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03-08-2016 3:23 AM
“In so far as a scientific statement speaks about reality, it must be falsifiable; and in so far as it is not falsifiable, it does not speak about reality,” wrote Karl Popper in The Logic of Scientific Discovery. Although Popper's notion of falsifiability as the linchpin of a scientific enterprise has been critiqued from inductivist schools of thought (see, for example, Grünbaum, 1976), it has been widely lauded as one of the most significant criteria required of scientific hypotheses (see, e.g., Ruse, 1982). Writes Michael Ruse:
“...a theory must be open to possible refutation. If the facts speak against a theory, then it must go. A body of science must be falsifiable. For example, Kepler's laws could have been false: if a planet were discovered going in squares, then the laws would have been shown to be incorrect.”
So we can see that falsifiability as a criterion for truly scientific hypotheses has become well-established within the scientific community, the objections from certain philosophical schools of thought notwithstanding. Indeed, this criterion has been used extensively in the debate over whether intelligent design qualifies as a scientific concept. Though the fires of that debate have now been reduced to barely visible embers – the Intelligent Design Movement has very starkly failed in its attempt to refute the Neo-Darwinian evolutionary synthesis and gain significant traction within the scientific community - the origin of the biochemical complexity which characterizes biological life remains a deeply difficult puzzle to put together.
In the essay that follows, I argue that present abiogenesis models for the origin of biological life on Earth are largely – if not wholly – unfalsifiable, and therefore should not be given the kind of gravitas accorded to legitimate scientific hypotheses. Furthermore, I propose that panspermia – a necessary model for any engineering-based scenarios for the origin of life – is in fact falsifiable and should thus be researched in greater depth than it has been.
However, before I elaborate on the above topic, I will present a brief overview of present origin of life models, providing the necessary backdrop to assess whether models of abiogenesis are properly falsifiable.
The RNA World
The RNA world hypothesis postulates that self-replicating RNA molecules preceded DNA- and protein-based cellular life (Orgel, 2003). Under this model, RNA was the carrier of biological information before the origin of DNA genomes, as well as the catalyst of chemical reactions in the first rudimentary life forms. Thus, in the RNA world, neither DNA nor proteins were necessary for the initiation of Darwinian evolutionary processes.
The ability of polynucleotides to base pair means that replication is relatively straightforward. One polynucleotide string acts as a template from which another is constructed. However, in the absence of a catalyst, such a mechanism of replication is inefficient (Alberts et al., 2002). Thus, in modern cells, the synthesis of nucleic acid polymers is driven by protein enzymes known as polymerases. Efficient self-replication in the RNA world is thought to have resulted from RNA functioning as a catalyst (Pace and Marsh, 1985). The discovery of enzymatic RNA molecules (see, e.g., Kruger et al., 1982), termed ribozymes, added plausibility to the RNA world hypothesis. Many naturally occurring ribozymes have been described, including the peptidyl transferase of the ribosome (Polacek and Mankin, 2005), ribonuclease P (Guerrier-Takada et al., 1983), and the hammerhead (Forster, 1987) and hairpin ribozymes (Fedor, 2000). Artificial ribozymes have also been created through in vitro selection methods. Significantly, Lincoln and Joyce (2009) have been able to construct ribozymes capable of self-sustained replication, despite the lack of proteins. Other studies have reinforced the plausibility of the RNA world. Although RNA is a very complex molecule, Powner and colleagues synthesized pyrimidine ribonucleotides using hypothesized prebiotic molecules (Powner et al., 2009).
Nonetheless, the RNA world hypothesis has been critiqued in numerous scientific papers, and has been described as "a prebiotic chemist's nightmare" (Benner et al., 2012) and “the worst theory of the early evolution of life (except for all the others)” (Bernhardt, 2012). Bernhardt (2012) succinctly outlined many of the problems with the RNA world hypothesis, while offering some possible responses. One of the difficulties with the RNA world hypothesis is the inherent instability of the RNA molecule, which could have prevented the accumulation of RNA molecules in the prebiotic environment (Bernhardt, 2012). Furthermore, the plausibility of prebiotic RNA synthesis has been questioned, and Benner et al. (2012) criticized aspects of the work of Powner et al., 2009. Other dilemmas remain. It is thought by some researchers that only long RNA sequences are capable of catalytic activity (Bernhardt, 2012); one of the most efficient ribozymes created to date is approximately 190 bases long (Bernhardt, 2012). It is difficult to envision how a ribozyme of that length could arise by stochastic assembly. Shorter catalytic RNAs are not unknown, however. Small self-cleaving RNAs can be 50 nucleotides in length, and a study by Vlassov et al. (2005) explored ribozymes with even shorter lengths. A ribozyme that is just 5 nucleotides long has also been isolated in vitro (Turk, 2010).
Further objections to the RNA world hypothesis will be briefly summarized. The metabolic needs of the RNA world may have been greater than the catalytic repertoire of RNA (Bernhardt, 2012); it has been argued that the RNA world makes no reference to a possible energy source (Kurland, 2010); and there is phylogenetic evidence that ribosomal proteins and rRNA co-evolved (Harish and Caetano-Anollés, 2012), with neither component originating first.
On Falsifying the RNA World
Finally, we come to the issue of falsifiability or refutability. In the words of Eugene Koonin (in a review of Bernhardt, 2012), “[t]he RNA World scenario is bad as a scientific hypothesis: it is hardly falsifiable and is extremely difficult to verify due to a great number of holes in the most important parts.”
Indeed, one will find it a rather perplexing task to imagine an experiment that would falsify the RNA world scenario. It should be noted that the RNA world hypothesis attempts to provide an answer to a historical question; namely, how life on Earth arose. As such, no amount of evidence for the plausibility of the RNA world hypothesis will be able to establish the historical accuracy of that hypothesis. Yet much (if not most) of the evidence for the RNA world hypothesis merely strengthens its plausibility. For example, observations which demonstrate that RNA can catalyze its own replication say nothing about whether self-replicating RNA was indeed historically the precursor to modern cellular life.
I will finish this section with the following question for the reader to ponder: what experiment, if any, would falsify the RNA world scenario? If no experiment – or series of experiments – could reasonably falsify the RNA world model, then any notions as to its validity as a scientific hypothesis must be heavily scrutinized.
Metabolism first models propose that autocatalytic metabolism arose prior to self-replicating nucleic acids. The metabolism of virtually all modern life forms is based around the tricarboxylic (TCA) cycle, and it has been asserted that a reverse TCA cycle could result in an overall autocatalytic reaction (Morowitz et al., 2010). Under such a scenario, autocatalytic reactions form the basis of self-replicating systems from which Darwinian evolution could proceed. The reaction system could be improved by the addition of a protein enzyme.
In a landmark publication, Günter Wächtershäuser (1988) suggested that the first life forms – named “pioneer organisms” – evolved in hydrothermal vents under high temperatures. These primal organisms possessed catalytic transition metal centers which were involved in the catalysis of carbon fixation pathways. This allowed the production of small organic molecules. Under this model, a primitive metabolism was thereby manifested early in the evolution of life.
Compartmentalization of the metabolic systems would result in the first cells. Gradual evolution of these cells (e.g., the evolution of nucleic acid replication) would then follow, ultimately producing the last universal common ancestor from which modern life diversified.
The crucial difference between metabolism first and the RNA world hypothesis is that in the former model protein enzymes arise before the appearance of nucleic acid replicators. Several observations have been cited as support for the metabolism first hypothesis. The core metabolic reactions of prokaryotic autotrophs are quite similar to the chemistry of H(2)-CO(2) redox couples that is harbored by hydrothermal vents, suggestive of Wächtershäuser’s (1988) model. Further, the possibility of a reverse TCA cycle has been established by Buchanan and Arnon (1990).
Yet there is a large body of data that casts doubt on the validity of the metabolism first models. Pross (2004) argues that “there is no substantive evidence for a 'metabolism first' mechanism for life's emergence.” Moreover, there is a lack of evolvability in autocatalytic metabolic networks (Vasas et al., 2010), and Orgel (2008) pointed out that the occurrence of metabolic cycles on the prebiotic earth is implausible.
On Falsifying Metabolism First
Like the RNA world scenario, it becomes a challenging ordeal to imagine what kind of experiment would refute the metabolism first model. And if no amount of experiments can falsify such a model, should it really be treated as a strictly scientific hypothesis? While exhaustive work has been conducted on assessing the plausibility of metabolism first, little has been done to root this model in the reality of biological history.
The Panspermia Model
Terrestrial life may not have originated on Earth, but could have instead originated elsewhere in the universe before being transported to Earth from outer space. Although this concept, known as “panspermia,” does not enjoy widespread support from the scientific community, a number of publications have viewed it favorably. The panspermia hypothesis is attractive because life would have more time to originate than if life evolved on Earth. Over the years, most of the major difficulties with panspermia have been refuted (Rampelotto, 2010), and tentative evidence in favor of panspermia has grown. For instance, there is some geologic evidence that genes encoding Aib-polypeptides were one of the driving forces behind species extinctions during the K/T transition, and that these genes were from cosmic pathogens that infected the earth’s biosphere (Wallis, 2003).
Mechanisms for the interstellar transport of microbial organisms have been extensively discussed. For instance, microcosms consisting of meteorite interiors provide an effective medium for panspermia (Mautner, 2002). A variety of material is now known to move naturally throughout the solar system and it is accepted that rock fragments can be ejected from and exchanged among planetary surfaces (Melosh, 2003), so there is no fatal difficulty with the transport of microbial cells from one planet to another.
Unlike the RNA world and metabolism first hypotheses, panspermia does not address the initial origin of biological life; instead, it merely explains where terrestrial life may have come from. While panspermia does give more time and chemical resources for life to evolve, it fails to furnish a mechanism for the origin of the biochemical complexity that is at the heart of life.
However, I argue that although panspermia only addresses how life emerged on Earth, it is in fact a properly falsifiable scientific hypothesis.
On Falsifiability and Panspermia
Natural – that is non-directed – panspermia is inherently falsifiable. Most plausible panspermia scenarios involve lithopanspermia, wherein highly resilient biological cells are housed in meteorites which splash down on planetary surfaces. These meteorites provide protection from the enormous amount of heat generated during ejection from a planet and subsequent landing on another planet. They also protect against the vacuum of space, which would otherwise desiccate any microbes wafting through the vastness of space. They do not, however, offer complete protection against radiation (which largely consists of high-energy protons). Thus, any microbes transported through space to another planet via meteorites must have molecular machinery which protect them from radiation.
Both hyperthermophile Archaea and bacteria like Deinococcus radiodurans and B. subtilis have high radiation resistance. There are several molecular mechanisms behind the extraordinary radiation resistance of microbes like D. radiodurans (see Krisko and Radman, 2013):
(1) Redundant antioxidant pathways and an abundance of metabolites leads to low production of reactive oxygen species, resulting in a radio-protective effect.
(2) A high degree of proteolytic efficiency means that microbes can quickly rebuild their proteins during recovery from exposure to ionizing radiation.
(3) With as many as 90 ABC transporters utilized for peptide and amino acid uptake, D. radiodurans can – again – quickly rebuild protein components after exposure to radiation.
In short, D. radiodurans (as well as other radiation-resistant microbes) house a relatively large number of genes which code for catabolic enzymes and unique molecular pathways; these enzymes are responsible for protection against radiation by virtue of their production of small antioxidant molecules.
What does all this mean? It means that for panspermia to take place, microbes must be more than mere cell membranes with a sprinkling of protein parts. No – they must be relatively complex organisms with sufficient molecular machinery (and therefore genes) to protect against radiation. When this is taken into consideration, it is plain to see that panspermia becomes remarkably easy to falsify:
If it could be demonstrated that the last universal common ancestor (LUCA) was a population of very simple cells that did not have the necessary protein parts to survive extensive radiation, then non-directed panspermia will have been effectively falsified.
That this is a viable approach to falsifying panspermia has been borne out in the scientific literature; for example, the panspermia scheme has been criticized by Di Giulio (2010), who argued that life has passed through progenotic stages (that is, stages where life was not able to survive transport through space) and that this was evidence against panspermia. Di Giulio (2010) noted that the existence of split tRNA genes in Nanoarchaeum equitans suggests that tRNA molecules evolved through the assembly of two hairpin structures and that these split genes are ancient, indicative of a progenotic LUCA. An initial phylogenetic study of N. equitans concluded that N. equitans is a basal archaeal lineage – representing a novel archaeal kingdom, termed Nanoarchaeota (Waters et al., 2003). The tRNA split genes in N. equitans could therefore have been ancestral and ancient. If this were the case, it would be strong molecular evidence against the panspermia hypothesis. However, a subsequent and more thorough phylogenetic analysis found that N. equitans nests within the archaeal phylum Euryarchaeota, and is probably related to Thermococcales (Brochier et al., 2005). Thus, the current phylogenetic evidence indicates that N. equitans is not a basal archaeal lineage, and consequently the thesis that the tRNA split genes in N. equitans are ancient is of dubious merit. Based on the phylogenetic positioning of N. equitans in the archaeal tree of life, it is logical to conclude that the tRNA split genes in N. equitans are a relatively recent innovation (and evidence from tRNA gene introns support this), and not the relics of a progenote world.
Another possibility for the refutation of the panspermia hypothesis emerged with T. Cavalier-Smith's 2006 paper, “Rooting the tree of life by transition analyses” (Cavalier-Smith, 2006). In this paper, Cavalier-Smith used the classical transition analysis approach employed in paleontology and applied it to molecular systems in an attempt to root the tree of life. Transition analyses, in principle, are able to root phylogenies in this way: by finding characters that could only have evolved in one direction (for instance, reptile legs evolving into wings is far more plausible than the reverse for mechanistic reasons), these characters polarize the phylogeny under consideration.
Based on a number of such character polarizations among prokaryotes, Cavalier-Smith concluded that the LUCA “was more primitive than other eubacteria in probably lacking lipopolysaccharide, hopanoids, cytochrome b, catalase, the HslV ring protease homologue of proteasomes, spores, the machinery based on outer membrane (OM) protein Omp85 used by more advanced negibacteria to insert outer membrane proteins, type I, type II, and type III secretion mechanisms, and TonB-energized OM import systems.”
In other words, if these transition analyses are correct, then the LUCA would have lacked a good deal of molecular machinery. Of particular importance it would have lacked efficient proteases like the HslV ring, and efficient proteases are needed by radiation-resistance microbes. Although Cavalier-Smith did not set out to refute the notion of panspermia, this study had the potential to do so.
However, his tree polarizations based on molecular transition analyses are refuted by rigorous molecular phylogenies. For example, he argued – based on transition analyses – that the TonB system first emerged in gram-negative bacteria, when later phylogenetic work by Marmon (2013), using maximum-likelihood methods combined with statistical analysis of GC-content of various bacteria phyla, indicated that the TonB system first arose in a gram-positive phylum – upending Cavalier-Smith's transition analysis.
After a brief survey of current origin of life models, I have argued the following:
(1) Both the RNA world and metabolism first scenarios for the origin of life are largely unfalsifiable, arguably moving them beyond the purview of proper scientific hypotheses. Most work on these models consists of establishing their plausibility, rather than their historical actuality.
(2) The panspermia hypothesis is falsifiable based on the fundamental requirement that microbes traveling through space be resistant to galactic cosmic rays. This requirement, in turn, necessitates the presence of particular protein parts that the LUCA would not have required had it emerged on Earth.
(3) At present, the panspermia hypothesis has yet to be effectively falsified – and attempts to do so do not have merit when seen under the light of more recent advances in molecular phylogenetics.
A word of caution: the reader may be inclined to believe that I am dismissing the value of abiogenesis models outright. Far from it! I am, instead, adding a critical voice to the current methodological bent of most origin of life studies with the hopes that future research will ground such studies in historical reality rather than mere plausibility. Furthermore, if panspermia is a more proper scientific hypothesis than the RNA world or metabolism first scenario, as I have argued here, then it makes sense that the panspermia model should be investigated with more depth.
Addendum: See Message 107.
Popper, K., 1959. The Logic of Scientific Discovery, p. 316.
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Waters, E., et al., 2003. The genome of Nanoarchaeum equitans: insights into early archaeal evolution and derived parasitism. Proc Natl Acad Sci.
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Marmon, L., 2013. Elucidating the origin of the ExbBD components of the TonB system through Bayesian inference and maximum-likelihood phylogenies. Molecular Phylogenetics and Evolution.
Edited by Genomicus, : No reason given.