Genesis: The Scientific Quest for Life's Origin

by Robert M. Hazen

  p. 158 “polymerization on the rocks”: Orgel (1998b). See also Acevedo and Orgel (1986).

  p. 158 One possible answer: Chen et al. (2004). Subsequent work by Szostak's group reveals that a wide variety of powdered minerals promotes similar vesicle formation.

  p. 159 Gustaf Arrhenius: Arrhenius and co-workers' studies of double-layer hydroxides appear in Arrhenius et al. (1993), Gedulin and Arrhenius (1994), and Pitsch et al. (1995).

  p. 160 Joseph Smith: Smith's mineralogical proposal on “Biochemical evolution” appeared in J. V. Smith (1998), Parsons et al. (1998), and J. V. Smith et al. (1999).

  p. 160 A. G. (Graham) Cairns-Smith: The clay-life hypothesis first appeared in “The structure of the primitive gene and the prospect of generating life” (manuscript dated October 1964). The first publication was Cairns-Smith (1968); see also Cairns-Smith (1977). Important book-length elaborations include Genetic Takeover and the Mineral Origins of Life (Cairns-Smith 1982) and Clay Minerals and the Origin of Life (Cairns-Smith and Hartman 1986). Popular accounts of these ideas include Seven Clues to the Origin of Life (Cairns-Smith 1985a) and a Scientific American article, “Clays and the origin of life” (Cairns-Smith 1985b).

  p. 160 “I believe …”: Cairns-Smith (1985b, p. 900).

  p. 160 “Evolution did not …”: Cairns-Smith (1985a, p. 107).

  p. 161 “The answer”: Cairns-Smith (1985b, pp. 91-92).

  p. 161 “I'm an organic chemist …”: A. G. Cairns-Smith seminar, “Clay Minerals and the Origin of Life,” Carnegie Institution, June 16, 2003.

  p. 162 clay minerals commonly display: Varieties of clay defects are illustrated in Cairns-Smith (1988, 2001).

  p. 162 “In two-dimensional …”: Cairns-Smith (1985b, p. 96).

  p. 163 particularly stable sequences: Cairns-Smith writes: “The word stable sounds like thermodynamically most stable whereas in fact any informational structure has to be at least a little bit unstable. Like any genetic information it would owe its prevalence to indirect effects that favour its own survival and/or propagation—e.g., suppose that a particular defect arrangement catalyses (a little bit) the production of di- or tri-carboxylic acids, which in turn assist clay synthesis by transporting aluminum.” [A. Graham Cairns-Smith to RMH, 31 August 2004]

  p. 164 In 1988: Cairns-Smith (1988).

  p. 164 “The first step …”: Cairns-Smith (1988, p. 244).

  p. 164 “Can the material …”: [A. Graham Cairns-Smith to RMH, 18 December 2003]

  13

  LEFT AND RIGHT

  p. 167 “Assemblage on corresponding …”: Goldschmidt (1952, p. 101).

  p. 167 One of the stages: A vast literature addresses the origin of biological chirality. Comprehensive reviews have been presented by Bonner (1991, 1995).

  p. 169 global excess: Meticulous analyses of amino acids in some meteorites have revealed a small but significant excess of L-amino acids (Cronin and Pizzarello 1983, Engel and Macko 1997, and Pizzarello and Cronin 2000).

  p. 169 Louis Pasteur: Pasteur (1848).

  p. 169 polarized light: Numerous recent articles explore this idea (S. Clark 1999, Podlech 1999, and Bailey et al. 1998).

  p. 169 parity violations: See, for example, Salam (1991).

  pp. 169-170 local, as opposed to global: Some authors claim that an important philosophical distinction exists between deterministic global models of life (i.e., that some intrinsic feature of the universe demands left-handed amino acids) versus a chance local selection of left or right (i.e., life might have formed either way through stochastic processes). Note, however, that of the many symmetry-breaking models proposed, parity violations in beta decay provide the only truly universal chiral influence. Most authors conclude that this effect is so small as to be negligible in any realistic calculations of chiral selection (Bonner 1991, 1995). All other proposed symmetry-breaking mechanisms are local, though at vastly different scales (i.e., Popa 1997). Circularly polarized light from rapidly rotating neutron stars, for example, may selectively break down right-handed amino acids in one substantial volume of galactic space but will have the opposite effect in other volumes. Even if such a scenario led to a preponderance of left-handed amino acids in our region of the galaxy, an equal volume of space would have featured an excess of right-handed molecules.

  p. 170 local environments abounded: Goldschmidt (1952), Lahav (1999), and Hazen (2004).

  p. 171 Albert Eschenmoser: Eschenmoser (1994, 2004) and Bolli et al. (1997).

  p. 173 For most of the twentieth century: For example, Ferris and Ertem (1992, 1993), Arrhenius et al. (1993), Gedulin and Arrhenius (1994), Pitsch et al. (1995), Ferris et al. (1996), Ertem and Ferris (1996, 1997), Hill et al. (1998), Liu and Orgel (1998), J. V. Smith (1998), Parsons et al. (1998), and J.V. Smith et al. (1999). See Chapter 12.

  p. 173 three separate points: See, for example, Davankov (1997).

  p. 173 By the 1930s: Tsuchida et al. (1935) and Karagounis and Coumonlos (1938). More recent work by Bonner et al. (1975) casts doubt on these accounts.

  p. 173 experiments were flawed: For a more extensive discussion see Hazen and Sholl (2003) and Hazen (2004).

  p. 174 Edward Dana's A Textbook: Dana (1958).

  p. 181 Glenn's research: The study of amino acid racemization was pioneered by Ed Hare (Hare and Mitterer 1967, 1969; Hare and Abelson 1968) of the Carnegie Institution's Geophysical Lab (with whom Goodfriend worked for many years) and Jeffrey Bada (Bada et al. 1970, Bada and Schroeder 1972, and Bada 1972) of the Scripps Institution of Oceanography. Hare and Bada developed a bitter rivalry, fueled by disagreements over priority in this research.

  p. 181 But his biggest and boldest: Goodfriend and Gould (1997). See also Goodfriend et al. (2003).

  p. 183 aspartic acid had to be chemically modified: Goodfriend (1991).

  p. 184 We wrote up the results: Hazen et al. (2001). This episode highlights a recurrent problem in science: When does an experiment end (Galison 1987)? We had collected sufficient data, replicated on four crystals, and performed with duplicate runs and analyses, to provide statistically meaningful conclusions. This proof of concept therefore constituted a “publishable unit.”

  p. 185 visit from Steve Gould: Gould's (2002) mammoth book appeared in March 2002 to much notice and grudging admiration. In spite of his cancer, he returned to D.C. in April 2002 for book signings.

  INTERLUDE—WHERE ARE THE WOMEN?

  p. 187 “Where are the women?”: [Sara Seager to RMH, 14 November 2004]

  14

  WHEELS WITHIN WHEELS

  p. 191 “The origin of metabolism …”: Dyson (1985, 1999).

  p. 191 cosmic imperative: de Duve (1995a).

  p. 192 which one came first: The dichotomy between metabolism-first and genetics-first models is discussed by Lahav (1999, p. 189 et seq.) and Wills and Bada (2000, pp. 137-139). For varied viewpoints, see, for example, Dyson (1999), Morowitz (1992), de Duve (1995a), Orgel (1998a), and E. Smith and Morowitz (2004).

  p. 192 Those who favor genetics: E. Smith and Morowitz (2004, p. 21) note: “One of the striking sociological features of biology today is the extraordinary importance placed on the sequencing and interpretation of DNA.”

  p. 193 Self-Replicating Molecules: For a general overview of self-replicating molecules, see E. K. Wilson (1998).

  p. 194 Julius Rebek, Jr.: Much of Rebek's work on self-complementary molecules was performed while he was Camille Dreyfus Professor of Chemistry at MIT. This work is described in Tjivikua et al. (1990); Rebek (1994, 2002); Conn and Rebek (1994); and Wintner et al. (1994).

  p. 194 Reza Ghadiri: Lee et al. (1996). See also Kauffman (1996) and Yao et al. (1997).

  p. 194 Self-complementary strands: Von Kiedrowski (1986). See also Sievers and von Kiedrowski (1994) and Li and Nicolaou (1994).

  p. 196 “It has not escaped …”: Watson and Crick (1953, p. 737).

  p. 196 Stuart Kauffman: Many of Kauffman's ideas are summarized in two books, The Origins of Order (Kauffman 1993) and At Home in the Unive
rse (Kauffman 1995).

  p. 197 “autocatalytic networks”: An important theoretical treatment of the evolution of autocatalytic systems, called “the hypercycle,” has been developed by Manfred Eigen of the Max Planck Institute for Biophysical Chemistry (Eigen 1971; Eigen and Schuster 1977, 1978a, 1978b, 1979). For a useful analysis, see Fry (2000, pp. 100-111).

  p. 197 a certain degree of sloppiness: Darwinian natural selection is predicated on a certain degree of random variation in the characteristics of individuals, which leads to competition and selection. Maynard-Smith and Szathmáry (1999, p. 7) state: “Since, almost inevitably, one cycle would be more efficient in utilizing resources of the environment than the other, one would be ‘naturally selected.'”

  p. 198 “That's for the chemists …”: As quoted by Harold Morowitz to RMH, ca. 2001. This attitude prompted John Maynard-Smith to refer to Kauffman's work as “fact-free science” (Davies 1999, p. 141).

  p. 199 An unbroken chemical history: The principle of continuity—or congruity, as some call it—must apply to any origin-of-life scenario. Each increase in emergent complexity must arise in an unbroken sequence from the chemical processes of previous steps.

  p. 199 The Protenoid World: Fox and Harada (1958), Fox and Dose (1977), and Fox (1956, 1960, 1965, 1968, 1980, 1984, 1988).

  p. 199 “Fox,” Morgan would often remark: As quoted in Dick and Strick (2004, p. 40).

  p. 200 Fox's career thrived: Dick and Strick (2004, pp. 31-43), recount Fox's career and detail NASA's grant support of his work commencing in 1960.

  p. 200 “alive in some …”: Dick and Strick (2004, p. 41).

  p. 200 As early as 1959: S. L. Miller and Urey (1959b). This reply was in response to a letter by Fox (1959).

  p. 201 Protenoid World was influential: For objective analyses of Fox's influence, see Fry (2000, pp. 83-88) and Dick and Strick (2004, pp. 31-43). Fry concludes, “Though major parts of Fox's theory were later challenged by many researchers, his influence at the time was instrumental in turning the problem of the origin of life into a scientific subject.” (p. 88)

  p. 201 nonrandom and deterministic: Following the Miller–Urey experiments, the prevailing attitude favored models of origins by random chemical processes (Wald 1954).

  p. 201 marginalized: Wills and Bada (2000, pp. 52-55) recount the Fox story: “Over time, he became more and more of a maverick in the field. Sadly, at the Eleventh International Conference on the Origin of Life, held in Orleans, France, in 1996, he was reduced to having placards of protenoid microspheres paraded around in the manner of a cartoon sandwich man predicting the Second Coming.” (p. 55)

  p. 201 The Thioester World: Christian de Duve's hypothesis is articulated in a series of books and articles, including an accessible presentation for general readers, Vital Dust: Life as a Cosmic Imperative (de Duve 1995a). See also de Duve (1991, 1995b).

  p. 202 a “volcanic setting”: de Duve (1995b, p. 435).

  p. 202 carbon–sulfur bond: de Duve (1995a, 1995b) notes that the energy of the carbon–sulfur bond in thioesters is comparable to that of the phosphate bond in modern energy-rich molecules such as ATP. De Duve selects thioesters in his model because they are more plausible prebiotic molecules from a geochemical perspective.

  p. 202 steady supply: Some experimental evidence supports the assumption of a steady supply of thioesters. Huber and Wächtershäuser (1997) produced thioesters of acetic acid in experiments that mimicked hydrothermal conditions, while Weber (1995) described the production of amino acid thioesters under similar conditions.

  15

  THE IRON–SULFUR WORLD

  p. 205 “You don't mind …”: Günter Wächtershäuser as quoted in Radetsky (1998, p. 36).

  p. 205 Günter Wächtershäuser's: His theory is detailed in a series of papers, including Wächtershäuser (1988a, 1988b, 1990a, 1990b, 1991, 1992, 1993, 1994, 1997). For a comprehensive overview of Wächtershäuser's chemical ideas, along with those of other advocates of sulfide-driven prebiotic processes, see Cody (2004).

  p. 205 The contrast between heterotrophic and autotrophic: For discussions of the heterotroph-first versus autotroph-first debate, see Lazcano and Miller (1996), Lahav (1999), Wills and Bada (2000), and E. Smith and Morowitz (2004). Note that the autotroph-first position is also, by necessity, deterministic; and it represents a metabolism-first viewpoint.

  A measure of the relative complexity of autotrophs and heterotrophs is provided by the minimum number of genes required for cells to survive. Morowitz et al. (2004) estimate that heterotrophic cells, which obtain all essential molecules from their surroundings, require a minimum of approximately 500 genes. By contrast, modern autotrophic cells require at least 1,500 genes. This sharp contrast in genomic complexity is perhaps the strongest argument in favor of a heterotrophic origin.

  p. 206 irrelevant to the origin of life: Wächtershäuser (1988b, p. 453) states the case: “My theory contrasts sharply with the ingenious prebiotic broth theory of Darwin, Oparin, and Haldane for I deny the preexistence of any arsenal of organic building blocks for life (such as amino acids). Rather, I assume the concentration of dissolved organic constituents in the water phase is negligible.”

  pp. 206-207 precious little evidence: A number of theoretical studies, notably by Everett Shock (then at Washington University in St. Louis), lent support to the idea of hydrothermal organic synthesis in general, if not the Iron–Sulfur World hypothesis in detail (e.g., Shock 1990a, 1990b, 1992a, 1992b, 1993; and Shock et al. 1995). Shock (now a professor at Arizona State University) and his students use thermodynamic models based on the relative energies of chemical products and reactants. They demonstrate that the inherent lack of equilibrium between oxygen-poor hydrothermal fluids and more oxidized seawater can drive metabolism and the formation of carbon–carbon bonds. For example, Shock et al. (1995, p. 141) write, “The amount of energy available was more than enough for organic synthesis from CO2 or CO, and/or polymer formation, indicating that the vicinity of hydrothermal systems at the sea floor was an ideal location for the emergence of the first chemolithoautotrophic metabolic systems.” (A “chemolithoautotroph” is an autotroph that gets its energy from the chemical disequilibrium of minerals.) Our experimental group was greatly influenced by Shock's efforts, and for a time he was a NASA Astrobiology Institute co-investigator with the Carnegie Institution team. By contrast, Wächtershäuser, whose publications are typically characterized by copious references to other work, has rarely cited Shock's papers.

  p. 207 the initial tests: Drobner et al. (1990). A key aspect of this experiment was the exclusion of any oxygen, which might have poisoned the reaction by forming iron oxides. Hence, they describe “the formation of both pyrite and molecular hydrogen under fastidiously anaerobic conditions in the aqueous system of FeS and H2S” (p. 742). See also Blöchl et al. (1992). This group also studied amino acid polymerization (Keller et al. 1994).

  p. 207 Wolgang Heinen and Anne Marie Lauwers: Heinen and Lauwers (1996).

  p. 207 Subsequent experiments: Huber and Wächtershäuser (1997, 1998) and Huber et al. (2003).

  p. 207 Our research group: Cody et al. (2000, 2004). See also the commentary by Wächtershäuser (2000).

  p. 208 The Reverse Citric Acid Cycle: Wächtershäuser (e.g., 1992, pp. 129 et seq.) proposes that the reductive citric acid cycle is the basis for the first autocatalytic cycle. Harold Morowitz has elaborated on this idea (Morowitz et al. 2000, Smith and Morowitz 2004). Others are not persuaded, however. Orgel (1998a, p. 495) notes that in the absence of enzymes, “the chance of closing a cycle of reactions as complicated as the reverse citric acid cycle, for example, is negligible.”

  As one possible counterargument, Harold Morowitz now advocates the role of “small molecule catalysts” such as the amino acid proline, “which can act as a catalyst in aldol condensations. Small molecule catalysis can then act as a self-organizing principle in forming metabolic networks.” [Quoted from an announcement of Morowitz's lecture, “A Principle of Biochemic
al Organization: The Roots of Genetic Code Within the Intermediary Metabolism of Autotrophs,” delivered at the Krasnow Institute for Advanced Study, George Mason University, 13 September 2004]

  p. 208 a simple philosophy: These ideas are detailed in Morowitz (1992), in which he argues that “Metabolism recapitulates biogenesis.”

  p. 208 In the mid-1960s: Evans et al. (1966).

  p. 209 At a recent seminar: Morowitz's seminar entitled “The Feed-Down Principle” was delivered at the Krasnow Institute for Advanced Study, George Mason University, on February 2, 2004. His theme (from the abstract): “Biology appears to be organized in a hierarchical fashion with a biochemical core consisting of the tricarboxylic acid cycle (TCA cycle or reductive TCA cycle) and the reaction network producing all of the key biochemical building blocks.”

  p. 210 modern metabolic enzymes: See, for example, Adams (1992) and Beinert et al. (1997).

  p. 210 formation of pyrite: In Wächtershäuser's Iron–Sulfur World, the mineral pyrite plays a crucial role as the solid surface to which life clings. Under many geochemical conditions, pyrite has a positively charged surface, whereas the essential compounds in the reductive citric acid cycle are negatively charged molecules. The metabolic molecules thus bond strongly to the mineral surface—an essential characteristic of surface life. Otherwise, the metabolites would break free and be lost forever in the dilute ocean.

  In this regard, a word about nomenclature is in order. The molecules that form the citric acid cycle are all acids in their electrically neutral state: acetic acid, pyruvic acid, oxaloacetic acid, and so on. In solution, however, these molecules typically give up a hydrogen atom to become negatively charged molecules called acetate, pyruvate, oxaloacetate, and so on. For this reason the citric acid cycle is sometimes called the citrate cycle.

  p. 211 What do experiments: Cody et al. (2001b).