A little girl is about to be born. Just 200 days ago she was a single cell, a mote quickened into new life, yet made from the salvage of the inaccessibly old; a new combination of genes, passed down like heirlooms from the first men and women; the first fishes that ever crawled from the sea, the first things that were ever alive. Her genes are at the same time a treasury which belongs to her alone, and the heritage that belongs to all of us.
In 200 days she has grown from the edge of invisibility until she is bursting to get out. Her growth has been more than mere inflation. The single cell of a few months earlier has divided and multiplied to become trillions strong, with each cell in its own place in relation to all the others. There is a direction to her organization almost too intricate to follow: the child I shall soon see in all her wholeness is ordered on every level. She will have organs; a heart, arms and legs, brain and skin. Her organs will, in turn, be made of tissues, carefully assembled – ranks of muscles; a frame of cartilage, soon to become bone; neurones wiring themselves together.
Before the microscope was invented, organs and tissues were thought to be the indivisible atoms of life. Organisms without organs or tissues were not reckoned to be truly alive. Until the microscope revealed it, nobody suspected that organs and tissues had any kind of constituent structure, that the intricate order of a newborn baby goes beyond the limits of human sight – down to the submicroscopic communities of cells and chromosomes, to the genes themselves. My daughter, yet to emerge, will be not only an organism, unitary and independent in her own right, but a vast, tiered community, a hierarchy of systems, built on trillions of interlocking cells and thousands of genes, independent yet interdependent. All this from one egg cell and one sperm cell, in just 200 days.
From a single fertilized egg will have emerged a human, a unique individual with an identity and a name – and yet recognizably the same as the billions of humans already in existence. How can it be that a person can be made in so short a time and with such intricacy? How can a person be made to be unique, yet clearly a member of the human species?
A little girl is about to be born. All of a sudden, she is here. Her umbilical cord is cut and tied. After moments which pass in viscid slowness, she cries. A nurse calms her, weighs and inspects her. She is fine, she is OK – all of her – and the first step on her journey through life is complete. In many ways it is the most important and the most hazardous, for it is in the first few weeks of life that the genome does the work of a lifetime. In the first four weeks after conception, the genome takes a formless speck and shapes it into what is recognizable as a human being. No other comparable period of human life is as significant, as defining or as busy. The remarkable thing is that the genome can act both so quickly and so reliably: in the time it has taken you to read this paragraph, another 200 babies will have been born. Each will be slightly different from the next, but they will all be human, similar enough to share the joys and pains of life. The genome performs this delicate act of construction, shaping form from the formless, with breathtaking speed and – to judge from the crowds of human beings already on the planet – effortless reliability.
My daughter’s voyage began thirty-seven weeks before her birth, when one of many thousands of sperm met a single, receptive egg shed by one of the two ovaries of the mother-to-be.1 The sperm penetrates the egg, disappearing into its gelatinous confines. The egg responds by expanding outwards, offering a distended envelope as an obstacle to any other approaching sperm. The successful sperm is like millions of others, a package of genetic material propelled by a lashing tail, distinguished only by its luck in having got there first. But in victory lies annihilation. The tail and all the other parts of the sperm are dismembered by the egg; the genetic material, packed into the head, sinks downwards to the nucleus of the bloated egg and merges with it.
A fertilized egg is called a zygote. Its genome is unique – the germ of a new individual – but not new, being made of equal contributions from each parent. Within twenty-four hours, the zygote divides into two identical cells, lying within a common fertilization membrane. Just four days after conception, the embryo has become a ball of thirty-two cells straining at the confines of this same fertilization membrane. At this stage the embryo looks like a berry – in fact it is known as a morula, after the Latin for mulberry. After another day, a small pool of fluid starts to form in the middle of the morula, pressing the cramped cells up against the inside of the membrane. When this happens, the morula crosses the line to become a new stage, the blastocyst.
As these events unfold within the fertilization membrane, the germ of new life floats down the fallopian tube, from the site of fertilization and into the uterus. This is when the embryo performs its first act of defiance: the blastocyst bores a hole through the fertilization membrane and emerges, rather like a butterfly from a chrysalis, to become a free agent. This freedom is temporary, for the naked blastocyst immediately burrows its way into the spongy lining of the uterus, an event known as implantation.
The second week of gestation begins with some internal housekeeping as a knot of cells on one shore of the blastocyst cavity – the pool of fluid within the blastocyst – begins to organize itself into discrete layers. A second fluid-filled cavity forms between two of these layers and the blastocyst wall. This new, second cavity will eventually become the so-called amniotic cavity, whose rupture, months later, signals impending birth. The result of this process is the formation of the germinal disc – a flat, circular sheet, just two cells thick, suspended within the blastocyst, bounded on one side by the original blastocyst cavity (now called the yolk sac) and on the other by the amniotic cavity. Imagine two soap bubbles incompletely separated, joined by a common membrane.
By the end of the second week the pair of bubbles, joined at the germinal disc, is suspended by a thin stalk within a still larger bubble called the chorionic cavity. The whole arrangement buries itself into the uterine wall, stimulating the growth of blood vessels between mother and embryo that will become the placenta, the vehicle by which the growing embryo receives nourishment from its mother, and voids its waste. Everything in this elaborate structure constitutes tissues for the nurture and cosseting of the embryo. All, that is, except for the germinal disc, the minute part of the embryo that will actually become a new human being.
And yet there is nothing about this structure that makes it look like a child. There are no arms, legs, head, skeleton or internal organs. But it is at this stage, during the third week, when the rudiments of a human are sketched out. If the germinal disc is regarded as a map, a flat representation of a three-dimensional sphere, it is possible to see how a human might emerge. For my daughter, as with all other babies, the geography of the human form begins to emerge in the third week, when a furrow appears to plough itself across the top layer of cells in the germinal disc. This is the primitive streak, the Greenwich meridian of the early embryo.
The layer of cells in which the primitive streak forms is the ectoderm – the tissue that will eventually become the skin, nervous system, and much else. The lower layer of cells, or endoderm, continuous with the yolk sac, is the future digestive tract. At the beginning of the third week, cells from all over the ectoderm flow towards the primitive streak like water drawn by a weir, pouring over its edges, cascading downwards to collect between the ectoderm and endoderm.
This distinctive process, called gastrulation, creates a third, middle layer of cells, the mesoderm, between the ectoderm and the endoderm. This new layer of cells will become the muscle, skeleton and internal organs of the new human being. As this process continues during the third week, the primitive streak starts to shorten, leaving a trail in the underlying mesoderm in the form of a tube of tissue. This tube is the notochord, a stiffening rod that will become the backbone.
Towards the end of the third week from fertilization, after the primitive streak has disappeared, another furrow starts to form in the ectoderm, immediately above the notochord. Indeed, this new groove cannot form unless the notochord exists, because chemical signals secreted by the notochord cells are partly responsible for engendering this new structure. This is the neural groove, which will eventually become the spinal cord and the central nervous system.
Meanwhile, knots of mesoderm start to coagulate, in pairs, one of each pair on each side of the notochord, like rows of poplars lining a French country road. This coagulation starts at the front of the embryo – the region that in the weeks to come will form the base of the skull – and progresses back towards the tail end. These knots are the somites, the segmented ‘muscle blocks’ seen in all backboned animals, from which derive the vertebrae and other bones, the muscles, and other structures of the body, including the limbs. By the end of the third week, the brain begins to form as two patches of ectoderm on either side of what will become the front end of the neural groove.
The third week is a time of radical transformation, with the creation of a third layer of cells, and the formation of the tissues that will become the backbone, muscles, spinal cord and brain. But these changes are as nothing compared with the frenetic fourth week of gestation, perhaps the busiest week in the life of any human being. This fourth week begins with the process of neurulation, in which the edges of the neural groove grow upwards and inwards, meeting in the middle to form a closed tube. While the neural tube is closing, parts of the paired somites lying on either side grow inwards to surround the neural tube and notochord. While the neural tube is forming, something quite magical happens. A group of cells in the parallel edges of the neural tube migrate from the ectoderm of the neural tube, where they originate, and embark on a mission to transform parts of the rest of the embryo. As these cells, known collectively as the neural crest, travel through the body, they interact with a variety of rather ordinary cells and make them into something special. Much of the skin, the sense organs, the bones of the face, and many other structures owe their origin to the neural crest.
The majority of this activity – the formation of somites, the notochord, the neural tube, and so on – is concentrated in the upper surface of the embryo: in the ectoderm and the mesoderm immediately beneath it. By comparison, the growth of the endoderm is slow. This disparity puts the embryo under such strain that it can no longer remain a flat disc. The burgeoning upper surface curls round, downwards and inwards, surrounding the endoderm, the edges meeting beneath. In this way, the embryo folds itself round the stagnating yolk sac to create a gut tube, and a three-dimensional creature is realized from a two-dimensional map. In engineering terms, the embryo becomes a system of nested tubes rather than layers, making possible the development of those systems of tubes without which life is impossible – the heart, the major blood vessels, the stomach and intestines, and so on.
By the end of the fourth week a human embryo is about the size of a garden pea, and has acquired the rudiments of limbs, kidneys, and eyes, and the very first outlines of a face. It still has much to achieve, but subsequent events are essentially elaboration on a pattern laid down in the first four weeks after conception. Directing this fervid activity is the genome, the agent that creates form from the formless. That the genome sets in train events which create a recognizably human embryo from a single zygote in less than a month is indeed remarkable – yet many questions remain to be asked.
For example, if speed is of the essence, why is the process of human development quite so complicated? Would it not be more efficient to grow a baby from a ball of cells directly, without first flattening a spherical blastocyst into a germinal disc, only to roll it all up again later? Might there not be simpler ways to make an embryo? Possibly, but that isn’t the point: the genome has a history, and embryos are not created anew each time, as if from scratch. The genome is inherited, passed down through a chain of ancestors unbroken since the dawn of life, more than 3 billion years ago. So, as well as creating each new human, the activities of the genome reflect the evolutionary history of the human species as a whole. In the dance of its formation, an embryo is paying homage to the deeds of its ancestors. And some of those deeds were done an extremely long time ago.
More than 300 million years ago, our fishy and amphibian ancestors were creatures whose eggs, laid in water, were small and contained little yolk. That is true of the embryos of modern frogs, for example, and the yolk is entirely subsumed within the embryo. Because of this, frog embryos develop more or less directly from a ball of cells: at no stage is the ball rolled out flat to create a germinal disc which must be rolled up again later. Nevertheless, the presence of yolk – which, as in human embryos, is associated with the endoderm – makes the animal’s endoderm much slower to develop than the ectoderm.
When our remote ancestors, the earliest reptiles, started laying eggs with hard shells, on land, the embryos had to be supplied with enough yolk to feed them through a long period of incubation. In the egg of any reptile or bird, the volume of yolk is so great that the embryo is tiny by comparison, a flat disc of cells pressed up against the yolk like a lentil stuck to a watermelon. So it was with our egg-laying, reptilian ancestors. One lineage of reptiles evolved into mammals which nurtured their young in a womb. This event happened perhaps 100 million years ago, when our ancestors were small, rat-like creatures scuttling around in the shadows of the dinosaurs.
The yolk sac of a human embryo is a vestigial structure, nothing like the enormous yolks of birds or reptiles. At a very early stage in its development, the human embryo becomes implanted in the lining of the womb, where it produces blood vessels which tap into the maternal circulation, allowing it to feed directly from the mother. Yolk is therefore unnecessary – and neither, therefore, is the requirement that human embryos should be flattened into a disc, to make the most of the space between a large yolk and a hard shell, because neither yolk nor shell have existed in the human lineage for millions of generations. And yet, even now, each human embryo is rolled out to form a germinal disc, reptile-fashion, before rolling up again. There is no greater argument for the gradual evolution of humans than the continued existence of these ancient vestiges.
An echo of an even more distant time in our evolutionary history is found in the formation of the notochord, that rod-like structure which forms beneath the primitive groove in the third week after fertilization. In backboned animals, the notochord is a place-marker for the backbone that eventually replaces it. Long before a human baby is born, its notochord is replaced by vertebrae – the bones of the spine – and the notochord itself survives only in the disks of spongy tissue that separate and cushion the individual vertebrae.
A notochord is also possessed by creatures that never have a backbone at any stage of their life: the shy, rock-pool creatures known as tunicates or sea squirts, as well as superficially fish-like animals called lancelets. Most sea squirts lack a notochord as adults, but this structure is found in the tadpole-like larvae of many sea squirt species. In lancelets, and in the most primitive fishes, the notochord is retained throughout adult life. All animals with a notochord also have a hollow spinal cord, lying above the notochord – without which the spinal cord could not form. The creation of a hollow nerve cord from the rising and coalescence of twin wave-crests of tissue is common to all these creatures. Taken together, the notochord and spinal cord are a distinctive marker, demonstrating a close kinship between backboned animals, sea squirts and lancelets.
Lancelets are vaguely fish-like in outline, and are our closest relatives in the world of invertebrates, almost – but not quite – fishes.2 In many ways, lancelets seem like fishes only half-made: they have a notochord, a spinal cord and somites, but no bones, fins, eyes, ears, teeth or skin. They have virtually no brain and not much of a head. Lancelets always remind me of the last figure in Shakespeare’s seven ages of man – sans eyes, sans teeth, sans taste, sans almost everything. But the key difference between lancelets and ourselves is the neural crest, a kind of tissue found only in backboned animals, whose influence on other tissues creates much of the skull and skin, and many parts of the heart, limbs and sense organs. The lancelet is living proof of the importance of the neural crest, for it is as close to a backboned animal as it is possible to be in the absence of a neural crest.
Lancelets are the closest relatives of backboned animals that exist in the modern world. The neural crest evolved in the earliest ancestors of backboned animals, after their lineage had become distinct from that of lancelets. Given that fossils of backboned animals – very primitive fishes – have been found in rocks laid down 530 million years ago,3 the common ancestor of lancelets and backboned animals must have lived even earlier. The common ancestor of backboned animals, lancelets and sea squirts – that is, the first creature with a notochord – must have lived even earlier than that. In the gestation of any individual human, the notochord forms three weeks after fertilization and disappears as a discrete structure before birth. The neural crest cells appear in the fourth week, and soon disperse to work their special magic throughout the body. As episodes in a single pregnancy, they are fleeting; as markers of our heritage, they are incomprehensibly ancient.
Within the headlong rush of the first few weeks of the development of a single human embryo, it is possible to make out still fainter echoes of the story of human evolution. In the fourth and fifth week after fertilization, the neck and lower facial region of the newly folded embryo start to pucker into a series of folds and ridges – the pharyngeal arches. There are five pairs of these ridges, one member of each pair on each side of the embryo. The fates of the pharyngeal arches are many and varied. Tissues from the first arch – nearest the head end of the embryo – become the jawbone, the muscles concerned with chewing, and the hammer and anvil bones of the middle ear; the second arch gives rise to the stirrup bone in the middle ear, the hyoid bone, parts of the tongue, the muscles of facial expression, and so on. Tissues from successive pharyngeal arches contribute to the thyroid cartilage (‘Adam’s apple’), the larynx and part of the aorta – a major blood vessel that emerges from the heart.
The pharyngeal arches form anew in each human embryo. At the same time, they are of great antiquity, dating from a time when our remote ancestors were simple sea creatures that fed by straining particles of food carried in sea water. They sucked water in through their mouths and expelled it through a series of clefts in the pharynx, retaining any particles with sieve-like organs which covered the clefts. This mode of feeding can be seen today among sea squirts and lancelets. The young of primitive, jawless fishes called lampreys are also filter feeders, even though adult lampreys have abandoned this peaceable habit for a life of parasitic predation. The habits of young lampreys represent a memory of a time when, between 400 and 500 million years ago, the extinct relatives of lampreys were filter feeders even as adults.
Pharyngeal clefts can also be seen in obscure sea creatures called acorn worms, which are more closely related to starfishes and sea urchins (known collectively as the echinoderms) than they are to backboned animals, or even to sea squirts and lancelets. Some extinct echinoderms had structures very like pharyngeal clefts, although no modern echinoderm has anything similar; and the last echinoderm with structures resembling pharyngeal clefts died out more than 300 million years ago. The presence of pharyngeal clefts in such a wide range of animals, from human embryos to the long-extinct cousins of starfishes, implies that this characteristic arose in the common ancestor of all these creatures – long before the evolution of the notochord in the more exclusive common ancestor of sea squirts, lancelets and backboned animals. This creature must have lived at least 550 million years ago.
It is a source of wonder that the attributes that define and justify our everyday humanity – our faces, our expressions, our voices, even the beating of our hearts – all stem from the feeding gear of some emotionless, expressionless animal which dwelt in a rock pool more than half a billion years ago. Such is the depth of our heritage. Even so, it is important to remember that the pharyngeal clefts in human embryos resemble the gills of a larval lamprey only inasmuch as a caricature resembles the real thing. The pharyngeal arches in human embryos are never used in feeding. (Indeed, they are never even perforated.)
All these vestiges do is remind us that individual development has an evolutionary history, too. The genome, which is ultimately responsible for this development, cannot produce a human being in what would seem to us a simple and direct way, without reference to the passage of its own evolutionary adventures over billions of years. The germinal disc thus represents not just a stage in the development of an individual human, but a stage in the evolution of humanity and of life as a whole over more than 3 billion years.
Passed down from generation to generation, the genome is the common thread that runs through all the organisms that have ever existed on our planet. But the passage of the genome from parent to offspring is not so assured that mistakes cannot be made. Sometimes these mistakes lead to stillbirths, or to monsters. Not all mistakes are so destructive, and their accumulation over countless generations leads to variation: variation between individuals, and between different species. Variation is the staff and life of evolution. Without variation, change cannot happen, and it is in the heritable genome that any change is cemented and memorialized. Because the genome has been evolving for such a long time – about a quarter of the age of the Universe – the accumulation of variation has led not only to the otherwise inexplicable richness of the development of individuals, but to an amazing abundance of different species.
The exact number of species that have ever existed is unknowable, but likely to be very large indeed. Current estimates of the number of species living today – an instant in the history of the Earth – average in the low tens of millions.4 People in this environmentally depleted and increasingly urbanized world might find the scale of this diversity exceedingly hard to grasp. For those of us unable to go hiking in Amazonia, the closest we can get to the true biodiversity experience is to seek out an unreconstructed museum created at the triumphal height of the Victorian age, when London could command every corner of the Earth, and when the reaction of curators to the impending doom of species was not to conserve or breed the remaining individuals, but to kill and embalm them for ‘posterity’.
One such museum – and a particular favourite of mine for its undisguised contempt for postmodern, politically correct squeamishness – is the Rothschild Zoological Museum, in the small town of Tring, a short drive north-west of London. It was founded by Lionel Walter Rothschild, later Lord Rothschild (1868–1937), an enigmatic and eccentric scion of the wealthy and influential Rothschild banking family.5 It is lovingly maintained in its Victorian state by the trustees of the more famous Natural History Museum in South Kensington – who have, thankfully, done their best to maintain the ambience of this spectacular tribute to the art of taxidermy. Rothschild started collecting natural history specimens as a boy. Thanks to a monomania backed by immense wealth, he had, by his death, amassed the greatest natural history collection ever made by one man.
The ranks of mounted trophy heads remind you that this collection was made at the zenith of the British Empire. All animal life is there in its bewildering variety – an Alexandrian library of the possibilities of nature, from elephants to elephant seals, pipefishes to pangolins. There is an impressive collection of stuffed domestic dogs, a great polygonal case of humming-birds, and a lion at the head of a staircase who would look commanding were he not quite so threadbare. There are birds in marvellous profusion: orioles and oropendolas, kittiwakes and cormorants. There are giraffes, gorillas, giant tortoises, a belfry of bats and a room devoted to zebras. There is even a case of fleas, each dressed in costume (and if that in itself is not a testament to eccentricity, I don’t know what is). Many of the animals on display in the museum are now extremely rare in the wild, if not actually extinct. There is a case of endangered and extinct birds, in which the Carolina parakeet rubs plumage with the passenger pigeon, and all hold court before that epitome of extinct birds, the dodo.
The collection is so rich and so diverse that first-time visitors to Rothschild’s museum are overwhelmed. Even seasoned visitors come away having seen something new in the seemingly unchanging cabinets. The collections may contain animals that visitors will never have dreamed existed. Rothschild clearly spent a lot of time making his collection comprehensive. For example, you might be unfamiliar with the pangolin – an animal armoured with triangular, overlapping scales, so that it looks like a gigantic pine cone. Well, the museum has a whole case of them, showing pangolin species large and small. You come away from the building with the impression that evolution has produced this cornucopia of diversity with a degree of insouciance that borders on effrontery.
The scale of the diversity of nature, especially in the tropics, had a lasting impact on another Victorian collector, the young Charles Darwin, whose five-year voyage on the Beagle instilled in him the germ of what was to become his theory of evolution by natural selection. Before Darwin, the variation of nature was held to be the visible sign of a fallen world. His great insight was to see that variation was not an irritating consequence of imperfection, but the very engine of change and the ultimate source of the diversity that confronted him. Although Darwin had little clear idea about precisely how animals and plants passed on their traits to their descendants, he grasped an essential quality of the genome – its continuity between past and future, with diversity a simple consequence of the genome’s antiquity. It is no coincidence that the only illustration in the Origin of Species depicts evolution as a tree, with a root and stock giving rise to ever-bifurcating branches and twigs.
In any tree, whether growing in a forest or used as a metaphor for evolution, the branches are not divided into neat segments. In a real tree the trunk leads to boughs, branches and twigs in smooth continuity. Any decision about where the trunk ends and the branches begin is likely to be arbitrary. So it is with the metaphorical tree of life. Modern evolutionary biologists are deeply concerned with the problems posed by attempts to demarcate one species from another: the sheer difficulty has ramifications in fields as rarefied as the philosophy of taxonomy, and as practical as drawing up policies for the conservation of wildlife. The problem of imposing lines on diversity is met in another guise in the creation of form from the formless, the development of a new individual from a zygote. Those committees whose unenviable brief it is to articulate the ethics of research into human reproduction often end up trying to answer an impossible question – at what point does a new life begin?
I could argue that the formation of the germinal disc marks the start of a new life, for it is at that point that one can clearly discern the germ of a new human amid those structures destined only to support its growth, and which will be discarded later. However, I should not like to press the point, and it would be just as great a mistake to cleave too rigorously to the idea that a new life begins precisely at conception. To be sure, conception is the moment when a new and unique genetic constitution is initiated – the combination of genes from both mother and father that will frame the new child’s physiology and, to an extent, their character – but this step was itself long in preparation.
Even before fertilization, maternal genes in the egg cell act to dispose various substances around the cell that influence the course of development once fertilization has taken place. Maternal genes direct the geography within which the embryo subsequently finds itself, determining its north, its south, its east and west. Maternal genes are responsible for igniting the new genome and directing its first steps, regulating the activities of genes in the zygote which, in turn, dictate the basic ground plan of the embryo. These zygotic genes would not work at all but for maternal genes which are active even before fertilization. And in this sense we can see that the conception of my daughter, although unique as an instance, did not spring from nothingness but was the continuation of an ongoing process, part of the skein of life.
Once an embryo is formed, almost the first thing it does is prepare for the generations to come. This can be seen as early as the second week after fertilization, when the embryo is still in the germinal-disc stage. At that time a small group of cells in the ectoderm detaches itself from the embryo and migrates to the yolk sac. These are the primordial germ cells – the ancestors of the eggs or sperm of the adult. In the fourth week, when the embryo has folded in on itself, the primordial germ cells return to the embryo, coming to rest in two patches on the back wall of the body cavity. Their journey complete, these prodigal cells stimulate the development of structures that will eventually become the sex organs – the ovaries of the female, the testes of the male. The implication is that the bodies of men and women prepare for the engendering of their own offspring long before they are born themselves, or indeed before they were any more fully formed than germinal discs inside the wombs of their own mothers.
Such themes of continuity with the past and future make it very hard to point to any event in the career of an embryo and declare that it marks the origin of new life. Does life begin at conception, with the germinal disc, or at birth? In this light, it could be argued that the life of any individual begins not with the creation of their unique genome at the point of fertilization, but with the conceptions of its parents, or of any of its progenitors to an arbitrarily remote degree. The debate is fuelled by the misconception that there is a clear dividing line between the lives of individuals, when what actually exists is a strand of continuity which runs back to the beginning, and, by extension, into the future. Our parents give us all the faults they had, but we see in the development of individuals more than the likenesses of our parents: for in such development we can hear the echoes of our evolutionary past.