The undreamt-of breakthrough of molecular biology has made the problem of the origin of life a greater riddle than it was before: we have acquired new and deeper problems. — Karl R. Popper, 1974 (.2)
The RNA World
Virtually all biologists now agree that bacterial cells cannot form from nonliving chemicals in one step. If life arises from nonliving chemicals, there must be intermediate forms, "precellular life." Of the various theories of precellular life, the leading contender is the RNA world.
There is a lot to learn about RNA, and research like this is how we learn it. But these and other similar findings, arrived at in highly orchestrated experiments that start with biologically produced RNA, are very far from proving that the RNA world is the pathway between nonlife and life. In nature, far from the sterilized laboratory, uncontaminated RNA strands of any size would be unlikely to form in the first place. "... The direct synthesis of ... nucleotides from prebiotic precursors in reasonable yield and unaccompanied by larger amounts of unrelated molecules could not be achieved by presently known chemical reactions" (5).
At the Salk Institute for Biological Studies, in 1994, Leslie Orgel observes, "Because synthesizing nucleotides and achieving replication of RNA under plausible prebiotic conditions have proved so challenging, chemists are increasingly considering the possibility that RNA was not the first self replicating molecule..." (9).
Apparently NASA has lost enthusiasm for the RNA world as well. In the Final Report issued after the "Astrobiology Workshop" held September 9-11, 1996 at Ames Research Center, California, we read (10),
It has been postulated that there was a time in protobiological evolution when RNA played a dual role as both genetic material and a catalytic molecule ("the RNA world"). However, this appealing concept encounters significant difficulties. RNA is chemically fragile and difficult to synthesize abiotically. The known range of its catalytic activities is rather narrow, and the origin of an RNA synthetic apparatus is unclear.
In spite of the intense level of work on the RNA world in the last decade, there is no consensus theory for precellular life. There are many theories. Here are some of the others —
To go from a bacterium to people is less of a step than to go from a mixture of amino acids to a bacterium. — Lynn Margulis (21.5)
The only premise that all of the precellular theories share is that it would be an extremely long time before the first bacterial cells evolved. If precellular life somehow got going, it could then conceivably begin to crank out, by some precellular process, random strings of nucleotides and amino acids, trying to luck into a gene or a protein with advantages which would lead to bacterial life. There is no evidence in life today of anything that produces huge quantities of new, random strings of nucleotides or amino acids, some of which are advantageous. But if precellular life did that, it would need lots of time to create any useful genes or proteins. How long would it need? After making some helpful assumptions we can get the ratio of actual, useful proteins to all possible random proteins up to something like one in 10^500 (ten to the 500th power). So it would take, barring incredible luck, something like 10^500 trials to probably find one. Imagine that every cubic quarter-inch of ocean in the world contains ten billion precellular ribosomes. Imagine that each ribosome produces proteins at ten trials per minute (about the speed that a working ribosome in a bacterial cell manufactures proteins). Even then, it would take about 10^450 years to probably make one useful protein. But Earth was formed only about 4.6 x 10^9 years ago. The amount of time available for this hypothetical protein creation process was maybe a few hundred million or ~10^8 years. And now, to make a cell, we need not just one protein, but a minimum of several hundred.
So even if we allow precellular life, there is a problem getting from there to proteins, genes and cells. The random production of proteins does not succeed as an explanation. Other intermediate, unspecified stages must be imagined. We could call these stages post-precellular life. By whatever means, life's evolution through these stages would have to be time-consuming.
One advocate of the RNA world, Gerald Joyce, allows 400 million years for "The Rise and Fall of the RNA World" (22):
...At some point RNA organisms began to dabble in the use of short peptides, leading eventually to the development of protein synthesis. Other "experiments" led to the discovery of DNA, which provided a more stable repository for genetic information. By 3.6 to 3.8 billion years ago all of these events had come to pass; the RNA world had fallen and the DNA/protein world had risen in its place.
But other researchers see evidence for prokaryotic cells in the first 100 million years, maybe even immediately. "...Actual cells have been found in the earth's oldest unmetamorphosed sediments...," says Gould in Wonderful Life (23). Bada says that cyanobacteria may have emerged only ten million years after the first precellular life (24). In November, 1996, S. J. Mojzsis of the Scripps institution of Oceanography and others reported isotopic evidence that cellular metabolism was under way before 3.8 billion years ago (25). Even before the research by Mojzsis et al., Francis Crick was worried by the time problem. "...The real fossil record suggests that our present form of protein based life was already in existence 3.6 billion years ago.... This leaves an astonishingly short time to get life started" (26). Another researcher, Yale biochemist Peter B. Moore, says this about the time problem (27):
Of one thing we can be certain: The RNA world—if it ever existed—was short-lived. The earth came into existence about 4.5 x 10^9 years ago, and fossil evidence suggests that cellular organisms resembling modern bacteria existed by 3.6 x 10^9 years before the present.... There are even hints that those early organisms engaged in photosynthesis, which is likely to have been a protein-dependent process then, as now. Thus it appears likely that organisms with sophisticated, protein based metabolisms existed only 0.9 x 10^9 years after the planet's birth.
The "window of opportunity" for the RNA world was much shorter than 0.9 x 10^9 years. The earth's surface was uninhabitable at the beginning due to heat generated by meteoric bombardment and its geological differentiation. ...Thus, the interval in which the biosphere could have been dominated by RNA-based life forms may be less than 100 million years. Incidentally, when one starts thinking along these lines, one must consider the unthinkable, i.e., that the length of time that RNA-based proteins actually bestrode the earth might be zero.
We said that research in the RNA world is a medium-sized industry. This research has demonstrated how exceedingly difficult it would be for living cells to originate by chance from nonliving matter in the time available on Earth. That demonstration is a valuable contribution to science. Additional research will be valuable as well. But to keep insisting that life can spontaneously emerge from nonliving chemicals in the face of the newly comprehended difficulties is puzzling. It is reminiscent of the persistent efforts of medieval alchemists to turn lead into gold.
There is another scientific explanation for the origin of life on Earth. It is that whole cells arrived here from space. (Life "in the first place" is a separate issue, dealt with elsewhere on this website.)
Nitrogen Oxide Concentrations in Natural Waters on Early Earth by Sukrit Ranjan et al., Geochemistry, Geophysics, Geosystems; and commentary by Jennifer Chu, MIT (+Physorg.com), 12 Apr 2019.
If life pops up readily in Earth-like conditions, surely it should have started many times right here on Earth — Paul Davies, 2011
Prebiotic phosphorylation of 2-thiouridine provides either nucleotides or DNA building blocks via photoreduction by Jianfeng Xu et al., Nature Chemistry, 01 Apr 2019.
From molecular to cellular form: modeling the first major transition during the arising of life by Shaolin Yin, Yong Chen et al., doi:10.1186/s12862-019-1412-5, BMC Evolutionary Biology, 03 Apr 2019.
03 Mar 2019: A review of The Demon in the Machine by Paul Davies.
Redox and pH gradients drive amino acid synthesis in iron oxyhydroxide mineral systems by Laura M. Barge et al., doi:10.1073/pnas.1812098116, PNAS, 25 Feb 2019.
...How Surfaces May Have Helped Early Life on Earth Begin, Newswise, 28 Feb 2019.
Hachimoji DNA and RNA: A genetic system with eight building blocks by Shuichi Hoshika and Nicole A. Leal, doi:10.1126/science.aat0971, Science, 22 Feb 2019. We report DNA- and RNA-like systems built from eight nucleotide "letters"... that form four orthogonal pairs. These synthetic systems meet the structural requirements needed to support Darwinian evolution.
Earth First Origins Project Seeks To Replicate the Cradle of Life, Rensselaer Polytechnic Institute, 14 Feb 2019.
A Prebiotic Synthesis of Canonical Pyrimidine and Purine Ribonucleotides by Hyo-Joong Kim and Justin Kim, doi:10.1089/ast.2018.1935, Astrobiology, online 30 Jan 2019.
Prebiotic Oligomer Assembly: What Was the Energy Source? by David Ross and David Deamer, doi:10.1089/ast.2018.1918, Astrobiology, online 01 Feb 2019. "...evaporating pools in which a favorable entropy change is produced when high surface/volume ratios concentrate reactants at the air/water interface in continuous cycles of wetting and drying."
24 Jan 2019: ...the impact of a Mars-sized planet....
13 Jan 2019: If you give me 8-mers, I'll give you life.
Inosine, but none of the 8-oxo-purines, is a plausible component of a primordial version of RNA by Seohyun Chris Kim et al., doi:10.1073/pnas.1814367115, PNAS, 26 Dec 2018.
The Making of Life by Michael L. Wong, The Planetary Society (+PhysOrg by Keith Cooper), 18 Dec 2018.
Abiotic synthesis of amino acids in the recesses of the oceanic lithosphere by Bénédicte Ménez et al.; and commentary: The rocky road to biomolecules by John A. Baross, Nature, 07 Nov 2018.
Inosine, but none of the 8-oxo-purines, is a plausible component of a primordial version of RNA by Seohyun Chris Kim et al., doi:10.1073/pnas.1814367115, PNAS, online 03 Dec 2018.
New Study Reveals Common Table Salt May Have Been Crucial for the Origins of Life, Tokyo Institute of Technology (+Newswise), 29 Nov 2018. Starting from hydrogen cyanide, the one-pot synthesis of cyanamide and precursors to simple sugars in water – using gamma rays in the presence of ammonium and chloride salts – offers a way forward for engineering complex mixtures that can evolve important, potentially prebiological compounds.
From Molecules to Pre-LUCA World with illustrative poster by Ulrich Schreiber and Christian Mayer, presented at the EANA Conference, Berlin, 24-28 Sep 2018.
How biologists are creating life-like cells from scratch by Kendall Powell, Nature, 07 Nov 2018. The minimal cell needs only a few hundred genes to have something that looks sort of alive.
05 Nov 2018: ...an understatement.
Chemists find a recipe that may have jump-started life on Earth by Robert F. Service, Science, 18 Oct 2018.
Ground-breaking lab poised to unlock the mystery of the origins of life on Earth and beyond, McMaster University, 04 Oct 2018.
Nonenzymatic Polymerization into Long Linear RNA Templated by Liquid Crystal Self-Assembly by Marco Todisco et al., doi:10.1021/acsnano.8b05821, ACS Nano, online 03 Oct 2018.
Molybdenum(VI)-Catalyzed Rearrangement of Prebiotic Carbohydrates in Formamide, a Candidate Prebiotic Solvent by Eric W. Ziegler, Hyo-Joong Kim and Steven A. Benner, doi:10.1089/ast.2017.1742, Astrobiology, online 01 Sep 2018.
Who's Who at the Dutch Synthetic Cell Symposium by Suzan Mazur, Oscillations.net, 08 Aug 2018.
A Century-Old Model for Life's Origin Gets Significant Substantiation, Weizmann Institute of Science (+Newswise), 25 Jul 2018. ...lipids can exert enzyme-like catalysis, similar to ribozymes.
NASA Funds Rutgers Scientists' Pursuit of the Origins of Life, Rutgers Today (+Newswise), 09 Jun 2018.
Molecular Evolution in a Peptide-Vesicle System by Christian Mayer et al., doi:10.3390/life8020016, Life, online 24 May 2018.
11 Apr 2018: ...another, hitherto unrecognized environment is proposed as a site for the origin of life on Earth.
Constraining the Time Interval for the Origin of Life on Earth by Ben K.D. Pearce et al., Astrobiology, online 12 Mar 2018.
Horizontal transfer of code fragments between protocells can explain the origins of the genetic code without vertical descent by Tom Froese et al., Nature Scentific Reports, online 23 Feb 2018.
Mineral surface chemistry control for origin of prebiotic peptides by Valentina Erastova, Matteo T. Degiacomi et al., Nature Communications, online 11 Dec 2017.
Linked cycles of oxidative decarboxylation of glyoxylate as protometabolic analogs of the citric acid cycle by Greg Springsteen et al., Nature Communications, online 08 Jan 2018; and commentary: Chemists Discover Plausible Recipe for Early Life on Earth, The Scripps Research Institute (+Newswise), 08 Jan 2018.
Abiotic synthesis of purine and pyrimidine ribonucleosides in aqueous microdroplets by Inho Nam et al., doi:10.1073/pnas.1718559115, PNAS, 02 Jan 2018.
Phosphorylation, oligomerization and self-assembly in water under potential prebiotic conditions by Clémentine Gibard et al., doi:10.1038/nchem.2878, Nature Chemistry, 06 Nov 2017; and commentary: Scientists Find Potential "Missing Link" in Chemistry That Led to Life on Earth, The Scripps Research Institute (+Newswise), 03 Nov 2017.
New Theory Addresses How Life on Earth Arose from the Primordial Muck, UNC Healthcare (+Newswise), 01 Nov 2017.
Life's Late Digital Revolution and Why It Matters for the Study of the Origins of Life (Hypothesis) by David A. Baum and Niles Lehman, doi:10.3390/life7030034, Life, online 25 Aug 2017.
19 Oct 2017: panel discussion, LoC, Mar 2016; and direct link:
The Origins of the RNA World, panel discussion among Walter Gilbert, W. Ford Doolittle, George Fox and Ray Gesteland at the Library of Congress, 17 Mar 2016.
Nitrogen Oxides in Early Earth's Atmosphere as Electron Acceptors for Life's Emergence by Michael L. Wong et al., doi:10.1089/ast.2016.1473, Astrobiology, Oct 2017.
Origin of the RNA world: The fate of nucleobases in warm little ponds by Ben K. D. Pearce et al., doi:10.1073/pnas.1710339114, PNAS, online 02 Oct 2017; and commentary: Evidence suggests life on Earth started after meteorites splashed into warm little ponds, PhysOrg.com, 02 Oct 2017. Podcast by Ralph Pudritz and Ben Pearce.
Surveying the sequence diversity of model prebiotic peptides by mass spectrometry by Jay G. Forsythe et al., doi:10.1073/pnas.1711631114, PNAS, online 28 Aug 2017; and commentary: Was the Primordial Soup a Hearty Pre-Protein Stew?, Georgia Tech via Newswise, 05 Sep 2017.
01 Sep 2017: an interview with Nigel Goldenfeld.
Was the Origin of Life a Fluke? Or Was It Physics? by Ian O'Neill, Live Science, 28 Aug 2017.
Foldamer hypothesis for the growth and sequence differentiation of prebiotic polymers by Elizaveta Guseva et al., doi:10.1073/pnas.1620179114, PNAS, online 22 Aug 2017; and commentary: New Computational Model of Chemical Building Blocks May Help Explain the Origins of Life, Stony Brook University (+Newswise), 23 Aug 2017.
...Could Life Begin in Oil?, Saint Louis University (+Newswise), 16 Aug 2017.
Ribosomes are optimized for autocatalytic production, by Shlomi Reuveni, Måns Ehrenberg and Johan Paulsson, Nature, 20 Jul 2017. Rather than being relics of an evolutionary past, the unusual features of ribosomes may reflect an additional layer of functional optimization that acts on the collective properties of their parts.
Can life begin on Enceladus? A perspective from hydrothermal chemistry, by David Deamer and Bruce Damer, doi:10.1089/ast.2016.1610, Astrobiology, 06 Jul 2017.
Experiments test how easy life itself might be, by Eric Hamilton, Wisconsin Institute for Discovery (+Newswise), 05 Apr 2017.
The Emergence of Life as a First-Order Phase Transition, by Cole Mathis et al., doi:10.1089/ast.2016.1481, Astrobiology, 01 Mar 2017.
Remnants of an Ancient Metabolism without Phosphate, by Joshua E. Goldford et al., Cell, 02 Mar 2017.
26 Feb 2017: ...the common ancestor ...did encode many of the protein domains of all three super-kingdoms.
the origin of life, email to Ted Steele, 17 Feb 2017.
Synchronized chaotic targeting and acceleration of surface chemistry in prebiotic hydrothermal microenvironments, by Aashish Priye et al., doi:10.1073/pnas.1612924114, PNAS, 07 Feb 2017. Our results suggest that chaotic thermal convection may play a previously unappreciated role in mediating surface-catalyzed synthesis in the prebiotic milieu.
Crystal structure of Pistol, a class of self-cleaving ribozyme, by Laura A. Nguyen et al., doi:10.1073/pnas.1611191114, PNAS, 31 Jan 2017.
06 Jan 2017: Either life developed here super-fast or it came full-on as DNA life from afar — Gary Ruvkun, SETG.
09 Dec 2016: The History and Philosophy of Origin Research (Tokyo conference report).
Meteorites and the RNA World: A Thermodynamic Model of Nucleobase Synthesis within Planetesimals, by Ben K. D. Pearce and Ralph E. Pudritz, Astrobiology, online 09 Nov 2016.
01 Nov 2016: ...Then, perhaps within minutes, the first cell came into existence.
A viscous solvent enables information transfer from gene-length nucleic acids in a model prebiotic replication cycle, by Christine He et al., doi:10.1038/nchem.2628, Nature Chemistry, online 10 Oct 2016. ...suggesting that viscosity-mediated replication is possible for a range of genetic polymers, perhaps even for informational polymers that may have preceded RNA.
Autocatalytic, bistable, oscillatory networks of biologically relevant organic reactions, by Sergey N. Semenov et al., doi:10.1038/nature19776, Nature, 29 Sep 2016. By using small organic molecules to build a network of organic reactions with autocatalytic, bistable and oscillatory behaviour, we identify principles that explain the ways in which dynamic networks relevant to life could have developed.
...RNA World Deep Beneath the Surface, by Mary L. Martialay, Rensselaer Polytechnic Institute (+Newswise), 06 Sep 2016.
Amplification of RNA by an RNA polymerase ribozyme by David P. Horning and Gerald F. Joyce, doi:10.1073/pnas.1610103113, PNAS, online 15 Aug 2016; and commentary: TSRI Scientists Take Big Step Toward Recreating Primordial 'RNA World' of Four Billion Years Ago, The Scripps Research Institute, 15 Aug 2016.
Life may have emerged not once, but many times on Earth by Penny Sarchet, New Scientist, 17 Aug 2016.
The physiology and habitat of the last universal common ancestor by Madeline C. Weiss, Filipa L. Sousa et al., doi:10.1038/nmicrobiol.2016.116, Nature Microbiology, 25 Jul 2016.
A violent sun and a sky full of laughing gas could have led to life on Earth, by Sarah Kaplan, Washington Post, 23 May 2016.
Life's origins may result from low-energy electron reactions in space, PhysOrg.com, 13 Jun 2016. ...Low-energy, electron-induced condensed phase reactions may contribute to the interstellar synthesis of prebiotic molecules previously thought to form exclusively via UV photons....
Beyond prebiotic chemistry by Leroy Cronin and Sara Imari Walker, doi:10.1126/science.aaf6310, Science, 03 Jun 2016. Progress in understanding the origin of life may come from studying how simple chemical networks can transform into living networks.
Making RNA in the prebiotic world by Sidney Becker, Ines Thoma et al., doi:10.1126/science.aad28, Science, 13 May 2016. This nucleoside formation pathway can be fused to sugar-forming reactions to produce pentosides, providing a plausible scenario of how purine nucleosides may have formed under prebiotic conditions. Commentary: Building blocks for 'RNA world' made from simple ingredients by Davide Castelvecchi, Nature, 12 May 2016.
Comet Craters - Literal Melting Pots for Life on Earth, Trinity College Dublin (+Newswise), 04 May 2016.
Missing Links Brewed in Primordial Puddles?, Georgia Institute of Technology (+Newswise), 25 Apr 2016. Using two molecules known as barbituric acid and melamine, the researchers formed proto-nucleotides so strongly resembling two of RNA's nucleotides that it is tempting to speculate that they are indeed their ancestors.
Dynamics of prebiotic RNA reproduction illuminated by chemical game theory by Jessica A. M. Yeates et al., doi:10.1073/pnas.1525273113, PNAS, online 18 Apr 2016. ...Three RNA genotypes can stably coexist in a rock-paper-scissors analog.
Ribose and related sugars from ultraviolet irradiation of interstellar ice analogs by Cornelia Meinert et al., doi:10.1126/science.aad8137, v352 Science, 08 Apr 2016.
12 Mar 2016: I don't think anybody feels any more confident about how life got going in the first place than they did 30 years ago. — Sir Patrick Bateson
The Origin of Life in Alkaline Hydrothermal Vents by Victor Sojo et al., doi:10.1089/ast.2015.1406, Astrobiology, online 03 Feb 2016 (see right).
A Strategy for Origins of Life Research, by Caleb Scharf et al., doi:10.1089/ast.2015.1113, Astrobiology, 12 Nov 2015.
20 Oct 2015: Carbon isotopes that may point to life have been found in 4.1 billion-year-old zircon.
Alexei V. Tkachenko and Sergei Maslov, "Spontaneous emergence of autocatalytic information-coding polymers" [article], doi:10.1063/1.4922545, n 045102 v 143, The Journal of Chemical Physics, 2015; and commentary: "New Computer Model Could Explain how Simple Molecules Took First Step Toward Life," Newswise, 28 Jul 2015.
Cleaves H. James II, Meringer Markus, and Goodwin Jay, "227 Views of RNA: Is RNA Unique in Its Chemical Isomer Space?" [abstract], doi:10.1089/ast.2014.1213, Astrobiology, 7 Jul 2015.
Jay G. Forsythe et al., "Ester-Mediated Amide Bond Formation Driven by Wet- Dry Cycles: A Possible Path to Polypeptides on the Prebiotic Earth" [abstract], doi:10.1002/anie.201503792, Angewandte Chemie, 15 Jul 2015; and commentary:
Did a puddle in flux spark life on Earth?, Georgia Institute of Technology (+Newswise), 20 Jul 2015.
John A. Baross and William F. Martin, "The Ribofilm as a Concept for Life's Origins" [abstract], doi:10.1016/j.cell.2015.06.038, p 13-15 v 162, Cell, 2 Jul 2015.
Why 'RNA world' theory on origin of life may be wrong after all by Bob Holmes, New Scientist, 24 Jun 2015.
23 Jun 2015: The Origin of Life Circus, by Suzan Mazur.
Scientists find new evidence of key ingredient during dawn of life, University of North Carolina (+SpaceDaily), 18 Jun 2015; and earlier: New evidence emerges on the origins of life on Earth, University of North Carolina (+Newswise), 1 Jun 2015."Their findings... fly in the face of the problematic 'RNA world' theory...."
Wim Hordijk, "The Living Set", The Scientist, 1 Jun 2015. "Mathematical and computational approaches are making strides in understanding how life might have emerged and organized itself from the basic chemistry of early Earth."
Martin Ferus et al., "Meteorite-catalyzed synthesis of nucleosides and other prebiotic compounds" [abstract], doi:10.1073/pnas.1507471112, Proc. Natl. Acad. Sci. USA, online 28 May 2015.
Life's Elusive X-Factor?... by Suzan Mazur, Huffington Post, 22 May 2015. "...Nothing much has happened since Miller-Urey yet scientists keep pursuing the same lines of investigation," says biochemist Pier Luigi Luisi.
Remembering Origin of Life Trailblazer Harry Lonsdale by Suzan Mazur, Huffington Post, 5 Jan 2015. He died 11 Nov 2014.
Dorian S. N. Parker et al., "Gas Phase Synthesis of (Iso)Quinoline and its Role in the Formation of Nucleobases in the Interstellar Medium" [abstract], doi:10.1088/0004-637X/803/2/53, The Astrophysical Journal, 1 May 2015; and commentary: A Hot Start to the Origin of Life? by Kate Greene, Berkeley Lab (+PhysOrg.com), 5 May 2015.
A. Roldan et al., "Bio-inspired CO2 conversion by iron sulfide catalysts under sustainable conditions" [Open Access abstract], doi:10.1039/C5CC02078F, Chem. Commun., online 24 Mar 2015; and commentary: Hydrothermal Vents Able to Create Simple Organic Molecules, Sci-News.com, 29 Apr 2015.
Christian Mayer, Ulrich Schreiber and María J. Dávila, "Periodic Vesicle Formation in Tectonic Fault Zones—an Ideal Scenario for Molecular Evolution" [abstract], doi:10.1007/s11084-015-9411-z, Origins of Life and Evolution of Biospheres, online 27 Feb 2015. By email, Ulrich writes, "We can show the development of vesicles, peptides (and next nucleotides) under conditions of the upper continental crust (open systems in tectonic fault zones) in super critical CO2. We detected the first organic chemistry in quartz minerals of tectonic fault zones in Archean quartz dykes of Western Australia."
Nitrogen Oxide Concentrations in Natural Waters on Early Earth by Sukrit Ranjan et al., Geochemistry, Geophysics, Geosystems; and commentary by Jennifer Chu, MIT (+Physorg.com), 12 Apr 2019.
|The Origin of Handheld Calculators: A spoof on origin-of-life theories in terms of the computer analogy (see A Cell is Like a Computer): |
The fossil record indicates that there were handheld calculators with at least 240 kilobytes of stored programs in existence almost as soon as the earth cooled. Possibly, handheld calculators originated when special conditions allowed the formation of silicon chips and circuit boards (primitive genes). Heat, perhaps generated by radioactivity, volcanoes or meteor impacts, melted some sand to form a silicon flake. Random splashing of molten metal caused metal filaments to form a circuit board on the flake. Oily film on ponds dried into the hard plastic material needed for the shell.
Lightning provided the first source of electrical power. Prototypes in seawater, at just the right distance from the strike, received sufficient voltage without being destroyed. Batteries (allowing independent metabolism) came later. The first batteries were iron acid batteries, formed in mud pockets. Lithium batteries were a very late development.
This primitive protocalculator somehow acquired ten to 25 bytes of stored programs (40 to 100 nucleotides) that enabled it to have some function that made it useful. Now we find evidence for only the fully evolved handheld calculators similar to the ones used today, with function keys and lengthy installed programs, because the fossil record is incomplete.