HOW MOLECULAR FORCES AND ROTATING PLANETS CREATE LIFE: THE EMERGENCE AND EVOLUTION OF PROKARYOTIC CELLS – Jan Spitzer (2021)

I thought I understood a thing or two about biology, and, more specifically, its genetic and general molecular side as well. I’ve read a couple of introductory level university course textbooks, like Biology, Evolution and Human Nature by Goldsmith & Zimmerman (2001), which was already pretty heavy on chemistry for somebody without an academic background in hard sciences, and a few more specific books, like the excellent The Flexible Phenotype by Piersma & Van Gils (2011) and Alex Rosenberg’s brilliant, rigorous Darwinian Reductionism, Or, How to Stop Worrying and Love Molecular Biology (2006).

I also thought I had a bit of grasp on origin of life theory, since I read Nick Lane’s excellent The Vital Question: Energy, Evolution and the Origins of Complex Life (2015), a book I can’t say I understood completely, but enough so to enjoy it a lot.

Last year, I was absolutely gobsmacked by Contingency and Convergence: Towards a Cosmic Biology of Body and Mind by Russell Powell, a 2020 publication in the Vienna Series of Theoretical Biology, and so when I checked what else was published in that series, I didn’t hesitate to buy How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells by Jan Spitzer – I was intrigued by the subject matter because of Lane’s book, and if I’d survived that, how hard could it be?

Well, it turns out this was harder, much harder, yet I probably enjoyed it even more. Part of that enjoyment is witnessing other people’s genius, but the main reason I enjoyed it so much was because it provided entirely new and much more detailed insight in the miracle that is our existence.

Before I get to a more detailed discussion of the book, please consider the following drawing – a typical representation of a bacterial cell I found somewhere on the public domain.

This is the way most people are taught about cells. We tend to think we *understand* cells this way – at least, if we study some more of these drawings – including ones that zoom in a bit – and the accompanying chapters on cell biology carefully.

Now consider this fragment from Jan Spitzer’s book, and, for starters, compare the way the cytoplasm is represented in the generic textbook drawing with what Spitzer writes about it.

From a purely chemical point of view, a bacterial cell is exceedingly complicated. The cytoplasm contains in round numbers ~2,500,000 protein molecules of ~1,000 different kinds, ~200,000 transfer RNAs of ~50 kinds, ~1,500 short-lived messenger RNAs of ~400 kinds. (…) The number of ribosomes can vary between 2,000 for a slow-growing population and 70,000 in a fast-growing population. These biomacromolecules are hydrated by a relatively concentrated (~4%) electrolyte – a multicomponent buffered solution of simple ions, particularly potassium ions and phosphate, and other low-molecular weight metabolites from biochemical pathways (…). All this chemistry of long DNA double helices (partly condensed or coacervated by cationic proteins and amines), RNAs, and their protein complexes, all in their correct three-dimensional conformations, and all exhibiting their molecular motions – from bond rotations to large conformational motions and rotational and translational Brownian diffusion, taking place on timescales of many orders of magnitude, from femtosecond infrared motions to physiological motions at milliseconds, seconds, and hours – all this molecular motion is crowded and enclosed within the hydrophobic cell envelope. The cell envelope contains a lipid bilayer membrane, studded with a large number of integral hydrophobic proteins that sense the physicochemical state of both the external nutrient environment and the internal cytoplasmic side of the membrane and adjust the molecular and ionic traffic across the membrane accordingly. (…) The overall chemical system is in cyclic disequilibrium, where cells approximately double in size and then divide on the physiological timescale of seconds to hours.

Additionally, in all this, also the positions of all those different molecules matter, as there is no “bulk aqueous reservoir where chemical potentials (concentrations) are independent of position”, and so the cell system is “thus vectorial”, with aqueous nano-channels and nano-pools of dissolved ions and molecules.

It is yet another example of the huge gap that exists between what people – even highly educated people – think they know, and how the world actually is. It makes books like Spitzer’s humbling and full of wonder – even if that wonder is abstract, dry, and highly complex. Do we truly appreciate the wonder of life enough?

There’s one important caveat: however detailed that quote might seem, it only scratches the surface too. Or, to quote Spitzer again: “Today the molecular crowdedness of a living cell is an uncontroversial and well-appreciated fact, but its overall spatiotemporal complexity remains poorly understood.”

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Just to be clear: I’m not the target audience for Spitzer’s book. Certain parts – when he got into the nuts and bolts of detailed chemical stuff – were way too advanced for me. I’d say about 1/3rd of the text was too technical for my current brain. But that doesn’t mean I couldn’t understand Spitzer’s general message – it only meant that I could not contradict him on the technicalities. The fact that the main text is only 170 pages, but about 1/3rd of the full volume is academic credentials (20 pages of notes, 26 pages of references, a 5 page index) is indicative of its intellectual rigorousness.

I think one of the reasons that makes this book successful is that Spitzer approached it as a hobby. He has had no academic career in biology, but he is a physical chemist (PhD) and a chemical engineer (MS) with expertise in thermodynamics and aqueous colloids, who worked as a industrial R&D manager, on synthetic latexes and emulsion polymerization processes. The fact that he is retired and has no skin in the game allowed him to write freely and thoroughly. More information on Jan Spitzer and his ideas can be found here.

In the remainder of this text, I will try to summarize Spitzer’s main points, and conclude with a list of quotes & fragments of knowledge that struck me and that I wish to keep record of. Most of those should also be worthwhile to readers with an advanced interest in science, but you might need a dictionary depending on your prior knowledge – I know I needed one. As a coda, there’s a shortened version of a reading list Spitzer himself provides in his introduction.

For a review by someone with an academic background in these matters, I refer you to the Small Things Considered blog. It has a good, fairly detailed outline of the book. It is the only review of the book I found online, so I hope I contribute a bit to Spitzer’s dissemination with my own review – especially for those that are looking for more information about it without easy access to academic libraries.

Do I recommend it? I loved it, but if you’re not academically trained in these matters ymmv, so much is clear – if you’re adventurous, like a serious challenge, and want to keep your mind limber, go for it, I’d say. It’s also crystal clear that this is mandatory reading for anybody with a serious academic interest in the matter.

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BIG PRINCIPLES

For a more general outline & scope of the book I refer to the Small Things Considered review. What I merely try to do here is explain Spitzer’s core ideas in a manner that is hopefully understandable also for those of you without any knowledge of molecular biology or cell biology, and doing so I will highlight a few things Small Things Considered glances over.

What Spitzer basically says is that cells are entities of phase separated chemicals, more specifically:

The bacterial cell is a continuous process of phase separation of “four multicomponent compartments”, the “cell envelope”/”cell wall”/”plasma membrane”, the “nucleoid of the DNA double helix”, the “ribosomes” and the “”unstructured” cytosol and cytogel”.

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living biological cells must exist as compartments with permeable boundaries

This phase separation happens according to the Pauling-Delbrück premise from 1940 – an rather obscure premise, so don’t sweat it if you’ve never heard of it – which Spitzer updated to this: “only biochemical reactions and non-covalent molecular forces ensure the functional folding and associations (crowding) of cytoplasmic biomacromolecules in vivo”.

According to Spitzer “this premise has remained unexplored in origins research”.

But the second thermodynamic law makes it so that molecules that are ordered neatly (like in phase separated systems) tend to become less ordered, making cellular life impossible. The question then is, how come cells don’t disintegrate, but, even more important for origins research, how come they did get ordered in the first place? And where did the energy come from to do so?

In a nutshell, the second law asks: Which physicochemical mechanisms exploited environmental energies to counteract the molecular drift to disorder at the historical transition from prebiotic chemistry to Archaean microbiology?

Or, restated:

All molecules in the prebiotic pool would exhibit Brownian diffusion toward maximum molecular chaos (…). Inherent molecular motions (i.e., heat content) can help organize molecules into life, but only if there is crowding and confinement, when molecules attract each other through non-covalent molecular forces, and energies available outside the confinements.

Spitzer’s answer is to be found in the title: our rotating planet, which, together with the moon, provides more or less stable & constant tidal movement and diurnal solar radiation.

Did life emerge spontaneously? I use “spontaneously” here in the sense of chemical thermodynamics, as a total negative free energy for a given set of physicochemical processes. Clearly then, the answer is that life did not emerge spontaneously; it did not spontaneously self-assemble its first life. Similarly, from a top-down perspective, an extant molecular crowded bacterial cell, when taken apart, cannot self-reassemble spontaneously from its own molecules; it cannot re-emerge on its own from its own highly evolved soup of molecules and start living. The second law of thermodynamics, the thermal diffusion of molecules toward maximum molecular disorder, does not permit the spontaneous generation of concentration gradients, an essential feature of living cells. By the same token, the emergence of life from prebiotic molecules could not have been a spontaneous physicochemical process on early Earth.
If life did not emerge spontaneously, did it emerge naturally? Putting aside religious explanations, and discarding the possibility that Maxwell’s demons or scientists were creatively defeating the second law and manipulating prebiotic chemistry during the Hadean-Archaean transition, this leaves only natural planetary energies to drive the prebiotic CHONSP chemistries toward living states. This is nothing new, and many energy sources have been suggested, from UV radiation, ion (…) gradients at hydrothermal vents, fluctuating environments bring about hydration-dehydration cycles, and many others. The cyclic environmental energies look the most plausible to me as the natural agents of life’s creation. Adopting Occam’s razor, I take a simplifying view that two natural cyclic engergies arising from Earth’s rotation – solar radiation and seawater tides – were the most important (…).

It is of note that Spitzer didn’t come up with all this by himself. The importance of “cyclic energetic tidal environments driven by the unique Earth-Moon system” for the emergence of life have already been “promulgated to different degrees of detail” by Noam Lahav in 1999 and Richard Lathe in 2004 and 2005.

It is also important to stress that Spitzer doesn’t provide fully clear pathways, not at all. That would be impossible in this phase of scientific development – even though today most scientists consider the origin of life to be a problem that is ultimately solvable. But not today, because, for starters, “[a]biotic cyclic chemistry is still “terra incognita”, so this book is just at the beginning of a possible solving of the puzzle. And as per the bafflingly complex composition of bacterial cells (see the very first quote), this process of creation must have been extremely complex, consisting of “hundreds of millions of evolutionary chemical steps”.

The crowding transition makes a strong case for assuming that the astonishingly sophisticated three-dimensional structures of today’s nucleic acids and proteins, as well as their transient interactions within and with cell envelopes, are the result of hundreds of millions of evolutionary chemical steps in the microbiological part of the puzzle. (…) Extant biomacromolecules emerged and evolved without direct contact with their environments in permeable compartments, under cycling, confined, and crowded physiochemical conditions.

Spitzer also stresses that the primordial soup was very complex chemically, and we need to think of the emergence of life as a kind of chemical simplification of that primordial soup, because, in a way, the phase separations – going against the second thermodynamic law – create more order, i.e. simplicity. This view is at odds with the more dominant assumption that life is a movement from (chemical) simplicity to complexity.

How did prebiotic pools of countless kinds of carbon molecules in cyclic diurnal disequilibria phase separate and eventually get simplified into cellular life based on only 20 amino acids and five nucleotides and their biopolymers (and about 200 low-molecular-weight metabolites), a great majority of which involve phosphates esters (and ethers)? (…) In other words, the current constructive paradigm of origins research – the complexification of small prebiotic molecules into nucleic acids and proteins and their (“miraculous”) self-assembly into living cells – has to be put away; it does not correspond to historical or experimental facts. And crucially, the complexification paradigm lacks a “self-assembly” mechanism, that is, it does not explain which forces counteracted the diffusional drift to disorder – the operation of the second law of thermodynamics – and how.

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(…) there is one assumption that can be taken as historical fact: prebiotic Earth contained a multicomponent and multiphase mixture of carbon compounds of the CHONSP chemistries. They ended up in seawater, dissolved, or dispersed and were deposited in tidal zones as macroscopic films with internal colloidal structures. (…)

Spitzer says that it is in these tidal zones that molecules started to chemically co-evolve. This next part refutes the idea of complexification again, and also stresses co-evolution of cellular parts:

Thus, heredity depends on being alive, and being alive depends on nutrient environments and on cellular compartments; the latter are created by phase separations – a macroscopic manifestation of non-covalent molecular forces. The Pauling-Delbrück premise, taken together with the absolute requirement for compartments and for (nutrient) energies, makes it likely that compartments, proteins, and nucleic acids coevolved. This triple coevolution of compartments, proteins, and nucleic acids sounds awfully complicated, and it is. But it is preferable to asking the chicken-or-egg question about whether informational nucleic acids or metabolic proteins (or cell envelopes for that matter) were the first to evolve – a question that has an uncomfortable air of anthropocentric predestination. The question gives the superficial appearance of trying to simplify the larger problem of life’s origins into a sequence of separate (simpler and smaller) chemical problems (i.e., the origins of metabolism, genetics, and compartments) – as if small abiotic molecules “knew” how to evolve from some beginning toward a predestined end. (…) The chicken-or-egg question is a frequent subject in research on life’s origins because the question persists at the level of molecular biology: nucleic acids are replicated and transcribed by proteins, but proteins are coded for by nucleic acids, so which happened first? The obvious answer – coevolution – is well know (e.g. Noble 2006). (…) This chemical triple coevolution, as complicated as it sounds, is less mystifying than a simple, orderly chemical evolution – from life’s building blocks to biopolymers, which were eventually encapsulated into single-cell ancient organisms. This complexification paradigm, “from the simple to the complex,” in addition to its anthropocentric air of predestination, hides a number of unexplained transitions, such as the self-assembly of proto-biopolymers into a proto-cell or the creation of indispensable concentration gradients of metabolites.

This concludes the general outline of Spitzer’s main thoughts. Throughout the book he goes into much, much more specific physiochemical & molecular biological detail, and I want to stress again that these details were generally beyond me. That said, even though I can’t fathom those details, I found the above line of reasoning very convincing – and even if his proposals don’t turn out to be valid, at the very, very least Spitzer brings up questions that need answering, and he also proposes a solid conceptual framework & ways for future research.

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SOME TASTY TIDBITS

As in most of my non-fiction reviews, I end with some nuggets of wisdom I’ve learned while reading How Molecular Forces and Rotating Planets Create Life: The Emergence and Evolution of Prokaryotic Cells. The usual caveats apply: these nuggets are not a summary at all, and are not intended as a representative sample of the actual content of the book. They are just here as a reminder for myself, and maybe some of them will strike you too. I’ve again decided to quote extensively rather than summarize, to give you a taste of the book’s prose.

> “Life is a relationship among molecules and not a property of any molecule” (Pauling’s adage)

> “Only in the first half of the 20th century “molecules became actual material objects, albeit very small ones, invisible under a microscope, which obeyed physical laws”. “The Brown-Einstein-Perrin understanding that the movement of Brown’s pollen particles, visible under the microscope, is caused by collisions of very tiny molecules of water is not generally regarded as a scientific revolution – perhaps because it took about 100 years to solidify it as a fact, relying on unrelated advances in physics and chemistry”, but is is.”

> “How did the abiotic (molecular and macroscopic) motions of non-life evolve into the biological (organismal) motions of the first growing and dividing cells? All these motions require an expenditure of energy, generating waste heat.”

> “it is not so much that a bacterial nucleoid self-replicates; it is rather that the cell replicates the nucleoid.”

> “Biology has still fewer differential equations than chemistry; (…) The lesser degree of quantification in biology arises from the fact that living cells and organisms are dynamically and molecularly more complicated than inanimate matter – they are multicomponent, multiphase, and molecularly crowded in cyclic non-equilibria, and they exchange matter and energy with their nutrient environments.”

> “It is useful to keep in mind that living biological matter is in cyclic disequilibria, unlike dead biological or biochemical matter (…). Determining whether a bacterial cell is dead or alive or in-between – a “zombie” – is not as easy as one might expect. The problem of dormant, non-metabolizing cells or quiescent cells (non-growing, with very low metabolism) in stressful environments is clearly highly relevant to life’s emergence (…).”

> “The idea that RNA molecules can be considered alive in a biological sense and exhibit Darwinian evolution [“the RNA World” hypothesis] cannot be accepted from a physiochemical standpoint, and I suspect also from a microbiological standpoint. (…) That the cell unit is a biological matter cannot be denied by chemistry. No molecules can self-replicate. Nucleic acids get replicated in downward causation by cellular organisms. Only when cells are alive can they replicate their DNA (and viral DNA or RNA) and thus reproduce and evolve or enable viruses to do so. The problem of life’s origin cannot be solved by saying that “informational” molecules are special – alive in the biological sense – and that they actually can self-replicate and evolve.”

> “There is thus no Schrödinger-like dichotomy between the complex, exquisitely well-organized, and controlled molecular processes of a cell in vivo and chemical thermodynamics (…). Biological cells are non-equilibrium open thermodynamic systems – chemical micro-reactors excreted products (e.g., ethanol) and generating heat but also of using them to make copies of themselves. As Albert Claude remarked, the cell “knows” physical chemistry – and I dare say chemical engineering and process control also – better than we can currently recognize.”

> “These developments in electron microscopy established the fact that a bacterial nucleoid is not in any way enclosed in its own compartment and that its position and morphology change during the cell cycle (…). Electron microscopy also suggested that nucleoid “excrescences” reach into the plasma membrane, indicating that the nucleoid also has a structural role, particularly when the cell begins to divide (…).”

> “In general terms, non-covalent molecular forces are the ultimate reason for diverse kinds of phase separations, including the many nano-phases materializing within crowded bacterial cells as they grow and divide. It feels natural to imagine that such physicochemical sophistication could only have come about through the evolutionary processes of chemical reactions and concurrent phase separations, especially colloidal phase separations on nano- to micrometer scales. Even though such an evolutionary scenario is dreadfully unspecific, the principle is clear (…) it makes the emergence of life conceivable with what we know today.”

> “A real bacterial cell cycle, at a high density of cells, is subject to changing nutrient environments and direct interactions between cells, which bring about variable rates of growth. These changes around each cell cause variable gene expression and variable nucleoid replication – heritable “errors” leading to modified nucleoids.” (That we call them errors is anthropocentric according to Spitzer, and I agree.)

> “There can be little doubt that a bacterial cell is not only phase separated from the aqueous nutrient solution (and from other bacterial cells) but also phase separated within.”

> “Thus, it is truly mind-boggling that a phase-separated cell in vivo – phase separated from without and within – maintains the integrity of its nano-phase separation processes quite precisely, though not perfectly, during each cell cycle, especially when considering that proteins at high crowding tend to agglomerate.”

> “It is noteworthy that cell fusions evolved into natural sophisticated processes in eukaryotic multicellular organisms, especially in regard to sex – the sperm penetrating the egg. It is truly amazing, from a colloidal point of view, that the cloning of animals, which also involves the breaking and resealing of cell envelopes, actually works in what superficially looks like a relatively simple mechanical process.”

> Atkins in 2011: “We have to be cautious in interpreting a change in a bit of DNA as the emergence of information. At a molecular level everything is junk and all changes are random. A protein is built on the basis of the structure of DNA, and in that sense DNA carries information, but the structure of DNA itself has not been constructed with a message in mind. In other words, that a particular strip of molecular junk results in a successfully modified organism leads us retrospectively to regard that particular junk as embodying useful information (….)” (This quote from the notes made me want to read 2017’s From Matter to Life: Information and Causality, edited by Sara Imari Walker, Paul Davies and George Ellis even more, and I started it quickly after I finished Spitzer’s book. I’ve read it partly, but Spitzer’s book kind of ruined it for me – read my review on Goodreads here.)

> A day used to last only about 4 hours, and the impact that created the moon “elongated the length of one Earth day” to ~17 hours at the end of the Hadean eon. Since the Archean eon, about 3.5 billion years ago, Earth’s rotation has slowed “to the current 24-hour day”. Obviously, all this had an effect on the tidal cycles. More about this here.

> “Any living organism can defeat the second law, but only locally and temporarily. The second law guarantees the “mortality” of individual biological organisms – the ever-present drift toward diffusional disorder, which cannot be counteracted forever by available energies.”

> “These processes of paleo-colloidal natural biochemistry – natural fusion experiments – driven by the cyclic gradients of the rotating Earth, extend further to the appearance and evolution of organismic multicellularity. Thus, the Medawar-like story of emergence continues through the same scenario of the daily dehydrating and hydrating fusions of multiple prokaryotes, together with single-cell eukaryotes in tidal seashore biofilms under solar irradiation. They radiated evolutionarily into other geochemical environments, giving rise to proto-multicellular organisms, which began to appear in the Precambrian fossil record perhaps as early as 1.5 million ears ago. Darwinian evolution arose naturally and inevitably as a consequence of non-ideal cellular reproduction. There can be no doubt that Darwinian evolution is both gradual via molecular micro-evolution, as assumed by Darwin, and also supra-macromolecular or “saltational” as intuited by Woese.”

> “Because all molecules are subject to physicochemical laws only, the molecules and macromolecules that comprise, for instance, bacterial cells, do not have any inherent capability to self-assemble, self-replicate, “start living,” or exhibit Darwinian evolution beyond what chemistry and physics allow. Equally importantly, but less appreciated, is the fact that living bacterial cells also have no fundamental capability for Darwinian evolution: they cannot help but exhibit Darwinian evolution because of the inevitable errors that occur during the cyclic transmission of genetic information. (…) nothing in the origin of life and in its Archaean evolution makes sense except in light of the chemistry of rotating planets: their solar and tidal energies drive cyclic chemical reactions, cyclic phase separations, cyclic hybridizations of nuclei acids, the cyclic reassembly of molecular machines, and cyclic fusions of dead and living cells.”

> “Thus, the twenty-first century represents a cusp in the evolution of Homo sapiens – between unintentional Darwinian evolution that got us where we are, taking 3.5 billion years, and the beginning of intentional evolution. [More specifically electric and electronic interfacing; and advances in research of human embryonic stem cells.]” (More generally, intentional evolution is not new, take for instance the breeding of domesticated animals, or, more recent, GMOs. See also Inheritance Systems and the Extended Synthesis by Eva Jablonka & Marion Lamb for an overview of other forms of evolution, the so-called neo-Darwinian view of evolution.)

> “organisms (…) have “brought” seawater with them in their body fluids but not inside their cells (e.g., the ex-cellular ionic composition of human blood is similar to that of seawater).”

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CODA: Spitzer’s reading list

In the book’s introduction, Spitzer provides a list of the crucial books that helped him get oriented on the origin of life problem – obviously only a fraction of what he read on the matter. He wrote a few sentences on each book, but I decided to present the list just as titles. Books are not computers, and you are reading this one a connected device, so if you’re interested, a quick search online will tell you a whole lot more on each of these.

Peter Atkins, On Being (2011)
Dennis Bray, Wetware: A Computer in Every Living Cell (2009)
David Deamer and Gail Fleischaker, Origins of Life: The Central Concepts (1994)
Franklin Harold, In Search of Cell History: The Evolution of Life’s Building Blocks (2014)
Iris Fry, The Emergence of Life on Earth: A Historical and Scientific Overview (2000)
Bill Mesler & James Cleaves, A Brief History of Creation: Science and the Search for the Origin of Life (2016)
Fredrick Neidhardt, John Ingraham & Moselio Schaechter, Physiology of the Bacterial Cell: A Molecular Approach (1990)
Denis Noble, The Music of Life: Biology beyond Genes (2006)
Jan Sapp, The New Foundations of Evolution: On the Tree of Life (2009)
Robert Shapiro, Origins: A Skeptic’s Guide to the Creation of Life on Earth (1986)
Suzan Mazur, The Origin of Life Circus: A How to Make Life Extravaganza (2014)

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