DNA, RNA, and proteins (see online book).
From that principle, Shapiro advocated a return to scenarios with environmental cycles involving simple molecules. These thermodynamic or “metabolism first” scenarios are only popular among about a third of OOL researchers at this time. Notable subscribers include Harold Morowitz, Gunter Wachtershauser, Christian de Duve, Freeman Dyson and Shapiro himself. Their hypotheses, too, have certain requirements that must be met: an energy source, boundaries, ways to couple the energy to the organization, and a chemical network or cycle able to grow and reproduce. (The problems of genetics and heredity are shuffled into the future in these theories.)
How are they doing? “Over the years, many theoretical papers have advanced particular metabolism first schemes, but relatively little experimental work has been presented in support of them,” Shapiro admits. “In those cases where experiments have been published, they have usually served to demonstrate the plausibility of individual steps in a proposed cycle.” In addition, “An understanding of the initial steps leading to life would not reveal the specific events that led to the familiar DNA-RNA-protein-based organisms of today.” Nor would plausible prebiotic cycles prove that’s what happened on the early earth. Success in the metabolism-first experiments would only contribute to hope that prebiotic cycles are plausible in principle, not that they actually happened.
Nevertheless, Shapiro himself needed to return to the miracles he earlier rejected. “Some chance event or circumstance may have led to the connection of nucleotides to form RNA,” he speculates. Where did the nucleotides come from? Didn’t he say their formation was impossibly unlikely? How did they escape rapid destruction by water? Those concerns aside, maybe nucleotides initially served some other purpose and got co-opted, by chance, in the developing network of life. Showing that such thoughts represent little more than a pipe dream, though, he admits: “Many further steps in evolution would be needed to ‘invent’ the elaborate mechanisms for replication and specific protein synthesis that we observe in life today.”
Time for Shapiro’s grand finale. For an article predominantly discouraging and critical, his final paragraph is surprisingly upbeat. Recounting that the highly-implausible big-molecule scenarios imply a lonely universe, he offers hope with the small-molecule alternative. Quoting Stuart Kauffman, “If this is all true, life is vastly more probable than we have supposed. Not only are we at home in the universe, but we are far more likely to share it with unknown companions.”
Update Letters to the editor appeared in Science1 the next day, debating the two leading theories of OOL. The signers included most of the big names: Stanley Miller, Jeffrey Bada, Robert Hazen and others debating Gunter Wachtershauser and Claudia Huber. After sifting through the technical jargon, the reader is left with the strong impression that both camps have essentially falsified each other. On the primordial soup side, the signees picked apart details in a paper by the metabolism-first side. Concentrations of reagants and conditions specified were called “implausible” and “exceedingly improbable.”
Wachtershauser and Huber countered that the “prebiotic soup theory” requires a “protracted, mechanistically obscure self-organization in a cold, primitive ocean,” which they claim is more improbable than the volcanic environment of their own “pioneer organism” theory (metabolism-first). It’s foolish to expect prebiotic soup products to survive in the ocean, of all places, “wherein after some thousand or million years, and under all manner of diverse influences, the magic of self-organization is believed to have somehow generated an unspecified first form of life.” That’s some nasty jabbing between the two leading camps.
--------------------------------------------------------------------------------
1Letters, “Debating Evidence for the Origin of Life on Earth,” Science, 16 February 2007: Vol. 315. no. 5814, pp. 937 - 939, DOI: 10.1126/science.315.5814.937c.
An important survey of the origin-of-life (OOL) field has been published in Scientific American. Robert Shapiro, a senior prize-winning chemist, cancer researcher, emeritus professor and author of books in the field, debunks the Miller experiment, the RNA World and other popular experiments as unrealistic dead ends. Describing the wishful thinking of some researchers, he said, “In a form of molecular vitalism, some scientists have presumed that nature has an innate tendency to produce life’s building blocks preferentially, rather than the hordes of other molecules that can also be derived from the rules of organic chemistry.”
Shapiro had been explaining that millions of organic molecules can form that are not RNA nucleotides. These are not only useless to life, they get in the way and clog up the beneficial reactions. He went on to describe how extrapolation from the Miller Experiment produced an unearned sense of euphoria among researchers: “By extrapolation of these results, some writers have presumed that all of life’s building could be formed with ease in Miller-type experiments and were present in meteorites and other extraterrestrial bodies. This is not the case,” he warned in a section entitled, “The Soup Kettle Is Empty.” He said that no experiment has produced amino acids with more than three carbons (life uses some with six), and no Miller-type experiment has ever produced nucleotides or nucleosides, essential for DNA and RNA.
Shapiro described in some detail the difficult steps that organic chemists employ to synthesize the building blocks of RNA, using conditions highly unrealistic on the primitive earth. “The point was the demonstration that humans could produce, however inefficiently, substances found in nature,” he said. “Unfortunately, neither chemists nor laboratories were present on the early Earth to produce RNA.” Here, for instance, is how scientists had to work to create cytosine, one of the DNA bases:
"I will cite one example of prebiotic synthesis, published in 1995 by Nature and featured in the New York Times. The RNA base cytosine was prepared in high yield by heating two purified chemicals in a sealed glass tube at 100 degrees Celsius for about a day. One of the reagents, cyanoacetaldehyde, is a reactive substance capable of combining with a number of common chemicals that may have been present on the early Earth. These competitors were excluded. An extremely high concentration was needed to coax the other participant, urea, to react at a sufficient rate for the reaction to succeed. The product, cytosine, can self-destruct by simple reaction with water. When the urea concentration was lowered, or the reaction allowed to continue too long, any cytosine that was produced was subsequently destroyed. This destructive reaction had been discovered in my laboratory, as part of my continuing research on environmental damage to DNA. Our own cells deal with it by maintaining a suite of enzymes that specialize in DNA repair."
There seems to be a stark difference between the Real World and the imaginary RNA World. Despite this disconnect, Shapiro describes some of the hype the RNA World scenario generated when Gilbert first suggested it in 1986. “The hypothesis that life began with RNA was presented as a likely reality, rather than a speculation, in journals, textbooks and the media,” he said. He also described the intellectual hoops researchers have envisioned to get the scenario to work: freezing oceans, drying lagoons, dry deserts and other unlikely environments in specific sequences to keep the molecules from destroying themselves. This amounts to attributing wish-fulfillment and goal-directed behavior to inanimate objects, as Shapiro makes clear with this colorful analogy:
"The analogy that comes to mind is that of a golfer, who having played a golf ball through an 18-hole course, then assumed that the ball could also play itself around the course in his absence. He had demonstrated the possibility of the event; it was only necessary to presume that some combination of natural forces (earthquakes, winds, tornadoes and floods, for example) could produce the same result, given enough time. No physical law need be broken for spontaneous RNA formation to happen, but the chances against it are so immense, that the suggestion implies that the non-living world had an innate desire to generate RNA. The majority of origin-of-life scientists who still support the RNA-first theory either accept this concept (implicitly, if not explicitly) or feel that the immensely unfavorable odds were simply overcome by good luck."
Realistically, unfavorable molecules are just as likely to form. These would act like terminators for any hopeful molecules, he says. Shapiro uses another analogy. He pictures a gorilla pounding on a huge keyboard containing not only the English alphabet, but every letter of every language and all the symbol sets in a typical computer. “The chances for the spontaneous assembly of a replicator in the pool I described above can be compared to those of the gorilla composing, in English, a coherent recipe for the preparation of chili con carne.” That’s why Gerald Joyce, Mr. RNA-World himself, and Leslie Orgel, a veteran OOL researcher with Stanley Miller, concluded that the spontaneous appearance of chains of RNA on the early earth “would have been a near miracle.”
Boy, and all this bad news is only halfway through the article. Does he have any good news? Not yet; we must first agree with a ground rule stated by Nobel laureate Christian de Duve, who called for “a rejection of improbabilities so incommensurably high that they can only be called miracles, phenomena that fall outside the scope of scientific inquiry.” That rules out starting with complex molecules like DNA, RNA, and proteins (see online book).
From that principle, Shapiro advocated a return to scenarios with environmental cycles involving simple molecules. These thermodynamic or “metabolism first” scenarios are only popular among about a third of OOL researchers at this time. Notable subscribers include Harold Morowitz, Gunter Wachtershauser, Christian de Duve, Freeman Dyson and Shapiro himself. Their hypotheses, too, have certain requirements that must be met: an energy source, boundaries, ways to couple the energy to the organization, and a chemical network or cycle able to grow and reproduce. (The problems of genetics and heredity are shuffled into the future in these theories.)
How are they doing? “Over the years, many theoretical papers have advanced particular metabolism first schemes, but relatively little experimental work has been presented in support of them,” Shapiro admits. “In those cases where experiments have been published, they have usually served to demonstrate the plausibility of individual steps in a proposed cycle.” In addition, “An understanding of the initial steps leading to life would not reveal the specific events that led to the familiar DNA-RNA-protein-based organisms of today.” Nor would plausible prebiotic cycles prove that’s what happened on the early earth. Success in the metabolism-first experiments would only contribute to hope that prebiotic cycles are plausible in principle, not that they actually happened.
Nevertheless, Shapiro himself needed to return to the miracles he earlier rejected. “Some chance event or circumstance may have led to the connection of nucleotides to form RNA,” he speculates. Where did the nucleotides come from? Didn’t he say their formation was impossibly unlikely? How did they escape rapid destruction by water? Those concerns aside, maybe nucleotides initially served some other purpose and got co-opted, by chance, in the developing network of life. Showing that such thoughts represent little more than a pipe dream, though, he admits: “Many further steps in evolution would be needed to ‘invent’ the elaborate mechanisms for replication and specific protein synthesis that we observe in life today.”
Time for Shapiro’s grand finale. For an article predominantly discouraging and critical, his final paragraph is surprisingly upbeat. Recounting that the highly-implausible big-molecule scenarios imply a lonely universe, he offers hope with the small-molecule alternative. Quoting Stuart Kauffman, “If this is all true, life is vastly more probable than we have supposed. Not only are we at home in the universe, but we are far more likely to share it with unknown companions.”
Update Letters to the editor appeared in Science1 the next day, debating the two leading theories of OOL. The signers included most of the big names: Stanley Miller, Jeffrey Bada, Robert Hazen and others debating Gunter Wachtershauser and Claudia Huber. After sifting through the technical jargon, the reader is left with the strong impression that both camps have essentially falsified each other. On the primordial soup side, the signees picked apart details in a paper by the metabolism-first side. Concentrations of reagants and conditions specified were called “implausible” and “exceedingly improbable.”
Wachtershauser and Huber countered that the “prebiotic soup theory” requires a “protracted, mechanistically obscure self-organization in a cold, primitive ocean,” which they claim is more improbable than the volcanic environment of their own “pioneer organism” theory (metabolism-first). It’s foolish to expect prebiotic soup products to survive in the ocean, of all places, “wherein after some thousand or million years, and under all manner of diverse influences, the magic of self-organization is believed to have somehow generated an unspecified first form of life.” That’s some nasty jabbing between the two leading camps.
--------------------------------------------------------------------------------
1Letters, “Debating Evidence for the Origin of Life on Earth,” Science, 16 February 2007: Vol. 315. no. 5814, pp. 937 - 939, DOI: 10.1126/science.315.5814.937c.