Granted that, as de Duve says, we are compelled by our calling to insist at all times on strictly naturalistic explanations; life must, therefore, have emerged from chemistry. Granted also that simple organic molecules were present at the beginning, in uncertain locations, diversity and abundance. Leave room for contingency, some rare chemical fluctuation that may have played a seminal role in the inception of living systems; and remember that you may be mistaken. With all that, I still cannot bring myself to believe that rudimentary organisms of any kind came about by the association of prefabricated organic molecules, born of purely chemical processes in their environment. Did life begin as a molecular collage? To my taste, that idea smacks of the reconstitution of life as we know it rather than its genesis ab initio. It overestimates what Harold Morowitz called the munificence of nature, her generosity in providing building blocks for free. It makes cellular organization an afterthought to molecular structure, and offers no foothold to autopoiesis. And it largely omits what I believe to be the ultimate wellspring of life, the thermodynamic drive of energy dissipation, creating mounting levels of structural order for natural selection to winnow. If it is true that life resides in organization rather than in substance, than what is left out of account is the heart of the mystery: the origin of biological order. (Harold 2001: 250)

(….) It would be agreeable to conclude this book with a cheery fanfare about science closing in, slowly but surely, on the ultimate mystery; but the time for rosy rhetoric is not yet at hand. The origin of life appears to me as incomprehensible as ever, a matter for wonder but not for explication. Even the principles of biopoiesis still elude us, for reasons that are as much conceptual as technical. The physical sciences have been exceedingly successful in formulating universal laws on the basis of reproducible experiments, accurate measurements, and theories explicitly designed to be falsifiable. These commendable practices cannot be fully extrapolated to any historical subject, in which general laws constrain what is possible but do not determine the outcome. Here knowledge must be drawn from observation of what actually happened, and seldom can theory be directly confronted with reality. The origin of life is where these two ways of knowing collide. The approach from hard science starts with the supposition that physical laws exercise strong constraints on what was historically possible; therefore, even though one can never exclude the intervention of some unlikely but crucial happenstance, one should be able to arrive at a plausible account of how it could have happened. This, however, is not how matters have turned out. The range of permissible options is to broad, the constraints so loose, that few scenarios can be firmly rejected; and when neither theory nor experiment set effective boundaries, hard science is stymied. The tools of “soft,” historical science unfortunately offer no recourse: the trail is too cold, the traces too faint. (Harold 2001: 251-252)

The tell a story of Max Delbrück, one of the pioneers of molecular genetics and the ironic inventor of DNA, whom I was privileged to meet during his later years at the California Institute of Technology. He had stopped reading papers on the origin of life, Max once observed; he would wait for someone to produce a recipe for the fabrication of life. So are we all waiting, not necessarily for a recipe but for new techniques of apprehending the utterly remote past. Without such a breakthrough, we can continue to reason, speculate and argue, but we cannot know. Unless we acquire novel and powerful methods of historical inquiry, science will effectively have reached a limit. (Harold 2001: 252)

— Franklin M. Harold (2001) The Way of the Cell: Molecules, Organisms and the Order of Life. Oxford University Press.

[T]he origin of life is not what Darwin’s mechanism for evolutionary biology is about, as he himself wrote in the Origin of Species. Complaining that Darwinian evolution can’t explain life’s origin is like complaining that your Mercedes can’t fly. It wasn’t supposed to do that in the first place…. In the case of Darwin’s theory of evolutionary biology, this is providing a causal mechanism by which organisms like newts, monkeys, tuna, spiders, and ostriches attained their current diversity…. [I]t is very important to realize that studies of abiogenesis comprise a distinct field of science, one that does not draw on the same mechanisms relevant to Darwinian evolutionary biology. (Asher 2012: 184)

— Robert J. Asher (2012) Evolution and Belief: Confessions of a Religious Paleontologist. Cambridge University Press.

Conceptualizing Cells

We should all take seriously an assessment of biology made by the physicist David Bohm over 30 years ago (and universally ignored):

“It does seem odd … that just when physics is … moving away from mechanism, biology and psychology are moving closer to it. If the trend continues … scientists will be regarding living and intelligent beings as mechanical, while they suppose that inanimate matter is to complex and subtle to fit into the limited categories of mechanism.” [D. Bohm, “Some Remarks on the Notion of Order,” in C. H. Waddington, ed., Towards a Theoretical Biology: 2 Sketches. (Edinburgh: Edinburgh Press 1969), p. 18-40.]

The organism is not a machine! Machines are not made of parts that continually turn over and renew; the cell is. A machine is stable because its parts are strongly built and function reliably. The cell is stable for an entirely different reason: It is homeostatic. Perturbed, the cell automatically seeks to reconstitute its inherent pattern. Homeostasis and homeorhesis are basic to all living things, but not machines.

If not a machine, then what is the cell?

— Woese, Carl R. (2005) Evolving Biological Organization. In Microbial Phylogeny and Evolution: Concepts and Controversies (Jan Sapp, ed.). Oxford: Oxford University Press, p. 100.

The science of biology enters the twenty-first century in turmoil, in a state of conceptual disarray, although at first glance this is far from apparent. When has biology ever been in a more powerful position to study living systems? The sequencing juggernaut has still to reach full steam, and it is constantly spewing forth all manner of powerful new approaches to biological systems, many of which were previously unimaginable: a revolutionized medicine that reaches beyond diagnosis and cure of disease into defining states of the organism in general; revolutionary agricultural technology built on genomic understanding and manipulation of animals and plants; the age-old foundation of biology, taxonomy, made rock solid, greatly extended, and become far more useful in its new genomic setting; a microbial ecology that is finally able to contribute to our understanding of the biosphere; and the list goes on. (Woese 2005: 99)

All this is an expression of the power inherent in the methodology of molecular biology, especially the sequencing of genomes. Methodology is one thing, however, and understanding and direction another. The fact is that the understanding of biology emerging from the mass of data that flows from the genome sequencing machines brings into question the classical concepts of organism, lineage, and evolution as the same time it gainsays the molecular perspective that spawned the enterprise. The fact is that the molecular perspective, which so successfully guided and shaped twentieth-century biology, has effectively run its course (as all paradigms do) and no longer provides a focus, a vision of the biology of the future, with the result that biology is wandering will-nilly into that future. This is a prescription for revolution—conceptual revolution. One can be confident that the new paradigm will soon emerge to guide biology in this new century…. Molecular biology has ceased to be a genuine paradigm, and it is now only a body of (very powerful) technique…. The time has come to shift biology’s focus from trying to understand organisms solely by dissecting them into their parts to trying to understand the fundamental nature of biological organization, of biological form. (Woese 2005: 99-100)

(….) When one has worked one’s entire career within the framework of a powerful paradigm, it is almost impossible to look at that paradigm as anything but the proper, if not the only possible, perspective one can have on (in this case) biology. Yet despite its great accomplishments, molecular biology is far from the “perfect paradigm” most biologists take it to be. This child of reductionist materialism has nearly driven the biology out of biology. Molecular biology’s reductionism is fundamentalist, unwavering, and procrustean. It strips the organism from its environment, shears it of its history (evolution), and shreds it into parts. A sense of the whole, of the whole cell, of the whole multicellular organism, of the biosphere, of the emergent quality of biological organization, all have been lost or sidelined. (Woese 2005: 101)

Our thinking is fettered by classical evolutionary notions as well. The deepest and most subtle of these is the concept of variation and selection. How we view the evolution of cellular design or organization is heavily colored by how we view variation and selection. From Darwin’s day onward, evolutionists have debated the nature of the concept, and particularly whether evolutionary change is gradual, salutatory, or of some other nature. However, another aspect of the concept concerns us here more. In the terms I prefer, it is the nature of the phase (or propensity) space in which evolution operates. Looked at one way, variation and selection are all there is to evolution: The evolutionary phase space is wide open, and all manner of things are possible. From this “anything goes” perspective, a given biological form (pattern) has no meaning outside of itself, and the route by which it arises is one out of an enormous number of possible paths, which makes the evolution completely idiosyncratic and, thus, uninteresting (molecular biology holds this position: the molecular biologist sees evolution as merely a series of meaningless historical accidents). (Woese 2005: 101)

The alternative viewpoint is that the evolutionary propensity space is highly constrained, being more like a mountainous terrain than a wide open prairie: Only certain paths are possible, and they lead to particular (a relatively small set of) outcomes. Generic biological form preexists in the same sense that form in the inanimate world does. It is not the case that “anything goes” in the world of biological evolution. In other words, biological form (pattern) is important: It has meaning beyond itself; a deeper, more general significance. Understanding of biology lies, then, in understanding the evolution and nature of biological form (pattern). Explaining biological form by variation and selection hand-waving argumentation is far from sufficient: The motor does not explain where the car goes. (Woese 2005: 101-102)

(….) Evolutionary limitations imposed by a primitive translation mechanism. One cannot look at the cellular translation apparatus without being overwhelmed by its complexity, by the number of parts and their possible interactions. It is even more daunting to contemplate the evolution of such a mechanism. In a very real sense the evolution of translation is the evolution of the cell: Translation is the heart of the evolving cell design. Cellular evolution requires entire suites of novel proteins never before seen on Earth, and it is the performance characteristics of the primitive apparatus that determine what general types of proteins can and cannot evolve. (Woese 2005: 107)

A translation apparatus today must do two main things: accurately match codons with corresponding amino acids across an entire message RNA (perhaps thousands of nucleotides in length) and maintain the correct reading frame throughout the process. It seems impossible that a simple primitive translation mechanism could perform with the requisite precision to accurately produce a large (modern) protein. (The point here is not only common sense but can be inferred from the fact that the structure of the genetic code appears to have been optimized to reduce the phenotypic consequences of codon recognition error.) Primitive cells, then, would comprise only small proteins, which, of course, has broad implications as to the nature of the evolving cells. In almost cases the primitive version of a particular function would be less sophisticated and precise than its modern counterpart…. A name has been given to cells that have primitive translation capacities. The name, “progenote,” signifies that the genotype-phenotype link has yet to complete its evolution. (Woese 2005: 107)

(….) How translation might have began. If we know how modern translation worked, we would be on far safer grounds in conjecturing how it began. (….) The progenote model sees organisms as genetically communal and the community as evolving as a whole, not the individual cell lines therein…. The real mystery, however, is how this incredibly simple, unsophisticated, imprecise communal progenote—cells with only ephemeral genealogical traces—evolved to become complex, precise, integrated, individualized modern cells, which have stable organismal genealogical records. This shift from a primitive genetic free-for-all to modern organisms must by all accounts have been one of the most profound happenings in the whole of evolutionary history. Although we do not yet understand it, the transition needs to be appropriately marked and named. “Darwinian threshold” (or “Darwinian Transition”) seems appropriate: crossing the threshold means entering a new stage, where organismal lineages and genealogies have meaning, where evolutionary descent is largely vertical, and where the evolutionary course can begin to be described by tree representation. (Woese 2005: 109)

The most important, if not the only, thing that can be said right now about the progression from pre-Darwinian progenote to cells typical of the Darwin era (i.e., modern cells), is that in the process the cell design becomes more integrated. Connectivity, coupling (among componentry) is key to the nature of that transition. The cell is a complex dynamic system. Complex dynamic systems characteristically undergo saltations at “critical points.” Drastic changes in the system result. An increase in the connectivity of a system is one factor that can bring it to such a critical point. Does the Darwinian Threshold, then, denote a critical point in the evolutionary process? I say it does. We can be confident in any case that in the full evolutionary course, from an abiotic earth to modern cells and organisms, evolutionary saltations must have occurred. The transition from the nondescript, horizontally [non-Darwinian] intermeshed, and simple progenote to the complex individual cell lineages (with stable genealogical traces and vertical descent) that we know surely has the feel of a saltation. (Woese 2005: 109)