What Is Life? | Reflections & Notes

Paul Nurse. What Is Life? Understand Biology in Five Steps. David Fickling Book, 2020. (212 pages)

“To survive the challenges that face the human race today–from climate change, to pandemics, loss of biodiversity and food security–it is vital that we all understand what life is.”


For some time I have figured that there were still two great mysteries of the universe. How did chemistry become biology, and how did biology become conscious. Nurse has quite handily provided the response to the former. I am now left with the conundrum of the latter.

As I continue to pursue the answer to consciousness, and the consecutive dilemmas of social ethics, one basic explanatory principle was deployed in this book that I now consider extremely helpful; understanding the simple is the pathway for explaining the complex. This kind of “explanatory” non-fiction is what makes Nurse’s writing so approachable, and accessible. Lay readers with a mere elementary understanding of biology will greatly benefit from this book.

Last, and perhaps most important, Nurse’s plea with society to utilize explanatory science as the bedrock of addressing all issues concerning human life. In the penultimate chapter, Changing The World, Nurse writes:

But the time for politics is after the science not before. The world has seen too often how things can go horribly wrong when the reverse is true. … Debates about the public good need to be driven by knowledge, evidence and rational thinking, and not by ideology, unsubstantiated beliefs, greed or political extremes.

But make no mistake, the value of science itself is not up for debate. The world needs science and the advances it can offer. As self-aware, ingenious and curiosity-driven humans, we have a unique opportunity to use our understanding of life to change the world. (p.186)

He concludes the chapter with these words:

The living world around us not only provides us humans with an endless source of wonder, it also sustains our very existence. (p.187)

I wholeheartedly agree.

If you care about life, you’ll want to first answer the question, “What is Life?” This book will go a long way towards illuminating the answer.



1. The Cell
Biology’s Atom

If you had an egg for breakfast, consider the fact that the whole of its yolk is just one single cell. Some cells in our bodies are also huge. There are, for example, individual nerve cells that reach from the base of your spine all the way to the tip of your big toe. (8)

Biology’s atom is the cell. …the basic functional unit of life. …the smallest entities that have the core characteristics of life. (8) …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. (9)

One of the things [Robert] Hooke looked at was a thin slice of cork. He saw that the cork wood was made up of row after row of walled cavities, very similar to the cells in the onion root tips I saw as a schoolboy 300 years later. Hooke named these cells after the Latin word cella, meaning a small room or cubicle. (10)

We now know that bacteria and other sorts of microbial cells (‘microbe’ is a general term for all microscopic organisms that can live as single cells) are by far the most numerous life forms on Earth. … for each and every one of our 30 trillion or more human cells, we have at least one microbial cell. You–and every other human being–are not an isolated, individual entity, but a huge and constantly changing colony made up of human and non-human cells. (11)

In 1839 the botanist Matthias and zoologist Theodore Schwann, summarized work from themselves and many other researchers, and wrote ‘we have seen that all organisms are composed of essentially parts, namely of cells’. Science had reached the illuminating conclusion that the cell is the fundamental structural unit of life. (12)

…every animal appears as a sum of vital units, each of which bears in itself the complete characteristics of life. – Rudolf Virchow, 1858

There was, however, an important gap in cell theory,… (13) It did not describe how new cells came into being. That gaps closed when biologists recognized that cells reproduce by dividing themselves from one cell into two, and concluded that cells are only ever made by the division of a pre-existing cell in two. (14)

Omnis cellular e cellula’, that is, all cells come from cells. This phrase also helped to counter the incorrect idea, still popular amongst some at the time, that life arises spontaneously from inert matter all the time–it does not. (14)

| Cell division is the basis of the growth and development of all living organisms. It is the first critical step in the transformation of a single, uniform fertilized egg of an animal into a ball of cells and then, eventually, into a highly complex and organized living being, an embryo. (14)

This means that all living organisms, regardless of their size or complexity, emerge from a single cell. (15)

Cell division also explains the apparently miraculous ways the body heals itself. … Cancer is caused by the uncontrolled growth and division of cells that can spread their malignancy, damaging or even killing the body. (15)

| Growth, repair, degeneration and malignancy are all linked to changes in the properties of our cells, in sickness and in health. in youth and in old age. In fact, most diseases can be traced back to the malfunction of cells, and understanding what (15) goes wrong in cells underpins how we develop new ways to treat disease. (16)

Quite a lot of what we know about the uncontrolled cell divisions of cancer cells came first from studying the humble yeasts. (17)

…the intricate and often very beautiful structures within cells. The largest of these structures are called organelles, which are each wrapped in their own layer of membrane. Of these, the nucleus is a command centre of the cell, since it contains the genetic instructions written into the chromosomes, while mitochondria…act as miniature power plants, supplying the cell with the energy it needs to gro wand survive. (17)

The presence or absence of a nucleus divides life into two major branches. Those organisms whose cells contain a nucleus–such as animals, plants and fungi–are called eukaryotes. Those without a nucleus are called prokaryotes, which ar either bacteria or archaea. (18)

Although just two molecules thick, [its] outer membrane forms a flexible ‘wall’ or barrier that separates each cell from its environment, (18) defining what is ‘in’ and what is ‘out’. Both philosophically and practically, this barrier is crucial. Ultimately, it explains why life forms can successfully resist the overall drive of the universe towards disorder and chaos. Within their insulating membranes, cells can establish and cultivate the order they need to perate, whilst at the same time creating disorder in their local surroundings outside the cell. That way life does not contravene the Second Law of Thermodynamics. (19)

[via: The cell “defines” itself via a boundary.]

| All cells can detect and respond to changes in their inner state and in the state of the world around them. So although separated from the environment they live in, they are in close communication with their surroundings. They are also constantly active and working to maintain the internal conditions that allow them to survive and to flourish. (19)

In fact, cells share many characteristics with all kinds of animals, plants and fungi. They grow, they reproduce, they maintain themselves, and in (19) doing all of this they display a sense of purpose: an imperative to persist, to stay alive and to reproduce, come what may. (20)

2. The Gene
The Test of Time

cf. Gregor Mendel, Abbot of Brno Monastery, now in the Czech Republic

Mendelism proposes that inherited characteristics are determined by the presence of physical particles, which exist as a pair. These ‘particles’ are what Mendel called ‘elements’ and we now call genes. …it gradually became clear that these conclusions not only applied to peas, but to all sexually reproducing species, from a yeast to humans and all organisms in between. Every one of your genes exists as a pair; you inherited one from each of your biological parents. (26)

…first spotted in the 1870s by a German military physician turned cell biologist called Walther Flemming. Using the best microscopes of his day, he described how these microscopic threads behaved in an intriguing way. As a cell got ready to divide. Flemming saw these threads splitting in half lengthwise, before becoming shorter and thicker. Then, when the cell divided into two, the threads were separated, with one half ending up in each of the newly formed daughter cells. (27)

What Flemming called ‘threads’, we now call chromosomes. (28)

…Belgian biologist Edouard van beneden…saw through his microscope that the first cell of each newly fertilized embryo contained four chromosomes. It received precisely two from the egg and two from the sperm. (28)

Starting with a clearly interpretable experiment with a simple biological system can lead to a wider insight relevant more generally to how life works. (29)

Apart from a few specialized exceptions–like red blood cells which, as they mature, lose their entire nucleus and therefore all their genes–every cell in your body contains a copy of your entire complement of genes. (30)

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. Through some miracle of packing, it all fits into a cell that measures no more than a few thousandths of a millimetre across. What is more, if you could somehow join together and then stretch out all the DNA coiled up inside your body’s several trillion cells into a single, slender thread, it’d be about 20 billion kilometres long. That’s long enough to stretch from Earth to the sun and back sixty-five times! (32)

…genes are made of DNA. Once that truth finally sank in, it signalled the birth of a new era for genetics and for biology as a whole. Genes could finally be understood as chemical entities: stable collections of atoms that obeyed the laws of physics and chemistry. (33)

| However, it was the elucidation of the structure of DNA, in 1953, that truly ushered in this brave new era. … Rosalind Franklin, Raymond Gosling, Maurice Wilkins, Francis Crick, James Watson … (33)

The real beauty of the DNA double helix they proposed is not the elegance of the gracefully spiralling structure itself. Rather, it is the way the structure explains the two key things that the hereditary material must do to underpin the survival and perpetuation of life. First, DNA must encode the information that cells and whole organisms need to grow, maintain and reproduce themselves. Second, it must be able to replicate itself, precisely and reliably, so that each new cell, and each new organism, can inherit a complete set of genetic instructions. (34)

A can only pair with T, and G can only pair with C. This means that if you know the order of bases along one strand of DNA, you immediately know the order of the nucleotide bases on the other strand. It follows, therefore, that if you break the double helix apart into its two strands, each strand can act as a template to recreate a perfect copy of its original partner strand. (36)

Genes exert their major influence on the behaviour of cells, and ultimately whole organisms, by instructing the cell how to construct particular proteins. (36)… To do this, cells translate between two alphabets: the four-letter alphabet of DNA, made up of the ‘letters’ A, T, G and C; and the more complex alphabet of proteins, which consists of ordered strings of 20 different building blocks called amino acids. (37)

This relationship is known as the ‘genetic code’ and it presented biologists with a true cryptographic puzzle. (37)

…the four-letter alphabet of DNA is arranged into three-letter ‘words’ along each strand of the DNA ladder, with most of those short words corresponding to one specific amino acid building block of a protein. The DNA ‘word’ GCT for example, tells the cell to add an amino acid called alanine to a new protein, whereas TGT would call for an amino acid called cysteine. (38)

cell cycle, the process that orchestrates the birth of every new cell. (42)

| DNA is copied early in the cell cycle, during a period of DNA synthesis called S-phase, and (42) the separation of the newly copied chromosomes occurs later, during a process called mitosis. (43)

Mutations occur when the DNA sequence of a gene has been altered, rearranged or deleted. … By some estimates, an average of just three small mutations occur each time one of your cells divides: an impressively low error rate of about one per billion DNA letters copied. But once mutations have occurred, they can create different forms of genes that produce altered proteins, which in turn can alter the biology of the cells that inherit them. (45)

Life cannot exist without genes: each new generation of cells and organisms must inherit the genetic instructions they need to grow, function and reproduce. This means that for living things to persist in the long term, genes must be able to replicate themselves very precisely and carefully. Only that way can the DNA sequences be kept constant through multiple cell divisions, so genes can withstand the ‘test of time.’ … The DNA sequence of the huge majority of the 22,000 genes that control your cells is almost completely identical to those of all other people on this planet today. (52) … Altogether, the mutations that differentiate your inborn characteristics from mine, and both of us from our prehistoric ancestors, add up to a tiny fraction–less than one per cent–of your total complement of DNA code. (53)

Life is constantly experimenting, innovating and adapting as it changes the world and the world changes around it. For this to be possible, genes must balance the need to preserve information by staying constant, with the simultaneous ability to change, sometimes substantially so. (56)

3. Evolution by Natural Selection
Chance and Necessity

All species–including our own–are in a state of perpetual change, eventually becoming extinct or developing into new species. (60)

…evolution by natural selection pushes us to imagine (60) something much more at the edge of our comfort zone, but also more magnificent. It is a wholly undirected and incremental process, but when it is embedded in the inconceivably vast duration of time, what scientists sometimes call ‘deep time’, it becomes the most supremely creative force of all. (61)

‘E conchis omnia’, ‘everything from shells.’ – Erasmus Darwin

The idea of natural selection is based on the fact that populations of living organisms exhibit variations, and when these variants are caused by genetic changes, they will be inherited from generation to generation. Some of these variants will affect characteristics that make certain individuals more successful in producing offspring. (64) … This process is known as natural selection since constraints imposed by all manner of natural factors, such as competition for food or mates or the presence of diseases and parasites, ensure that some individuals fare better and therefore reproduce more than others. (65)

Humans have actually been hijacking the same process for thousands of years, using it to breed organisms possessing particular characteristics. This is called artificial selection,… (66)

For evolution by natural selection to take place, living organisms must have three crucial characteristics. (67)

| First, they must be able to reproduce. (67)

| Second, they must have a hereditary system, whereby information defining the characteristics of the organism is copied and inherited during their reproduction. (68)

| Third, the hereditary system must exhibit variability, and this variability must be inherited during the reproductive process. (68)

Additionally, for this to work efficiently, living organisms must die. That way, the next generation, potentially containing genetic variants that give them a competitive edge, can replace them. (68)

This means the error rate itself is subject to natural selection. If that error rate is too high the information stored by the genome will degenerate and become meaningless, and if errors are too rare, the possibility for evolutionary change is reduced. Over the long term, the most successful species will be those that can maintain the right balance between constancy and change. (69)

In complex eukaryote organisms, further variability is introduced during the process of sexual reproduction, when parts of chromosomes are reshuffled during the cell divisions that produce sex cells (also known as germ cells: sperm cells and egg cells in animals, and pollen and ovules in flowering plants), which are made by the process called meiosis. (69)

Many other organisms introduce variation by exchanging DNA sequences directly, between different individuals. This is common in less complex organisms like bacteria, which can swap genes between one another, but also with more complex organisms. This process is called horizontal gene transfer. (70)

One profound consequence of evolution by natural selection is that all life is connected by descent. This means that as the tree of life is traced backwards, the branches increasingly converge into bigger branches and eventually into a single trunk. The conclusion therefore, is that we human are related to every other life form on the planet. (71)

Natural selection not only takes place during evolution; it is also taking place at the level of the cell inside our bodies. (76)

It is paradoxical that the very circumstances that allowed human life to evolve in the first place are also responsible for one of the most deadly human diseases. More practically, it also means that population and evolutionary biologists should be able to contribute significantly to our understanding of cancer. (77)

4. Life as Chemistry
Order from Chaos

…earthly life is directed by mysterious forces that are unique to living things. (80)

| This way of thinking is called ‘vitalism,’ and its origins trace back to the classical thinkers Aristotle and Galen, and probably even further. (81)

Most aspects of life can be understood rather well in terms of physics and chemistry, albeit an extraordinary form of chemistry that is highly ordered and organized, and of a sophistication that cannot be matched by any inanimate process. (81)

The scientific study of fermentation began with the eighteenth-century French nobleman and scientist Antoine Lavoisier, one of the founders of modern chemistry. Unfortunately for him, and unfortunately for science as a whole, his part-time activities as a tax collector meant he lost his head in May 1794, during the French Revolution. The judge of the kangaroo political court that sentenced him declared that the ‘Republic has no need for savants and chemists.’ We scientists obviously have to treat politicians with caution! There is an unfortunate tendency for politicians, especially those of a populist bent, to ignore ‘experts,’ particularly when that expertise counters their poorly substantiated opinions. (84)

| Before his untimely encounter with the guillotine, Lavoisier had become fascinated by the process of fermentation. He concluded that ‘fermentation was a chemical reaction in which the sugar of the starting grape juice was converted into the ethanol of the finished wine.’ … proposed that there (84) was something called a ‘ferment’, which seemed to come from the grapes themselves, which played a key role in the chemical reaction. He couldn’t say what this ‘ferment’ was, however. (85)

He argued that chemical reactions were not just an interesting feature of cellular life–they were once of life’s defining features. Pasteur summarized this brilliantly when he said that ‘chemical reactions are an expression of the life of the cell‘. (86)

| We now know that within the cells of all living organisms many hundreds, even thousands, of chemical reactions are being carried out simultaneously. These reactions build up the molecules of life, which form the components and structures of cells. They also break molecules down, to recycle cellular components and release energy. Together, the vast array of chemical reactions occurring in living organisms is called metabolism. It is the basis of everything living things do: maintenance, (86) growth, organization and reproduction, and the source of all the energy needed to fuel these processes. Metabolism is the chemistry of life. (87)

Invertase is an enzyme. Enzymes are catalysts: that means they facilitate and speed up chemical reactions, often dramatically. (87) … The discovery of enzymes laid the foundations for today’s consensus view–shared by all biologists–that most phenomena of life can be best understood in terms of chemical reactions that are catalyzed by enzymes. (88)

Most enzymes are made from proteins, which are built by the cell as long, chain-like molecules called polymers. … As well as most enzymes and all other proteins, all the lipid molecules that make up cell membranes, all the fats and carbohydrates that store energy, and the nucleic acids responsible for heredity, deoxyribonucleic acid (DNA) and the closely related ribonucleic acid (RNA), are all polymers. (88)

| These polymers are built principally from the atoms of just five chemical elements: carbon, (88) hydrogen, oxygen, nitrogen and phosphorus. Of these five, carbon plays a particularly central role, largely because it is more versatile than the other elements. Whereas hydrogen atoms, for example, make only one connection–that is, a chemical bond–with other atoms, each carbon atom can bond to four other atoms. This is the key to carbon’s polymer-making abilities: two of carbon’s four potential bonds can be linked to two other atoms, often other carbon atoms, creating a chain of linked atoms–the core of each polymer. That leaves each carbon with two further bonds available to link with other atoms. These extra bonds can then be used to add other molecules to the sides of the main polymer chain. (89)

Each protein is a carbon-based polymer built by joining smaller amino acid molecules together, one at a a time, into a long chain. Invertase, for example, is a protein molecule made by linking together 512 amino acids in a specific, ordered sequence. (90)

| Life uses twenty different amino acids. Each of these amino acids have side molecules, branching off from the main polymer chain, that grants them distinct chemical properties. For example, some amino acids have positive or negative charges, others are either attracted to or repelled by water, and some are capable of easily forming bonds with other molecules. By stringing together different combinations of amino acids, each with different side molecules, cells can create a huge range of different protein polymer molecules. (90)

| Then, once these linear protein polymer (90) chains are assembled, they fold, twist and combine together to create complex three-dimensional structures. … This leap from the one-dimensional to three-dimensional is crucial, since it means each protein has a distinctive physical shape and a unique set of chemical properties. (91)

Enzymes execute almost all the chemical reactions that form the basis of cellular metabolism. … They act as quality controllers, they ferry (91) components and messages between different regions of the cell, and they transport other molecules in and out of the cell. Others still are on the lookout for invaders, activating the proteins that defend cells and therefore our bodies from disease. (92)

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. (92)

Although the vast array of chemical reactions that occur simultaneously in cells may appear chaotic, it is in fact very highly ordered. For them to function properly, each of the different reactions requires its own particular chemical conditions. Some require more acid or alkaline surroundings; others demand particular chemical ions like calcium, magnesium, iron or potassium; others need or are slowed down by the presence of water. Yet somehow all these different chemistries must be carried out both simultaneously and very close together in the narrow (94) confines of the cell. … Many of these metabolic reactions still need to be kept separate from one another, however. They must not interrupt each other, and all their specific chemical requirements must be met. Key to answering this challenge is compartmentation. (95)

| Compartmentation is a way to get complex systems of all kinds to work. Take cities. They only work efficiently i they are organized into different compartments with particular functions: railway stations, schools, hospitals, factories, police stations, power stations, sewage disposal plants, and so on. … They have to be separate to work effectively, but they also need to be relatively close together and connected. It is just the same for (95) cells, which need to create a distinct set of chemical micro-environments that are separated from each other, either in physical space or across time, but also connected. Living things achieve this by constructing systems of interacting compartments that exist at a range of scales, from the very large to the extremely small. (96)

| The biggest of these scales will probably be most familiar: the different tissues and organs of multicellular organisms like plants, and animals–like you and me. (96)

In fact, the cell is the fundamental example of the compartmentation of life. (96)

The cell itself contains successive layer of compartmentation. The largest of these compartments are the membrane-bounded organelles, such as the nucleus and the mitochondria. (97)

The smallest chemical compartments within the cell are the surfaces of the enzyme molecules themselves. (97)

Combining the tiny effects of individual proteins, working in very large numbers across many cells, leads to the real-world consequences we see all around us. (101)

Today, the great majority of life forms around us ultimately derive their energy from the sun. This is what the chloroplast,…achieves. … Chloroplasts are the sites of photosynthesis: (103) the set of chemical reactions that uses energy from sunlight to drive the transformation of water and carbon dioxide into sugar and oxygen. (104)

chlorophylls are the reason grass looks green: they absorb energy from the blue and red parts of the spectrum of light, using it to power photosynthesis, resulting in them reflecting the green wavelengths. (104)

Life seems to have first appeared around 3.5 billion years ago, which is the age of the oldest fossils so far discovered. These were single-celled microbes, which probably derived their energy from geothermal sources. Because there was no photosynthesis during the earliest period of life on Earth, there was no major source of oxygen. As a result, there was almost no oxygen in the atmosphere, and when the planet’s early life forms did encounter oxygen it would have caused them problems. (105)

| Although we think of oxygen as a life-sustaining, as indeed it is, it is also a highly chemically (105) reactive gas which can damage other chemicals, including the polymers essential for life, such as DNA. Once microbes evolved the ability to photosynthesize, they multiplied, over the millennia, to such an extent that the amount of oxygen in the atmosphere spiked. What followed, between 2 and 2.4 billion years ago, is called the Great Oxygen Catastrophe. All organisms that existed at that time were microbes, either bacteria or archaea, but some researchers think most of them were wiped out by the appearance of all that oxygen. It is ironic that lif created conditions that nearly ended life as a whole. The minority of life forms that survived would have either retreated to places where they were less exposed to oxygen, perhaps at the bottom of the sea or deep underground, for example, or they had to adapt and evolve new chemistries needed to thrive in an oxygenated world. (106)

cellular respiration. (107)

The principal role of mitochondria is to generate the energy that cells need to power the chemical reactions of life. … In strictly chemical terms, cellular respiration reverses the reaction at the core of photosynthesis. Sugar and oxygen react with each other to make water and carbon dioxide, releasing a lof of energy, which is captured for later use. The mitochondria ensure this multi-step chemical reaction is highly controlled and takes place in an orderly, stepwise way, without too much energy being lost, and without reactive oxygen and electrons escaping and damaging the rest of the cell. (107)

When a chemical reaction within a cell needs energy the cell breaks ATP’s (adenosine triphosphate) high-energy bond, turning ATP into adenosine diphosphate (ADP), a process that releases energy that the cell can use to trigger a chemical reaction or a physical process, such as each of the steps taken by a molecular motor. (110)

All living things need a constant and reliable supply of energy and, ultimately, they all make their energy through the same process: controlling the flow of protons across a membrane barrier to make ATP. If there is anything remotely like a ‘vital spark’ that sustains life, it is perhaps this tiny flow of electric charge across a membrane. (111)

When we look at the beautiful and highly elaborate pictures produced by the powerful microscopes of today, we are looking at a complex and constantly changing network of organized and interconnected chemical micro-environments. This view of the cell is worlds away from that of (111) cells as mere Lego-like building blocks for the more complex tissues and organs of plants and animals. Each cell is a complete and highly sophisticated living world in its own right. (112)

…biologists have come to recognize that even the most complex behaviours of cells and of multi-cellular bodies can be understood in terms of chemistry and physics. (112)

It turned out that the Cdc2 protein was an enzyme called a protein kinase. These enzymes catalyze a reaction called phosphorylation that adds a small phosphate molecule, which has a strong negative charge, to other proteins. (113)

Ultimately, life emerges from the relatively simply and well-understood rules of chemical attraction and repulsion, and the making and breaking of molecular bonds. Somehow these (115) foundational processes, operating en masse at a minuscule molecular scale, combine to create a bacteria that can swim, lichens that grow on rocks, the flowers we tend in our gardens, flitting butterflies, and you and me, who are able to write and read these pages. (116)

[via: I wrote in the margins, “HOW?!” In other words, the “somehow,” has yet to still be answered?!]

We are drowning in data but thirsty for knowledge. – Sydney Brenner

5. Life as Information
Working as a Whole

For living organisms to work effectively as complex, organized systems they need to constantly collect (118) and use information about both the outer world they live in and their internal states within. (119)

Closely linked with their reliance on information is the way living things act with a sense of purpose. The information the butterfly was gathering meant something. It was being used by the butterfly to help it decide what to do next to achieve some specific end. That meant it was acting with purpose. (120)

In a book called Critique of Judgment, [Emmanuel] Kant argued that the parts of a living body exist for the sake of the whole being, and that the whole being exists for the sake of its parts. He proposed that living organisms are organized, cohesive and self-regulating entities that are in control of their own destiny. (121)

It’s through homeostasis that your body works to maintain a consistent temperature, fluid volume and blood sugar, for example. (124)

The critical fact about DNA is that each gene is a linear sequence of information written in the four-letter language of DNA. Linear sequences are a familiar and highly effective (124) strategy for storing and conveying information; it’s the one used by the words and sentences that you are reading here, and also the one used by the programmers who wrote the code for the computer on your desk and the phone in your pocket. (125)

One great advantage of digital codes is that they are readily translated from one coding system into another. (125)

The second example where information is key to understanding life is gene regulation, the set of chemical reactions cells use to turn genes ‘on’ and ‘off’. (127) … 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. (128)

Gene regulation also means that exactly the same set of genes can be used to create dramatically different creatures at different stages of their lives. (128)

Ripening apple cells produce a gas called ethylene, which acts to both accelerate ripening and to increase the production of ethylene. (136)

If we can understand the cell’s different modules and see how cells link them together to manage information, we don’t necessarily need to know all the minute molecular details of how each module works. The overriding ambition should be to capture meaning, rather than simply catalogue complexity. (138)

…Dennis Bray coined the insightful term ‘wetware’ to describe the more flexible computational material of life. (140)

As well as signalling through space, cells need ways to signal through time. To achieve this, biological systems must be able to store information. (142)

…Conrad Waddington…is best known for coining the word epigenetics. He used it to describe the way cells gradually take on more specialized roles during the development of (143) an embryo. Once the growing embryo instructs cells to commit to these roles, they remember that information and rarely change track. That way, once a cell has committed to forming part of the kidney, it will remain part of the kidney. (144)

| Today, the way most biologists use the word epigenetics is based on Waddington’s ideas. It describes the set of chemical reactions that cells use to turn genes either on or off in fairly enduring ways. …they often work by adding chemical ‘tags’ to the DNA, or to proteins that bind to that DNA. (144)

How all of this spatial order develops is one of the more challenging questions in biology. (146)

Understanding how structures form at larger scales, in objects such as organelles, cells, organs and whole organisms is more difficult. Direct molecular interactions between components cannot explain how these structures form. (147)

One way that developing embryos generate the information they need to transform a uniform cell or group of cells into a highly patterned structure is by making chemical gradients. If you put a small drop of ink into a bowl of water, it will slowly diffuse away from the location of the original drop. The intensity of the ink colour gets lower further away from the drop, making a chemical gradient. That gradient can be used as a source of information: for example, (148) if the concentration of ink molecules is high, we know we are close to the centre of the bowl, where the ink was dripped in. (149)

| Let’s now replace the bowl with a ball of identical cells and, instead of ink, we inject one side of the ball with a dose of a particular protein that can change the properties of cells. (149)

[Alan Turning] came up with an alternative, and imaginative, suggestion for how embryos generate spatial information from within. He devised a set of mathematical equations that predicted the behaviour of chemical substances interacting with each other, and so undergoing specific chemical reactions as they diffuse through a structure. Unexpectedly, his equations, which he called reaction-diffusion models, could arrange chemical substances into elaborate and often rather beautiful spatial patterns. By tweaking the parameters of his equations, the two substances could organize themselves into evenly spaced spots, stripes or blotches, for example. The attractive thing about Turing’s model is that the patterns emerge spontaneously, according to relatively simple chemical rules of interaction between the two substances. (150)

…all of these genetic ‘updates’ mean that the whole system of the cell will gradually tend to become more complex with time. This can lead to redundancy: some components will have overlapping functions; others will be the relics of superseded parts; and some will be wholly unnecessary for normal functioning but might be able to compensate if the primary components breaks. (152)

| This all means that 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. (152)

The fact that information management occurs at all scales, from the molecular to the planetary biosphere, has important implications for how biologists try to make sense of life’s processes. Often, it is best to seek explanations close to the level of the phenomenon being studied. To be satisfactory, those explanations do not always need to be reduced down to the molecular-scale realm of genes and proteins. (157)

| However, it may well be that there are commonalities between the way information is managed at one scale that can illuminate how things work in a system that is either larger or smaller. For example, the logic underpinning feedback modules that control metabolic enzymes, regulate genes or maintain bodily homeostasis, will have similarities with the feedback modules that allow ecologists to make better predictions about how natural environments are likely to change when specific species go extinct or migrate out of their traditional ranges as a result of climate change or habitat destruction. (157)

Changing the World

Throughout history, most human lives have been ended not by old age, but by infectious diseases. (162)

Where vaccines, sanitation and antimicrobial drugs are available, we have the tools we need to prevent, treat or contain (162) a wide range of once-deadly infectious diseases. … After millennia in which healthcare relied chiefly upon superstition, vague explanations and a host of unproven and sometimes risky remedies, this transition is a truly miraculous change. It all rests upon our knowledge of life, generated by science, and then applied to the world. (163)

It is also astonishing that politicians in some developed nations should have ignored advice from scientists and experts and have weakened measures to deal with epidemics and pandemics such as these. This neglect has already led to grave consequences. Putting all this right should be an urgent priority for humanity. (164)

[via: It is perhaps “astonishing” because Nurse is a biologist, not a social psychologist! ;-)]

…rejecting proven, clinically approved vaccines is a question of morality. By doing so they are not just imperilling the safety of themselves and their families, but also that of many others around them by disrupting (164) herd immunity and allowing infectious diseases to spread more easily. (165)

Cancers begin when cells acquire new genetic changes and mutations that cause them to start dividing and growing in uncontrolled ways. They flourish because they have a selective advantage: they can monopolize the body’s resources, grow more than the non-mutated cells around them, and ignore the body’s ‘stop’ signals. (167)

Because cancer is an inevitable result of the cell’s capacity to adapt and evolve, we will never entirely eliminate it. But as our understanding of life gets better we will increasingly be able to spot cancer early and treat it more effectively. I am confident there will come a time when cancer no longer arouses fear, as it still does today. (168)

The interactions between genes and environment are so complex that the researchers who study them are stretching the limits of presently available techniques, including new approaches such as machine learning. (170)

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? (171)

…for the time being, it is extremely reckless to attempt to edit the DNA of early stage human embryos, which would result in genetic changes in all the cells of ht person born, and those of any children they might have in the future. At present there is a risk that gene-based therapies might accidentally change other genes in the genome. However, even if only the desired gene is edited, those genetic changes could also cause hard-to-predict and potentially dangerous side effects. We simply don’t yet understand our genomes well enough to know for sure. (173)

Ageing is the end product of the combined damage, death and pre-programmed shutdown of a body’s cells and organ systems. (176)

Is it really acceptable to deny the world’s poorest access to inventions that could help their (179) health and food security, especially if that denial is based on fashion and ill-informed opinion rather than sound science? There is nothing intrinsically dangerous or poisonous about foodstuffs made using GM methods. What really matters is that all plants and livestock should be similarly tested for their safety, efficiency and predicted environmental and economic impact, regardless of how they have been made. (180)

In the coming decades, I think that we will have to use genetic engineering techniques more … synthetic biology could make an impact. Synthetic biologists seek to go beyond the more focused and incremental approaches traditionally used in genetic engineering, to write more radical changes to organisms’ genetic programming. (180)

With GM and synthetic biology we could reorganize and repurpose life’s chemical brilliance in powerful new ways. It should be possible to use synthetic biology to create nutritionally enhanced crops and livestock, but it could be applied more broadly than that. It could see us creating re-engineered plants, animals and microbes that produce entirely new types of pharmaceuticals, fuels, fabrics and building materials. (181)

Progress in all these applications requires better understanding of life and how it works. (183)

To feed applied science by starving basic science is like economizing on the foundations of a building so that it may be built higher. It is only a matter of time before the whole edifice crumbles. – George Porter

This creates fresh questions and further problems, however. How do we agree on what we mean by the ‘public good’? If new cancer therapies are hugely expensive, who should get them and who (184) 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 Huntingdon’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? (185)

…it is society as a whole that must take the lead in the discussions. (185)

[via: This is a tall order, even if it is the most important item on the menu.]

But the time for politics is after the science not before. The world has seen too often how things can go horribly wrong when the reverse is true. … Debates about the public good need to be driven by knowledge, evidence and rational thinking, and not by ideology, unsubstantiated beliefs, greed or political extremes. (186)

| But make no mistake, the value of science itself is not up for debate. The world needs science and the advances it can offer. As self-aware, ingenious and curiosity-driven humans, we have a unique opportunity to use our understanding of life to change the world. (186) … The living world around us not only provides us humans with an endless source of wonder, it also sustains our very existence. (187)

What is Life?

This is a big question. The answer I got at school was something like the MRS GREN list, which states that living organisms exhibit Movement, Respiration, Sensitivity, Growth, Reproduction, Excretion and Nutrition. It is a neat summary of the sorts of things that living organisms do, but it is not a satisfying explanation of what life is. (188)

The ability to evolve through natural selection is the first principle I will use to define life. … To evolve, living organisms must reproduce, they must have a hereditary system, and that hereditary system must exhibit variability. Any entity that has these features can and will evolve. (190)

| My second principle is that life forms are bounded, physical entities. They are separated from, but in communication with, their environments. (190)

My third principle is that living entities are chemical, physical and informational machines. They construct their own metabolism and use it to maintain themselves, grow and reproduce. These living machines are co-ordinated and regulated by managing information, with the effect that living entities operate as purposeful wholes. (191)

| Together, these three principles define life. Any entity which operates according to all three of them can be deemed to be alive. (191)

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. (192)

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. (196)

…there is not a single known species of animal, plant or fungus that can generate its own cellular chemistry entirely from scratch. (197)

Life on Earth belongs to a single, vastly interconnected ecosystem, which incorporates all living organisms. This fundamental connectedness comes not only from their deep interdependency, but also from the fact that all life is genetically related through its (199) shared evolutionary roots. (200)

Francis Crick argued that the flow of information from DNA to RNA to protein was so fundamental to life that he (200) called it the ‘Central Dogma’ of molecular biology. (201)

These deep commonalities in life’s chemical foundations point to a remarkable conclusion: life as it is on Earth today started just once. (201)

If all life is part of the same vast family tree, what kind of seed did that tree grow from? (201)

…we should remember that evolutionary change can only happen efficiently when some members of a population fail to survive and reproduce. So although life as a whole has proved itself to be tenacious, long-lasting and highly adaptable, individual life forms tend to have a limited lifespan and a restricted ability to adapt when their environment changes. Which is where natural selection comes into play, killing off the old order and, if more suitable variants exist in a population, making way for the new. It seems that it is only through death that there can be life. (207)

As far as we know, we humans are the only life forms who can see this deep connectivity and reflect on what it might all mean. That gives us a special responsibility for life on this planet, made up as it is by our relatives, some close, some more distant. We need to care about it, we need to care for it. And to do that we need to understand it. (212)

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  1. Pingback: Every Life Is On Fire | Reflections & Notes | vialogue

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