A Review and thoughts on Peter Hoffmann’s book, “Life’s Ratchet: How Molecular Machines Extract Order from  Chaos”, Basic Books, 2012. 

This is a relatively technical book, one whose title, with its definite mechanistic spin, nearly stopped me from reading it. In this Hoffmann begins with a history of science and how we have looked at life as a remarkable process from the days of Aristotle to today and how that has shaped our inquiry and our capacity to understand it. Is life possible only because of some inexplicable, and yet unknown, ‘vital’ force? Are organisms endowed with this gift of life by a creator? or are there physical laws which shape and determine life? There has been a long ‘battle’ waged between the various ‘vitalists’ and mechanists, the later who once viewed an organism as a special machine, popularly comparable to a watch or clock, animated by a ‘vital’ force, who over time evolved their search into that of more recent times of seemingly fantastical molecular mechanisms, ‘engines’, within an organism which, because of their nano-scale can perform and behave in ways that appear incredible to the layperson.

The bulk of Hoffmann’s book focuses on the workings of these ‘mechanisms’, as science has come to understand them, operating within the various organelles, the cytoplasm, nucleus and membranes which compromise a cell, doing much of the actually ‘work’ of transportation within them, regulating the conditions inside and outside their membranes, aiding the performance of many steps in the conversion of chemical energy held within the bonds of ‘food’ into the electrical energy which powers many cell processes and, importantly, ‘harvest’ energy from the ambient heat of matter itself, the chaotic movement of atoms and molecules, utilizing it in purposeful and precise action. Hoffman spends a lot of time here discussing the latter. He addresses a major ‘problem’ here, namely the question of how these molecular machines can harvest/utilize the high entropy energy of what he terms the ‘molecular storm’, the chaotic and constant movement of atoms which occurs in the presence of ‘heat’.  The laws of thermodynamics argues that such waste heat is unavailable for ‘work’ that machines and engines must rid it of themselves in order to continue operating…but these tiny, specialized, molecules have through evolution devised ways/structures that can utilize this without violating these ‘laws’…through their nanoscale ratcheting structures, structures of particular protein molecules. Structures, the effects of which, are observable through highly specialized  technologies scientists have developed.

I found it helpful to go beyond simple diagrammatic drawings of these machines and found this video helpful to my understanding. Keep in mind that the precise structure and function of these ‘machines’ is not known, as even with our most advanced technologies we are unable to examine them, but we have devised techniques which render their effect and function visible indirectly. Here is a video of one of these machines in operation, the ATP Synthase, a machine that exists in the thousands in the membrane of the many mitochondria within each cell recharging ‘spent’ ADP molecules with another phosphate group which will later find their way to the countless sites of specific chemical reactions, release their recently added phosphate and, in the process, donate its bonding charge to the chemical process. ATP is essential for much of the bio-chemical activity in all cells and organisms.

The actions of these ‘molecular mechanisms’, a term I still have trouble with because of my associations of the term with macro-scale mechanically engineered machines we use every day, goes a long way in explaining how a cell actively shapes itself, how that shape helps determine the outcome of countless living processes and in cases such as in muscle cells, how these tiny, molecular actions, are ‘amplified’ as these processes occur within the larger number of cells which comprise a muscle group and that into the motion of a multi-celled organism’s larger body. He looks into the mechanisms which accomplish the process of the replication of DNA which is essential for cell division. In a separate process every cell manufactures many thousands of proteins, continuously, to meet their own needs via the transcription (reading) of the DNA within their cell nucleus, where they copy the precise ‘instructions’ into messenger RNA, which carries it to the ribosome, which will ‘translate’ and assemble it into the needed protein molecule. This is not a book for a beginner in terms of the organism’s metabolic processes, but rather for someone more comfortable with the basic processes of life and the jargon used to describe it…nor is it aimed at the advanced college student. It offers the reader a look into the complexity of life at a molecular level.

Plants do not grow simply because they photosynthesize, nor do animals and fungi simply digest food and thereby live. All of these processes are complex and begin with those processes operating at a scale visible to us only through the use of advanced technologies, but are there nevertheless. Life is supported and powered, limited and controlled, by the broader conditions around it, as well as by those which it helps create and maintain within itself generally utilizing countless, complex reactions which efficiently capture and transform the energies available to them. The author began as a physicist and quickly became interested in the physics of life. We have a tendency to look for quick, obvious answers. Hoffman’s book takes a look at life through the several sciences which attempt to describe it and has greatly added to my understanding of its complexity and processes which, all combined, ‘are’ living organisms.

I in particular think the author’s section, ‘Evolution’ in one of his later chapters, ‘The Watch and the Ribosome’, is notable and would suggest that even if you skim the rest of the book, that you read this section closely. Here he argues that without the physical laws which govern the universe, of matter and energy, the information contained in DNA, is meaningless. Life and the processes of evolution are not random. When life follows the ‘recipes’ contained in DNA, the physical/chemical forces in effect, play a central role in determining what ‘forms’ are produced, what . will in fact manifest. A protein’s shape, its translation from a set of ingredients into a ‘cake’, or in the case of an organism, into the many precisely structured proteins, set in their place and time to perform particular roles thus making that organism possible. DNA is an ordered list of ingredients, which, when assembled, are the neucleotides, the necessary component parts of proteins, not the proteins themselves…not the organism. Once assembled these must then take on their particular qualities and shape of necessary proteins and do so because they must—within the physical laws acting across all of life and matter. DNA alone is not ‘responsible’ for the life of a given organism. The physical laws in effect across the universe, which define the relationships between matter’s ‘bits’ reduces randomness, increasing the probabilities of a range of possibilities. Matter, particularly at a molecular level, ‘behaves’ as it does, because it must. While ‘randomness’ may produce options the laws of necessity favor particular forms. The ‘product’ of those possibilities then shapes those to follow always consistent with the physical laws and forces in effect. 

As Hoffman writes, “The exquisite order and the amazing variety we see in nature at every level–from galaxies to molecules–is the result of the fruitful interaction of chance and necessity.” Additionally, without RNA and all of a cell’s processes which conduct and support the translation of RNA into proteins, DNA is of little value. Out of context, he writes, DNA is meaningless. Organism’s are functional ‘wholes’. Their ‘secret’ lies in no particular part. Life is a product of the universe, its laws ‘bias’ the processes of evolution. Chance and necessity.  Organisms are ’emergent phenomena. “Development of an organism needs information about proteins, but also needs space, time, physics, and complex feedback loops. None of these are encoded in DNA.”

In the concluding section of this same chapter he titles, ‘There is No Other Way…’, Hoffmann writes, “Looking at molecular machines has made me realize that evolution is the only way these machines could’ve come to exist. As we have seen life exploits all aspects of the physical world in the fullest: Time and space, random thermal motion, the chemistry of carbon, chemical bonding, the properties of water. Designed machines are different. They are often based on a limited set of physical properties and are designed to resist any extraneous influences. The tendency of molecular machines to use chaos rather than resist it provides a strong case for evolution. Why? If life started by itself without a miracle then life had to start at the molecular scale. The molecular scale has always been dominated by the molecular storm. The ability of life to somehow incorporate thermal randomness as an integral part of how it works— as opposed to giving into the chaos— shows that life is a bottom up process. It is not designed from the top down. A top-down design would have avoided the complications of thermal motion by making the fundamental entities of life larger so they could resist the molecular storm more easily. This is what machines designed by humans do—until recently as nanotechnologies have learned from life‘s nano bots to create tiny machines of their own.

“Molecular machines exquisite adaptation to their molecular environment is also a strong argument for evolution. Evolution is tinkering—The gradual improvement and better adaptation of biological structures. The history of life has been long and evolution had ample time to create these amazing physics-exploring machines that run our bodies. To achieve such near perfection, you need a process that designs dynamically. A one time design is not enough. Conditions change over time and our molecular machines need to remain adaptable. An external designer would do best if the designer used evolution to do the work. Adaptation is assisted by the fact that physical laws provide the missing ingredient. For example many structures in our cells are made through self-assembly processes which are the result of physical forces (vesicles, collagen, etc.) [Provided with the right ‘simple’ ingredients these structures form on their own outside of an organism]. Evolution does not over design: It designs just enough to take advantage of physical laws. If physics does the work for you, then why bother designing what is already designed?”

I’m going to back up a little here. Organisms require supportive ambient conditions to live. They cannot exist in the cold of deep space, or even beyond the relatively narrow limits extent on Earth, even if they have all of the necessary gases of our atmosphere, and nutrients that they require. Central to an organism’s existence is heat, heat from either an external source, like our sun, from the combustion of fuels or via the chemical breakdown of food releasing its energy which degrades into heat after having done ‘work’ on its ‘way’ to being freely dissapated. What is heat? It is the random, kinetic motion of atoms and molecules, the ‘thermal storm’, Hoffman writes of. Organisms exist within a narrow range of temperature conditions. This level of chaos, warms, excites all of the matter within a given organism. It propels all of our integrated ‘parts’ within us into action, action which the molecular machines, Hoffmann writes of, are essential for life. Heat is not a neutral, background element. It does not simply speed up chemical reactions. It is necessary and one of the determining ‘shapers’ of life and its structures. While we consume and process food to provide the nutrients and low entropy forms of energy we require to complete many specific processes, the energy of the thermal storm around and within us provides a base energy/activity level, a continuous ‘kick’, within our cells without which our cells would cease their life activity. While the materials and energy contained within our food or within light’s photons, are absolutely essential to our lives, propelling us forward, the thermal, ‘molecular’, storm, prepares the way, kick-starting and providing the propelling force of our many molecular machines which have evolved a way to utilize it, a ‘ratcheting’ mechanism within the machine which takes advantage of the energy of ‘appropriately’ directed protons and other tiny ions that comprise the fluids within and around the cell. Such energized ‘particles’ advance the mechanism while others have little or no effect. The scale and rate of ‘bombardment’ drives these machines. 

Energy moves from more ordered, potent forms, to less so. Converting harvested kinetic energy into ordered action before ‘releasing’ it once again as ‘waste’ heat. Physicists speak of energy moving from low to high entropy, which is a measure of its randomness. In classical physics, high entropy energy such as ambient heat, was thought to be inaccessible, lost, and in a sense it is. As energy degrades it inevitably tends to effect matter with which it interacts by producing more complex structures as it does so. Eventually it is lost to the gigantic, even endless ‘sink’ that is outer space. But on Earth, under the appropriate conditions this heat still contributes to the processes of life. Energy passes from the sun to plants to various animals and fungi, degrading at each step, increasing in entropy. Life is not simple. We are complex, dynamic, near perfectly attuned organisms, ‘emergent pheneomena’, products of universal processes, as Hoffman puts it, that have arisen naturally from our environment which is itself continuously evolving, the sun’s energy flowing through the Earth’s countless systems, cycles and feedback loops, capturing it, utilizing it to reshape and drive the many billions of organisms and their structures, through their lives and on into the next. Organisms are products of nature which in turn influence what is to come. All life plays a role in this process. None are favored. All are necessary in the moment. They change together driving the process ahead or retarding it. Each is a part of and essential to the other. Each is subject to change as the overall ‘system’ evolves into the future.

Hoffman’s book is another eye-opener for me which has helped me draw my understanding of life into a tighter more integrated whole.

For those interested, here’s a link to an annotated lis of books I’ve been reading on the science of life, titles covering topics from evolution to quantum biology and quantum physics with the goal of understanding just what is life and what goes on within organisms, processes and structures which are remarkably similar across all species. On Life: An Annotated Reading List of Titles Exploring the Physics, Biology, Evolution, Natural Selection and the Generative Power of Far Out of Equilibrium Dissipative Structures (Organisms)

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