"How Life Works" by Philip Ball

This book radically transformed my understanding of cellular biology. 

I'm not a biologist but I was a science teacher and I taught that the genome programs cells; that sections of DNA unwind and are used as templates to make strands of messenger RNA which then float out into the cytoplasm and are in turn used as templates for making proteins. That's not false. But, as Ball points out, that doesn't explain how some of my body cells develop into neurons and others, which have exactly the same DNA, into skin cells and others into blood cells and others into heart, lung, liver, spleen ...

By describing recent research on protein synthesis and embryo development, Ball shows that:

• Genes rarely have a unique function. The same gene which does one thing in a fruit fly can do something totally different in a human.
• Many morphologies are the result of combinations of genes.
• Genes can be 'switched' off or on by proteins. 
• Messenger RNA molecules seem to be made up of bits of heterogeneous nuclear RNA fragmented and then stitched together.
• The cells in multicellular life forms operate differently from bacterial cells.  
• Proteins fold because some sections of the protein chain attract water, others repel it. This also means that proteins can embed themselves into a cell wall.
• Changes in gene function can be caused by signals coming from outside the nucleus or even outside the cell itself. These signals can be electrochemical (as in neuron transmission), chemical (eg hormones), or even mechanical (eg when a cell is stretched). 
• Many developments involving proteins are combinatorial. This reduces 'noise' and makes the system more robust. If one enzyme doesn't work, another may be found to do the job. Molecular promiscuity with combinatorial fuzzy logic might be the only way for genetically identical cells to work together in diverse but specialised states. This also means that protein networks can develop new functions without losing old ones, which enables evolution to happen.
• Multicellularity has only happened twice: for plants and for animals (fungi don't count). There were significant changes in the ways that genes developed and communicated after the evolution of mammals and particularly placental mammals.  
• The epigenetic landscape is composed of a variety of bifurcating river valleys down which the cell tends to progress in a process called canalization. This landscape develops as the cells grow producing "a delicate dance of contingency and inevitability” like the growth of a city. (Ch 6) The valleys in the landscape can act as 'attractors' but genetic changes can alter where these attractors are.
• Cells have an awareness of their environment. Perhaps awareness of one’s surroundings is a fundamental feature of life.
• A random mixture of two morphogens, one an activator and one an inhibitor, in which the inhibitor diffused faster than the activator, creates patches in which one or the other morphogen predominates. This is responsible for eg patterned skins, the arrangement of hair follicles or feathers, the fractal branching of lung tissue, and even fingers (and fingerprints). 

This book also explained how a living cell, which appears to flout the second law of thermodynamics which insists that in an equilibrium system randomness tends to increase, can become increasingly organised. It points out that there are systems in physics, such as phase separation and crystallisation, which are inherently organised and that life appears to use these.  

I also learned:

• How tortoise shell cats get their markings and why 2999/3000 are female. 
• Why identical twins can be different from birth.
• Why planarian flatworms are effectively immortal. 
• How a human embryo develops and how an undeveloped embryo can be found inside the brain of itself developed twin. 
• That there is a gene called Sonic hedgehog. 
• How cells can 'request' the blood system to provide them with capillaries.
• Why humans mostly have their liver on the right, and their stomach and spleen on the left.

It was hard work. The information is very condensed and I needed to concentrate and take notes. But in the end I was rewarded in spectacular fashion. This is one of those books that provokes a paradigm shift, a revolution in the way one thinks.

Other brilliant books by Philip Ball that I have read include:

• Critical Mass: How One Thing Leads to Another 
• H2O: A Biography of Water
• The Devil's Doctor: Paracelsus and the World of Renaissance Magic and Science
• The Water Kingdom: A Secret History of China
• Beyond Weird: Why Everything You Thought You Knew About Quantum Physics is Different 

Selected quotes:

• “Looking to the genome for an account of  how life works is rather like ... looking to a dictionary to understand how literature works.” (Prologue)
• “There has never been a machine made by humankind that works as cells do.” (Prologue)
• “Life is a hierarchical process, and each level has its own rules and principles.” (Prologue)
• “The price of metaphor is eternal vigilance.” (Ch 1)
• “Cells commit to fates by noticing and assessing what their neighbours are doing. It's rather like voting with a show of hands: we might sneak a look at how others are voting before deciding.” (235)
• “Life doesn't make systems that can do or construct a single thing, that produces entities ... that embody a wide range of options ... In normal circumstances, the system converges on the outcome(s) favoured by natural selection, while still maintaining enough phenotypic variability to be evolvable. Evolution does not know ... what it is going to need tomorrow - so it must keep its options open.” (Ch 7)
• “Life ... can be considered as a computation that aims to optimise the acquisition, storage, and use of ... meaningful information.” (Ch 9) 

A superb book. August 2024; 460 pages

This review was written by the author of Bally and Bro, Motherdarling  and The Kids of God