The view of living systems as machines is based on the idea of a fixed sequence of cause and effect: from genotype to phenotype, from genes to proteins and to life functions. This idea became the Central Dogma: the genotype maps to the phenotype in a one-way causative fashion, making us prisoners of our genes.
How did this dogma become entrenched? One of the great achievements of twentieth-century science was the discovery of the structure of genetic material, DNA (deoxyribonucleic acid). It heralded a new era of biological understanding, but it also created a gene-centric view, the gene as a ‘code’ or ‘blueprint’ for life. By unravelling the ‘code’ we could find the ultimate or ‘primary’ cause of life and its functions. It led to the new field of genomics, which would seek to associate particular genes, or groups of genes, with particular functions. But if all functions could be reduced to genes, then this produces a problem: where lies the agency of organisms? Could this also be reduced to genes? Are we driven by genes? The answer presented by those central to what came to be called the Modern Synthesis was that it could – even to the point of arguing that our freedom to act (free will) and our agency is an illusion.
This dogma is a distorted view because it separates genes, as replicators, from the organism, as a vehicle. Genes are seen as both the driving force and the goal of organisms. Yet, while genes are essential in making proteins, an ability that must be passed on through the generations, they are part of a regulatory system and not its directors. The director is the self-regulating organism. The organism does not wait for commands given by genes. Just as musical notes can be arranged in many ways to create compositions, organisms use their genetic heritage, implementing a diverse range of possible outcomes. Furthermore, when their heritage is inadequate to cope with environmental stress, organisms can alter their genes. Thus, organisms can change their genetic heritage.
What Is a Gene?
There are two key misconceptions about genes, concerning (1) what they are and (2) what they do. In common language when we talk today about genes we tend to think of DNA, codes, a book of life or a blueprint. But do we really understand what we mean by genes? We talk about genes as though we know what they are. Genetics is a major subject, along with genomics. Students of biology learn about Mendelian inheritance. Mendel discovered that inheritance could be viewed as discrete, and that there exist dominant and recessive forms of each discrete inherited characteristic. He showed this by demonstrating the probabilistic nature of inheritance. Different characters can be determined by whether a gene is said to be dominant or recessive. But the gene of Mendelian genetics is very different from the concept used by those who study genes today. Significantly, it is different from that used by Richard Dawkins in his book The Selfish Gene, which changes from context to context. In fact, the gene as a concept has become slippery, like a conjurer’s sleight of hand. One moment it is an independent inherited characteristic; the next, it is a DNA sequence. But these are not identical, and confounding the two creates a conceptual muddle.
An example of gene confusion was shown in a debate in 2009 between Richard Dawkins and Lynn Margulis. Margulis, who demonstrated symbiogenesis (the coming together of two species to form a new one) as a significant step in evolution, challenged Dawkins by saying that there is more involved in the inheritance of a character than DNA.
‘I would embrace that gladly as a new “honorary” gene. That’s fine,’ Dawkins quickly replied as the audience groaned.
‘Why not, why not?’ Dawkins insisted.
So, in that sense, Dawkins’ trick is that a gene is anything and everything that is inherited. Yet the thesis of The Selfish Gene requires genes to be discrete entities whose frequencies can be measured.
Can a Gene Be Selfish?
You might think this is simply a problem of semantics, but it is important in understanding what genes do. A gene cannot be selfish if it is simply part of something else that is the purposive entity – the organism. Only the purposive entity could be considered selfish. Genes do not and cannot make choices; organisms can and do. You might also think that ‘selfish gene’ is simply a colourful metaphor. If that is so, then it is a powerful misrepresentation of the concept of selfishness, which can only be attributed to wilful beings performing deliberate acts. Yet it is a seductive argument: we are selfish because of our genes, since we exist to pass genes from one generation to another. As Dawkins writes, the genes are ‘manipulating it [the organism] by remote control’.
Slippery or not, genes are insufficient to account for development and function. Genes alone are not responsive to changing circumstances. Their expression is a function of the system as a whole, not of the gene itself. Genes are not ‘swarming within us’, controlling our function, and certainly not on a moment-to-moment basis. On the contrary, they are highly regulated; else, we as organisms would have no coherence. So, just as the paint on an artist’s pallet cannot alone form a picture, so genes cannot create an organism.
Genes Do Not Make Choices
In this sense of being used by the system, genes are not agents in causality; they are templates, tools enabling the organism to develop and function. Indeed, much of what is necessary for organisms to function is not inherited at all. It develops with the organism and might require learning. The functional development of our visual system, for example, requires experience of our visible world. The number of synapses (the tiny functional connections between nerve cells) in the visual cortex per hemisphere is around 32 billion in rats and a staggeringly large number in humans. These are honed after birth and during early life. The complex connections of our brains continue developing into our late twenties. So interactions with the environment are involved in guiding and organising these complex functional anatomical arrangements. Genes alone are not sufficient.
Similarly, our social functioning requires interactions as social beings. The amygdala, for example, is an area of the brain that is thought to attach emotional value to faces, enabling us to recognise expressions such as fear and trustworthiness, while the posterior superior temporal sulcus predicts the end point of the complex actions created when we as agents act upon the world. That is, we anticipate the world, and in large part this requires learning. These complex interactions are not governed by genes, which is why early-life experiences may have such critical effects upon us – on our emotions and character traits.
A False Dichotomy
Even if we could clearly define genes as discrete entities, their contribution to our functionality cannot be understood apart from organisms or their habitats and life experiences. So, for a large part of our lives, there is no need for genes other than in some of our capacities to act (see Chapter 4). Most of our decisions as humans do not engage with genes directly at all. If we decide to be kind to someone, we do not engage a kindness gene; if we are cruel, we do not engage a cruelty gene. Even entirely unconscious functions such as our heartbeats, so essential to life, do not directly involve genes.
Early Transitions in Evolution
One of the major transitions in the evolution of life was the cooperation of microscopic cellular organisms to form multicellular organisms. They can range from simple aggregations of many similar unicellular organisms into colonies, as for example in Volvox, the globe algae that can form spherical colonies of as many as 50,000 cells. At the other extreme are organisms like us with many colonies of separately specialised cells, arranged as individual organs and tissues.
That change to multicellularity enabled living organisms to become much larger. But it also created a problem. Cells need to access food and respiratory gases. Single-cell organisms can do that by exchanging material directly with the watery environment in which they grow and divide. The molecules simply diffuse within the water. However, there is a limit to the distance over which this can occur sufficiently quickly, and that limit is microscopic. It is around 50 micrometres (µm), which is only about one-twentieth of a millimetre, about the thickness of a hair. Incredibly, all the cells in our bodies are bathed in moving fluids that get this close to the cells. This is the circulatory system, and at its centre lies a pump, the heart, while out in the rest of the body it branches into a fine meshwork of capillaries. They bathe all the cells of our bodies sufficiently rapidly that they can all take up nutrients and oxygen and pass back carbon dioxide and other molecules they need to get rid of.
The First Organ
Something needs to work to push the fluids around the body, and it needs to develop as the first functioning organ of the body. The embryo cannot grow beyond a very tiny mass of cells unless this happens. Long before any other organs and body shapes such as limbs and digits form, a tiny tube of cells starts beating. In humans, this may be as early as 3–4 weeks after conception. But you would not be able to hear this heartbeat until a little later (it can be picked up on hand-held ultrasound or stethoscope at around 8 weeks).
How does it do that? The heartbeat is extremely robust. In a typical human lifetime, it will continue for 3 billion times over a period of 70 or more years. Like other critical life processes, it has therefore to be very robust.
Genes and the Heartbeat
What role do genes, as DNA sequences, play in this critically important process? The answer is that they enable the essential proteins for heart rhythm to be made. They provide the templates from which all the types of proteins are made, which then sit in the cell membrane and enable ions (electrically charged atoms) to cross the heart cell membrane. It is through these channels that tiny electrical currents flow to initiate the heartbeat; and it is this electrical activity that is picked up in an electrocardiogram (ECG). But what controls this process? The answer is, the heart cell itself. The cells literally tell the genome how much of each type to make. The genes do not themselves generate heart rhythm.
The reasons for that are interesting. There are ways in which a DNA sequence could be involved in a cyclical process that generates rhythm. The daily rhythm we call circadian sometimes does involve a causal sequence that involves a DNA sequence.
But heart rhythm could not possibly do that. It is far too fast. It takes tens of minutes or even hours for the production of protein to occur after the activation of a gene. The heartbeat is usually faster than 1 per second. There is no time for any change in the production of particular proteins.
What happens therefore is that the proteins and their interactions with each other, membranes, and many other chemicals somehow generate rhythm. How they do this is fascinating.
The story has so far developed over around 60 years of research. In 1960 one of the authors (DN) was working with his thesis supervisor on a very few of the proteins that form ion channels in the heart. At that time only four channels were known: a rapidly activated sodium channel, two potassium channels, one of them very slowly activated, and an anion (a negative ion) channel. But this was enough to show a very important property of cells. The interactions between the proteins, the membranes and the networks within which they find themselves can automatically produce a rhythm as important as the heartbeat. They do so by using a universal electrical property of cells. Their membranes and proteins can generate and maintain large electrical differences between their interiors and their exteriors. Expressed as a voltage, it is small, typically lying between minus 100 mV (only 0.1 volts) and about plus 50 mV (0.05 volts). But the membrane is extremely thin, so these voltage fields can be as large as 30 million volts per metre. That is a huge field strength, equivalent to a bolt of lightning.
Now we come to an important consequence of the strength of that field. It can cause proteins to change shape. In the case of ion channel proteins, the shape change can be the difference between the channel being open and being closed.
When they are open, the channels themselves cause changes in the voltage, since they carry charged particles into or out of the cell. So the proteins and the cell membrane form an automatic feedback loop (Figure 1.1). A change in protein shape can cause a change in field, which in turn causes the channel to open or close. Some channels open when the cell electrical potential becomes positive, others close.
Figure 1.1 Feedback loop between cell voltage and protein channels. Changes in cell voltage open and close protein channels, which then change cell voltage.
What was shown 60 years ago is that this feedback loop is sufficient to produce electrical rhythm. No single protein, nor the gene forming its template, can do that alone. The interaction is the key. It can and does generate rhythm, and at about the same frequency as natural heart rhythm.
So was the problem of heart rhythm solved 60 years ago? Yes and no. Yes, because it was possible to show mathematically that rhythm of the right frequency could be generated by this mechanism (Figure 1.2). No, because the rhythmic mechanism is very fragile. Knock out any one of those four proteins, or their DNA templates, and the rhythm would suddenly stop.
Figure 1.2 The first mathematical model of electrical heart rhythm, based on early experiments on sodium and potassium channels in heart cell membranes. The calculated voltage changes show voltage changes during heart rhythm very similar to that in a real heart. The rhythm is generated by the opening and closing of ion protein channels and results from the feedback interaction (Figure 1.1) between the channels and the cell voltage.
What subsequent research has shown is that many more than four proteins are involved. So many that, even when one of the key proteins is knocked out or blocked, the rhythm continues.
This is a fundamental property of the networks of interactions in living organisms. They are fail-safe. That robustness depends on the involvement of many genes and their proteins. Even when one is absent, the networks still function well. This is the fundamental reason why association between any one gene and function in the organism has been found to be exceptionally low. It is also a reason why getting your DNA sequenced will usually only tell you a limited amount of information on the diseases you are likely to suffer from. Only if you suffer from a serious but rare genetic disease will the information be useful. But you and your doctor will usually know that anyway from your symptoms and family history.
Genes and Causation
So the problem of genes arises not only from how they are defined, but also from how we view what they do or why they are needed. Most of the time, from moment to moment, life carries on its vital functions without directly using the store of templates that we call genes. Those are used only when more proteins need to be made. Giving causal primacy to what is inherited has led to a profound misunderstanding of organisms and life. Yet modern science has given these poorly defined entities a role both as primary causal agents and as the ultimate measurable objective of life. In that view, we exist to preserve our genes.
The difficulty of providing an acceptable definition of a gene is the key to a surprising proposition. The problem can be put in one simple question: do genes exist? This may seem an absurd question. Yet it is a necessary one – because genes do not exist in the way that is often assumed or thought. In large part the gene is illusory, at least in the sense that there is not a gene for this and a gene for that. Nor are genes directly causal of function. Let us examine this further.
More Is Inherited Than the Genome
If the word gene is taken to mean anything inherited, then we are left with a tautology. It is definitively true that an extended version of ‘gene’ must be anything inherited. This gets us nowhere. The circularity of this argument is apparent. If we end up saying a trait is a gene, then the concept of a gene as a causal factor in a trait is meaningless.
Consider the complexity of arrangements in an economy. The goods you get from a store are not themselves accountable for you purchasing them. Inheritance is a process, not a discrete, measurable entity. What we inherit is a propensity to do things. So we inherit not in two discrete parts, cause (gene) and effect (trait). We inherit a capacity of becoming or being, where cause and effect are one, as in generating heart rhythm. There isn’t a gene that determines the price of goods; there is a complex interaction between producers and consumers. Nor is there a gene that determines that you will always buy the cheapest. If you think this is insignificant, consider that your life and how you live are primarily influenced by this interaction. Nor is there a gene or genes for the most significant aspect of our lives, our habitats. It might be said that markets operate on the assumption that we are inherently selfish; but it might equally be the case that we are selfish because of the way markets operate. Behaviourally, functionality is not directly influenced by genes.
Yet we inherit our created environments, for the most part, modifying them and passing them on to generations to come. This includes our homes and the things we use in our lives. The same is true of our culture. We also inherit our ideas and develop them, changing our view of the world in which we live. This is why we write books, plan and work together in solving problems. Where something does not work, it can be discarded or changed. This is not in our genes. This is the nature of the environment within which our behaviour evolves and changes. It is too simple to see us as hunter-gatherers living in a concrete jungle, for our biology changes in relation to our environment. We continually create and are part of our environment. This active creation influences us, body and mind. This is a continuous process of change and adaptation. Understanding how our built environment influences our wellbeing is important. Just as we see in our hearts, genes are not directing our behaviour.
Genes Are Not Agents
So inheritance and genes are two separate concepts. Adopting too readily the idea of genes as the sole agents of inheritance is a mistake. Genes can have no such agency and furthermore cannot contain all the information that life needs. We should move from ‘genes for everything’ to a more refreshing view that life requires no such discrete agency. If genes are not agents, perhaps we don’t need them, or the gene of the textbook does not exist. So, then, what is a gene? The common view of the gene is that it is a package of information that is used to create something or do something. However, as we have seen, the meaning of the word ‘gene’ depends on its usage. When challenged with evidence for inheritance independent of DNA, Richard Dawkins replied that the word ‘gene’ includes anything that is inherited. As we have seen, this is meaningless. Genes in that sense are vague and malleable rather than the discrete functional entities required in the context of the ‘selfish gene’. We certainly need tools that enable organisms to build proteins and maintain the fabric of cells, tissues and organs. But this is undoubtedly not Dawkins’ gene. So where did the contemporary concept of the gene come from?
The Modern Synthesis
The concept of a gene as an independent hereditary unit was formulated as the Modern Synthesis of evolutionary biology in the 1930s and 1940s. This was not a Darwinian synthesis, since it specifically rejected some of Darwin’s key ideas, including the inheritance of acquired characteristics, sexual selection and much else. The objective was to reduce Darwin’s ideas to a narrow version of what he actually said. The only synthetic aspect was to incorporate Mendel’s work. The assumption is that each gene is responsible for specific characters. It focuses on genes by assuming that characters are determined by genes. It formed the basis of what is now called population genetics, based on calculating the frequencies of ideally independent characters as genes.
With the discovery of the structure and role of DNA in the 1950s, the concept of a gene changed again, producing a specific molecular basis for the gene: DNA sequences, forming templates for proteins. Seeing genes as discrete functional entities of inheritance led to another sleight of hand: conceptually separating the genome from the organism and then regarding organisms as vehicles for passing genes from one generation to the next. Thus, maintaining genes in the population became both a measure of life’s success and its ultimate purpose.
A Conceptual Error
Conceptually, genes were given a life of their own in life’s narrative, as if they were manipulating organisms to their own ends. Like drivers of cars, they were seen to be controlling the destination. In this view, genes are primary causal agents, and because they are discretely passed from generation to generation, it is the genes themselves that are the subjects of natural selection in evolution. Organisms were reduced to mere vehicles, carrying genes to the next generation, with the survival of genes the primary objective of life. It is a curious fairy tale in which genes are selected, phenotypes are not. The story came with a fantasy land called the ‘gene pool’. Yet it is the phenotype that acts in nature.
The ‘Gene Pool’ Mythology
This gene-centric view is now culturally embedded; so much so that it is difficult to challenge. Thus the myth of genes as causative agents was born, a belief system that traits are determined by genes. Yet counting genes in a ‘gene pool’ as the objective of life is a meaningless concept. It carries little weight in terms of functionality, just as counting shoelaces tells us little about the function of boots and shoes, other than that they might require different lengths of lace. It is certainly not the purpose of boots to carry shoelaces.
The Dualist Problem
The mechanistic view of life has prevailed and has led to a mistaken view of causality in living systems. René Descartes thought that living organisms were like machines. All animals are automata. This created a fundamental problem that persists to this day, which is that, if this is so, where does our freedom of will to act come from? Descartes’ solution to this problem was to suggest that only humans have a soul and could feel pain. This separation of mind and body is now called Cartesian dualism. Humans had the (mechanical) body of an animal, but the freely acting separate soul of a human.
Descartes was both a scientist and a philosopher. In the seventeenth century it was not unusual for scholars to cover both disciplines. In many ways, it is a pity that people now think science and philosophy are separate disciplines. We are taught that scientists study facts while philosophers merely speculate. But the way in which we interpret facts depends on how we see them, in what context, and on what they might mean. We make assumptions about the world, not all of which are directly testable. But it is better that we know this, for it can prevent simple errors of interpretation. Everything we see, hear or feel depends on how we interpret our senses.
This separation of mind and body and the gene-centric view have something in common, which is that they both look for an organiser of something that is in fact self-organising: the organism.
In his treatise on man (De l’homme), published posthumously in 1662, Descartes explained his ideas on the embryo:
If one had a proper knowledge of all the parts of the semen of some species of animal in particular, for example of man, one might be able to deduce the whole form and configuration of each of its members from this alone, by means of entirely mathematical and certain arguments, the complete figure and the conformation of its members.
The Gene-Centred Duality
It is a beguiling idea. When we look down a microscope at a cell, we see a distinct nucleus containing a large part of the cell’s DNA in the chromosomes. It is easy enough to perceive the nucleus as a central governing structure, sending out its instructions to the cell, a bit like central government in London or Washington DC. But it isn’t, and it doesn’t. On the contrary, it is controlled by the cell and by the organism.
This idea of a central governing structure is at the origin of the development of a great twentieth-century illusion: the Central Dogma of biology. Descartes expresses the idea very clearly. It is that by knowing all the component parts of the semen one could mathematically predict the development of the embryo and the future adult. The modern version is of course the idea that the development of the embryo is specified by the genome, sometimes itself called ‘The Book of Life’.
The Central Dogma and the Human Genome Project make a fundamental error in attributing purpose to genes. However, genes are not alive and can do nothing without the organism. This conceptual separation of the genome from the organism has produced a new kind of dualism where the genome is considered to be the main driving force of all our behaviour, and makes the fundamental error of assuming that organisms only exist to preserve the genome.
