A beautiful world

Science and philosophy suggest that the cult of beauty is much more than a simple cultural norm.

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The identification of aesthetic beauty and moral beauty has accompanied mankind throughout history. (Credit: Kaho Mitsuki/Wikipedia.)

IT IS NOT something easy to define, and yet all of us recognise beauty when we see it before us. Humankind’s obsession with beauty, especially with human beauty itself, spans millennia. Poets were already writing about it three thousand years ago; today, their works are an insinuation of the boundless character of beauty, and suggest that its roots are deeper than could be expected from a mere cultural concept.

Although the standards of what we consider ‘attractive’ have seen themselves undeniably altered with the passage of centuries, due to a certain cultural influence, the truth is that physical beauty is something real beyond any subjectivity, and possesses an unquestionable biological function. Physical attractiveness plays an important role in every animal species when it comes down to finding a mate; in contrast to what is often said, it is not merely a superficial attribute, but an indicator that reveals, at a glance, crucial information about the state of youth, health and fertility of a potential mate — which are, in turn, signs of that indefinable but indispensable ‘genetic quality’ that every organism wishes for its progeny. It is not a coincidence that most facial make-up products are based on reddish or pinkish pigments, selected to imitate the colour provided by a generous blood flow in the skin, which is an undeniable indicator of good health.

Numerous studies, for their part, have proved facts that can seem disquieting, or even offensive, in the context of modern society, such as that more attractive people tend to enjoy better health and greater fertility than less attractive people, or that considering certain facial features as attractive is more than a cultural construct. In one particular study, both African and European people found the same Asian women attractive. This suggests that physical beauty is more a biological quality than a cultural one. Although the cult of beauty is considered today as superficial, and perhaps pernicious, it is not difficult to imagine the utility that it probably had for our distant ancestors.

More than 150 years ago, Charles Darwin himself was already perplexed by the role of beauty in the natural world, which was not easily explained. The bright forms and colours displayed by animals with the aim of finding a mate not only imply most valuable energy expenditure, but also make the animal an easy prey, as illustrated by the extravagant plumage of many tropical birds. In order to explain the evolutionary importance of beauty, Darwin conceived the concept of ‘sexual selection’. As opposed to the well-known natural selection, by which only those individuals that are fit enough to reach maturity are able to pass their genes on to the next generation, sexual selection implies that certain individuals — the more attractive ones — have the chance to mate more often than others.

Although Darwin was right, sexual selection was neither proven nor understood in depth until the beginning of this century. This is due, in part, to the fact that understanding the aesthetic preferences of each animal requires an exhaustive study of its sensory capabilities. In fact, the incredibly varied peculiarities of sight, smell, touch, taste and hearing of each species are fundamental factors in its perception of sexual attractiveness. A clear example are the cichlids that live in the waters of Lake Victoria, in Africa. These bony fish gather in two distinct populations that, despite belonging to the same species, have stopped mating with each other due to discrepancies in the selection of reproductive mates — that is, in what individuals of each population consider ‘attractive’. The divergence between both groups is such that it even affects the type of proteins that their eyes employ for perceiving different colours, called photoreceptors. One of the cichlid populations lives in shallow waters, where the sunlight penetrates in a large variety of colours. These fish can perceive a wide range of tonalities, and males — the sex that usually puts all its charm on display to attract a mate — exhibit designs of bluish hues in their scales; it is possible that this constitutes a strategy for hiding from the birds that forage near the surface, while remaining visible to the females, who have no problem distinguishing their adornments. The second cichlid population resides in deeper waters, safe from the birds’ sight. Here, light acquires a reddish hue, which fish perceive thanks to specific photoreceptors; in consequence, the males’ scales present scarlet designs, which are readily spotted by the females. Despite living at a few meters’ distance from each other, these populations do not intermix, because the females in each one prefer — and select — the males they can see more easily. If these two fish groups continue to diverge, the accumulation of differences between them will give rise to two different species. The cichlids’ case invites us to consider that adaptations in animal sensory systems, sparked by environmental needs, could exert a selective pressure capable of causing the inception of new species in short periods of time.

However, this does not clarify the apparent relationship between physical appearance and ‘genetic quality’. It is frequently difficult or impossible to link beauty traits to an evident selective advantage; in fact, in many cases the sumptuous decoration of the suitors should be a disadvantage in the presence of more discreet organisms, which are harder to spot for their predators. The so-called ‘handicap hypothesis’ tries to explain this incongruity by suggesting that the presence of flashy adornments may act as a sign that the bearer has enough strength or health to bear up under the negative effects of these traits — which, ironically, makes it more attractive for the opposite sex. On the other hand, some scientists believe that the traits associated with beauty are also related to other signs of health and resistance. One illustration of this is given by the common yellowthroat warbler, a little North American bird whose females show preference for those males having either large, bright yellow pectoral feathers, or a large black mask around the eyes, depending on the region in which they live. Curiously, both traits are linked to the same genetic characteristic: a greater variation in the genes of the major histocompatibility complex, a key component of the immune system. Greater diversity in these genes enhances resistance against various infection types. This suggests that both the yellow feathers and the black masks, although they do not confer greater resistance to the male, offer information about it to the females, which explains why the latter pay attention to one or other trait in a rather indiscriminate way. It is the information encoded by them that matters in the eyes of sexual selection.

The male yellowthroat warbler displays yellow feathers and a black mask as a lure to females. (Credit: Distant Hill Gardens/Flickr.)

In this regard, human beings are not very different from the rest of animals. Beauty exerts huge power over our civilisation, a power with an indubitable biological — besides cultural — basis. Psychologists have demonstrated how our conscience and our subconscious react to beauty: a study revealed that, if people are given a button that allows them to see a beautiful face for a longer time, they will push it unceasingly, just as a laboratory mouse would do to obtain food or narcotic substances. That moment when we cannot look away from a beautiful face or body, no matter how long we had seen it already, does not sound unfamiliar in the least. Not even babies can help looking more frequently at more attractive faces. The vision of beauty triggers a response in the brain’s self-reward system, fuelled by dopamine and associated also with stimuli such as sex or drugs. If our species is obsessed with beauty it is because this is, from a biological point of view, pleasant and addictive. A negative consequence of this effect is positive discrimination towards nicer-looking people; it has been proven, for instance, that more attractive students receive better grades, and more attractive defendants, milder sentences. Besides feeling the need to protect those people who attract us, we subconsciously tend to presuppose that they are good people, as well as to stress their positive virtues above the negative. Our sympathy for beauty, through our own subconscious, affects our world in an imperceptible but omnipresent manner. Everything seems to indicate that, at some point in our evolution, physical and moral beauty were irremediably intermixed — or maybe the latter was born from the former. Hence thinkers like the writer Oscar Wilde have toyed with the idea that beauty might be even beyond all moral judgement, might be worthy of existing just by itself, requiring no justification and no purpose other than that of being admired.

Some scientists and philosophers, on the other hand, have proposed that beauty is not only something that transcends cultures due to a biological foundation, but that there exists a so-called ‘objective beauty’. For them, this is the reason that humans can find pleasure in appreciating a flower, a sunset or a symphony. Flowers, for example, despite having evolved to attract insects, have always fascinated man. The images of galaxies and nebulae captured by space telescopes, unseen by anyone before, radiate a beauty that transcends any taste or instinct, a universal beauty that does not correspond to any fad or sexual desire, and which, however, only a human being is capable of noticing. For those who defend objective beauty, there are aesthetic truths that are as certain and objective as any physical law. This abstract beauty may be responsible for our deep love of art, which stretches back to the dawn of humanity, and which today generates more than fifty billion dollars annually.

With a closer look, it becomes evident how deeply embedded beauty is in our world. Everything around us has qualities that we can appreciate as attractive or beautiful, from other people to natural landscapes, to man-made objects and structures designed to couple elegance and utility or, simply, as a pure receptacle for beauty. Beauty surrounds us from so early on in life that we barely notice it, but the obsession that it provokes in us shape us as living beings and as civilisations, both for better and for worse. We are, inevitably, unconscious and conscious slaves, consumers and creators of beauty, and this is, in itself, part of what makes us humans. Maybe Oscar Wilde was right in saying that beauty need no reason for existing other than itself. What would have become of this world, of us, without it?

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

References:
Wald, C. The aesthetic brain. Nature (2015).
Maxmen, A. Come mate with me. Nature (2015).
Q&A Karl Grammer: Innate attractions. Nature (2015).
Q&A David Deutsch: Objective beauty. Nature (2015).
Wald, C. Beauty: 4 big questions. Nature (2015).

Un mundo de belleza

La ciencia y la filosofía sugieren que el culto a la belleza es mucho más que una simple norma cultural.

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La identificación de la belleza estética con la belleza moral ha acompañado al ser humano a lo largo de la historia. (Imagen: Kaho Mitsuki/Wikipedia.)

NO ES algo fácil de definir, y sin embargo todos reconocemos la belleza cuando la tenemos delante. La obsesión del ser humano por la belleza, especialmente por la propia belleza humana, abarca milenios. Los poetas ya escribían sobre ella hace tres mil años; hoy en día, sus obras son una insinuación del carácter trascendental de la belleza, y sugieren que las raíces de la misma son más profundas de lo que podría esperarse de un mero concepto cultural.

Aunque los estándares de lo que consideramos ‘atractivo’ se han visto innegablemente alterados con el paso de los siglos, a causa de una cierta influencia cultural, la verdad es que la belleza física es algo real más allá de toda subjetividad, y posee una función biológica incuestionable. El atractivo físico juega un papel indispensable en toda especie animal a la hora de encontrar pareja; al contrario de lo que a menudo se dice, no se trata de un atributo meramente superficial, sino de un indicador que revela, a golpe de vista, información crucial acerca del estado de juventud, salud y fertilidad de una pareja en potencia —los cuales son, a su vez, indicios de esa indefinible pero imprescindible ‘calidad genética’ que todo organismo desea para sus descendientes—. No es coincidencia que todos los productos de maquillaje facial estén basados en pigmentos de tonos rojizos o rosados, escogidos para imitar el color provocado por un flujo generoso de sangre en la piel, el cual es un indicador innegable de buena salud.

Por su parte, numerosos estudios han demostrado hechos que pueden sonar alarmantes, e incluso ofensivos, en el contexto de la sociedad moderna, tales como que la gente más atractiva tiende a gozar de mejor salud y mayor fertilidad que la gente menos atractiva, o que el considerar ciertos rasgos faciales como atractivos es algo más que un producto cultural. En un estudio en particular, tanto personas africanas como europeas dijeron considerar atractivas a las mismas mujeres de etnia asiática, lo que sugiere que la belleza física es más una cualidad biológica que una construcción social. Aunque hoy en día el culto a la belleza física se considera superficial, y quizás pernicioso, no es difícil imaginar la utilidad que probablemente tuvo para nuestros ancestros lejanos.

Hace más de 150 años, ya el propio Charles Darwin se hallaba perplejo por el papel de la belleza en el mundo natural, que no resultaba fácil de justificar. Los brillantes colores y formas de que los animales hacen gala con objeto de encontrar pareja no sólo suponen un gasto de valiosísima energía, sino que hacen del animal una presa fácil, como ilustra el extravagante plumaje de muchas aves tropicales. Para explicar la importancia evolutiva de la belleza, Darwin concibió el concepto de ‘selección sexual’. A diferencia de la tan conocida selección natural, por la cual sólo los individuos lo suficientemente aptos como para alcanzar la madurez tienen la posibilidad de pasar sus genes a la siguiente generación, la selección sexual implica que ciertos individuos —los más atractivos— tienen ocasión de aparearse con mayor frecuencia que otros.

Aunque Darwin estaba en lo cierto, la selección sexual no fue demostrada y comprendida en profundidad hasta principios de este siglo. Esto se debe, en parte, a que entender las preferencias estéticas de cada animal requiere un estudio exhaustivo de la capacidad sensorial del mismo. De hecho, las increíblemente variadas particularidades de la vista, el olfato, el oído, el tacto y el gusto de cada especie son factores fundamentales en su percepción del atractivo sexual. Un claro ejemplo son los cíclidos que habitan las aguas del Lago Victoria, en África. Estos peces óseos se congregan en dos poblaciones diferenciadas que, aunque pertenecen a la misma especie, han dejado de reproducirse entre sí debido a discrepancias en la selección de parejas reproductivas —es decir, en lo que los individuos de cada población consideran ‘atractivo’—. La divergencia entre ambos grupos es tal que afecta incluso al tipo de proteínas que sus ojos emplean para percibir diferentes colores, llamadas fotorreceptores. Una de las poblaciones de cíclidos vive en aguas poco profundas, donde la luz del sol penetra en una gran variedad de colores. Estos peces son capaces de reconocer un amplia abanico de tonalidades, y los machos —el sexo que normalmente despliega todo tipo de encantos con objeto de atraer pareja— exhiben diseños de tonos azulados en sus escamas; es posible que esto constituya una estrategia para ocultarse de las aves que buscan alimento cerca de la superficie, sin dejar por ello de ser visibles a los ojos de las hembras, que distinguen sin problema sus adornos. La segunda población de cíclidos reside en aguas más profundas, a salvo de la vista de las aves. Aquí, la luz adquiere tonos más rojizos, que los peces ven gracias a fotorreceptores específicos; en consecuencia, las escamas de los machos presentan diseños encarnados, más fáciles de divisar por las hembras. A pesar de vivir a pocos metros de distancia, ambas poblaciones no se entremezclan, debido a que las hembras de cada una prefieren —y seleccionan— a los machos a los que pueden ver con mayor facilidad. Si estos dos grupos de peces continúan divergiendo, la acumulación de diferencias entre ellos dará origen a dos especies diferentes. El caso de los cíclidos invita a pensar que las adaptaciones en el sistema sensorial animal, fomentadas por necesidades del entorno, podrían ejercer una presión selectiva capaz de provocar la aparición de nuevas especies en periodos cortos de tiempo.

Sin embargo, esto no aclara la aparente relación entre la apariencia física y la ‘calidad genética’. Con frecuencia, es difícil o imposible relacionar los atributos de la belleza con una ventaja selectiva evidente; de hecho, en muchos casos la ostentosa decoración de los pretendientes debería suponer una desventaja frente a organismos más discretos y, por tanto, más difíciles de detectar para sus predadores. La llamada ‘hipótesis del hándicap’ trata de explicar esta incongruencia sugiriendo que la presencia de adornos llamativos puede actuar como una señal de que el portador cuenta con suficiente fuerza o salud para sobrellevar los efectos negativos de estos rasgos —lo que, irónicamente, lo hace más atractivo para el sexo opuesto—. Por otra parte, algunos científicos opinan que los rasgos asociados a la belleza lo están también a otras señales de salud y resistencia. Un ejemplo es la mascarita común, un pequeño pájaro de Norteamérica cuyas hembras sienten preferencia por aquellos machos con plumas pectorales grandes y de un amarillo brillante, o bien con una gran máscara negra alrededor de los ojos, según la región en la que vivan. Curiosamente, ambos rasgos están ligados a la misma cualidad genética: una mayor variación en los genes del complejo mayor de histocompatibilidad, una pieza clave del sistema inmunitario, lo que incrementa la resistencia frente a múltiples tipos de infecciones. Esto insinúa que tanto las plumas amarillas como las máscaras negras, si bien no confieren al macho una mayor resistencia, ofrecen información acerca la misma a las hembras, lo que explica que éstas se fijen en uno u otro rasgo de manera un tanto indiscriminada. Es la información subyacente lo que importa a ojos de la selección sexual.

Los machos de mascarita común muestran plumas amarillas y máscaras negras como reclamo para las hembras. (Imagen: Distant Hill Gardens/Flickr.)

En este aspecto, el ser humano no muy es diferente al resto de animales. La belleza ejerce un enorme poder en nuestra civilización, un poder con una indudable base biológica, además de cultural. Los psicólogos han demostrado cómo nuestra conciencia y nuestro subconsciente reaccionan ante la belleza: un estudio desveló que si a una persona se le da un botón que le permita ver un rostro atractivo durante más tiempo, lo pulsará sin cesar, del mismo modo que un ratón de laboratorio haría para obtener comida o sustancias narcóticas. Esa situación en la que no podemos apartar la vista de un rostro o un cuerpo hermoso, por mucho que lo hayamos visto, no suena nada extraña; ni siquiera los bebés pueden evitar mirar con mayor frecuencia las caras más atractivas. La visión de la belleza provoca una respuesta en el sistema de autorrecompensa del cerebro, alimentado por la dopamina y asociado también con estímulos como el sexo o las drogas. Si nuestra especie está obsesionada con la belleza es porque ésta es, desde un punto de vista biológico, placentera y adictiva. Una consecuencia negativa de este efecto es la discriminación positiva hacia las personas más agraciadas físicamente; está demostrado, por ejemplo, que los estudiantes más atractivos reciben mejores notas, y los acusados más atractivos, sentencias más leves. Además de sentir la necesidad de proteger a las personas que nos atraen, tendemos inconscientemente a presuponer que son buenas personas, así como a destacar sus virtudes positivas sobre las negativas. Nuestra simpatía por la belleza, a través de nuestro propio subconsciente, afecta a nuestro mundo de un modo imperceptible pero omnipresente. Todo parece indicar que, en algún punto de nuestra evolución, la belleza física y la belleza moral se entremezclaron irremediablemente —o quizás la segunda nació de la primera—. Así, pensadores como el escritor Oscar Wilde han jugado con la idea de que la belleza pueda estar incluso más allá de todo juicio moral, pueda ser digna de existir por sí misma, sin necesidad de ninguna justificación ni de ningún otro propósito que el de ser admirada.

Algunos científicos y filósofos, por otra parte, proponen que la belleza no es sólo algo que trasciende culturas debido a un fundamento biológico, sino que existe una llamada ‘belleza objetiva’. Para ellos, ésta es el motivo por el que el ser humano puede encontrar placer en apreciar una flor, un atardecer o una sinfonía. Las flores, por ejemplo, a pesar de haber evolucionado para atraer a los insectos, han fascinado al hombre desde siempre. Las imágenes de galaxias y nebulosas captadas por telescopios espaciales, que hasta ahora nadie había podido ver, emanan una belleza que trasciende cualquier gusto o instinto, una belleza universal a la que no subyace ninguna moda o deseo sexual, y que, no obstante, sólo un ser humano es capaz de percibir. Para los que defienden la belleza objetiva, existen verdades estéticas que son tan ciertas y objetivas como cualquier ley física. Esta belleza abstracta puede ser la responsable de nuestro profundo amor por el arte, que se extiende hasta los albores de la humanidad y que hoy en día genera más de cincuenta mil millones de dólares al año.

Con un poco de atención, resulta evidente cuán profundamente imbuida está la belleza en nuestro mundo. Todo a nuestro alrededor posee cualidades que podemos apreciar como atractivas o hermosas, desde otras personas hasta paisajes naturales, pasando por objetos y estructuras diseñados por el hombre para combinar elegancia y utilidad o, simplemente, como puro receptáculo de belleza. La belleza nos rodea desde tan temprano en la vida que apenas reparamos en ella, pero la obsesión que despierta en nosotros nos moldea como seres vivos y como civilización, tanto para bien como para mal. Somos, inevitablemente, esclavos conscientes e inconscientes, consumidores y creadores de belleza, y esto es, en sí mismo, parte de lo que nos hace humanos. Tal vez Oscar Wilde tenía razón al decir que la belleza no necesita más razón que sí misma para existir. ¿Qué sería de este mundo, de nosotros, sin ella?

Referencias:
Wald, C. The aesthetic brain. Nature (2015).
Maxmen, A. Come mate with me. Nature (2015).
Q&A Karl Grammer: Innate attractions. Nature (2015).
Q&A David Deutsch: Objective beauty. Nature (2015).
Wald, C. Beauty: 4 big questions. Nature (2015).

Este artículo fue publicado en el periódico El Día el 19/04/2016.

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).

Un eterno campo de batalla

Uno de los conflictos primordiales de la naturaleza se revela como una fuerza propulsora de la evolución.

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La estructura física de las partículas de algunos virus bacteriófagos son un ejemplo perfecto de la sofisticación alcanzada por estos organismos. (Imagen adaptada de original por Michael Wurtz.)

NOS GUSTE o no, la guerra es el motor más potente del progreso material en nuestro planeta. Así lo atestiguan inventos tan indispensables como el radar, el ordenador o el motor de reacción, que vieron la luz en el seno del más horrendo de los conflictos, la Segunda Guerra Mundial. Es un error típico de una mentalidad antropocéntrica, sin embargo, pensar que la guerra, junto con el acelerado desarrollo que desencadena, es algo intrínsecamente humano. La competencia agresiva entre seres vivos no sólo se remonta a los orígenes de la vida en la Tierra, sino que, de manera análoga, puede ser la causa que subyace a la sobrecogedora variedad y complejidad de la vida que vemos a nuestro alrededor. Y de entre todos los conflictos que han propulsado la evolución de la vida, el más importante, prolongado y encarnizado es sin duda el que enfrenta a organismos víricos (virus) y organismos celulares (compuestos de una o más células). Esta guerra lleva rugiendo, silenciosa pero incansablemente, durante cada segundo de los últimos tres mil millones de años, y aún sigue su curso en este preciso instante, en el suelo que pisamos, en los objetos que usamos, en los alimentos que comemos, y en nosotros mismos. El cuerpo humano, con sus diez billones de células, es el hogar de un número diez veces mayor de microorganismos, tales como bacterias, y cien veces mayor de partículas víricas, o viriones (esos minúsculos agentes que erróneamente conocemos como ‘virus’). Muchos de estos ‘compañeros’ no sólo no afectan negativamente a nuestra salud, sino que son necesarios para mantenerla. Esto no resta importancia al hecho de que cada uno de nosotros es un inmenso escenario donde la guerra más antigua de este mundo prosigue su curso; una contienda por la supervivencia y la dominación, basada en la constante invención, mejora y robo de armas moleculares, que es reflejo del carácter despiadado y maravilloso de la vida.

Por otra parte, es cierto que todas las formas de vida celular —animales, plantas, hongos, bacterias, protozoos, cromistas y arqueas, en todas sus variantes— compiten inagotablemente entre sí. ¿Qué es, pues, lo que hace a la guerra entre virus y células tan única y esencial para la vida? La respuesta nace de una polémica serie de descubrimientos que sitúan el origen de los virus en un mundo extraordinariamente antiguo, anterior a la vida pluricelular y poblado por microorganismos mucho más primitivos que los que nos rodean hoy en día. La rivalidad entre virus y células, por tanto, lleva existiendo desde los comienzos de la evolución, con lo que su impacto sobre ésta ha sido probablemente mayor que el de ningún otro factor.

Los virus son sin duda las entidades biológicas más misteriosas de este planeta; prácticamente cualquier aspecto de ellos, desde su definición como seres vivos o como simples partículas orgánicas, hasta su origen o su papel en la biosfera, es testigo de un choque entre opiniones y teorías radicalmente opuestas. Definir la naturaleza de un virus implica nada menos que dibujar la línea que separa lo que consideramos ‘vida’ de lo que no. A lo largo del siglo XX, el estudio detallado de partículas víricas condujo a una imagen universal de los virus como meros conjuntos de proteínas y ácidos nucleicos que, amparados por la selección natural, escaparon de la célula y lograron explotar su maquinaria para replicarse a sí mismos; un producto indeseable de la evolución. Aún hoy en día, muchos biólogos describen a los virus como ‘ladrones genéticos’ que nacen y evolucionan mediante el robo sistemático de genes celulares. La importancia del impacto de los virus en la evolución de la vida ha sido, asimismo, abrumadoramente desestimada.

El cambio radical en la opinión de la ciencia hacia los virus se desencadenó en 2002, con el descubrimiento de los llamados virus gigantes. Durante el estudio de microorganismos que infectan ciertas especies de ameba, investigadores franceses hallaron lo que, en base a su tamaño, parecía ser una bacteria. No obstante, pronto quedó patente que este microbio era genética y físicamente diferente a cualquier organismo celular. Se trataba de un virus de dimensiones nunca vistas, capaz de superar a muchas bacterias tanto en tamaño físico como genómico. A este primer virus gigante, bautizado como mimivirus, le siguieron sin demora otras especies, como el marsellavirus o el pandoravirus. La definición de los virus, originalmente basada en el carácter ‘invisible’ de los mismos al microscopio, exigía por fuerza ser replanteada. Algunos de los investigadores responsables del descubrimiento propusieron un nuevo sistema de clasificación de los seres vivos, el cual los divide en dos grandes grupos: organismos celulares y organismos virales.  Como principal argumento de que los virus son formas de vida legítimas, estos científicos señalaron lo que sucede durante la etapa infecciosa del ciclo vital de un virus. Una vez que las partículas víricas (viriones) han conseguido invadir una célula, tiene lugar un fenómeno extraordinario: una nueva estructura —visible al microscopio— aparece en la célula infectada, la cual alberga y protege el material genético (genoma) del virus. Mientras esta estructura, denominada factoría viral, se dedica a fabricar miles de nuevos viriones cargados con copias del genoma invasor, los sistemas ofensivos del virus degradan el genoma de la propia célula. El resultado es una célula sin genoma funcional —es decir, sin vida—, en la que el genoma del virus se expresa y se multiplica aceleradamente, haciendo uso, para ello, de la sofisticada maquinaria de la célula asesinada. Por tanto, el organismo que vemos al microscopio en este punto no es de ninguna manera una célula con miles de pequeños ‘virus’ en su interior; es nada menos que un virus en su estado vivo, que utiliza el envoltorio y la maquinaria celular de su víctima para fabricar un ejército de viriones con el que propagarse a otras células. Los viriones, esas partículas inertes consideradas como la forma definitiva del virus durante más de cien años, se revelan en realidad como simples ‘semillas’ o ‘esporas’ que el virus emplea para dispersar sus genes. Esto significa que, durante más de un siglo, al confundir al virus con su virión, la ciencia ha cometido un error tan terrible como confundir un árbol con una semilla, o un ser humano con un espermatozoide. Un virión no es más inerte que una semilla, incapaz de crecer y reproducirse hasta que se encuentra en el entorno propicio. La diferencia radica en que, al igual que otros parásitos intracelulares —como las bacterias del género Rickettsia—, un virus necesita invadir una célula y hacer uso de sus recursos para vivir. En este sentido, los virus son, de hecho, organismos celulares, ya que durante su etapa metabólicamente activa cuentan siempre con una célula, aunque se trate de una célula ‘prestada’. Esto revela la extrema inteligencia y elegancia que subyacen bajo el diseño minimalista de los virus, fruto de una evolución inconcebiblemente prolongada. 

Factoría viral de un mimivirus (centro) y viriones en diferentes fases de desarrollo (hexágonos) a su alrededor, en el interior de una ameba infectada. (Imagen: Didier Raoult.)

Aun con todo esto, numerosos biólogos continúan rechazando la idea del virus como ser vivo. El mimivirus, sin embargo, aún tenía algo que aportar a este respecto: su propia prueba de vida. Al estudiar el virus gigante, los investigadores hallaron partículas de un segundo virus, mucho más pequeño, en torno al primero. Cuando este pequeño virus satélite, apodado sputnik, estaba presente junto con el gigante mimivirus en el interior de una ameba infectada, los biólogos pudieron comprobar cómo el mimivirus encontraba dificultades para reproducirse, dando a la ameba la oportunidad de sobrevivir al ataque. Sputnik fue el primer virófago jamás descubierto, un virus que infecta exclusivamente a otros virus. La posibilidad de que un virus pudiera ser infectado por otro nunca había sido contemplada, y constituye una prueba capital de que un virus tiene vida, dado que sólo un ser vivo puede ser infectado por un virus. ¡Es decir, los virus han demostrado por sí solos su propia condición de seres vivos!

¿Cuál es, entonces, el verdadero origen de los virus y su papel en la evolución de la vida? Al contrario de lo que muchos científicos piensan, los virus no son ‘ladrones genéticos’ que sobreviven gracias al robo de genes celulares. Más bien al contrario; gran parte de las proteínas víricas no tienen equivalente en ninguna célula conocida, indicando que el origen de los virus es extremadamente antiguo, remontándose hasta un mundo poblado no por las células de hoy en día, sino por otras más primitivas que, con el paso del tiempo, dieron lugar a aquéllas. Una hipótesis razonable es que los virus proceden de un grupo de células primigenias que se adaptaron gradualmente a la vida parasitaria, simplificando enormemente su estructura y su genoma conforme desarrollaban una mayor dependencia de los genes y componentes de otras células. Este fenómeno, denominado evolución reductiva, halló en los virus su máxima expresión. Haciendo uso de un minúsculo número de proteínas, estos organismos han sido capaces de desarrollar estructuras asombrosamente complejas e ingeniosas, específicamente diseñadas para sortear cada una de las defensas de sus víctimas, y donde una sola proteína puede adoptar multitud de papeles diferentes. Miles de millones de años de evolución han hecho de los virus los seres vivos mejor diseñados y adaptados del planeta; es por ello que ningún organismo —ni siquiera el ser humano, ni siquiera los propios virus— puede escapar definitivamente a su ataque.

La idea de que los virus han tenido un impacto fundamental en la evolución de la vida en la Tierra nace de la observación de que estos organismos son auténticos manantiales de diversidad genética; su capacidad para mutar en periodos mínimos de tiempo les permite desarrollar nuevos genes. No sólo esto, sino que son precisamente las células, y no los virus, los ‘ladrones’ que acogen un flujo constante de genes víricos. Un ejemplo de esto son los virus que infectan a bacterias (bacteriófagos), los cuales juegan un importante papel en la transferencia directa de ADN entre estos organismos, promoviendo procesos evolutivos independientes del tradicional flujo de genes de padres a hijos. En cuanto a nosotros respecta, es revelador el dato de que en torno al cuarenta y dos por ciento del material genético humano es de origen vírico. Una parte de este material genético ha tenido indudablemente un papel crucial en el curso de nuestra evolución; sin ir más lejos, uno de los genes esenciales en el desarrollo de la placenta fue confeccionado hace millones de años por un virus, antes de acabar ‘insertado’ en el genoma de algún ancestro del primer mamífero de la historia. No menos sorprendente es el hecho de que la principal diferencia entre nuestro genoma y el del chimpancé es precisamente el número, variedad y localización de elementos de origen vírico que forman parte del material genético de ambas especies. Algunas teorías van tan lejos hasta sugerir que el origen del propio ADN, así como de los mecanismos de replicación del mismo, surgieron por primera vez en los virus y fueron luego adoptados por células primitivas, hasta entonces basadas en ARN, un tipo más simple de ácido nucleico.

La verdadera diversidad de los organismos víricos es sin duda enorme y permanece en gran parte inexplorada. Es evidente, sin embargo, que el papel de los virus en la historia de la vida ha sido inmensamente mayor de lo que muchos todavía piensan. Nuestra visión ‘celulocéntrica’ del mundo nos ha llevado a pasar por alto el efecto de la eterna contienda entre el virus y su anfitrión, que no obstante contribuye a encauzar el maravilloso proceso de la evolución, del que todas las formas de vida se benefician. De este modo, el mundo celular y el mundo vírico han evolucionado de forma paralela, pero esencialmente distinta; uno, hacia formas cada vez más complejas; el otro, hacia la máxima simplicidad. Esta depredación de tres mil millones de años de antigüedad, con su inagotable y siempre cambiante repertorio de armas, tácticas y engaños, es probablemente la responsable de que todos los seres vivos, ya sean virus, bacterias, amebas, árboles o humanos, sean como son hoy en día. Al fin y al cabo, nada encaja mejor con la naturaleza inimitable de este mundo que la idea de que la fascinante complejidad de la vida pueda ser fruto de la creatividad del más simple de los seres.

 

Referencias:
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).

Este artículo fue publicado en el periódico El Día el 10/01/2016.

The unleashed cancer

The most ancient and widespread tumour on Earth reveals unwonted aspects of cancer.

Lee este artículo en español

Canine transmissible venereal tumour cells are an infectious parasite of dogs from all around the world. (Credit: Olga Glebova.)

CANCER is the cause of one in eight deaths worldwide, and its treatment is generally complex and riddled with side effects. All this has turned cancer into the most feared disease of the developed world. The term ‘cancer’ actually encompasses more than a hundred different diseases, each sharing an identical origin. Cancer is an almost unavoidable consequence of natural selection at the cellular level; sporadically, a single cell can acquire the ability to replicate itself uncontrollably, due to alterations in its DNA, hence being gifted a selective advantage in the face of its neighbours. It could be said that this cell is ‘better adapted’ to its microscopic environment, a fact that increases its likelihood of success. But what is beneficial for a single cell is not always so for a whole organism. The immune system, in consequence, swiftly eradicates any cell that has lost control of its own proliferation.

Some cells, however, go much further. They are able to develop molecular counter-measures that avoid their detection or defeat by the hand of this army that patrols every micrometre of the body. These cells thus obtain the go-ahead to exploit natural selection mechanisms, growing, reproducing, spreading and invading the organism. The cancer, made up of increasingly ‘better’ — more aggressive — cells, takes over the body, giving no chance for defence. Because cancer cells have the ability to reproduce indefinitely, they are usually said to be immortal. Paradoxically, cancer itself turns out to be, however, a very short-lived biological entity. The emergence of a tumour normally leads to two possible endings: the death of the tumour, thanks to treatments of ever-increasing efficacy, or the death of the entire organism. Some types of cancer, on the other hand, have managed to escape this fate of self-destructive voraciousness. Due to an extraordinary series of biological circumstances, these tumours developed adaptations that allowed them to leave the body wherein they originated and to infect many others, thereby adopting a parasitic way of life that has granted them a condition of true immortality. These are the so-called transmissible cancers.

Canine transmissible venereal tumour (CTVT) was the first cancer recognised as being transmissible. This tumour, present in at least 90 countries of all the inhabited continents, arose in a dog of a breed closely related to the Siberian Husky, which lived and died around eleven thousand years ago. This places the birth of CTVT at the end of the ‘ice age’, in the time of the last mammoths, not long after the domestication of the first dogs. The cells that escaped the body of this dog kept living and multiplying in others, as they still do today, after the spread and colonisation of humans and dogs across the world. The total number of CTVT cells that have existed and exist since then far exceeds the number of cells comprising the body of the animal wherein they initially arose. This makes CTVT not only the most widespread and ancient cancer known, but surely the oldest living organism on Earth.

CTVT is common in tropical and subtropical countries, and is frequently found in stray dogs, guard dogs or hunting dogs, rather than in domestic animals. Its appearance ranges from microscopic nodules to masses of more than fifteen centimetres in diameter. As the name indicates, it is usually located in the genital area; during coitus, the tumour promptly tears and bleeds, allowing the transfer of living cancer cells that will seed a new tumour in a new host. Nevertheless, the progression of the disease is closely linked to the animal’s immunological condition. In dogs with a weakened immune system or in poor general state of health, the cancer can advance to the phase of metastasis, aggressively invading different areas of the body and causing the host’s death. But metastasis is not the only cause of death related to this disease; the fragility of the tumour and its exposure to the environment can lead to severe infection, while, in certain cases, the tumour reaches such dimensions that it completely obstructs the urinary duct of the animal. Fortunately, most CTVT cases are easily treatable with chemotherapy or surgery; in dogs with a robust immune system, the tumour can even remit without treatment.

CTVT developing inside a female dog's vagina. (Credit: Anna Czupryna.)

The eleven-thousand-year-old DNA of this cancer suggests that its links with mankind, through the omnipresent canine company, go back much farther than previously thought. Supporting this is the first written mention of this venereal tumour by the veterinarian Delebere Blaine, who depicted it as a common condition in stray dogs of the Georgian London. Although the history of CTVT stretches back to a much more distant past — it is known that its worldwide spread coincided with the time of the conquest of new continents by European powers — its transmissible nature was not conjectured until decades ago. Thanks to the impressive advances in fields such as molecular biology, genomics and DNA analysis technologies, today we know not only that this cancer requires no intermediary to go from one dog to another, but also that its origin corresponds to well-known mutational mechanisms, and that CTVT and certain human cancers are not as different as it might seem.

It is evident that a succession of implausible events allowed CTVT to surpass the multiple barriers that exist between any tumour and the ability to spread between individuals, to the point of becoming a real parasite of thousands of animals the world over. The first such barrier, the need for physical contact, was resolved with the settling — perhaps since the first moment, or during the first stages of its evolution — of CTVT as a venereal tumour that thrives around the genital region of infected animals. The second barrier, imposed by the immune system of the recipient animal (the new host), is similarly outsmarted by means of mechanisms that remain partially unclear. CTVT is capable of aborting the organism’s response in the face of cells that are evidently alien and invasive. The study of these immune-suppression mechanisms could spark great advances in areas such as organ transplantation, where it is necessary to neutralise the recipient’s immune system for the foreign organ not to be rejected.

Eleven millennia of life on Earth add a new hurdle to those already mentioned: maintaining a complement of genes (genome) sufficient to keep living, despite the unavoidable accumulation of mutations over the centuries. The genome of CTVT contains about two million mutations, hundreds of times more genetic alterations than would be observed in a typical cancer. The accumulation of mutations, which is initially cancer’s fundamental tool for evolving into a more aggressive form, at some point — a point that cannot be attained by a human cancer — turns itself into a serious threat to tumour survival. Even though mutations have the potential to improve the cancer’s adaptation to its environment, the likelihood that the next modification will be lethal to the cell necessarily increases over time, especially in such a long-lived genome. In this scenario, natural selection again exerts its influence on the cancer, favouring those cells that acquire new mutations more slowly. It is likely that less aggressive tumours, with less capacity to put their host’s health at risk, also benefitted in the long term. This idea is supported by the exceptionally stable genetic profile of today’s CTVT, which makes it possible that tumours found in dogs from Australia, Venezuela, United States, Cape Verde, Malawi, Russia, Ukraine or South Africa present a nearly identical genome. As a consequence, CTVT provides a way to study a stage of evolution that has been denied to any other cancer type. This peculiarity has made the oldest living cancer into an object of special scientific attention. Researchers from different countries study CTVT with the aim of shedding light on the evolutionary processes that affect any cancer, but which are normally undetectable due to the short life of this disease.

A transmissible cancer is an extremely unusual natural phenomenon, which has been described only three times in the animal world. In humans, transfer of tumours has occurred on a few notable occasions: from mother to foetus during pregnancy, or by means of a surgical accident or an organ transplant. A case of particular scientific and ethical interest is that of the experiments performed by Chester Southam in the United States during the sixties and seventies, which proved that cancer can be transferred between humans under certain conditions. However, the spontaneous emergence of a cancer capable of transmission between individuals demands specific adaptations and unwonted natural situations. Thanks to a series of events so astonishingly extraordinary that they defy imagination, cancer, this ‘mere’ genetic disease, has evolved to become a parasitic organism of admirable efficacy, perhaps with a much greater historical impact on the evolution of the animal immune system than we now imagine. If the ability of canine transmissible venereal tumour to remain one step ahead of its host is sustained over time, the fate of this ageless cell lineage is to become the oldest, most successful life form on the planet.

 

If, as a veterinary professional, you believe that you may have identified a CTVT case, please contact the Transmissible Cancer Group on ab2324@cam.ac.uk.

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

References:
Stratton, M.R. et al. The cancer genome. Nature (2009).
Strakova, A., Murchison, E.P. The cancer which survived: insights from the genome of an 11000 year-old cancer. Curr. Opin. Genet. Dev. (2015).
Ganguly, B. et al. Canine transmissible venereal tumour: a review. Vet. Comp. Oncol. (2013).