Evolution’s struggle for existence

This article is a revised version of Evolution in evolution (2019), written for the Magdalene College Magazine (2024–25).

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The conception of Evolution as proceeding through the gradual transformation of masses of individuals by the accumulation of impalpable changes is one that the study of genetics shows immediately to be false. Once for all, that burden so gratuitously undertaken in ignorance of genetic physiology by the evolutionists of the last century may be cast into oblivion.

William Bateson (1909), p. 289

The first edition of Charles Darwin’s On the Origin of Species by Means of Natural Selection (1859).
(Credit: Scott Thomas Images.)

THERE IS A WIDESPREAD popular construction of scientific revolutions as singular events which unfold, bolt-like and final, in the blink of an eye. Names like Galileo, Newton or Einstein are typically invoked as those of mythical figures with a miraculous capacity single-handedly to transform the way we see the world. It appears, however, that the kind of sweeping, dramatic breaks of paradigm which we have come to associate with scientific revolutions are rather hard to come across today. One may speculate — and be forgiven for it — that this may be the result of certain changes in the nature of academic work, by which the progress of research has been throttled to make space for an ever-swelling volume of inescapable paperwork. But the truth is that, rather than stalling, scientific progress is now considerably faster than it has ever been. The actual reason why sharp and sudden scientific revolutions of the kind encountered in popular science books are nowhere to be found today, is that such events are not revolutions in the usual sense of the word. Rather than cataclysmic changes, these are painfully protracted processes which require decades of cumulative scientific work to mature and develop. While both science popularisers and scientists themselves — not to mention the film industry — are very often guilty of misrepresenting scientific discoveries by filtering them through an almost Wagnerian dramatic lens, the reality is that, academics being sceptical and proud creatures by nature, every great conceptual shift must be slowly percolated, rather than poured, into the pool of accepted knowledge. To name but one example, the double-helix structure of the DNA molecule, now hailed as the central biological breakthrough of the second half of the twentieth century, was regarded by many as little more than a theoretical possibility years after it was first proposed. Even Sir Isaac Newton, that weary archetype of supernatural scientific genius, had to endure a decades-long intellectual war of attrition with his Continental competitors before his law of universal gravitation became widely accepted outside Britain.

Among the documented cases of gradually unfolding scientific revolutions, one stands out for being both particularly interesting and surprisingly obscure; this is the story of how Charles Darwin’s theory of evolution by natural selection came to be the main unifying idea of biology. Contrary to popular belief, this was no swift revolution, but rather a drawn-out process of fierce scholarly debate which began with the publication of Darwin’s ideas in 1859, and which would not relent until the late 1940s. During this period, the differentiation of biology into several new disciplines created the conditions for a chasm to grow between classically trained naturalists and a new breed of experimental biologists. As a result, evolutionary thought split into two mutually opposed currents which would only be reconciled with the eventual development of a unified theory of evolution.

During his lifetime, Darwin witnessed his theory of natural selection gain acceptance and esteem among a small circle of naturalists and evolutionary biologists. This cadre of early Darwinians included Alfred Newton, the first Professor of Zoology at Cambridge, who wrote: ‘I never doubted for one moment, then nor since, that we had one of the grandest discoveries of the age — a discovery all the more grand because it was so simple’ (Newton, 1888, p. 244). This limited success notwithstanding, Darwin never experienced the ultimate development of his theory into the undisputed cornerstone of biology which it is today — a status best encapsulated by Theodosius Dobzhansky’s famous aphorism that ‘Nothing in biology makes sense except in the light of evolution’. In fact, it might be difficult for present-day biologists even to conceive the extremes of opposition which so-called ‘Darwinism’ faced throughout the late nineteenth century, and until as late as the 1930s.

At the time, Darwinism was only one among a number of discordant theories attempting to explain the processes whereby biological species develop. Some of these, now referred to as ‘essentialist’ theories, were built on a notion of species as uniform ‘lines’ of virtually identical individuals, each made in the image of an unchanging ‘essence’ (a concept plainly borrowed from Platonism). Essentialist thinking therefore rejected the existence of significant natural variation within a species. On the other hand, ‘populationist’ theories viewed species as populations composed of distinct, unique individuals, and thus inevitably carrying a substantial degree of natural biological variation; examples of such variation could be differences in adult size, coat colour or leaf shape. Furthermore, some theories presumed the existence of ‘soft inheritance’, characterised by the notion that the hereditary material (what we now call ‘genes’) can be altered to some extent through the interaction of the organism with its environment. Lamarck’s theory of evolution by inheritance of acquired characters stands out as a notorious example of this current, positing that any physiological changes acquired by an individual during its life will be inherited by its descendants. Other theories, in contrast, admitted only ‘hard inheritance’, by which the hereditary material cannot be modified through interaction with the environment, meaning that the characters acquired by an individual during its own life are not passed to its offspring. Modern biology has supplied overwhelming evidence against the notion of soft inheritance; we know that, at least in animals, the germ cells which transmit an individual’s genes to the next generation are sequestered away from other tissues, such that environmental modification of the genetic material in these cells is prevented. (This does not include systemic exposure to certain aggressive agents not normally found in nature, such as X-rays and chemical carcinogens, which are known to induce changes to the germ cells’ DNA; furthermore, while recent discoveries of heritable epigenetic changes in some species have been argued to challenge the notion of strict hard inheritance, the validity of such arguments is still under debate.) It might therefore come as a surprise that nearly all the early theories of evolution, including Darwin’s, allowed some degree of soft inheritance. In particular, Darwinism originally assumed a certain plasticity of the genetic material, such that it could be modified to an extent through the use or disuse of certain organs during life; Darwin believed that such a process would assist natural selection in allowing species to adapt effectively to their environment. Some of Darwin’s supporters, notably the biologists August Weismann and Alfred Russell Wallace, would later develop an elaboration of Darwin’s theory known as ‘neo-Darwinism’, which definitely rejected the possibility of any kind of soft inheritance. Through his own extensive studies of natural populations in Southeast Asia, Wallace had independently arrived at a theory of evolution which was fundamentally similar, though less developed, than Darwin’s; it was knowledge of this fact which finally spurred Darwin to publish the theory on which he had been quietly working for two decades. Before the publication of Darwin’s book, Darwin and Wallace (1858) decided to present a summary of their conclusions in a joint communication to the Linnean Society.

Based on principles such as soft and hard inheritance, essentialism and populationism, a diverse array of evolutionary theories was put forward between the 1860s and the 1940s, of which Darwinism was seldom among the favourites. The chief factor compelling authors to support one theory over another was their particular field of expertise, and the number and variety of such fields within biology was expanding as never before, with emergent disciplines including embryology, cytology and ecology. Yet, from the standpoint of evolutionary thought, one of these new sciences was undoubtedly more impactful than any other: the science of genetics, born out of the unexpected rediscovery of Gregor Mendel’s laws of biological inheritance in the year 1900. The early geneticists built on the knowledge recovered from Mendel’s writings and began developing a detailed understanding of the principles of genetic mutation and inheritance. The spark of this new understanding, however, far from kindling any concerted progress in evolutionary biology, would serve to ignite a long and vicious conflict among the different biological disciplines.

Illustration of the inheritance of seed characters in pea (from Fig. 3 in Bateson 1909). A plant from a variety with green round seeds, when fertilised with pollen from a variety with yellow wrinkled seeds, produces yellow round (YR) seeds (F1). In genetic terms, this indicates that the characters of ‘yellowness’ and ‘roundness’ are both dominant. When crossed among themselves, however, the seeds borne by these new plants (F2) present a distribution of characters which is closely predicted by Mendel’s laws of inheritance.

From the outset, the founding fathers of genetics stood in opposition to Darwin’s idea of natural selection as the main driving force in evolution. Both the first geneticists and the earlier palaeontologists interpreted their own observations as being plainly in accordance with the hypothesis that new biological forms emerge by means of discontinuous change, or ‘mutation’. A mutation was defined as a discrete modification of the genetic material causing a visible and often disruptive physiological change in the organism. Such events, the geneticists argued, would sometimes result in the instantaneous transformation of an existing species into a new one, without the production of intermediate forms. This theory, which drew implicitly on essentialist principles, was known as ‘saltationism’ because of its belief in speciation by ‘saltation’ — a large evolutionary leap leading from one form to another. It provided a counterpoint to Darwin’s theory, which relied on a ‘gradualist’ conception of evolution derived from populationist thinking, whereby species gave rise to new species in a gradual manner, through a continuous succession of intermediate forms. Outlandish as it may sound today, saltationism fitted the experimental observations of geneticists, as well as prior palaeontological evidence, outstandingly well. The extreme sparsity of the fossil record meant that palaeontologists could never witness a continuous progression of forms linking two related species, whereas geneticists were accustomed to working with uniform stocks of nearly identical individuals — typically plants or mice — as a means of minimising experimental interference. The mutants produced in these genetic experiments presented dramatic physical modifications which were inherited by their offspring in accordance to Mendel’s laws. It seemed logical, then, to suppose that mutations such as these, infrequent but highly disruptive events, were the force behind the origin of new species. In the geneticists’ defence, it must be pointed out that we now know of cases where new species have indeed emerged through a singular genetic alteration, such as the duplication of the entire genome in some plants. The idea of speciation by saltation is therefore not impossible, but saltationism as a theory lacks the generality required to explain the evolution of most known species.

Furthermore, there was an additional problem plaguing Darwinism. The physiological basis of inheritance was entirely unknown in the nineteenth century, and Darwin had implicitly made recourse to a theory known as ‘blending inheritance’, according to which an organism’s constitution is a smooth average of its parents’ constitutions. The rediscovery and confirmation of Mendel’s work quickly proved that inheritance does not operate in this way, but rather through the segregation of discrete, individual genes from parent to offspring. Indeed, it could be shown mathematically that blending inheritance would lead to a situation where every individual in a species would display the exact same form of every trait, rendering evolution impossible. Geneticists thus argued that Darwin’s entire notion of gradual evolution, based on continuous variation, blending inheritance and natural selection, was simply untenable in the light of their experimental results. Some of the most distinguished early geneticists, including T. H. Morgan and William Bateson — the latter of whom translated Mendel’s work into English and coined the very term ‘genetics’ — went so far as to declare that genetics had finally put an end to Darwinism (see Bateson’s words at the beginning of this article). It should be borne in mind, however, that genetics was itself a controversial discipline at the time, composed of multiple competing strands; and the early geneticists, or ‘Mendelians’, were just as anxious to establish the validity of their own views on heredity as were the Darwinians to see their evolutionary ideas vindicated. Moreover, in spite of their opposition to Darwinism, the contributions of this first generation of geneticists — most notably the elucidation of the laws of heredity, the discovery of genes and chromosomes, and the refutation of the notion of soft inheritance — would ultimately prove essential to the refinement of evolutionary theory.

In contrast to the geneticists, those biologists who had been trained as naturalists, including zoologists and botanists, were used to deriving their conclusions from the direct study of natural populations, and they insisted that their observations of natural diversity were in perfect agreement with Darwin’s theory of gradual evolution through natural selection. The true root of the disagreement probably lay in the utter lack of communication between the two camps: naturalists and geneticists not only held competing theories, but also followed very distinct approaches to scientific enquiry, pursued divergent biological questions, attended different meetings, read and published in different journals, and even employed distinct vocabulary, including incompatible definitions for such fundamental terms as ‘species’ and ‘mutation’. In addition, geneticists appeared to view naturalists as speculation-lovers who were incapable of subjecting their ideas to proper testing, while naturalists had a tendency to dismissing geneticists as narrow-minded experimentalists who lacked experience of real natural populations. Misunderstanding and resentment compounded easily under such an atmosphere, gradually carving an ever deeper chasm between both disciplines. Astonishing proof of this circumstance comes from the fact that, when a younger generation of theoretical and experimental geneticists — including Sir Ronald Fisher, J. B. S. Haldane, Sewall Wright and H. J. Muller — began to obtain, from the late 1910s, fresh results demonstrating how the accumulation of effects from many discretely inherited genes can give rise to the continuous diversity described by naturalists (see figure below), and therefore how Mendelism and neo-Darwinism were in fact compatible, this did little to bridge the huge divide between geneticists and naturalists. Instead, because of the alienation brought about by constant hostility, scholarly communication was impaired to such an extent that the naturalists would spend decades persevering in their efforts to refute the already obsolete ideas of the earlier geneticists.

Illustration of Fisher’s (1918) ‘infinitesimal model’, explaining the emergence of continuous biological variation from the combined contribution of a large number of discrete Mendelian genes, or loci. Each row in the diagram presents a simulated distribution of population values for a trait determined by an increasing number of individual genes. The bars on the left-hand side indicate the individual effect of each gene contributing to the trait (ranging from only two genes in the top case to 500 in the bottom case). The right-hand side provides the corresponding distributions of trait values in the simulated population, showing how the values for a trait become more normally distributed as the number of genes increases. This explains why many physiological characters in humans and other species follow a normal (or Gaussian) distribution. (Credit: Chamaemelum/Wikimedia Commons.)

In this way, naturalists and geneticists would go on treading along separate paths for the first three decades of the twentieth century, each dragging their own conceptual burdens: the naturalists held obsolete views about the nature of genetic mutation and inheritance; the geneticists were hampered by saltationist views and by the belief that the evolution of species could be understood by extrapolation from the evolution of single mutations in experimental settings. Even as late as the 1930s, when crucial experiments in artificial selection, together with the work of the first mathematical geneticists, were demonstrating beyond any doubt the reality of evolution by natural selection, specialist textbooks still listed up to six potentially correct theories of evolution.

This stagnant atmosphere would finally be cleared in the 1940s, mainly through the insight of one palaeontologist, George Simpson, and two zoologists, Julian Huxley and Bernhard Rensch. Perhaps the only scientists of their generation who had amassed a profound knowledge of the latest advances in each of the relevant disciplines, they published three independent books (Huxley, 1942; Simpson, 1944; Rensch, 1947) describing how the findings of zoologists, botanists, geneticists, palaeontologists and others could be integrated into one self-consistent theoretical framework which could explain the entire evolutionary process. In his book (which happened to be published first due to circumstances arising from the Second World War), Huxley christened this new theory with the name by which it is known today: the ‘modern evolutionary synthesis’. The modern synthesis states that the gradual evolution of species can be explained in terms of the accumulation of myriad genetic mutations with generally small effects, in conjunction with recombination (the shuffling of genetic material as it is passed from parent to offspring), and the action of both natural selection and stochastic processes on the genetic diversity produced by mutation and recombination. One key feature of the theory is that it explains how these low-level genetic and selective mechanisms give rise to high-level evolutionary processes, including the origin of species, genera and higher taxonomic levels.

The forging of the modern evolutionary synthesis was not in itself a scientific revolution, but rather the conclusion of a protracted paradigm shift initiated by Darwin and Wallace nearly a century earlier. Such a conclusion did not entail the victory of one scientific tradition over another, but the fusion of two radically different conceptual frameworks — naturalism and experimentalism — into one whole. For such a milestone to arrive, a number of obstacles, grown through the persistent isolation between the opposing camps, first had to be cleared up. In the end, this was achieved by those who, rather than focusing on their own narrow specialism, were sufficiently curious to learn about the advances made in other fields, and sufficiently open-minded to notice the commonalities latent underneath the conflict. The legacy of the modern synthesis was the unification of evolutionary biology into a single field; after its arrival, the discord and hostility which had reigned for half a century gave way to widespread agreement. And the bridges erected then would remain solidly in place until the present day: although there is still debate regarding particular aspects of the theory — such as the conceptual implications of epigenetic memory and horizontal exchange of genes between organisms — the basic framework of the synthesis has remained essentially intact since the 1940s.

The history of the modern evolutionary synthesis, our current framework for understanding evolution, is of value to scientists and historians alike. The long series of discoveries and conceptual advances linking Darwin’s original theory to our unified interpretation of the evolutionary process provides an illuminating example of the consequences of such phenomena as have manifested themselves time and again in the history of science: resistance to new ideas, deficient communication compounded by semantic differences, and excessive specialisation leading to tribalistic sentiments of superiority towards foreign disciplines. Hopefully, this story also offers a lesson in how exploring the history of scientific ideas allows much deeper understanding than the mere study of their definitions; for while definitions carry a pretension to simplicity and finality, the history of science conveys the truth that science is a living process, the progress of which is fundamentally arduous, incremental, and positively fraught with quarrel.

References
Bateson, W. (1909). Mendel’s Principles of Heredity (Cambridge University Press).
Darwin, C., Wallace, A.R. (1858). On the Tendency of Species to form Varieties; and on the Perpetuation of Varieties and Species by Natural Means of Selection. Journal of the Proceedings of the Linnean Society of London. Zoology, 3 (9): 45–62.
Darwin, C. (1859). On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life (John Murray).
Fisher, R.A. (1918). The Correlation between Relatives on the Supposition of Mendelian Inheritance. Transactions of the Royal Society of Edinburgh, 52 (2): 399–433.
Huxley, J. (1942). Evolution: The Modern Synthesis (Allen and Unwin).
Mayr, E. (1980). ‘Some Thoughts on the History of the Evolutionary Synthesis’, in The Evolutionary Synthesis: Perspectives on the Unification of Biology (Harvard University Press).
Newton, A. (1888). Early days of Darwinism. Macmillan’s Magazine, 57: 241–249.
Rensch, B. (1947). Neuere Probleme der Abstammungslehre (Enke).
Simpson, G.G. (1944). Tempo and Mode in Evolution (Columbia University Press).

The causes of ageing

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To get back my youth I would do anything in the world, except take exercise, get up early, or be respectable.

Oscar Wilde, The Picture of Dorian Gray

Detail from Old woman and boy with candles (c. 1616–1617) by Peter Paul Rubens.

EVERLASTING YOUTH is one of humanity’s perpetual aspirations. None of us are impervious to the effects of old age, either in ourselves or in those we love. Yet, more than an inescapable element of the human condition, ageing is in fact a universal biological feature of complex animals, and possibly of all life. Biologically speaking, ageing is a gradual decline in the capacity of the cells and tissues in a body to preserve their integrity and carry out their central physiological functions. The ultimate consequence of this process is the body’s inability to sustain its own existence, leading to an inevitable death from ‘old age’. Regardless of how much effort is devoted to prolonging life, humans and other animals seem to carry an intrinsic ‘expiry date’. But why should this be so? How did such an implacable force of decay come to exist, and why do we humans seem unable to vanquish it?

The question of what causes ageing, which can be traced as far back as Aristotle, is in fact composed of two very distinct questions. The first is the question of why we age: what is the ultimate biological reason for the fact that animals have never evolved the capacity to live forever? The second question is that of how we age: what are the immediate physiological processes which cause bodies gradually to decay over time? The degree to which we understand ageing may be expected to vary between these two levels of analysis — but it may come as a surprise that it should be our understanding of how we age, rather than why we age, which remains very much undeveloped. The following presents our current scientific perspective on these two dimensions of the ageing process.

Why we age: Evolutionary causes of ageing

The universality of ageing among animals was a troublesome fact to early evolutionary biologists. In the mid-nineteenth century, Charles Darwin had proposed that the biological traits of organisms were the outcome of evolution by natural selection, and therefore had probably been useful for the survival and reproduction of previous generations. How is it, then, that evolution has not crafted organisms with the clearly beneficial capacity to maintain their youth indefinitely?

The first evolutionary explanation of ageing was proposed by the nineteenth-century biologist August Weismann. An early supporter of Darwin’s ideas, Weismann was a key figure in the development of early theories of biological heredity. To him, the evolutionary paradox of ageing could be resolved if one assumed that an animal’s longevity is indeed the product of natural selection — but not because of any benefit to the animal itself, but rather to the species as a whole. He proposed that the duration of life — the lifespan — has evolved to an optimal value which spares the population from being smothered by a preponderance of old individuals. In Weismann’s account, ageing is therefore a death mechanism explicitly evolved for the purging of older, less competitive generations, enabling the success of younger individuals. Remarkably, this theory was in fact a Darwinian makeover of the views of the ancient Roman poet and philosopher Lucretius.

Weismann’s explanation of ageing, although intuitively cogent, was found by later evolutionary biologists to be flawed. For one thing, the argument that older individuals should be purged because they are less fit than younger ones immediately invokes an assumption that individuals experience physiological ageing. But to infer the evolutionary origins of ageing, we must begin with a population whose individuals do not age, and thus can only die through extrinsic forces such as predation, infection, starvation or accident. In such a population, there is no reason to assume that older individuals should be at a disadvantage — if anything, the fact that they have survived for longer implies that they are, on average, better survivors. Moreover, older individuals should have amassed precious expertise in the manoeuvres and tactics of living, such that they should offer formidable competition to youngsters. Therefore, without the assumption of an ageing process, the death of older individuals cannot easily be defended as of benefit to the species.

Another powerful argument against Weismann’s theory is the now-established fact that traits which benefit the collective at the expense of the individual are evolutionarily unstable. In most situations, natural selection operates overwhelmingly at the level of the individual: if one deer is, for instance, able to outrun the others, it will be less likely to be preyed upon, and hence more likely to leave offspring, which will inherit its superior speed. In the same manner, if a species were to evolve an ageing process that were beneficial to the species but disadvantageous to the individual, then any individual happening to age more slowly than the rest would be at a considerable advantage, just like the faster-running deer, and so this trait would be favoured by natural selection. Ageing therefore cannot have evolved for the sole benefit of the species; if Weismann appears here to have misjudged the implications of Darwin’s theory, it may be said in his defence that Darwin himself would have fared no better. It is only after one and a half centuries of thought that we have come to understand ageing not as a consequence of the direct action of natural selection — but rather of its failure.

One of the earliest hints at the concept which underlies modern evolutionary theories of ageing was advanced by the influential mathematical geneticist JBS Haldane. During an inspired series of lectures in 1940, Haldane noted in passing that natural selection should have little power to suppress a deleterious trait if such a trait only manifests itself late in life. To see why this is the case, let us consider Haldane’s case of interest — Huntington’s disease. Despite its devastating and fatal effects, this degenerative condition typically has its onset after the age of thirty, and hence has little impact on a person’s ability to have children. By the time the disease is diagnosed, the patient’s children may already have inherited the responsible gene. Haldane correctly saw this as the reason why such a pernicious gene has not been purged by evolution. The impact of Huntington’s disease is confined to adulthood, a period of life in which the strength of natural selection declines dramatically, since reproduction has already taken place. This period is now termed the ‘selection shadow’, because biological effects within it are effectively ‘out of sight’ for evolution.

Diagram illustrating the concept of the ‘selection shadow’, referring to the progressive decline in the strength of natural selection after the age of reproductive maturity (Credit: A Baez-Ortega).

The concept of the selection shadow was first developed into a complete theory of ageing by the Nobel laureate Sir Peter Medawar, who in the 1950s attempted to explain ageing as the combined effect of a collection of ‘mutant genes’ — altered versions of ‘normal’ genes — whose effects only arise late in life. Just as in the case of Huntington’s disease, age-related conditions such as cataracts, arthritis and osteoporosis have a late onset and no impact on reproduction, which precludes natural selection from weeding off the implicated ‘mutant genes’. A large number of these problematic genes will therefore accumulate in the ‘shadow’ of selection, their effects amalgamating into what we call ageing. Medawar also grasped the significance of extrinsic mortality, that is, the rate of death from environmental forces such as predation: the later in life the effects of a gene are realised, the less individuals will remain alive to experience them. Thus, a gene which contributes to prolonging the health of heart muscle for many decades may be very beneficial to an elephant, but it is of no use to a mouse that will almost certainly be preyed upon before the age of two.

Building on Medawar’s work, a later theory proposed that ageing may arise from genes which not only have negative effects in old age, but also have beneficial effects in youth, when natural selection is at its strongest. In this theory, ageing would be a detrimental late by-product of processes which have evolved because they are beneficial earlier in life. The current scientific consensus is that each of these two theories is probably correct in some cases, such that certain components of ageing have arisen through accumulation of purely detrimental mutant genes, while others are late side-effects of advantageous genes.

An important aspect of these two evolutionary theories is that they define ageing as the result of the inability of natural selection to maintain physiological integrity for longer than is actually useful ‘in the wild’. The key insight is that it is not evolutionarily advantageous to live longer than we do, because our species has evolved so that we are able to develop and reproduce long before our bodies succumb to age. Furthermore, because the wild environment of early humans made it very unlikely for them to survive as long as we do, there has been no evolutionary need for greater longevity. Notably, our evolutionary explanation of ageing, which is theoretically and empirically well supported, does not depend on which specific physiological mechanisms are responsible for ageing. In other words, we certainly understand why the process of ageing has evolved in the first place; the scene is rather different, however, when it comes to the question of how this process unfolds in organisms.

How we age: Mechanistic causes of ageing

Luckily for junior scientists, our mechanistic theories of ageing are much more abundant and less clearly supported than our evolutionary theories. Perhaps the most immediate question regarding the actual process of ageing is whether it results from a single physiological mechanism, or from multiple mechanisms whose effects are roughly synchronised. Given the conclusion that ageing is a consequence of the ineffectiveness of natural selection, it follows that it must come about through multiple, possibly many, unrelated mechanisms.

As a crude analogy, let us imagine owning a car in a very unsafe city, where vehicles are constantly being stolen or damaged. In such circumstances, we should be wise to buy a cheap car which might last a few years, and to spend as little as possible in maintenance, as otherwise the return on our investment may never materialise. Nevertheless, if by a stroke of fortune, we find ourselves owning the same car after a good number of years, we should expect it to come apart by virtue of its being cheap and poorly maintained. This analogy unflatteringly exposes the ultimate reason for ageing — insufficient quality and care — yet it sheds no light as to which of the car’s components is expected to fail first. Given that the car’s decay is caused by deficient maintenance, we might expect multiple of its components to misbehave with increasing frequency, up to the point where the machine as a whole cannot function. Moreover, different processes might be responsible for each component’s failure: the transmission may expire out of sheer friction, while the pistons might succumb to soot. Hence, even though the ultimate cause of ageing may be universal, the processes immediately involved are manifold.

As suggested by this analogy, current research on ageing focuses on the challenging task of establishing which physiological processes contribute to ageing, and how significant each is. A large number of distinct processes have indeed been proposed as mechanistic causes of ageing. Among the most interesting of these are ‘nutrient signalling pathways’, which are functional networks of molecules responsible for transmitting the physiological signals produced when we acquire nutrients. The most popular molecule in this network is insulin, essential for the regulation of blood glucose levels. Yet in addition to the well-known relationship between deficient insulin signalling and diabetes, it has been found that interventions which interfere with nutrient signalling can considerably prolong the lifespan of many species, both vertebrate and invertebrate. For instance, a treatment known as ‘dietary restriction’, whereby the supply of food (or of certain nutrients) is permanently reduced, is considered the most reliable way of extending animal lifespan. Furthermore, the deactivation of certain nutrient signalling genes, by either mutation or pharmacological treatment, produces similar effects to those of dietary restriction. In the 1990s, Cynthia Kenyon and her colleagues discovered that mutations in such a gene led to a doubling of lifespan in nematode worms, a finding followed by similar reports in fruit flies by the groups of Dame Linda Partridge and Marc Tatar. On the other hand, nutrient signalling also regulates body growth and development, and animals subjected to these life-prolonging interventions tend to be stunted and ill-developed. Interestingly, although the network of effects whereby nutrient signalling modulates development and longevity is not yet fully characterised, it is believed to be the reason why smaller dog breeds live longer than larger ones.

A second leading candidate among possible mechanisms of ageing is molecular damage. Cells are constantly exposed to many kinds of chemical damage, which can alter their constituent molecules and impair the efficiency of cellular processes. The types of molecules subject to such damage include proteins (which are both the cell’s building blocks and its working tools) and DNA (which carries the organism’s genetic information, including the instructions for protein synthesis). One extensively studied type of DNA modification with potential roles in ageing is the shortening of telomeres — long stretches of DNA which are placed at the ends of chromosomes to protect them from fraying, like the aglet in a shoelace. Telomeres are slightly shortened every time a cell divides into two new cells, and eventually become too short to allow further cell division, which is thought to be an important barrier against the emergence of cancer — but might also be a cause of ageing. Recently, the biologist María Blasco and her team reported the striking finding that the rate of telomere shortening in a species is related to its lifespan, such that telomeres erode faster in shorter-lived species. Nevertheless, this relationship is obscured by the fact that shorter-lived species also tend to be smaller, and body size itself is thought to influence many aspects of animal physiology.

Fluorescence microscopy image showing the location of telomeres (white) at the ends of human chromosomes (grey). Telomeres preserve the integrity of DNA inside chromosomes, and their shortening over time has been proposed as a cause of ageing (Credit: NASA/Wikimedia Commons, public domain).

Working with Alex Cagan, Iñigo Martincorena and other researchers at the Wellcome Sanger Institute, I recently explored the relationship between animal lifespan and another common form of DNA modification — somatic mutations. This term refers to the changes that accrue in our DNA over time; such mutations are not present initially in any of our cells, but are acquired by individual cells as our bodies grow and age. Somatic mutations were first hypothesised to contribute to ageing in the 1960s, but their exact role remains elusive. Cagan and I characterised the rate of mutation across sixteen species of mammals, from mice to giraffes, and found a very similar relationship to that described for telomeres: shorter-lived species mutate faster than longer-lived ones, such that a mouse cell acquires as many mutations in two years as a human cell might do in eighty. Crucially, we determined this result to be unaffected by the relationship between longevity and body size: at least in mammals, the mutation rate can be used to predict a species’ lifespan, regardless of its size. The fact that the rates of different forms of molecular damage present similar relationships with lifespan suggests — but does not prove — that these forms of damage may be involved in ageing.

Diagram showing the inverse relationship between lifespan and the rate of somatic mutation in 16 species of mammals. The mutation rate of each species is inversely proportional to its lifespan, such that all species carry a similar number of mutations in their cells’ DNA at the end of their respective lifespans. This relationship is indicated by the blue line, with the shaded area marking a two-fold deviation from this line (Source: Cagan, Baez-Ortega et al., 2022).

It might seem inconsistent that processes as unrelated as nutrient signalling and molecular damage might all contribute to ageing. But these processes are not so distant when viewed in the light of a theory known as the ‘disposable soma’ theory of ageing. According to this, the physiology of complex organisms includes a central energy trade-off, such that the energy acquired from food is distributed between the processes of somatic maintenance (the preservation of the body via repair of molecular damage) and reproduction (the preservation of genes via their transmission to offspring). Rather than grappling with the evolutionary origin of ageing, this theory provides a framework for its physiological regulation. Because our body (the ‘soma’) is ultimately perishable, the energy trade-off between maintenance and reproduction has presumably been optimised by evolution to favour the expensive process of reproduction in times of nutrient abundance, and to promote maintenance instead when nutrients are limited. It is thus possible that nutrient signalling disruption modifies the speed of ageing by interfering with the ‘gauge’ of this energy allocation system, whereas molecular damage may simply be the force which opposes somatic maintenance processes. Despite the remarkable coherence of the disposable soma theory, the evidence for the existence of a universal energy trade-off in animals is currently inconclusive. It is possible that, like so much else in biology, energy trade-offs are crucial but not universal: they might be relevant only for some species, or in certain organs, or at particular periods in life. Even in this time of unparalleled scientific progress, an immensity of knowledge remains to be discovered regarding the physiological processes involved in ageing.

The battle against ageing

Since the days of Darwin and Weismann, we have come to understand ageing not as a death force evolved for the benefit of the species, but rather as an inextricable consequence of the manner in which evolution works. Animal bodies have not evolved to live forever, but to succeed in surviving and reproducing amidst a ruthless environment. The biology of our bodies is such as it is precisely because our ancestors managed to succeed in these tasks, not because they managed to live forever.

Whatever the causes of ageing, the essential question for humanity is whether we shall ever be able to throttle them — perhaps not with a view to living forever, but at least to enjoying longer-lasting health and a happier old age. It seems clear that this target will remain out of reach so long as we fail to understand what exactly ‘ageing’ means at the molecular level. Someday we might gain the power to manipulate the processes by which our bodies fend off the effects of time, or even to combat such effects directly; we may finally be able to subdue and domesticate the process of ageing. But such miracles lie still beyond the horizon, and for years to come we must keep drawing on the power of conventional medicine to manage individual age-related conditions.

When it comes to growing older, the personal theory of the essayist, poet and former Master of Magdalene College, AC Benson, may be more helpful than those discussed here: ‘I have a theory that one ought to grow older in a tranquil and appropriate way, that one ought to be perfectly contented with one’s time of life, that amusements and pursuits ought to alter naturally and easily, and not be regretfully abandoned’. Too modest a theory, perhaps; he goes on to concede that ‘It is easier said than done’. Yet, even as we feel the gentle, impassive slipping away of youth between our fingers, we should be wise to keep in mind the words of Longfellow:

For age is opportunity no less

Than youth itself, though in another dress,

And as the evening twilight fades away

The sky is filled with stars, invisible by day.

References
Weismann, A. ‘The duration of life’ (1881). In Essays Upon Heredity and Kindred Biological Problems (tr. Poulton, EB, Schönland, S, Shipley, AE). Clarendon, 1889.
Haldane, JBS. New Paths in Genetics. Allen & Unwin, 1941.
Kenyon, C, Chang, J et al. A C. elegans mutant that lives twice as long as wild type. Nature, 1993.
Hughes, KA, Reynolds, RM. Evolutionary and mechanistic theories of aging. Annual Review of Entomology, 2005.
Kirkwood, TBL. Understanding the odd science of aging. Cell, 2005.
Flatt, T, Partridge, L. Horizons in the evolution of aging. BMC Biology, 2018.
Whittemore, K, Vera, E et al. Telomere shortening rate predicts species life span. Proceedings of the National Academy of Sciences, 2019.
Cagan, A, Baez-Ortega, A et al. Somatic mutation rates scale with lifespan across mammals. Nature, 2022.

This article was originally published in the 2021–22 Magdalene College Magazine.
The author is grateful to James Raven and Aude Fitzsimons for their comments on the original manuscript.

Evolution in evolution

The story of how we came to understand evolution is a fascinating example of the real character of scientific revolutions.

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The first edition of On the Origin of Species, published by Charles Darwin in 1859.
(Credit: Scott Thomas Photography.)

IT IS NATURAL to imagine scientific revolutions as events that unfold in the blink of an eye, like thunderbolts of blinding truth. We tend to depict the likes of Galileo, Newton, Darwin and Einstein as bold figures who utterly and single-handedly transformed our understanding of the world, to everyone’s shock and awe. It is rather hard to find, however, quite so many examples of such breathtaking shifts of paradigm developing nowadays. This is not, of course, because scientific research has in any way stalled; in fact, its progress is now faster and more impressive than ever before. The true reason that we cannot recall too many contemporary scientific revolutions is that these are not actually revolutions as such — sudden, dramatic transformations — but rather long processes which normally evolve and develop over decades. While popular narratives like to depict key scientific discoveries in an overly dramatic atmosphere of climax, enlightenment and triumph, the reality is that, because scientists are sceptical by nature, every great change of paradigm has taken many years to become accepted. All ideas in science, even the most transformative ones, are subjected to a considerably slow-paced process of academic scrutiny, and, if possible, experimental validation, until they gradually become part of the established scientific canon. The double-helical structure of DNA, for instance, despite being so highly praised today, was regarded as little more than a possibility for years after it was first proposed by Watson and Crick. Even Newton, the archetype of scientific genius and achievement, had to go through decades of bitter intellectual competition before his law of universal gravitation became widely recognised outside of England.

Among the many possible narratives of gradually unfolding scientific revolutions, one is arguably as fascinating as it is obscure: this is the story of how Charles Darwin’s famed theory of evolution by natural selection became the supreme dogma of biology (a story brilliantly recounted by Ernst Mayr in the 1980 book The Evolutionary Synthesis). Contrary to popular belief, this occurred not as a swift change of paradigm, but as a protracted process of fierce scholarly debate which would not come to an end until the mid-1940s, almost a century after Darwin first published his theory in 1859. During this time, the forking of biology into new fields of knowledge prompted an irreconcilable divide between classically trained naturalists and experimental biologists, leading to a pervasive chasm in evolutionary thought that would only be bridged with the forging of a new unified theory of evolution. This theory, which we know today as the modern evolutionary synthesis, states that the gradual evolution of species can be explained in terms of the accumulation of small genetic alterations, recombination (the shuffling of the genetic material as it passes from parents to offspring), and the action of natural selection on this genetic diversity. The key feature of the modern synthesis is that it explains how these low-level mechanisms give rise to higher-level evolutionary processes, such as speciation and macroevolution.

In his lifetime, Darwin saw his theory gain acceptance and regard among some naturalists, but he never witnessed its ultimate development into the unquestionable pillar of biology which it is today. In fact, it might be difficult for us to conceive the extreme opposition which the Darwinian theory of evolution faced throughout the late nineteenth century, and until as late as the 1930s. At the time, Darwinism was only one of a number of different theories which attempted to explain the processes whereby biological species originate. Some of these, known as essentialist theories, were based on the notion that species were uniform ‘pure lines’ composed of virtually identical individuals, and thus claimed that no significant natural variation existed within each species. In contrast, populationist theories interpreted species as populations composed of distinct, unique individuals, and therefore harbouring a considerable amount of biological variation. Furthermore, some theories accepted the existence of soft inheritance, characterised by the notion that the genetic material can be modified to some extent by the interaction of the organism with its environment; a particularly notorious example of this current was Lamarck’s theory of the inheritance of acquired characters, which posited that the physiological changes acquired by an individual during its lifetime are inherited by its descendants. Other theories recognised only hard inheritance, meaning that the hereditary material cannot be altered by the action of the environment. Today, we consider soft inheritance to be false, and the genetic material to be immutable by means of interaction with the environment (although recent discoveries of heritable epigenetic variation in some species may potentially pose a challenge to this idea). It might therefore appear surprising that nearly all of the early theories of evolution, including Darwinism, recognised some degree of soft inheritance. In particular, Darwin’s theory assumed a certain ‘plasticity’ of the genetic material, such that it could be modified to some extent through the use or disuse of biological traits. Neo-Darwinism, an elaboration of the theory developed by some of Darwin’s supporters, among them the naturalist Alfred Russel Wallace, later rejected this possibility for an inheritance of acquired characters, adopting a hard-inheritance standpoint.

Based on these and other principles, a wide array of evolutionary theories were developed between the 1860s and the 1940s, of which Darwinism was seldom among the favourites. The main factor which compelled authors to support one theory or another was their field of expertise, and the number of these was growing as never before. Over the second half of the nineteenth century, the broad science of biology, theretofore split into the disciplines of zoology and botany, rapidly differentiated into several new fields, including embryology, cytology and ecology. From the viewpoint of evolutionary theory, however, the most influential of the new disciplines was arguably genetics, the study of genes and heredity, which was born from the rediscovery of Gregor Mendel’s laws of genetic inheritance in 1900. From this year onwards, geneticists would develop an increasing understanding of the principles of mutation and inheritance; this fresh knowledge, however, rather than sparking advances in the study of evolution, would ignite a long and vicious conflict between the different biological disciplines.

From the outset, the founding fathers of genetics were firm opposers of Darwinism and natural selection. The very first geneticists, together with the palaeontologists, thought that the emergence of new species happened by means of discontinuous changes; in their view, an isolated and disruptive modification of the genetic material (which they termed a mutation) produced a radical physiological change in the organism, resulting in the instantaneous transformation of one species into another, without any intermediates. This theory, based on essentialist principles, was known as saltationism, because of its belief in speciation by ‘saltation’, or huge evolutionary leaps leading from one species to the next. Bizarre as it may sound today, this explanation fitted the initial observations of geneticists, as well as previous palaeontological evidence, remarkably well. In their experiments, geneticists relied on uniform ‘stocks’ of nearly identical individuals (normally fruit flies, which were relatively easy to breed and study), as a means of avoiding experimental interference. In their stocks of flies, the early geneticists observed that isolated genetic mutations led to drastic, heritable modifications of traits such as eye colour or wing shape. It seemed reasonable, then, to suppose that evolution proceeded in the same manner: mutations were infrequent and highly disruptive events, causing the instantaneous transformation of one species into another. Gradual evolution by means of natural selection acting on existing natural variation within a species appeared to be in complete contradiction with these early results, and some geneticists went as far as to declare that Darwinian evolution had been positively disproved by genetics. Notwithstanding these misconceptions, genetics made some significant contributions to evolutionary theory during this period, most notably the refutation of the existence of soft inheritance.

On the other hand, those biologists who had been trained as naturalists, such as zoologists and botanists, were used to deriving their conclusions directly from the study of natural populations, and insisted that all their observations supported Darwin’s theory of gradual evolution, rather than saltationism. The root of the disagreement, however, was certainly the lack of communication between both fields: naturalists and geneticists did not only defend different theories, but also had distinct approaches to science, pursued divergent biological interests, attended different meetings, published in different scientific journals, and even used distinct vocabulary (including incompatible definitions for essential concepts such as ‘species’ and ‘mutation’). In addition, geneticists tended to regard naturalists as speculative scholars who could never test their ideas in the laboratory, and therefore possessed no objectivity; naturalists, in turn, viewed geneticists as myopic experimentalists who had no real knowledge about natural populations, and were insensitive to the crucial difference between heredity and evolution. All this inevitably led to mounting misunderstanding and resentment, and perhaps more importantly, to an immense communication lag between both disciplines. An astonishing proof of this circumstance is given by the fact that, when a younger generation of geneticists — including names such as Hermann Muller, J.B.S. Haldane and Ronald Fisher — began to obtain, from the late 1910s onwards, new evidence against saltationism and in favour of neo-Darwinism and natural selection, this did not help to bridge the gap between geneticists and naturalists. Instead, because of the utter alienation brought about by the endless disagreements between both fields, communication was damaged to such an extent that naturalists would spend decades persevering to refute the already obsolete ideas of the earlier geneticists. It was mainly because of this abysmal academic segregation that the arrival of the modern evolutionary synthesis was deferred until the 1940s.

In this way, naturalists and geneticists progressed along isolated paths for the first three decades of the twentieth century, each dragging their own conceptual burdens: the former held wrong and obsolete views about the nature of genetic mutation and inheritance, while the latter were dominated by the belief that the evolution of species and higher taxonomic levels could be understood by simple extrapolation from knowledge about how single genes evolve in isolated, ideal populations. Up until the 1920s, when crucial experiments on artificial selection, together with the work of the first mathematical geneticists, contributed to establish a firm belief in natural selection, specialist textbooks still presented up to six theories of evolution as being potentially valid.

This bleak scientific panorama was completely transformed in the 1940s, thanks to the insight of one palaeontologist, George Gaylord Simpson, and two zoologists, Julian Huxley and Bernhard Rensch. Perhaps the only scientists of their generation who had amassed a detailed knowledge of all the latest advances in each of the relevant disciplines, they published three independent books in which they demonstrated how the findings of zoologists, palaeontologists, geneticists and others could be integrated in order to explain all of evolution, from the emergence of changes in individual genes to the origin of species, genera and higher levels, within a single consistent framework. In his book, Huxley christened this new theory with the name by which it is known today — the modern synthesis.

The forging of the modern evolutionary synthesis was not in itself a scientific revolution, but rather the completion of a shift of paradigm initiated by Darwin nearly a century earlier. Moreover, the synthesis did not imply the victory of one scientific tradition over another, but rather the fusion of two radically different conceptual frameworks — naturalism and experimentalism — into a new harmonious whole. For this fusion to arrive, it was first necessary to remove conceptual misunderstanding and communication barriers between the opposing camps, something that could only be achieved by those who, rather than focusing on narrow specialisation, were curious enough to learn about the advances made outside their own respective fields, and open-minded enough to appreciate commonality rather than disagreement. The real impact of the modern synthesis was the unification of evolutionary biology into a single field; after its arrival, the complete discord and hostility which had reigned over the three previous decades was replaced by widespread agreement. Bridges had been built which would remain solidly in place until the present day; although discussion is still ongoing regarding some aspects of the theory (such as the role of epigenetic inheritance and horizontal gene transfer), the basic framework of the synthesis has remained essentially untouched since it was first outlined in the 1940s.

The history of the modern synthesis, our current framework for studying evolution, is of value to scientists and historians alike. The long series of discoveries and conceptual advances that led from Darwin’s original theory to the arrival of a unified interpretation of evolution are a particularly informative illustration of phenomena which have manifested time and again throughout the history of science: resistance to new ideas, exceeding specialisation, terminological barriers, communication lags, sentiments of superiority and hostility between disciplines, and the critical importance of collaboration and mutual understanding for scientific advance. The story of the modern synthesis thus reflects the true method of scientific progress, which is of course harder, messier and more gradual than we like to imagine. It also constitutes a telling example of how exploring the history of scientific ideas provides us with a much deeper understanding than the mere study of their definitions; for while the latter pretend to be static and set in stone, the former conveys the truth that science is alive and restless, and that the search for knowledge is fundamentally arduous, incremental, collaborative, and eternal.

References
Mayr, E. (1980). ‘Some Thoughts on the History of the Evolutionary Synthesis’, in The Evolutionary Synthesis: Perspectives on the Unification of Biology (Harvard University Press).
Huxley, J. (1942). Evolution: The Modern Synthesis (Allen and Unwin).
Simpson, G. G. (1944). Tempo and Mode in Evolution (Columbia University Press).
Rensch, B. (1947). Neuere Probleme der Abstammungslehre (Enke).

An eternal battleground

One of nature’s primordial conflicts could turn out to be the propelling force behind evolution.

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The physical structure of the particles of some bacteriophage viruses are the perfect example of the sophistication exhibited by these organisms. (Image adaptaded from original by Michael Wurtz.)

LIKE IT or not, war is the most powerful driving force of material progress on our planet. This is attested by such indispensable inventions as radar, the computer or the reaction engine, which were born in the most horrendous of conflicts, the Second World War. It is a typical error of an anthropocentric mentality, however, to think that war, together with the rapid development that it sparks, is something intrinsically human. Aggressive competition between living beings not only stretches back to the origins of life on Earth but, in a similar way, it may be the underlying cause of the imposing variety and complexity of life that we see all around us. And among all the conflicts that have propelled the evolution of life, the most important, prolonged and vicious one is that which brings viral organisms (viruses) and cellular organisms (composed of one or more cells) face to face. This war has been raging, silently but tirelessly, each second of the last three billion years, and is still raging in this precise instant, in the ground we step on, in the objects we use, in the food we eat, and in ourselves. A healthy human body, with its ten trillion cells, is the home of ten times as many microorganisms, such as bacteria, and a hundred times as many viral particles, or virions (those minuscule agents that we mistakenly know as ‘viruses’). Many of these ‘companions’ not only have no negative effect on our health, but are necessary to maintain it. This does not downplay the fact that, within each of us, the most ancient war on this world continues on its course: a struggle for survival and domination, based on the constant invention, upgrade and stealing of molecular weapons, which is a reflection of the ruthless and marvellous nature of life.

On the other hand, it is true that all the cellular life forms — animals, plants, fungi, bacteria, protozoa, chromists and archaea, in all their variants — compete tenaciously against each other. What, then, makes the war between viruses and cells so unique and essential for life? The answer arises from a controversial series of discoveries that place the origin of viruses in an extraordinarily ancient world, preceding multicellular life and inhabited by much more primitive microorganisms than those around us today. The antagonism between viruses and cells has thus existed since the dawn of evolution, and so its impact on it may have been greater than that of any other factor.

Viruses are undoubtedly the most mysterious biological entities on this planet; virtually any aspect of them, from their definition as living creatures or as simple organic particles, to their origin or their role in the biosphere, is witness to a clash of radically opposing views and theories. Defining the nature of a virus implies no less than defining the line that divides what we consider ‘life’ and what we do not. Throughout the twentieth century, the detailed study of viral particles led to a universal image of viruses as mere ensembles of proteins and nucleic acids that, sheltered by natural selection, escaped from the cell and managed to exploit its machinery in order to replicate themselves; a displeasing by-product of evolution. Manifold biologists today still describe viruses as ‘genetic pickpockets’ that arise and evolve by means of the systematic theft of cellular genes. The significance of the impact of viruses on the evolution of life has also been astonishingly undervalued.

The drastic turning point in science’s perception of viruses came in 2002, with the discovery of the so-called giant viruses. During the study of microorganisms infecting certain amoeba species, French researchers found something that, according to its size, seemed to be a bacterium. Nevertheless, it was soon clear that this microbe was genetically and physically different from any cellular organism. It was a virus of unprecedented dimensions, capable of exceeding many bacteria in both physical and genomic size. This first giant virus, baptised mimivirus, was followed all too soon by other species, such as the marseillevirus and the pandoravirus. The definition of viruses, originally stemming from their ‘invisible’ character under the microscope, was crying out to be reconsidered. Some of the researchers responsible for the discovery proposed a new classifying system for living organisms, which divided them into two major groups: cellular organisms and viral organisms.  As the main proof that viruses are legitimate life forms, they pointed to what happens during the infectious stage of a virus’ life cycle. Once the viral particles (virions) have managed to invade a cell, an extraordinary phenomenon takes place: a new structure — visible on the microscope — emerges in the infected cell, which contains and protects the virus’ genetic material (genome). While this structure, called the viral factory, manufactures thousands of new virions, charged with copies of the invading genome, the virus’ offensive systems degrade the cell’s own genome. The result is a cell without a functional genome — that is, without life — wherein the viral genome is rapidly expressed and multiplied, by making use of the sophisticated machinery of the murdered cell. Therefore, the organism that we see under the microscope at this stage is by no means a cell with thousands of tiny ‘viruses’ in it; it is no less than a virus in its living form, employing the cellular sheath and machinery of its victim to produce an army of virions, with the aim of spreading itself to other cells. The virions, those lifeless particles considered as the definitive form of the virus for more than a hundred years, actually reveal themselves as simple ‘seeds’ or ‘spores’ used by the virus for dispersing its genes. For more than a century, by mistaking the virus for its virion, science has committed a terrible error, comparable to mistaking a tree for a seed, or a human being for a spermatozoon. A virion is just as inert as a seed, incapable of growing and reproducing until it is placed in the appropriate environment. The difference lies in the fact that, similarly to other intracellular parasites — such as bacteria of the Rickettsia genus — a virus needs to invade a cell and make use of its resources to live. In this sense, viruses are, in fact, cellular organisms, since during their metabolically active phase they always have a cell, even if it is a ‘borrowed’ cell. This reflects the extreme intelligence and elegance that underlie the minimalist design of viruses — the fruit of an inconceivably prolonged evolutionary process. 

Mimivirus' viral factory (centre) and virions in different stages of development (hexagons) around it, inside an infected amoeba. (Credit: Didier Raoult.)

Even so, many biologists continue to reject the concept of viruses as living creatures. The mimivirus, however, still had something to contribute in this regard: its own proof of life. While studying the giant virus, the researchers found particles of a second, much smaller virus, around the first. When this tiny satellite virus, nicknamed sputnik, was present together with the giant mimivirus inside an infected amoeba, the biologists confirmed that the mimivirus had trouble reproducing, thus allowing the amoeba to survive the attack. Sputnik was the first known virophage, a virus that exclusively infects other viruses. The possibility that a virus could be infected by another had never been contemplated, and constitutes a capital proof that viruses are alive, insofar as only a living creature can be infected by a virus. That is, viruses have independently asserted themselves as living creatures!

What is, then, the true origin of viruses and their role in the evolution of life? In contrast to what numerous scientists believe, viruses are not ‘genetic pickpockets’ that survive by stealing cellular genes. Rather the opposite; most viral proteins have no equivalent in any cell known, indicating that the origin of viruses is extremely ancient, going back in time to a world inhabited not by today’s cells, but by more primitive ones that, over time, gave rise to those. A reasonable hypothesis is that viruses come from a group of primeval cells that gradually adapted to parasitic life; the structure and genome of these cells experienced enormous simplification as they developed a greater dependence on the genes and components of other cells. This phenomenon, termed reductive evolution, reached its pinnacle in viruses. Relying on a minute number of proteins, these organisms have been able to develop structures of an amazing complexity and ingenuity, specifically designed to dodge each one of their victims’ defences, and in which a single protein can play a multitude of roles. Billions of years of evolution have turned viruses into the best designed and adapted life forms on the planet; it is because of this that no organism — not even humans, not even viruses themselves — can definitively escape their attack.

The idea that viruses have had a fundamental impact on the evolution of life draws upon the observation that they are real cradles of genetic diversity; their ability to mutate in minimal time periods allows them to evolve new genes. Not only this, but it is actually cells, and not viruses, which are the ‘pickpockets’ gleaning a constant flow of new genes from viruses. A clear example of this are the viruses that infect bacteria (bacteriophages), which play a major role in the direct transfer of DNA between these organisms, promoting evolutionary processes that do not depend on the traditional gene flow from parents to offspring. As far as we humans are concerned, it might come as a surprise that around forty-two percent of human genetic material has a viral origin. Part of this material has undoubtedly had a pivotal role in the course of our evolution; as a matter of fact, one of the essential genes for the development of the placenta was concocted millions of years ago by a virus, before ending up ‘inserted’ in the genome of an ancestor of the first mammal. It is no less surprising that the major difference between our genome and that of the chimpanzee is precisely the number, variety and location of elements of viral origin that are part of the genetic material of both species. Some theories go as far as suggesting that the origin of DNA itself, as well as of its replication mechanisms, first emerged in viruses and was subsequently adopted by primitive cells, based until then on RNA, a simpler type of nucleic acid.

The true diversity of viral organisms is, beyond any doubt, huge, and it remains for the most part unexplored. It is evident, however, that the role of viruses in the history of life has been immensely more relevant than many still believe. Our ‘cellulocentric’ vision of the world has led us to overlook the effect of the eternal struggle between the virus and its host, which nevertheless contributes to channelling the marvellous process of evolution, from which every life form benefits. Therefore, the cellular and the viral worlds have evolved in parallel, but in essentially different ways; one, toward increasingly complex forms; the other, toward utter simplicity. This three-billion-year-old predation, with its inexhaustible and ever-changing repertoire of arms, tactics and deceptions, is probably responsible for every living creature, be it virus, bacterium, amoeba or human, as it is today. After all, nothing fits better with the inimitable nature of this world than the idea that the fascinating complexity of life may be the fruit of the creativity of the simplest of beings.

Special thanks are due to Isobelle Bolton for her invaluable help with translation.

References:
Raoult, D. How the virophage compels the need to readdress the classification of microbes. Virology (2015).
Raoult, D., Forterre, P. Redefining viruses: lessons from Mimivirus. Nature Reviews Microbiology (2008).
Forterre, P. The virocell concept and environmental microbiology. The ISME Journal (2013).
Nasir, A. et al. Untangling the origin of viruses and their impact on cellular evolution. Ann. N.Y. Acad. Sci. (2015).
Forterre, P., Prangishvili, D. The Great Billion-year War between Ribosome- and Capsid-encoding Organisms (Cells and Viruses) as the Major Source of Evolutionary Novelties. Ann. N.Y. Acad. Sci. (2009).