[Book Notes] 20 insights: What is Life

What is Life is an exploration of the 5 key principles/revelations of biology. The book’s author, Paul Nurse, is a Nobel prize winner. The book is very lucid to read and the 5 principles (namely cell, gene, natural selection, life as chemistry, life as evolution) have been explained from first principles. My notes from this book are as follows:


Cells are the smallest entities that have the core characteristics of life. This is the basis of what biologists call cell theory: to the best of our knowledge, everything that is alive on the planet is either a cell or made from a collection of cells. The cell is the simplest thing that can be said, definitively, to be alive.

All living organisms, regardless of their size or complexity, emerge from a single cell. I think we would all respect cells a little more if we remembered that every one of us was once a single cell, formed when a sperm and an egg fused at the moment of our conception.



Each of your chromosomes has at its core a single, unbroken molecule of DNA. These can be extremely long and each can contain hundreds or even thousands of genes arranged in a chain, one after another. Human chromosome number 2, for example, contains a string of over 1,300 different genes, and if you stretched that piece of DNA out, it would measure more than 8 cm in length. This leads to the extraordinary statistic that, together, the 46 chromosomes in each of your tiny cells would add up to more than two metres of DNA.



Natural selection is a profound idea, which has significance beyond biology. It has both explanatory power and practical utility in several other disciplines, not least economics and computer science. Today, for example, some aspects of software and some engineered components of machines, such as aircraft, are optimized by algorithms that mimic natural selection. These products are evolved, rather than designed in the traditional sense.



For evolution by natural selection to take place, living organisms must have three crucial characteristics. First, they must be able to reproduce. Second, they must have a hereditary system, whereby information defining the characteristics of the organism is copied and inherited during their reproduction. Third, the hereditary system must exhibit variability, and this variability must be inherited during the reproductive process. It is this variability that natural selection operates upon. It transforms a slow and randomly generated source of variability into the apparently boundless and constantly changing range of life forms that flourish around us.



The outcome of all of this protein diversity is a maelstrom of chemical reactions being carried out in every cell at all times. If you could imagine looking inside a living cell with eyes that could perceive the molecular world, your senses would be assaulted by a boiling tumult of chemical activities.

Some function like despatch drivers, carrying cellular components and chemicals to the part of the cell where they are needed. They do this by following the complex trackways, also made from proteins, that criss-cross the cellular interior rather like an elaborately branching railway network. Researchers have made films of these minute molecular motors in action, and seen them ‘walking’ around the cell like tiny robots. These motors have ratchet mechanisms, that keep them moving forward, and help them avoid being knocked off course by accidental collisions with other molecules.



The principal role of mitochondria is to generate the energy that cells need to power the chemical reactions of life. That’s why cells that need a lot of energy contain a lot of mitochondria: to keep your heart beating, each of the cells in the muscles of your heart must employ several thousand mitochondria. All together they occupy about 40% of the space available in those heart cells.

The tiny protein structures that act as the ‘turbines’ in the mitochondria even look a bit like the turbines in electric power stations, although they are miniaturized by a factor of several billion-fold! As protons rush through the molecular turbine, which has a channel only 10 thousandths of a millimetre wide, they turn an equally small molecular-scale rotor. That turning rotor drives the generation of an all-important chemical bond, creating a new molecule of a substance called adenosine triphosphate, or ATP for short. This happens at the rapid rate of 150 reactions per second.

To fuel all of the chemical reactions needed to support your body’s trillions of cells, your mitochondria together produce, amazingly, the equivalent of your entire bodyweight in ATP every day! Feel the pulse beating in your wrist, the heat of your skin, and the rise and fall of your chest as you breathe: it’s all fuelled by ATP. Life is powered by ATP.



And whilst computer systems must ‘write’ information onto a different physical medium in order to store it, the DNA molecule ‘is’ the information, which makes it a compact way to store data. Technologists have recognized this and are developing ways to encode information in DNA molecules to archive it in the most stable and space-efficient way possible.



Ultimately, the cells in each of your organs are different because they use very different combinations of genes. In fact, only about 4,000, or a fifth, of your total set of genes are thought to be turned on and used by all the different types of cells in your body to support the basic operations needed for their survival. The rest are only used sporadically, either because they perform specific functions only required by some types of cell, or because they are only needed at specific times.

There are proteins that function as so-called ‘repressors’ that turn genes off, or ‘activators’ that turn genes on. They do this by seeking out and binding to specific DNA sequences in the vicinity of the gene being regulated, which then makes it either more or less likely that a messenger RNA is produced and sent to a ribosome to make a protein.



The information-processing modules used by living things and those used in human-made electronic circuitries are in some respects very different. Digital computer hardware is generally static and inflexible, which is why we call it ‘hardware’. By contrast, the ‘wiring’ of cells and organisms is fluid and dynamic because it is based on biochemicals that can diffuse through water in the cells, moving between different cellular compartments and also between cells. Components can be reconnected, repositioned and repurposed much more freely in a cell, effectively ‘rewiring’ the whole system. Soon, our helpful hardware and software metaphors begin to break down, which is why the systems biologist Dennis Bray coined the insightful term ‘wetware’ to describe the more flexible computational material of life.



As well as signalling through space, cells need ways to signal through time. To achieve this, biological systems must be able to store information. This means that cells can carry with them chemical imprints of their past experiences, which we can think of as working a bit like the memories we form in our brains. These cellular memories range widely, from transient impressions of what happened just a moment ago, to the extremely long-term and stable memories held by DNA.



Living systems are often less efficient and rationally constructed than control circuits designed intelligently by human beings, another reason why analogies between biology and computing can only go so far. As Sydney Brenner observed, ‘Mathematics is the art of the perfect. Physics is the art of the optimal. Biology, because of evolution, is the art of the satisfactory.’ The life forms that survive natural selection persist because they work, not necessarily because they do things in the most efficient or straightforward way possible. All this complexity and redundancy makes the analysis of biological signalling networks and information flow challenging.



If genetic science advanced to the point where it could make a reasonably accurate prediction of when and how you are most likely to die, would you want to know? If new cancer therapies are hugely expensive, who should get them and who should not? Should advocating vaccine refusal without adequate evidence, or the misuse of antibiotics, be criminal offences? Is punishment for certain criminal behaviours right if they are strongly influenced by an individual’s genes? If germ line gene editing can rid families of Huntington’s disease, should they be free to use it? Can cloning an adult human ever be acceptable? And if tackling climate change means seeding the oceans with billions of genetically engineered algae, should it be done?



The ability to evolve through natural selection is the first principle I will use to define life. My second principle is that life forms are bounded, physical entities.This principle invokes a physicality of life, which excludes computer programs and cultural entities from being considered as life forms, even though they can appear to evolve. My third principle is that living entities are chemical, physical and informational machines.



DNA is one of them and its core purpose is to act as a highly reliable long-term store of information. To this end, the DNA helix shields its critical information-containing elements – the nucleotide bases – at the core of the helix, where they are stable and well-protected. So much so that scientists who study ancient DNA have been able to sequence DNA obtained from organisms that lived and died a very long time ago, including DNA from a horse that had been frozen in permafrost for nearly a million years!

But the information stored in the DNA sequence of the genes cannot remain hidden and inert. It must be transformed into action, to generate the metabolic activities and physical structures that underpin life. The information held in chemically stable and rather uninteresting DNA needs to be translated into chemically active molecules: the proteins.

Proteins are also carbon-based polymers, but in contrast to DNA, most of the chemically variable parts of proteins are located on the outside of the polymer molecule. This means that they influence the three-dimensional shape of the protein and also interact with the world.

I cannot imagine a more elegant solution: different configurations of linear carbon polymers generate both chemically stable information storage devices and highly diverse chemical activities.



Like carbon, silicon atoms can make up to four chemical bonds and we know they can form polymers: these are the basis of silicon sealants, adhesives, lubricants and kitchenware. In principle, silicon polymers might be large and varied enough to contain biological information. However, despite silicon being far more abundant on Earth than carbon, life here is based on carbon. That might be because under the conditions found on the surface of our planet silicon does not form chemical bonds with other atoms as readily as carbon does, and it does not therefore produce enough chemical diversity for life. It would be foolish, though, to rule out the possibility that silicon-based life, or for that matter life based on other chemistries altogether, might thrive in different conditions found elsewhere in the universe.



Viruses are the prime example. They are chemical entities with a genome, some based on DNA, others on RNA, which contains genes needed to make the protein coat that encapsulates each virus. Viruses can evolve by natural selection, thus passing Muller’s test, but beyond that things are less clear. In particular, viruses cannot, strictly speaking, reproduce themselves. Instead, the only way they can multiply is by infecting the cells of a living organism and hijacking the metabolism of the infected cells.

You could almost say that viruses cycle between being alive, when chemically active and reproducing in host cells, and not being alive, when existing as chemically inert viruses outside a cell.



Your familiar body is in fact an ecosystem made up of a mixture of human and non-human cells. Our own 30 trillion or so cells are outnumbered by the cells of diverse communities of bacteria, archaea, fungi and single-celled eukaryotes that live on us and inside us. Many people carry with them larger animals too, including a variety of intestinal worms and the tiny eight-legged mites that live on our skin and lay their eggs in our hair follicles. Many of these intimate, non-human companions depend heavily on our cells and bodies, but we also depend on some of them too. For example, bacteria in our guts produce certain amino acids or vitamins that our cells cannot make for themselves.



The mitochondria that produce the energy our bodies need were once entirely separate bacteria – ones that had mastered the ability to make ATP. Through some accident of fate that took place around 1.5 billion years ago, some of these bacteria took up residence inside another type of cell. Over time, the host cells became so dependent on the ATP made by their bacterial guests that the mitochondria became a permanent fixture. The cementing of this mutually beneficial relationship probably marked the beginning of the entire eukaryote lineage. With a reliable supply of energy, the cells of eukaryotes were able to become bigger and more complex.



But which came first? Replicating DNA-based genes, protein-based metabolism, or enclosing membranes? In today’s living organisms these systems form a mutually interdependent system that only works properly as a whole. DNA-based genes can only replicate themselves with the assistance of protein enzymes. But protein enzymes can only be built from the instructions held in the DNA. How can you have one without the other? Then there’s the fact that both genes and metabolism rely on the cell’s outer membrane to concentrate the necessary chemicals, capture energy and protect them from the environment. But we know that cells alive today use genes and enzymes to build their sophisticated membranes. It’s hard to imagine how one of this crucial trinity of genes, proteins and membranes could have come about on its own: if you take one element away, the whole system rapidly comes apart.

The formation of membranes might be the easiest part to account for. We know that the kind of lipid molecules that make up membranes can form via spontaneously occurring chemical reactions that involve substances and conditions thought to have been present on the young Earth. And when scientists put these lipids into water, they do something unexpected: they assemble themselves spontaneously into hollow, membrane-bounded spheres that are about the same size and shape as some bacterial cells.

The best solution scientists have yet found for this particular chicken and egg-type problem is to say that neither of them did! Instead, it may have been DNA’s chemical cousin, RNA, that came first. Like DNA, RNA molecules can store information. They can also be copied, with errors in that copying process introducing variability. That means RNA can act as a hereditary molecule that can evolve. That’s what RNA-based viruses still do today. The other crucial property of RNA molecules is that they can fold up to form more complicated three-dimensional structures that can function as enzymes. RNA-based enzymes are not nearly as complex or versatile as protein enzymes, but they can catalyze certain chemical reactions. Several of the enzymes crucial to the function of today’s ribosomes are made from RNA, for example. If these two properties of RNA were combined, they may have been able to produce RNA molecules that work as both gene and enzyme: a hereditary system and a primitive metabolism in the same package. What this would amount to is a self-sustaining, RNA-based living machine.



Exposing bacteria to antibiotics without actually killing them off entirely, makes it more likely that they will evolve resistance to the drugs. That’s why it is important to take the right dose of antibiotics – and only when truly needed – and to finish the course of treatment you are prescribed. Not doing so may not only put your health at risk, but also that of other people.